As the number of cases of early-onset colorectal cancer (CRC) diagnosed before age 50 continues to rise, early detection has become increasingly important.

A new study has identified four signs and symptoms that can serve as red flags to facilitate earlier detection of early-onset CRC. The signs and symptoms are abdominal pain, rectal bleeding, diarrhea, and iron-deficiency anemia.

Two symptoms in particular – rectal bleeding and iron-deficiency anemia – point to the need for timely endoscopy and follow-up, the researchers say.

“Colorectal cancer is not simply a disease affecting older people; we want younger adults to be aware of and act on these potentially very telling signs and symptoms – particularly because people under 50 are considered to be at low risk, and they don’t receive routine colorectal cancer screening,” senior investigator Yin Cao, ScD, with Washington University School of Medicine, St. Louis, said in a news release.

“It’s also crucial to spread awareness among primary care doctors, gastroenterologists, and emergency medicine doctors,” Dr. Cao added. “To date, many early-onset colorectal cancers are detected in emergency rooms, and there often are significant diagnostic delays with this cancer.”

The study was published online  in the Journal of the National Cancer Institute.

Although previous research has identified rectal bleeding, iron-deficiency anemia, and rectal/abdominal pain as symptoms of early-onset CRC, most studies “have aggregated symptoms till the time of diagnosis,” which limits their use for early detection, the authors explain.

In the current study, the researchers analyzed data from more than 5,000 cases of early-onset CRC and from more than 22,000 control patients using the IBM MarketScan commercial database.

Dr. Cao and colleagues found that between 3 months and 2 years before diagnosis, abdominal pain, rectal bleeding, diarrhea, and iron-deficiency anemia each indicated an increased risk for early-onset CRC.

Among patients with early-onset CRC, 19.3% presented with one or more of the four red flags between 3 months and 2 years prior to the index date; 15.6% had one symptom, and 3.7% had two or more.

After multivariable adjustment, having one symptom almost doubled the risk for early-onset CRC (odds ratio, 1.94); having two symptoms increased risk by more than threefold (OR, 3.59); and having three or more boosted the risk by more than 6.5-fold (OR, 6.52).

Abdominal pain was associated with a 34% higher risk of early-onset CRC (11.6% among case patients vs. 7.7% among controls; OR, 1.34).

Although not as common, rectal bleeding was associated with the highest odds for early-onset CRC (7.2% case patients vs. 1.3% controls; OR, 5.13).

The other predictive signs and symptoms included diarrhea (2.8% case patients vs. 1.4% controls; OR, 1.43) and iron-deficiency anemia (2.3% case patients vs. 0.9% controls; OR, 2.07).

No differences were observed by gender for each sign or symptom.

Among patients with a red-flag symptom who presented between 3 months and 2 years before diagnosis, for those with early-onset CRC, the median diagnostic interval was 8.7 months.

The researchers suggest that clinicians prioritize prompt diagnostic workups for patients younger than 50 who present with rectal bleeding and/or iron-deficiency anemia and that they also keep abdominal pain and diarrhea in mind as early symptoms.

Dr. Cao noted that since most early-onset CRC cases “have been and will continue to be diagnosed after symptom presentation, it is crucial to recognize these red-flag signs and symptoms promptly and conduct a diagnostic workup as soon as possible.

“By doing so, we can diagnose the disease earlier, which in turn can reduce the need for more aggressive treatment and improve patients’ quality of life and survival rates,” said Dr. Cao.

The study was supported by grants from the National Institutes of Health. The authors declared no conflicts of interest.

A version of this article originally appeared on Medscape.com.

As the number of cases of early-onset colorectal cancer (CRC) diagnosed before age 50 continues to rise, early detection has become increasingly important.

A new study has identified four signs and symptoms that can serve as red flags to facilitate earlier detection of early-onset CRC. The signs and symptoms are abdominal pain, rectal bleeding, diarrhea, and iron-deficiency anemia.

Two symptoms in particular – rectal bleeding and iron-deficiency anemia – point to the need for timely endoscopy and follow-up, the researchers say.

“Colorectal cancer is not simply a disease affecting older people; we want younger adults to be aware of and act on these potentially very telling signs and symptoms – particularly because people under 50 are considered to be at low risk, and they don’t receive routine colorectal cancer screening,” senior investigator Yin Cao, ScD, with Washington University School of Medicine, St. Louis, said in a news release.

“It’s also crucial to spread awareness among primary care doctors, gastroenterologists, and emergency medicine doctors,” Dr. Cao added. “To date, many early-onset colorectal cancers are detected in emergency rooms, and there often are significant diagnostic delays with this cancer.”

The study was published online  in the Journal of the National Cancer Institute.

Although previous research has identified rectal bleeding, iron-deficiency anemia, and rectal/abdominal pain as symptoms of early-onset CRC, most studies “have aggregated symptoms till the time of diagnosis,” which limits their use for early detection, the authors explain.

In the current study, the researchers analyzed data from more than 5,000 cases of early-onset CRC and from more than 22,000 control patients using the IBM MarketScan commercial database.

Dr. Cao and colleagues found that between 3 months and 2 years before diagnosis, abdominal pain, rectal bleeding, diarrhea, and iron-deficiency anemia each indicated an increased risk for early-onset CRC.

Among patients with early-onset CRC, 19.3% presented with one or more of the four red flags between 3 months and 2 years prior to the index date; 15.6% had one symptom, and 3.7% had two or more.

After multivariable adjustment, having one symptom almost doubled the risk for early-onset CRC (odds ratio, 1.94); having two symptoms increased risk by more than threefold (OR, 3.59); and having three or more boosted the risk by more than 6.5-fold (OR, 6.52).

Abdominal pain was associated with a 34% higher risk of early-onset CRC (11.6% among case patients vs. 7.7% among controls; OR, 1.34).

Although not as common, rectal bleeding was associated with the highest odds for early-onset CRC (7.2% case patients vs. 1.3% controls; OR, 5.13).

The other predictive signs and symptoms included diarrhea (2.8% case patients vs. 1.4% controls; OR, 1.43) and iron-deficiency anemia (2.3% case patients vs. 0.9% controls; OR, 2.07).

No differences were observed by gender for each sign or symptom.

Among patients with a red-flag symptom who presented between 3 months and 2 years before diagnosis, for those with early-onset CRC, the median diagnostic interval was 8.7 months.

The researchers suggest that clinicians prioritize prompt diagnostic workups for patients younger than 50 who present with rectal bleeding and/or iron-deficiency anemia and that they also keep abdominal pain and diarrhea in mind as early symptoms.

Dr. Cao noted that since most early-onset CRC cases “have been and will continue to be diagnosed after symptom presentation, it is crucial to recognize these red-flag signs and symptoms promptly and conduct a diagnostic workup as soon as possible.

“By doing so, we can diagnose the disease earlier, which in turn can reduce the need for more aggressive treatment and improve patients’ quality of life and survival rates,” said Dr. Cao.

The study was supported by grants from the National Institutes of Health. The authors declared no conflicts of interest.

A version of this article originally appeared on Medscape.com.

As the number of cases of early-onset colorectal cancer (CRC) diagnosed before age 50 continues to rise, early detection has become increasingly important.

A new study has identified four signs and symptoms that can serve as red flags to facilitate earlier detection of early-onset CRC. The signs and symptoms are abdominal pain, rectal bleeding, diarrhea, and iron-deficiency anemia.

Two symptoms in particular – rectal bleeding and iron-deficiency anemia – point to the need for timely endoscopy and follow-up, the researchers say.

“Colorectal cancer is not simply a disease affecting older people; we want younger adults to be aware of and act on these potentially very telling signs and symptoms – particularly because people under 50 are considered to be at low risk, and they don’t receive routine colorectal cancer screening,” senior investigator Yin Cao, ScD, with Washington University School of Medicine, St. Louis, said in a news release.

“It’s also crucial to spread awareness among primary care doctors, gastroenterologists, and emergency medicine doctors,” Dr. Cao added. “To date, many early-onset colorectal cancers are detected in emergency rooms, and there often are significant diagnostic delays with this cancer.”

The study was published online  in the Journal of the National Cancer Institute.

Although previous research has identified rectal bleeding, iron-deficiency anemia, and rectal/abdominal pain as symptoms of early-onset CRC, most studies “have aggregated symptoms till the time of diagnosis,” which limits their use for early detection, the authors explain.

In the current study, the researchers analyzed data from more than 5,000 cases of early-onset CRC and from more than 22,000 control patients using the IBM MarketScan commercial database.

Dr. Cao and colleagues found that between 3 months and 2 years before diagnosis, abdominal pain, rectal bleeding, diarrhea, and iron-deficiency anemia each indicated an increased risk for early-onset CRC.

Among patients with early-onset CRC, 19.3% presented with one or more of the four red flags between 3 months and 2 years prior to the index date; 15.6% had one symptom, and 3.7% had two or more.

After multivariable adjustment, having one symptom almost doubled the risk for early-onset CRC (odds ratio, 1.94); having two symptoms increased risk by more than threefold (OR, 3.59); and having three or more boosted the risk by more than 6.5-fold (OR, 6.52).

Abdominal pain was associated with a 34% higher risk of early-onset CRC (11.6% among case patients vs. 7.7% among controls; OR, 1.34).

Although not as common, rectal bleeding was associated with the highest odds for early-onset CRC (7.2% case patients vs. 1.3% controls; OR, 5.13).

The other predictive signs and symptoms included diarrhea (2.8% case patients vs. 1.4% controls; OR, 1.43) and iron-deficiency anemia (2.3% case patients vs. 0.9% controls; OR, 2.07).

No differences were observed by gender for each sign or symptom.

Among patients with a red-flag symptom who presented between 3 months and 2 years before diagnosis, for those with early-onset CRC, the median diagnostic interval was 8.7 months.

The researchers suggest that clinicians prioritize prompt diagnostic workups for patients younger than 50 who present with rectal bleeding and/or iron-deficiency anemia and that they also keep abdominal pain and diarrhea in mind as early symptoms.

Dr. Cao noted that since most early-onset CRC cases “have been and will continue to be diagnosed after symptom presentation, it is crucial to recognize these red-flag signs and symptoms promptly and conduct a diagnostic workup as soon as possible.

“By doing so, we can diagnose the disease earlier, which in turn can reduce the need for more aggressive treatment and improve patients’ quality of life and survival rates,” said Dr. Cao.

The study was supported by grants from the National Institutes of Health. The authors declared no conflicts of interest.

A version of this article originally appeared on Medscape.com.

ChatGPT, an artificial intelligence chatbot, can provide easily understandable, scientifically adequate, and generally satisfactory answers to common patient questions about colonoscopy, new research suggests.

“This study shows that a conversational AI program can generate credible medical information in response to common patient questions,” say the investigators, led by Tsung-Chun Lee, MD, division of gastroenterology and hepatology, Taipei Medical University Shuang Ho Hospital, New Taipei City, Taiwan.

“With dedicated domain training, there is meaningful potential to optimize clinical communication to patients undergoing colonoscopy,” they add.

The study was published online in Gastroenterology.

ChatGPT, developed by OpenAI, is a natural language processing tool that allows users to have personalized conversations with an artificial intelligence (AI) bot capable of providing a detailed response to any question posed.

For their first-of-its-kind study, Dr. Lee and colleagues assessed the quality of ChatGPT-generated answers to eight common patient questions about colonoscopy, including what a colonoscopy entails, why it’s performed, how to prepare for it, potential complications, what to expect after the procedure, and what happens with a positive/negative result.

They retrieved the questions from the websites of three randomly selected top hospitals for gastroenterology and gastrointestinal surgery and had ChatGPT (Jan. 30, 2023, version) answer the questions twice.

Using plagiarism detection software, they found that text similarity was extremely low between ChatGPT answers and those on hospital websites (0%-16%). Text similarity ranged from 28% to 77% between the two ChatGPT answers for the same question, except on the question of what to do after a positive colonoscopy result, which had 0% text similarity.

To objectively gauge the quality of the ChatGPT answers, four gastroenterologists (two senior gastroenterologists and two fellows) rated 36 pairs of common questions and answers on a seven-point Likert scale according to ease of understanding, scientific adequacy, and satisfaction with the answer.

The gastroenterologists rated the ChatGPT answers highly and similarly to non-AI answers for all three quality indicators, with some AI scores even higher than non-AI scores.

Interestingly, they could correctly identify AI-generated answers only 48% of the time. Three raters had an accuracy of less than 50%, whereas one (a fellow) was 81% accurate.

The researchers note that publications about ChatGPT in PubMed grew 10-fold from Feb. 3 to April 14, 2023, with topics such as board examinations authorship, editorial policies, medical education, and clinical decision support.

Although in their early days, ChatGPT and other AI bots may represent a “transformative innovation” in how medical information is created by physicians and consumed by patients, they say.

It could also be a time-saver for health care professionals.

“AI-generated medical information, with appropriate provider oversight, accreditation, and periodic surveillance, could improve efficiency of care and free providers for more cognitively intensive patient communications,” they add.

However, several challenges remain, such as the lack of clinical evidence in constructing AI-generated answers.

In addition, AI-generated answers were written at significantly higher reading levels than were answers on hospital websites, which could be a barrier for some patients.

The study received no specific funding. The authors have declared no relevant conflicts of interest.
 

A version of this article first appeared on Medscape.com.

ChatGPT, an artificial intelligence chatbot, can provide easily understandable, scientifically adequate, and generally satisfactory answers to common patient questions about colonoscopy, new research suggests.

“This study shows that a conversational AI program can generate credible medical information in response to common patient questions,” say the investigators, led by Tsung-Chun Lee, MD, division of gastroenterology and hepatology, Taipei Medical University Shuang Ho Hospital, New Taipei City, Taiwan.

“With dedicated domain training, there is meaningful potential to optimize clinical communication to patients undergoing colonoscopy,” they add.

The study was published online in Gastroenterology.

ChatGPT, developed by OpenAI, is a natural language processing tool that allows users to have personalized conversations with an artificial intelligence (AI) bot capable of providing a detailed response to any question posed.

For their first-of-its-kind study, Dr. Lee and colleagues assessed the quality of ChatGPT-generated answers to eight common patient questions about colonoscopy, including what a colonoscopy entails, why it’s performed, how to prepare for it, potential complications, what to expect after the procedure, and what happens with a positive/negative result.

They retrieved the questions from the websites of three randomly selected top hospitals for gastroenterology and gastrointestinal surgery and had ChatGPT (Jan. 30, 2023, version) answer the questions twice.

Using plagiarism detection software, they found that text similarity was extremely low between ChatGPT answers and those on hospital websites (0%-16%). Text similarity ranged from 28% to 77% between the two ChatGPT answers for the same question, except on the question of what to do after a positive colonoscopy result, which had 0% text similarity.

To objectively gauge the quality of the ChatGPT answers, four gastroenterologists (two senior gastroenterologists and two fellows) rated 36 pairs of common questions and answers on a seven-point Likert scale according to ease of understanding, scientific adequacy, and satisfaction with the answer.

The gastroenterologists rated the ChatGPT answers highly and similarly to non-AI answers for all three quality indicators, with some AI scores even higher than non-AI scores.

Interestingly, they could correctly identify AI-generated answers only 48% of the time. Three raters had an accuracy of less than 50%, whereas one (a fellow) was 81% accurate.

The researchers note that publications about ChatGPT in PubMed grew 10-fold from Feb. 3 to April 14, 2023, with topics such as board examinations authorship, editorial policies, medical education, and clinical decision support.

Although in their early days, ChatGPT and other AI bots may represent a “transformative innovation” in how medical information is created by physicians and consumed by patients, they say.

It could also be a time-saver for health care professionals.

“AI-generated medical information, with appropriate provider oversight, accreditation, and periodic surveillance, could improve efficiency of care and free providers for more cognitively intensive patient communications,” they add.

However, several challenges remain, such as the lack of clinical evidence in constructing AI-generated answers.

In addition, AI-generated answers were written at significantly higher reading levels than were answers on hospital websites, which could be a barrier for some patients.

The study received no specific funding. The authors have declared no relevant conflicts of interest.
 

A version of this article first appeared on Medscape.com.

ChatGPT, an artificial intelligence chatbot, can provide easily understandable, scientifically adequate, and generally satisfactory answers to common patient questions about colonoscopy, new research suggests.

“This study shows that a conversational AI program can generate credible medical information in response to common patient questions,” say the investigators, led by Tsung-Chun Lee, MD, division of gastroenterology and hepatology, Taipei Medical University Shuang Ho Hospital, New Taipei City, Taiwan.

“With dedicated domain training, there is meaningful potential to optimize clinical communication to patients undergoing colonoscopy,” they add.

The study was published online in Gastroenterology.

ChatGPT, developed by OpenAI, is a natural language processing tool that allows users to have personalized conversations with an artificial intelligence (AI) bot capable of providing a detailed response to any question posed.

For their first-of-its-kind study, Dr. Lee and colleagues assessed the quality of ChatGPT-generated answers to eight common patient questions about colonoscopy, including what a colonoscopy entails, why it’s performed, how to prepare for it, potential complications, what to expect after the procedure, and what happens with a positive/negative result.

They retrieved the questions from the websites of three randomly selected top hospitals for gastroenterology and gastrointestinal surgery and had ChatGPT (Jan. 30, 2023, version) answer the questions twice.

Using plagiarism detection software, they found that text similarity was extremely low between ChatGPT answers and those on hospital websites (0%-16%). Text similarity ranged from 28% to 77% between the two ChatGPT answers for the same question, except on the question of what to do after a positive colonoscopy result, which had 0% text similarity.

To objectively gauge the quality of the ChatGPT answers, four gastroenterologists (two senior gastroenterologists and two fellows) rated 36 pairs of common questions and answers on a seven-point Likert scale according to ease of understanding, scientific adequacy, and satisfaction with the answer.

The gastroenterologists rated the ChatGPT answers highly and similarly to non-AI answers for all three quality indicators, with some AI scores even higher than non-AI scores.

Interestingly, they could correctly identify AI-generated answers only 48% of the time. Three raters had an accuracy of less than 50%, whereas one (a fellow) was 81% accurate.

The researchers note that publications about ChatGPT in PubMed grew 10-fold from Feb. 3 to April 14, 2023, with topics such as board examinations authorship, editorial policies, medical education, and clinical decision support.

Although in their early days, ChatGPT and other AI bots may represent a “transformative innovation” in how medical information is created by physicians and consumed by patients, they say.

It could also be a time-saver for health care professionals.

“AI-generated medical information, with appropriate provider oversight, accreditation, and periodic surveillance, could improve efficiency of care and free providers for more cognitively intensive patient communications,” they add.

However, several challenges remain, such as the lack of clinical evidence in constructing AI-generated answers.

In addition, AI-generated answers were written at significantly higher reading levels than were answers on hospital websites, which could be a barrier for some patients.

The study received no specific funding. The authors have declared no relevant conflicts of interest.
 

A version of this article first appeared on Medscape.com.

A safety analysis following a landmark randomized phase 3 trial confirms that vomiting and nausea are quite common in patients who take the drug trastuzumab deruxtecan (T-DXd; Enhertu) to treat HER2-low metastatic breast cancer. Interstitial lung disease (ILD) also remains a concern, and it’s not clear if retreatment after resolution is warranted.

In general, however, “T-DXd demonstrates a manageable safety profile consistent with prior reports. Results from this safety analysis continued to support its use as a new standard of care in patients with HER2-low metastatic breast cancer,” said report lead author Hope Rugo, MD, of the University of California, San Francisco, during a presentation at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

T-DXd, an antibody-drug conjugate, received FDA approval in August 2022 for patients with HER2-low disease. The drug has been touted as “practice changing” and a “new standard of care.”

However, physicians have noted that the benefits of the drug come at the cost of significant adverse effects, including some that can cause hospitalization. There’s special concern about high-grade interstitial lung disease/pneumonitis, and an FDA boxed warning cautions clinicians about this possible side effect.

For the new analysis, researchers presented additional safety data from the industry-funded DESTINY-Breast04 trial, whose results was published in July 2022 in the New England Journal of Medicine. That study randomized 373 patients to T-DXd and 184 to physician’s choice of treatment. It found that, “among all patients, the median progression-free survival was 9.9 months in the trastuzumab deruxtecan group and 5.1 months in the physician’s choice group (hazard ratio for disease progression or death, 0.50; P < .001), and overall survival was 23.4 months and 16.8 months, respectively (hazard ratio for death, 0.64; P = .001).”

Exposure-adjusted incidence rates for any-grade treatment-emergent adverse events were lower for T-DXd versus physician’s choice of treatment (1.30 vs. 2.66). However, nausea and vomiting events were more than twice as common in patients who took T-DXd versus the physician’s choice (79.5% vs. 35.5%).

A total of 50.9% of patients in the T-DXd arm received antiemetic prophylaxis versus 37.2% in the physician’s choice arm. A single patient discontinued T-DXd treatment because of vomiting, and a single patient discontinued treatment because of nausea. No patients in the physician choice group discontinued treatment because of nausea or vomiting.

Neutropenia and febrile neutropenia were less frequent in the T-DXd arm versus physician’s choice (12.9% vs. 18.0% and 0.3% vs. 2.9%, respectively.)

ILD occurred in 45 patients (12.1%) of those in the T-DXd arm versus 1 (0.6%) in the physician choice arm. Ten patients of the patients in the T-DXd arm had not recovered by the data cutoff point.

Six patients with ILD were retreated following resolution; one discontinued because of an adverse event, two discontinued because of progressive disease, and three remained on the drug. “Given that there was only a small number of patients who were retreated with T-DXd, it’s difficult to make clinically meaningful conclusions on the effect of retreatment following grade IDL events that have resolved,” Dr. Rugo said.

In the big picture, “ILD pneumonitis remains an important identified risk and an adverse event of interest associated with T-DXd,” Dr. Rugo said. “It’s important that we adhere to management guidelines and updated toxicity management guidelines.”

In a discussion, Dr. Rugo said she prescribes three antiemetic drugs to help patients tolerate T-DXd therapy: “It makes a big difference. Anecdotally, it really has improved management of nausea. Start more and back down [as symptoms fade].”

Gustavo Werutsky, MD, PhD, of Moinhos de Vento Hospital, Porto Alegre, Brazil, the discussant for the presentation, also emphasized the importance of prevention and said he prescribes two or three prophylactic drugs. “In the beginning, we didn’t know these events were so important. A big part of the message is that patients from the beginning need to have a good prophylaxis for the nausea and vomiting.”

The researchers also presented a related report at the conference, an analysis of patient-reported outcomes from DESTINY-Breast02, a randomized phase 3 study of T-DXd (n = 406) versus physician’s choice of treatment (n = 202) in patients with HER2-positive metastatic breast cancer who were resistant/refractory to trastuzumab emtansine.

The analysis, led by Tanja Fehm, MD, of University Hospital Düsseldorf (Germany), found that the median time to definitive deterioration was longer with T-DXd versus the other arm per the EORTC QLQ-C30 global health status/quality of life score (14.1 vs. 5.9 months; HR, 0.56; 95% confidence interval, 0.44-0.71).

The studies were funded by Daiichi Sankyo and AstraZeneca, which make T-DXd. Dr. Hugo discloses relationships with Puma, NAPO, Blueprint, Scorpion Therapeutics, Merck, AstraZeneca, Gilead, Astellas, Daiichi Sankyo, F. Hoffmann–La Roche/Genentech, GlaxoSmithKline, Lilly, Novartis, OBI, Pfizer, Pionyr, Sermonix, Taiho Oncology, and Veru. Multiple other authors of both studies have various disclosures.

A safety analysis following a landmark randomized phase 3 trial confirms that vomiting and nausea are quite common in patients who take the drug trastuzumab deruxtecan (T-DXd; Enhertu) to treat HER2-low metastatic breast cancer. Interstitial lung disease (ILD) also remains a concern, and it’s not clear if retreatment after resolution is warranted.

In general, however, “T-DXd demonstrates a manageable safety profile consistent with prior reports. Results from this safety analysis continued to support its use as a new standard of care in patients with HER2-low metastatic breast cancer,” said report lead author Hope Rugo, MD, of the University of California, San Francisco, during a presentation at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

T-DXd, an antibody-drug conjugate, received FDA approval in August 2022 for patients with HER2-low disease. The drug has been touted as “practice changing” and a “new standard of care.”

However, physicians have noted that the benefits of the drug come at the cost of significant adverse effects, including some that can cause hospitalization. There’s special concern about high-grade interstitial lung disease/pneumonitis, and an FDA boxed warning cautions clinicians about this possible side effect.

For the new analysis, researchers presented additional safety data from the industry-funded DESTINY-Breast04 trial, whose results was published in July 2022 in the New England Journal of Medicine. That study randomized 373 patients to T-DXd and 184 to physician’s choice of treatment. It found that, “among all patients, the median progression-free survival was 9.9 months in the trastuzumab deruxtecan group and 5.1 months in the physician’s choice group (hazard ratio for disease progression or death, 0.50; P < .001), and overall survival was 23.4 months and 16.8 months, respectively (hazard ratio for death, 0.64; P = .001).”

Exposure-adjusted incidence rates for any-grade treatment-emergent adverse events were lower for T-DXd versus physician’s choice of treatment (1.30 vs. 2.66). However, nausea and vomiting events were more than twice as common in patients who took T-DXd versus the physician’s choice (79.5% vs. 35.5%).

A total of 50.9% of patients in the T-DXd arm received antiemetic prophylaxis versus 37.2% in the physician’s choice arm. A single patient discontinued T-DXd treatment because of vomiting, and a single patient discontinued treatment because of nausea. No patients in the physician choice group discontinued treatment because of nausea or vomiting.

Neutropenia and febrile neutropenia were less frequent in the T-DXd arm versus physician’s choice (12.9% vs. 18.0% and 0.3% vs. 2.9%, respectively.)

ILD occurred in 45 patients (12.1%) of those in the T-DXd arm versus 1 (0.6%) in the physician choice arm. Ten patients of the patients in the T-DXd arm had not recovered by the data cutoff point.

Six patients with ILD were retreated following resolution; one discontinued because of an adverse event, two discontinued because of progressive disease, and three remained on the drug. “Given that there was only a small number of patients who were retreated with T-DXd, it’s difficult to make clinically meaningful conclusions on the effect of retreatment following grade IDL events that have resolved,” Dr. Rugo said.

In the big picture, “ILD pneumonitis remains an important identified risk and an adverse event of interest associated with T-DXd,” Dr. Rugo said. “It’s important that we adhere to management guidelines and updated toxicity management guidelines.”

In a discussion, Dr. Rugo said she prescribes three antiemetic drugs to help patients tolerate T-DXd therapy: “It makes a big difference. Anecdotally, it really has improved management of nausea. Start more and back down [as symptoms fade].”

Gustavo Werutsky, MD, PhD, of Moinhos de Vento Hospital, Porto Alegre, Brazil, the discussant for the presentation, also emphasized the importance of prevention and said he prescribes two or three prophylactic drugs. “In the beginning, we didn’t know these events were so important. A big part of the message is that patients from the beginning need to have a good prophylaxis for the nausea and vomiting.”

The researchers also presented a related report at the conference, an analysis of patient-reported outcomes from DESTINY-Breast02, a randomized phase 3 study of T-DXd (n = 406) versus physician’s choice of treatment (n = 202) in patients with HER2-positive metastatic breast cancer who were resistant/refractory to trastuzumab emtansine.

The analysis, led by Tanja Fehm, MD, of University Hospital Düsseldorf (Germany), found that the median time to definitive deterioration was longer with T-DXd versus the other arm per the EORTC QLQ-C30 global health status/quality of life score (14.1 vs. 5.9 months; HR, 0.56; 95% confidence interval, 0.44-0.71).

The studies were funded by Daiichi Sankyo and AstraZeneca, which make T-DXd. Dr. Hugo discloses relationships with Puma, NAPO, Blueprint, Scorpion Therapeutics, Merck, AstraZeneca, Gilead, Astellas, Daiichi Sankyo, F. Hoffmann–La Roche/Genentech, GlaxoSmithKline, Lilly, Novartis, OBI, Pfizer, Pionyr, Sermonix, Taiho Oncology, and Veru. Multiple other authors of both studies have various disclosures.

A safety analysis following a landmark randomized phase 3 trial confirms that vomiting and nausea are quite common in patients who take the drug trastuzumab deruxtecan (T-DXd; Enhertu) to treat HER2-low metastatic breast cancer. Interstitial lung disease (ILD) also remains a concern, and it’s not clear if retreatment after resolution is warranted.

In general, however, “T-DXd demonstrates a manageable safety profile consistent with prior reports. Results from this safety analysis continued to support its use as a new standard of care in patients with HER2-low metastatic breast cancer,” said report lead author Hope Rugo, MD, of the University of California, San Francisco, during a presentation at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

T-DXd, an antibody-drug conjugate, received FDA approval in August 2022 for patients with HER2-low disease. The drug has been touted as “practice changing” and a “new standard of care.”

However, physicians have noted that the benefits of the drug come at the cost of significant adverse effects, including some that can cause hospitalization. There’s special concern about high-grade interstitial lung disease/pneumonitis, and an FDA boxed warning cautions clinicians about this possible side effect.

For the new analysis, researchers presented additional safety data from the industry-funded DESTINY-Breast04 trial, whose results was published in July 2022 in the New England Journal of Medicine. That study randomized 373 patients to T-DXd and 184 to physician’s choice of treatment. It found that, “among all patients, the median progression-free survival was 9.9 months in the trastuzumab deruxtecan group and 5.1 months in the physician’s choice group (hazard ratio for disease progression or death, 0.50; P < .001), and overall survival was 23.4 months and 16.8 months, respectively (hazard ratio for death, 0.64; P = .001).”

Exposure-adjusted incidence rates for any-grade treatment-emergent adverse events were lower for T-DXd versus physician’s choice of treatment (1.30 vs. 2.66). However, nausea and vomiting events were more than twice as common in patients who took T-DXd versus the physician’s choice (79.5% vs. 35.5%).

A total of 50.9% of patients in the T-DXd arm received antiemetic prophylaxis versus 37.2% in the physician’s choice arm. A single patient discontinued T-DXd treatment because of vomiting, and a single patient discontinued treatment because of nausea. No patients in the physician choice group discontinued treatment because of nausea or vomiting.

Neutropenia and febrile neutropenia were less frequent in the T-DXd arm versus physician’s choice (12.9% vs. 18.0% and 0.3% vs. 2.9%, respectively.)

ILD occurred in 45 patients (12.1%) of those in the T-DXd arm versus 1 (0.6%) in the physician choice arm. Ten patients of the patients in the T-DXd arm had not recovered by the data cutoff point.

Six patients with ILD were retreated following resolution; one discontinued because of an adverse event, two discontinued because of progressive disease, and three remained on the drug. “Given that there was only a small number of patients who were retreated with T-DXd, it’s difficult to make clinically meaningful conclusions on the effect of retreatment following grade IDL events that have resolved,” Dr. Rugo said.

In the big picture, “ILD pneumonitis remains an important identified risk and an adverse event of interest associated with T-DXd,” Dr. Rugo said. “It’s important that we adhere to management guidelines and updated toxicity management guidelines.”

In a discussion, Dr. Rugo said she prescribes three antiemetic drugs to help patients tolerate T-DXd therapy: “It makes a big difference. Anecdotally, it really has improved management of nausea. Start more and back down [as symptoms fade].”

Gustavo Werutsky, MD, PhD, of Moinhos de Vento Hospital, Porto Alegre, Brazil, the discussant for the presentation, also emphasized the importance of prevention and said he prescribes two or three prophylactic drugs. “In the beginning, we didn’t know these events were so important. A big part of the message is that patients from the beginning need to have a good prophylaxis for the nausea and vomiting.”

The researchers also presented a related report at the conference, an analysis of patient-reported outcomes from DESTINY-Breast02, a randomized phase 3 study of T-DXd (n = 406) versus physician’s choice of treatment (n = 202) in patients with HER2-positive metastatic breast cancer who were resistant/refractory to trastuzumab emtansine.

The analysis, led by Tanja Fehm, MD, of University Hospital Düsseldorf (Germany), found that the median time to definitive deterioration was longer with T-DXd versus the other arm per the EORTC QLQ-C30 global health status/quality of life score (14.1 vs. 5.9 months; HR, 0.56; 95% confidence interval, 0.44-0.71).

The studies were funded by Daiichi Sankyo and AstraZeneca, which make T-DXd. Dr. Hugo discloses relationships with Puma, NAPO, Blueprint, Scorpion Therapeutics, Merck, AstraZeneca, Gilead, Astellas, Daiichi Sankyo, F. Hoffmann–La Roche/Genentech, GlaxoSmithKline, Lilly, Novartis, OBI, Pfizer, Pionyr, Sermonix, Taiho Oncology, and Veru. Multiple other authors of both studies have various disclosures.

CHICAGO – The standard approaches to measuring flares in people with Crohn’s disease have some limitations, including an inability to signal a change in disease activity without laboratory testing or before symptoms arise.

A new device developed at Massachusetts Institute of Technology could change all that.

Using data collected via a passive at-home monitoring device (Emerald sensor, Emerald Innovations Inc.), researchers found that increases in breathing rate, more awakenings at night, and slower walking speed accurately predicted that a person’s Crohn’s disease activity was about to flare, according to a study presented May 7 at Digestive Disease Week^® (DDW) 2023.

In some cases, the prediction of a flare came up to 25 days sooner than via traditional measures.

“In order to provide optimal care, providers need to monitor patients closely with regard to accurate active disease.” said Joshua Korzenik, MD, a gastroenterologist at Brigham and Women’s Hospital and assistant professor of medicine at Harvard Medical School in Boston. “The problem is the clinical symptoms are not accurate.”
 

Tracking flares with technology

Traditionally, measuring flares in Crohn’s disease activity depends on imaging, colonoscopy, and/or laboratory measures of calprotectin or other biomarkers. These approaches can be costly, can involve delays, and can carry risks, Dr. Korzenik said.

“They are also a single snapshot in time,” he added.

To determine how well a noninvasive device could perform, investigators enrolled 120 people with 105 continuing in the study long enough to be evaluable; 44 people whose Crohn’s disease was in remission, 35 with active Crohn’s disease, as well as 26 healthy controls. Among those with Crohn’s disease, 83% were on biologic therapy.

The groups were matched for age and gender, with a mean age of 47 years and mean disease duration of 13 years.

People with certain medical conditions were excluded, as was anyone who owned a large dog that sometimes slept in bed with them because that might throw off the readings.

The participants put the device – which resembles a closed laptop or a large Wi-Fi router – in their homes and were monitored for a mean 306 days. Participants wore an ankle bracelet the first 2 weeks of the study so the device could learn to distinguish them from others in the home.

The device sent out radio waves with frequencies like Wi-Fi for researchers to measure the factors that may be associated with flares, such as sleep quality and cycles, breathing rate, and gait speed.

Traditional clinical measures based on blood and stool samples, along with patient-reported outcome surveys, were taken to compare with the accuracy of the device.

Data from the device were collected and transmitted securely to a cloud database without any interaction from the participant. Data included information on more than 25,000 nights of sleep, 200,000 hours of breathing signals, and 400,000 measurements of walking speed.

Sleep quality and cycles were straightforward, as was breathing rate. But gait speed was a little more complicated to measure. To illustrate, Dr. Korzenik showed the layout of an example apartment with data on how someone moved around. To distill the data, the researchers focused on one path in the home, relatively straight and not obstructed by furniture, and limited the measurements to a certain amount of time. People who spent more time at home during the COVID-19 pandemic did not skew the results, according to Dr. Korzenik, who added that it wasn’t total time walking around but a snippet in time.

A variety of sleep, breathing, and mobility metrics extracted by the device were integrated to assess disease activity. Investigators noted that during flares, sleep quality decreased, and more nocturnal awakenings occurred. They also found that gait speed slowed, and respiratory rate increased with flares.

When the investigators looked at sleep as a function of disease activity in the patient-reported surveys, they found a significant difference between people in remission and those with active disease. For example, people with active disease had a greater number of awakenings at night (P = .0016), less REM sleep at night (P = .0000), and less time in deep sleep (P = .000) compared with those in remission.

The technology “can identify flares with a predictive value that approaches fecal calprotectin,” Dr. Korzenik said.

Machine learning was used to look at severity of disease vs. fecal calprotectin values and “showed the data could be used as a marker of disease,” he added.

Use of a remote monitor, the comparison of validated vs. conventional data, and the large dataset were among the strengths of the study. The single-center design and exclusion of people with some comorbidities are potential limitations.

Further studies are warranted to confirm these findings and guide optimal care of people with Crohn’s disease, the investigators noted.
 

Earlier detection, earlier intervention

“The study is really important,” said session comoderator Raymond K. Cross Jr., MD, professor of medicine and director of the IBD program at the University of Maryland, Baltimore.

Monitoring devices like this “could be very useful,” Dr. Cross said. “It is not invasive, unless you consider a device in your house invasive. But, to me, I don’t think a box in my bedroom would be unnerving to me.”

Dr. Cross shared a couple of caveats. “The one devil in the details is always going to be cost,” he said. Also, it’s unclear who will read and interpret all the data generated by the device among “providers who are already overwhelmed with the volume of information.”

Moving forward, a device like this could offer multiple uses, Dr. Cross noted. If the device can detect relapses earlier, physicians could intervene sooner, he said. Also, the device could potentially flag people who are not taking their medications as recommended, or it could be used as a guide to optimize treatment response.

Whether data from the device could indicate when it’s appropriate to reduce the frequency or dose of medication or even when to withdraw therapy would be “really aspirational,” Dr. Cross added.

The study was funded by The Leona M. and Harry B. Helmsley Charitable Trust. Dr. Korzenik and Dr. Cross report no relevant financial relationships.
 

DDW is sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and The Society for Surgery of the Alimentary Tract (SSAT).

A version of this article first appeared on Medscape.com.

CHICAGO – The standard approaches to measuring flares in people with Crohn’s disease have some limitations, including an inability to signal a change in disease activity without laboratory testing or before symptoms arise.

A new device developed at Massachusetts Institute of Technology could change all that.

Using data collected via a passive at-home monitoring device (Emerald sensor, Emerald Innovations Inc.), researchers found that increases in breathing rate, more awakenings at night, and slower walking speed accurately predicted that a person’s Crohn’s disease activity was about to flare, according to a study presented May 7 at Digestive Disease Week^® (DDW) 2023.

In some cases, the prediction of a flare came up to 25 days sooner than via traditional measures.

“In order to provide optimal care, providers need to monitor patients closely with regard to accurate active disease.” said Joshua Korzenik, MD, a gastroenterologist at Brigham and Women’s Hospital and assistant professor of medicine at Harvard Medical School in Boston. “The problem is the clinical symptoms are not accurate.”
 

Tracking flares with technology

Traditionally, measuring flares in Crohn’s disease activity depends on imaging, colonoscopy, and/or laboratory measures of calprotectin or other biomarkers. These approaches can be costly, can involve delays, and can carry risks, Dr. Korzenik said.

“They are also a single snapshot in time,” he added.

To determine how well a noninvasive device could perform, investigators enrolled 120 people with 105 continuing in the study long enough to be evaluable; 44 people whose Crohn’s disease was in remission, 35 with active Crohn’s disease, as well as 26 healthy controls. Among those with Crohn’s disease, 83% were on biologic therapy.

The groups were matched for age and gender, with a mean age of 47 years and mean disease duration of 13 years.

People with certain medical conditions were excluded, as was anyone who owned a large dog that sometimes slept in bed with them because that might throw off the readings.

The participants put the device – which resembles a closed laptop or a large Wi-Fi router – in their homes and were monitored for a mean 306 days. Participants wore an ankle bracelet the first 2 weeks of the study so the device could learn to distinguish them from others in the home.

The device sent out radio waves with frequencies like Wi-Fi for researchers to measure the factors that may be associated with flares, such as sleep quality and cycles, breathing rate, and gait speed.

Traditional clinical measures based on blood and stool samples, along with patient-reported outcome surveys, were taken to compare with the accuracy of the device.

Data from the device were collected and transmitted securely to a cloud database without any interaction from the participant. Data included information on more than 25,000 nights of sleep, 200,000 hours of breathing signals, and 400,000 measurements of walking speed.

Sleep quality and cycles were straightforward, as was breathing rate. But gait speed was a little more complicated to measure. To illustrate, Dr. Korzenik showed the layout of an example apartment with data on how someone moved around. To distill the data, the researchers focused on one path in the home, relatively straight and not obstructed by furniture, and limited the measurements to a certain amount of time. People who spent more time at home during the COVID-19 pandemic did not skew the results, according to Dr. Korzenik, who added that it wasn’t total time walking around but a snippet in time.

A variety of sleep, breathing, and mobility metrics extracted by the device were integrated to assess disease activity. Investigators noted that during flares, sleep quality decreased, and more nocturnal awakenings occurred. They also found that gait speed slowed, and respiratory rate increased with flares.

When the investigators looked at sleep as a function of disease activity in the patient-reported surveys, they found a significant difference between people in remission and those with active disease. For example, people with active disease had a greater number of awakenings at night (P = .0016), less REM sleep at night (P = .0000), and less time in deep sleep (P = .000) compared with those in remission.

The technology “can identify flares with a predictive value that approaches fecal calprotectin,” Dr. Korzenik said.

Machine learning was used to look at severity of disease vs. fecal calprotectin values and “showed the data could be used as a marker of disease,” he added.

Use of a remote monitor, the comparison of validated vs. conventional data, and the large dataset were among the strengths of the study. The single-center design and exclusion of people with some comorbidities are potential limitations.

Further studies are warranted to confirm these findings and guide optimal care of people with Crohn’s disease, the investigators noted.
 

Earlier detection, earlier intervention

“The study is really important,” said session comoderator Raymond K. Cross Jr., MD, professor of medicine and director of the IBD program at the University of Maryland, Baltimore.

Monitoring devices like this “could be very useful,” Dr. Cross said. “It is not invasive, unless you consider a device in your house invasive. But, to me, I don’t think a box in my bedroom would be unnerving to me.”

Dr. Cross shared a couple of caveats. “The one devil in the details is always going to be cost,” he said. Also, it’s unclear who will read and interpret all the data generated by the device among “providers who are already overwhelmed with the volume of information.”

Moving forward, a device like this could offer multiple uses, Dr. Cross noted. If the device can detect relapses earlier, physicians could intervene sooner, he said. Also, the device could potentially flag people who are not taking their medications as recommended, or it could be used as a guide to optimize treatment response.

Whether data from the device could indicate when it’s appropriate to reduce the frequency or dose of medication or even when to withdraw therapy would be “really aspirational,” Dr. Cross added.

The study was funded by The Leona M. and Harry B. Helmsley Charitable Trust. Dr. Korzenik and Dr. Cross report no relevant financial relationships.
 

DDW is sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and The Society for Surgery of the Alimentary Tract (SSAT).

A version of this article first appeared on Medscape.com.

CHICAGO – The standard approaches to measuring flares in people with Crohn’s disease have some limitations, including an inability to signal a change in disease activity without laboratory testing or before symptoms arise.

A new device developed at Massachusetts Institute of Technology could change all that.

Using data collected via a passive at-home monitoring device (Emerald sensor, Emerald Innovations Inc.), researchers found that increases in breathing rate, more awakenings at night, and slower walking speed accurately predicted that a person’s Crohn’s disease activity was about to flare, according to a study presented May 7 at Digestive Disease Week^® (DDW) 2023.

In some cases, the prediction of a flare came up to 25 days sooner than via traditional measures.

“In order to provide optimal care, providers need to monitor patients closely with regard to accurate active disease.” said Joshua Korzenik, MD, a gastroenterologist at Brigham and Women’s Hospital and assistant professor of medicine at Harvard Medical School in Boston. “The problem is the clinical symptoms are not accurate.”
 

Tracking flares with technology

Traditionally, measuring flares in Crohn’s disease activity depends on imaging, colonoscopy, and/or laboratory measures of calprotectin or other biomarkers. These approaches can be costly, can involve delays, and can carry risks, Dr. Korzenik said.

“They are also a single snapshot in time,” he added.

To determine how well a noninvasive device could perform, investigators enrolled 120 people with 105 continuing in the study long enough to be evaluable; 44 people whose Crohn’s disease was in remission, 35 with active Crohn’s disease, as well as 26 healthy controls. Among those with Crohn’s disease, 83% were on biologic therapy.

The groups were matched for age and gender, with a mean age of 47 years and mean disease duration of 13 years.

People with certain medical conditions were excluded, as was anyone who owned a large dog that sometimes slept in bed with them because that might throw off the readings.

The participants put the device – which resembles a closed laptop or a large Wi-Fi router – in their homes and were monitored for a mean 306 days. Participants wore an ankle bracelet the first 2 weeks of the study so the device could learn to distinguish them from others in the home.

The device sent out radio waves with frequencies like Wi-Fi for researchers to measure the factors that may be associated with flares, such as sleep quality and cycles, breathing rate, and gait speed.

Traditional clinical measures based on blood and stool samples, along with patient-reported outcome surveys, were taken to compare with the accuracy of the device.

Data from the device were collected and transmitted securely to a cloud database without any interaction from the participant. Data included information on more than 25,000 nights of sleep, 200,000 hours of breathing signals, and 400,000 measurements of walking speed.

Sleep quality and cycles were straightforward, as was breathing rate. But gait speed was a little more complicated to measure. To illustrate, Dr. Korzenik showed the layout of an example apartment with data on how someone moved around. To distill the data, the researchers focused on one path in the home, relatively straight and not obstructed by furniture, and limited the measurements to a certain amount of time. People who spent more time at home during the COVID-19 pandemic did not skew the results, according to Dr. Korzenik, who added that it wasn’t total time walking around but a snippet in time.

A variety of sleep, breathing, and mobility metrics extracted by the device were integrated to assess disease activity. Investigators noted that during flares, sleep quality decreased, and more nocturnal awakenings occurred. They also found that gait speed slowed, and respiratory rate increased with flares.

When the investigators looked at sleep as a function of disease activity in the patient-reported surveys, they found a significant difference between people in remission and those with active disease. For example, people with active disease had a greater number of awakenings at night (P = .0016), less REM sleep at night (P = .0000), and less time in deep sleep (P = .000) compared with those in remission.

The technology “can identify flares with a predictive value that approaches fecal calprotectin,” Dr. Korzenik said.

Machine learning was used to look at severity of disease vs. fecal calprotectin values and “showed the data could be used as a marker of disease,” he added.

Use of a remote monitor, the comparison of validated vs. conventional data, and the large dataset were among the strengths of the study. The single-center design and exclusion of people with some comorbidities are potential limitations.

Further studies are warranted to confirm these findings and guide optimal care of people with Crohn’s disease, the investigators noted.
 

Earlier detection, earlier intervention

“The study is really important,” said session comoderator Raymond K. Cross Jr., MD, professor of medicine and director of the IBD program at the University of Maryland, Baltimore.

Monitoring devices like this “could be very useful,” Dr. Cross said. “It is not invasive, unless you consider a device in your house invasive. But, to me, I don’t think a box in my bedroom would be unnerving to me.”

Dr. Cross shared a couple of caveats. “The one devil in the details is always going to be cost,” he said. Also, it’s unclear who will read and interpret all the data generated by the device among “providers who are already overwhelmed with the volume of information.”

Moving forward, a device like this could offer multiple uses, Dr. Cross noted. If the device can detect relapses earlier, physicians could intervene sooner, he said. Also, the device could potentially flag people who are not taking their medications as recommended, or it could be used as a guide to optimize treatment response.

Whether data from the device could indicate when it’s appropriate to reduce the frequency or dose of medication or even when to withdraw therapy would be “really aspirational,” Dr. Cross added.

The study was funded by The Leona M. and Harry B. Helmsley Charitable Trust. Dr. Korzenik and Dr. Cross report no relevant financial relationships.
 

DDW is sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and The Society for Surgery of the Alimentary Tract (SSAT).

A version of this article first appeared on Medscape.com.

CHICAGO – Infliximab was associated with fewer discontinuations for lack of efficacy than vedolizumab during the maintenance phase of ulcerative colitis treatment, an updated meta-analysis of randomized clinical trials reveals.

At 1 year, 2% of people taking the anti–tumor necrosis factor (TNF) agent infliximab discontinued for lack of efficacy, compared with 24% of patients taking vedolizumab (Entyvio), an integrin receptor antagonist.

The safety profile of each agent is also important.

“We know that vedolizumab has less safety risks than an anti-TNF agent, but we also have the gut feeling that the anti-TNF agents are more efficacious,” lead author Marc Ferrante, MD, said in an interview.

“Of course, I don’t think we can really say that vedolizumab is the safest and infliximab is not safe, but there is some difference,” added Dr. Ferrante, a professor in the department of gastroenterology and hepatology, University Hospitals Leuven (Belgium).

The study was presented as a poster at the annual Digestive Disease Week (DDW).

The researchers conducted a pooled analysis of six randomized controlled trials from the past 10 years. They analyzed the NOR-SWITCH IV Q8W, the NCT02883452 SC Q2W, and LIBERTY-UC SC Q2W studies for infliximab, and the VISIBLE 1 SC Q2W, GEMINI 1 IV Q4W, and VARSITY IV Q8W trials for vedolizumab.

Their work expands on a meta-analysis by Dr. Ferrante and colleagues presented at DDW 2022. They added the 1-year results from the phase 3 LIBERTY-UC study to increase the number of participants taking infliximab or an infliximab biosimilar.

“Luckily, the results are very similar,” Dr. Ferrante said, and noted that they support previous findings that discontinuation of infliximab was lower than that of vedolizumab.

Most of the patients in the infliximab group were taking an infliximab biosimilar, whereas the vedolizumab group received the originator. Dr. Ferrante noted that the economic considerations involved in deciding between a biosimilar and an originator were not part of the research but that “there will be a difference in costs.”
 

Same mechanism, different route

The novel finding from the study includes the subcutaneous form of infliximab, which is not yet available in the United States, noted Joshua M. Steinberg, MD, director of inflammatory bowel disease at Gastroenterology of the Rockies, Denver, when asked to comment on the study. Currently, intravenously administered infliximab and vedolizumab are available in the United States.

A better comparator in the future would be looking at subcutaneous forms of both agents, especially “with the impending launch of subcutaneous vedolizumab in the United States,” said Dr. Steinberg, who is also a clinical instructor of medicine at the University of Colorado at Denver, Aurora.

He added that it’s reassuring overall that with a newer mode of administration but same mechanism of action, it is still feasible and durable for at least 1 year.

“The general consensus is that in terms of our biologics, vedolizumab is the safest because of its targeted mechanism of action. But sometimes the ‘safest choice’ isn’t the best choice,” Dr. Steinberg said. “I think in the right patient, the most effective treatment is going to be the one that works the best, and that’s not going to be universal.”

The study was sponsored by Celltrion, which makes an infliximab biosimilar. Dr. Ferrante receives honoraria as a consultant and speaker for Celltrion. Dr. Steinberg reported no relevant financial relationships.

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.

A version of this article first appeared on Medscape.com.

CHICAGO – Infliximab was associated with fewer discontinuations for lack of efficacy than vedolizumab during the maintenance phase of ulcerative colitis treatment, an updated meta-analysis of randomized clinical trials reveals.

At 1 year, 2% of people taking the anti–tumor necrosis factor (TNF) agent infliximab discontinued for lack of efficacy, compared with 24% of patients taking vedolizumab (Entyvio), an integrin receptor antagonist.

The safety profile of each agent is also important.

“We know that vedolizumab has less safety risks than an anti-TNF agent, but we also have the gut feeling that the anti-TNF agents are more efficacious,” lead author Marc Ferrante, MD, said in an interview.

“Of course, I don’t think we can really say that vedolizumab is the safest and infliximab is not safe, but there is some difference,” added Dr. Ferrante, a professor in the department of gastroenterology and hepatology, University Hospitals Leuven (Belgium).

The study was presented as a poster at the annual Digestive Disease Week (DDW).

The researchers conducted a pooled analysis of six randomized controlled trials from the past 10 years. They analyzed the NOR-SWITCH IV Q8W, the NCT02883452 SC Q2W, and LIBERTY-UC SC Q2W studies for infliximab, and the VISIBLE 1 SC Q2W, GEMINI 1 IV Q4W, and VARSITY IV Q8W trials for vedolizumab.

Their work expands on a meta-analysis by Dr. Ferrante and colleagues presented at DDW 2022. They added the 1-year results from the phase 3 LIBERTY-UC study to increase the number of participants taking infliximab or an infliximab biosimilar.

“Luckily, the results are very similar,” Dr. Ferrante said, and noted that they support previous findings that discontinuation of infliximab was lower than that of vedolizumab.

Most of the patients in the infliximab group were taking an infliximab biosimilar, whereas the vedolizumab group received the originator. Dr. Ferrante noted that the economic considerations involved in deciding between a biosimilar and an originator were not part of the research but that “there will be a difference in costs.”
 

Same mechanism, different route

The novel finding from the study includes the subcutaneous form of infliximab, which is not yet available in the United States, noted Joshua M. Steinberg, MD, director of inflammatory bowel disease at Gastroenterology of the Rockies, Denver, when asked to comment on the study. Currently, intravenously administered infliximab and vedolizumab are available in the United States.

A better comparator in the future would be looking at subcutaneous forms of both agents, especially “with the impending launch of subcutaneous vedolizumab in the United States,” said Dr. Steinberg, who is also a clinical instructor of medicine at the University of Colorado at Denver, Aurora.

He added that it’s reassuring overall that with a newer mode of administration but same mechanism of action, it is still feasible and durable for at least 1 year.

“The general consensus is that in terms of our biologics, vedolizumab is the safest because of its targeted mechanism of action. But sometimes the ‘safest choice’ isn’t the best choice,” Dr. Steinberg said. “I think in the right patient, the most effective treatment is going to be the one that works the best, and that’s not going to be universal.”

The study was sponsored by Celltrion, which makes an infliximab biosimilar. Dr. Ferrante receives honoraria as a consultant and speaker for Celltrion. Dr. Steinberg reported no relevant financial relationships.

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.

A version of this article first appeared on Medscape.com.

CHICAGO – Infliximab was associated with fewer discontinuations for lack of efficacy than vedolizumab during the maintenance phase of ulcerative colitis treatment, an updated meta-analysis of randomized clinical trials reveals.

At 1 year, 2% of people taking the anti–tumor necrosis factor (TNF) agent infliximab discontinued for lack of efficacy, compared with 24% of patients taking vedolizumab (Entyvio), an integrin receptor antagonist.

The safety profile of each agent is also important.

“We know that vedolizumab has less safety risks than an anti-TNF agent, but we also have the gut feeling that the anti-TNF agents are more efficacious,” lead author Marc Ferrante, MD, said in an interview.

“Of course, I don’t think we can really say that vedolizumab is the safest and infliximab is not safe, but there is some difference,” added Dr. Ferrante, a professor in the department of gastroenterology and hepatology, University Hospitals Leuven (Belgium).

The study was presented as a poster at the annual Digestive Disease Week (DDW).

The researchers conducted a pooled analysis of six randomized controlled trials from the past 10 years. They analyzed the NOR-SWITCH IV Q8W, the NCT02883452 SC Q2W, and LIBERTY-UC SC Q2W studies for infliximab, and the VISIBLE 1 SC Q2W, GEMINI 1 IV Q4W, and VARSITY IV Q8W trials for vedolizumab.

Their work expands on a meta-analysis by Dr. Ferrante and colleagues presented at DDW 2022. They added the 1-year results from the phase 3 LIBERTY-UC study to increase the number of participants taking infliximab or an infliximab biosimilar.

“Luckily, the results are very similar,” Dr. Ferrante said, and noted that they support previous findings that discontinuation of infliximab was lower than that of vedolizumab.

Most of the patients in the infliximab group were taking an infliximab biosimilar, whereas the vedolizumab group received the originator. Dr. Ferrante noted that the economic considerations involved in deciding between a biosimilar and an originator were not part of the research but that “there will be a difference in costs.”
 

Same mechanism, different route

The novel finding from the study includes the subcutaneous form of infliximab, which is not yet available in the United States, noted Joshua M. Steinberg, MD, director of inflammatory bowel disease at Gastroenterology of the Rockies, Denver, when asked to comment on the study. Currently, intravenously administered infliximab and vedolizumab are available in the United States.

A better comparator in the future would be looking at subcutaneous forms of both agents, especially “with the impending launch of subcutaneous vedolizumab in the United States,” said Dr. Steinberg, who is also a clinical instructor of medicine at the University of Colorado at Denver, Aurora.

He added that it’s reassuring overall that with a newer mode of administration but same mechanism of action, it is still feasible and durable for at least 1 year.

“The general consensus is that in terms of our biologics, vedolizumab is the safest because of its targeted mechanism of action. But sometimes the ‘safest choice’ isn’t the best choice,” Dr. Steinberg said. “I think in the right patient, the most effective treatment is going to be the one that works the best, and that’s not going to be universal.”

The study was sponsored by Celltrion, which makes an infliximab biosimilar. Dr. Ferrante receives honoraria as a consultant and speaker for Celltrion. Dr. Steinberg reported no relevant financial relationships.

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.

A version of this article first appeared on Medscape.com.

A 41-year-old man presented for evaluation of an extensive skin rash that had erupted more than a month earlier. The patient had received 2 doses of the Pfizer COVID-19 vaccine 3 weeks apart. Ten days after his second dose, the patient developed a rash all over his body. He described the rash as burning, itchy, and uncomfortable. The patient denied any triggers such as recent or previous infections, stressors, or drugs. The patient had no personal or family history of dermatologic disorders; his general medical history was unremarkable. The patient smoked and drank alcohol occasionally.

On physical exam, the patient had a diffuse rash, which initially had manifested on both of his hands, including the palms, and then spread to 60% to 70% of his total body surface area, including his face, ears, anterior and posterior chest, upper and lower extremities, and buttocks. The rash consisted of 10- to 15-mm white scaly plaques that did not bleed.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Diagnosis: Guttate psoriasis

Punch biopsies were obtained, and histopathology revealed diffuse compact hyperkeratosis with broad zones of parakeratosis. There was attenuation of the granular layer and regular elongation of the rete ridges associated with thinning of the suprapapillary epidermis and mild spongiosis. These pathologic findings were consistent with a diagnosis of psoriasis. There were no drug-related skin eruption features, such as apoptotic keratinocytes, eosinophils, or interface dermatitis. Periodic acid-Schiff stains for fungal organisms were negative. The combined clinical presentation (itchy, teardrop-shaped, scaly lesions) and histologic impression were consistent with guttate psoriasis.

Psoriasis can be seen in various forms. Subtypes of psoriasis include guttate psoriasis, inverse psoriasis, erythrodermic psoriasis, nail psoriasis, and pustular psoriasis.¹ Guttate psoriasis accounts for about 2% of psoriasis cases and usually is seen in patients younger than 30 years.² Guttate psoriasis is characterized by 1- to 10-mm teardrop-shaped pink papules with fine scaling.³

One study found that the average time of new onset of psoriasis or flare-up can be between 5 to 14 days after the COVID-19 vaccination.

Triggers for psoriasis. Vaccinations, medications, and infections (eg, group A beta-hemolytic streptococcal upper respiratory infections) can trigger guttate psoriasis.³ MRNA vaccines (eg, Moderna and Pfizer/BioNTech COVID-19 vaccines) have been associated with psoriasis episodes.¹ Other vaccines such as influenza, rubella, bacillus Calmette-Guerin, tetanus-diphtheria, and pneumococcal polysaccharide also have been known to trigger psoriasis.⁴ Medications that can trigger psoriasis include beta-blockers, lithium, antimalarial drugs, and (in some cases)­ nonsteroidal anti-inflammatory drugs.⁵

The impact of COVID-19 vaccine. We are still learning about the incidence and prevalence of adverse effects (such as psoriasis) that can follow COVID-19 vaccination. One study found that the average time of new onset­ of psoriasis or flare-up can be between 5 to 14 days after COVID-19 vaccination.⁶

Psoriasis following vaccination. The pathologic mechanism for the new onset or flare of psoriasis after COVID-19 vaccination is unknown. What is known is that the dysregulation of Th-1 and Th-17 plays an important role in the pathogenesis of psoriasis.⁷ Previously, it was found that psoriasis can manifest after tetanus-diphtheria vaccines due to an increase in the production of Th-17 cells.⁷ Th-1 and Th-17 production also increases after influenza vaccine and can cause an onset or flare-up of psoriasis.⁸

Continue to: The differential includes syphilis and exfoliative dermatitis

The differential includes syphilis and exfoliative dermatitis

The differential diagnosis includes various forms of psoriasiform dermatitis, such as secondary syphilis, chronic spongiotic dermatitis, psoriasiform drug eruption, exfoliative dermatitis, and pityriasis rubra pilaris. A combination of clinical and histopathologic findings is used to zero in on the diagnosis. The summary below highlights the clinical findings.

Secondary syphilis manifests with symmetric papular eruptions primarily on the trunk and extremities with involvement on the palms and soles. Lesions are red or reddish brown, can be smooth, and are rarely pustular.

Chronic spongiotic dermatitis manifests with a shiny, glazed, cracked appearance and itchy reddish lesions on the soles.

Psoriasiform drug eruption manifests after drug administration with a psoriasis-like rash with erythematous, squamous, thick, dry, and plaque-type lesions.

Exfoliative dermatitis manifests with erythematous single or multiple pruritic patches on the trunk, head, and genitals.

Continue to: Pityriasis rubra pilaris

Pityriasis rubra pilaris manifests in various ways. Patients may have plaques that are erythematous, scaly, or follicular. Sometimes, it may manifest as erythroderma with an “island of sparing,” which is normal-looking skin in the affected areas.

How to make the diagnosis

Psoriasis can be diagnosed by physical examination. A skin biopsy is not usually necessary but can be helpful for complex cases.

There are no laboratory or genetic tests to confirm the diagnosis of psoriasis. Depending on the case, routine bloodwork (eg, complete blood count and metabolic panel) and infectious disease tests (eg, HIV, hepatitis panel, and rapid plasma reagin for syphilis) can be helpful to rule out other etiologies of skin rash.

Treatment is based on patient factors and disease severity

Starting with a low- to medium-potency steroid, such as betamethasone valerate 0.1% cream twice per day or triamcinolone acetonide 0.1% cream twice per day for 2 weeks, provides high safety and efficacy for localized disease.⁹ An appropriate-potency steroid should be chosen based on the disease severity, location, and patient’s preference and age. Topical vitamin D analogues often are used in conjunction with topical steroids to treat psoriasis.⁹

Depending on the severity, patient age, comorbidities, and availability of treatment, other treatment options for psoriasis include oral methotrexate (2.5 mg to 25 mg weekly, starting with a low dose), acitretin (10 mg to 50 mg daily), apremilast (10 mg daily, gradually increasing to 30 mg twice per day in a divided dose), biologics, and narrowband ultraviolet light.

In this case, betamethasone dipropionate 0.05% cream twice daily for 2 weeks was not sufficiently effective due to the extent of the psoriasis. Following consultation with a dermatologist, clobetasol propionate 0.05% cream twice per day and oral apremilast (10 mg once per day on the first day and 10 mg twice per day afterward) were prescribed for 2 weeks. The patient’s psoriasis improved somewhat after 2 weeks of the treatment, but many plaques remained. Therefore, apremilast was stopped and subcutaneous adalimumab was started (initial loading dose, 80 mg, then 40 mg every other week). The psoriasis lesions cleared over the next 2 to 3 months. The patient was maintained on the adalimumab to avoid a recurrence of lesions.

A 41-year-old man presented for evaluation of an extensive skin rash that had erupted more than a month earlier. The patient had received 2 doses of the Pfizer COVID-19 vaccine 3 weeks apart. Ten days after his second dose, the patient developed a rash all over his body. He described the rash as burning, itchy, and uncomfortable. The patient denied any triggers such as recent or previous infections, stressors, or drugs. The patient had no personal or family history of dermatologic disorders; his general medical history was unremarkable. The patient smoked and drank alcohol occasionally.

On physical exam, the patient had a diffuse rash, which initially had manifested on both of his hands, including the palms, and then spread to 60% to 70% of his total body surface area, including his face, ears, anterior and posterior chest, upper and lower extremities, and buttocks. The rash consisted of 10- to 15-mm white scaly plaques that did not bleed.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Diagnosis: Guttate psoriasis

Punch biopsies were obtained, and histopathology revealed diffuse compact hyperkeratosis with broad zones of parakeratosis. There was attenuation of the granular layer and regular elongation of the rete ridges associated with thinning of the suprapapillary epidermis and mild spongiosis. These pathologic findings were consistent with a diagnosis of psoriasis. There were no drug-related skin eruption features, such as apoptotic keratinocytes, eosinophils, or interface dermatitis. Periodic acid-Schiff stains for fungal organisms were negative. The combined clinical presentation (itchy, teardrop-shaped, scaly lesions) and histologic impression were consistent with guttate psoriasis.

Psoriasis can be seen in various forms. Subtypes of psoriasis include guttate psoriasis, inverse psoriasis, erythrodermic psoriasis, nail psoriasis, and pustular psoriasis.¹ Guttate psoriasis accounts for about 2% of psoriasis cases and usually is seen in patients younger than 30 years.² Guttate psoriasis is characterized by 1- to 10-mm teardrop-shaped pink papules with fine scaling.³

One study found that the average time of new onset of psoriasis or flare-up can be between 5 to 14 days after the COVID-19 vaccination.

Triggers for psoriasis. Vaccinations, medications, and infections (eg, group A beta-hemolytic streptococcal upper respiratory infections) can trigger guttate psoriasis.³ MRNA vaccines (eg, Moderna and Pfizer/BioNTech COVID-19 vaccines) have been associated with psoriasis episodes.¹ Other vaccines such as influenza, rubella, bacillus Calmette-Guerin, tetanus-diphtheria, and pneumococcal polysaccharide also have been known to trigger psoriasis.⁴ Medications that can trigger psoriasis include beta-blockers, lithium, antimalarial drugs, and (in some cases)­ nonsteroidal anti-inflammatory drugs.⁵

The impact of COVID-19 vaccine. We are still learning about the incidence and prevalence of adverse effects (such as psoriasis) that can follow COVID-19 vaccination. One study found that the average time of new onset­ of psoriasis or flare-up can be between 5 to 14 days after COVID-19 vaccination.⁶

Psoriasis following vaccination. The pathologic mechanism for the new onset or flare of psoriasis after COVID-19 vaccination is unknown. What is known is that the dysregulation of Th-1 and Th-17 plays an important role in the pathogenesis of psoriasis.⁷ Previously, it was found that psoriasis can manifest after tetanus-diphtheria vaccines due to an increase in the production of Th-17 cells.⁷ Th-1 and Th-17 production also increases after influenza vaccine and can cause an onset or flare-up of psoriasis.⁸

Continue to: The differential includes syphilis and exfoliative dermatitis

The differential includes syphilis and exfoliative dermatitis

The differential diagnosis includes various forms of psoriasiform dermatitis, such as secondary syphilis, chronic spongiotic dermatitis, psoriasiform drug eruption, exfoliative dermatitis, and pityriasis rubra pilaris. A combination of clinical and histopathologic findings is used to zero in on the diagnosis. The summary below highlights the clinical findings.

Secondary syphilis manifests with symmetric papular eruptions primarily on the trunk and extremities with involvement on the palms and soles. Lesions are red or reddish brown, can be smooth, and are rarely pustular.

Chronic spongiotic dermatitis manifests with a shiny, glazed, cracked appearance and itchy reddish lesions on the soles.

Psoriasiform drug eruption manifests after drug administration with a psoriasis-like rash with erythematous, squamous, thick, dry, and plaque-type lesions.

Exfoliative dermatitis manifests with erythematous single or multiple pruritic patches on the trunk, head, and genitals.

Continue to: Pityriasis rubra pilaris

Pityriasis rubra pilaris manifests in various ways. Patients may have plaques that are erythematous, scaly, or follicular. Sometimes, it may manifest as erythroderma with an “island of sparing,” which is normal-looking skin in the affected areas.

How to make the diagnosis

Psoriasis can be diagnosed by physical examination. A skin biopsy is not usually necessary but can be helpful for complex cases.

There are no laboratory or genetic tests to confirm the diagnosis of psoriasis. Depending on the case, routine bloodwork (eg, complete blood count and metabolic panel) and infectious disease tests (eg, HIV, hepatitis panel, and rapid plasma reagin for syphilis) can be helpful to rule out other etiologies of skin rash.

Treatment is based on patient factors and disease severity

Starting with a low- to medium-potency steroid, such as betamethasone valerate 0.1% cream twice per day or triamcinolone acetonide 0.1% cream twice per day for 2 weeks, provides high safety and efficacy for localized disease.⁹ An appropriate-potency steroid should be chosen based on the disease severity, location, and patient’s preference and age. Topical vitamin D analogues often are used in conjunction with topical steroids to treat psoriasis.⁹

Depending on the severity, patient age, comorbidities, and availability of treatment, other treatment options for psoriasis include oral methotrexate (2.5 mg to 25 mg weekly, starting with a low dose), acitretin (10 mg to 50 mg daily), apremilast (10 mg daily, gradually increasing to 30 mg twice per day in a divided dose), biologics, and narrowband ultraviolet light.

In this case, betamethasone dipropionate 0.05% cream twice daily for 2 weeks was not sufficiently effective due to the extent of the psoriasis. Following consultation with a dermatologist, clobetasol propionate 0.05% cream twice per day and oral apremilast (10 mg once per day on the first day and 10 mg twice per day afterward) were prescribed for 2 weeks. The patient’s psoriasis improved somewhat after 2 weeks of the treatment, but many plaques remained. Therefore, apremilast was stopped and subcutaneous adalimumab was started (initial loading dose, 80 mg, then 40 mg every other week). The psoriasis lesions cleared over the next 2 to 3 months. The patient was maintained on the adalimumab to avoid a recurrence of lesions.

A 41-year-old man presented for evaluation of an extensive skin rash that had erupted more than a month earlier. The patient had received 2 doses of the Pfizer COVID-19 vaccine 3 weeks apart. Ten days after his second dose, the patient developed a rash all over his body. He described the rash as burning, itchy, and uncomfortable. The patient denied any triggers such as recent or previous infections, stressors, or drugs. The patient had no personal or family history of dermatologic disorders; his general medical history was unremarkable. The patient smoked and drank alcohol occasionally.

On physical exam, the patient had a diffuse rash, which initially had manifested on both of his hands, including the palms, and then spread to 60% to 70% of his total body surface area, including his face, ears, anterior and posterior chest, upper and lower extremities, and buttocks. The rash consisted of 10- to 15-mm white scaly plaques that did not bleed.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Diagnosis: Guttate psoriasis

Punch biopsies were obtained, and histopathology revealed diffuse compact hyperkeratosis with broad zones of parakeratosis. There was attenuation of the granular layer and regular elongation of the rete ridges associated with thinning of the suprapapillary epidermis and mild spongiosis. These pathologic findings were consistent with a diagnosis of psoriasis. There were no drug-related skin eruption features, such as apoptotic keratinocytes, eosinophils, or interface dermatitis. Periodic acid-Schiff stains for fungal organisms were negative. The combined clinical presentation (itchy, teardrop-shaped, scaly lesions) and histologic impression were consistent with guttate psoriasis.

Psoriasis can be seen in various forms. Subtypes of psoriasis include guttate psoriasis, inverse psoriasis, erythrodermic psoriasis, nail psoriasis, and pustular psoriasis.¹ Guttate psoriasis accounts for about 2% of psoriasis cases and usually is seen in patients younger than 30 years.² Guttate psoriasis is characterized by 1- to 10-mm teardrop-shaped pink papules with fine scaling.³

One study found that the average time of new onset of psoriasis or flare-up can be between 5 to 14 days after the COVID-19 vaccination.

Triggers for psoriasis. Vaccinations, medications, and infections (eg, group A beta-hemolytic streptococcal upper respiratory infections) can trigger guttate psoriasis.³ MRNA vaccines (eg, Moderna and Pfizer/BioNTech COVID-19 vaccines) have been associated with psoriasis episodes.¹ Other vaccines such as influenza, rubella, bacillus Calmette-Guerin, tetanus-diphtheria, and pneumococcal polysaccharide also have been known to trigger psoriasis.⁴ Medications that can trigger psoriasis include beta-blockers, lithium, antimalarial drugs, and (in some cases)­ nonsteroidal anti-inflammatory drugs.⁵

The impact of COVID-19 vaccine. We are still learning about the incidence and prevalence of adverse effects (such as psoriasis) that can follow COVID-19 vaccination. One study found that the average time of new onset­ of psoriasis or flare-up can be between 5 to 14 days after COVID-19 vaccination.⁶

Psoriasis following vaccination. The pathologic mechanism for the new onset or flare of psoriasis after COVID-19 vaccination is unknown. What is known is that the dysregulation of Th-1 and Th-17 plays an important role in the pathogenesis of psoriasis.⁷ Previously, it was found that psoriasis can manifest after tetanus-diphtheria vaccines due to an increase in the production of Th-17 cells.⁷ Th-1 and Th-17 production also increases after influenza vaccine and can cause an onset or flare-up of psoriasis.⁸

Continue to: The differential includes syphilis and exfoliative dermatitis

The differential includes syphilis and exfoliative dermatitis

The differential diagnosis includes various forms of psoriasiform dermatitis, such as secondary syphilis, chronic spongiotic dermatitis, psoriasiform drug eruption, exfoliative dermatitis, and pityriasis rubra pilaris. A combination of clinical and histopathologic findings is used to zero in on the diagnosis. The summary below highlights the clinical findings.

Secondary syphilis manifests with symmetric papular eruptions primarily on the trunk and extremities with involvement on the palms and soles. Lesions are red or reddish brown, can be smooth, and are rarely pustular.

Chronic spongiotic dermatitis manifests with a shiny, glazed, cracked appearance and itchy reddish lesions on the soles.

Psoriasiform drug eruption manifests after drug administration with a psoriasis-like rash with erythematous, squamous, thick, dry, and plaque-type lesions.

Exfoliative dermatitis manifests with erythematous single or multiple pruritic patches on the trunk, head, and genitals.

Continue to: Pityriasis rubra pilaris

Pityriasis rubra pilaris manifests in various ways. Patients may have plaques that are erythematous, scaly, or follicular. Sometimes, it may manifest as erythroderma with an “island of sparing,” which is normal-looking skin in the affected areas.

How to make the diagnosis

Psoriasis can be diagnosed by physical examination. A skin biopsy is not usually necessary but can be helpful for complex cases.

There are no laboratory or genetic tests to confirm the diagnosis of psoriasis. Depending on the case, routine bloodwork (eg, complete blood count and metabolic panel) and infectious disease tests (eg, HIV, hepatitis panel, and rapid plasma reagin for syphilis) can be helpful to rule out other etiologies of skin rash.

Treatment is based on patient factors and disease severity

Starting with a low- to medium-potency steroid, such as betamethasone valerate 0.1% cream twice per day or triamcinolone acetonide 0.1% cream twice per day for 2 weeks, provides high safety and efficacy for localized disease.⁹ An appropriate-potency steroid should be chosen based on the disease severity, location, and patient’s preference and age. Topical vitamin D analogues often are used in conjunction with topical steroids to treat psoriasis.⁹

Depending on the severity, patient age, comorbidities, and availability of treatment, other treatment options for psoriasis include oral methotrexate (2.5 mg to 25 mg weekly, starting with a low dose), acitretin (10 mg to 50 mg daily), apremilast (10 mg daily, gradually increasing to 30 mg twice per day in a divided dose), biologics, and narrowband ultraviolet light.

In this case, betamethasone dipropionate 0.05% cream twice daily for 2 weeks was not sufficiently effective due to the extent of the psoriasis. Following consultation with a dermatologist, clobetasol propionate 0.05% cream twice per day and oral apremilast (10 mg once per day on the first day and 10 mg twice per day afterward) were prescribed for 2 weeks. The patient’s psoriasis improved somewhat after 2 weeks of the treatment, but many plaques remained. Therefore, apremilast was stopped and subcutaneous adalimumab was started (initial loading dose, 80 mg, then 40 mg every other week). The psoriasis lesions cleared over the next 2 to 3 months. The patient was maintained on the adalimumab to avoid a recurrence of lesions.

ILLUSTRATIVE CASE

A 32-year-old primigravida at 10 weeks’ gestation presents for an initial prenatal visit. Medical history includes hypertension that is currently well controlled on labetalol 200 mg twice daily. The patient’s blood pressure (BP) at today’s visit is 125/80 mm Hg. Should labetalol be discontinued?

Chronic hypertension in pregnancy is hypertension that predates the pregnancy or with onset prior to 20 weeks’ gestation. Diagnostic criteria include systolic BP > 140 mm Hg or diastolic BP > 90 mm Hg, use of antihypertensive medications prior to pregnancy, or pregnancy-related hypertension persisting > 12 weeks postpartum.^2,3 Chronic hypertension affects 0.9% to 5% of pregnancies and is associated with increased risk for complications, such as superimposed preeclampsia, small-for-gestational-age infant, preterm birth, cesarean delivery, and neonatal intensive care unit admission.⁴ Superimposed preeclampsia occurs in about 17% to 25% of pregnancies affected by chronic hypertension, compared with 3% to 5% of the general population.³

Historically, a higher treatment threshold of 160/110 mm Hg was preferred to avoid theoretical complications of low placental perfusion.² Practically, this often meant discontinuing antihypertensives at the onset of prenatal care if BP was well controlled. A few small trials previously demonstrated that tight BP goals reduced the risk for severe hypertension, but they did not show an improvement in pregnancy outcomes.^5-7 This larger RCT evaluated whether treatment of mild chronic hypertension in pregnancy at lower BP thresholds is associated with improved pregnancy outcomes without negative impact on fetal growth.

STUDY SUMMARY

Active BP treatment yielded better pregnancy outcomes

In a US multicenter, open-label RCT, 2419 pregnant patients with chronic hypertension and singleton fetuses at gestational age < 23 weeks were randomized to receive either active pharmacologic treatment with a BP goal of 140/90 mm Hg or standard treatment, in which BP medication was withheld unless BP reached 160/105 mm Hg (severe hypertension). If medication was initiated in the standard-treatment group, the goal was also 140/90 mm Hg. Exclusion criteria included severe hypertension or suspected intrauterine growth restriction at randomization, known secondary hypertension, certain high-risk comorbidities (eg, cardiac or renal disease), or a major fetal anomaly.

The American College of Obstetricians and Gynecologists and the Society for Maternal– Fetal Medicine have issued statements recommending a change in practice based on this trial.

First-line medications were labetalol or extended-release nifedipine in the majority of patients in the active-treatment group and in standard-treatment patients who developed severe hypertension. Patients were followed until 6 weeks after delivery. Intention­-to-treat analyses were performed. The primary outcome was a composite of fetal or neonatal death before 28 days of life, superimposed preeclampsia with severe features up to 2 weeks postpartum, placental abruption leading to delivery, and medically indicated preterm birth before 35 weeks’ gestation. Safety outcomes included birthweight < 10th and < 5th percentile for gestational age.

Primary outcome events occurred in 30.2% of the active-treatment group compared with 37% of the standard-treatment group (adjusted risk ratio [aRR] = 0.82; 95% CI, 0.74-0.92; number needed to treat [NNT] = 15). Preeclampsia with severe features (23.3% vs 29.1%; aRR = 0.80; 95% CI, 0.70-0.92) and medically indicated preterm birth before 35 weeks (12.2% vs 16.7%; aRR = 0.73; 95% CI, 0.6-0.89) occurred less often in the active-treatment group compared with the standard-treatment group. There were no differences in rates of placental abruption, fetal or neonatal death, or small-for-gestational-age infants.

WHAT’S NEW

Target BP of < 140/90 mm Hg reduced risk

This trial provides high-quality evidence that initiating or maintaining treatment at a nonsevere BP threshold (< 140/90 mm Hg) in pregnant patients with mild chronic hypertension reduces maternal and neonatal risk without increasing the risk for small-for-­gestational-age infants. The American College of Obstetricians and Gynecologists and the Society for Maternal–Fetal Medicine have issued statements recommending a change in practice based on this trial.^8,9

Continue to: CAVEATS

 

 

CAVEATS

Patient characteristics and medication choices were limited

This trial does not identify a BP goal for patients who are at highest risk for complications of hypertension or who already have been given a diagnosis of a growth-restricted fetus, as those patients were excluded.

Most patients in the trial who required medications received labetalol or extended-­release nifedipine. It is unclear if other medications would produce similar outcomes.

CHALLENGES TO IMPLEMENTATION

Limited challenges anticipated

There should be limited challenges to implementation.

ILLUSTRATIVE CASE

A 32-year-old primigravida at 10 weeks’ gestation presents for an initial prenatal visit. Medical history includes hypertension that is currently well controlled on labetalol 200 mg twice daily. The patient’s blood pressure (BP) at today’s visit is 125/80 mm Hg. Should labetalol be discontinued?

Chronic hypertension in pregnancy is hypertension that predates the pregnancy or with onset prior to 20 weeks’ gestation. Diagnostic criteria include systolic BP > 140 mm Hg or diastolic BP > 90 mm Hg, use of antihypertensive medications prior to pregnancy, or pregnancy-related hypertension persisting > 12 weeks postpartum.^2,3 Chronic hypertension affects 0.9% to 5% of pregnancies and is associated with increased risk for complications, such as superimposed preeclampsia, small-for-gestational-age infant, preterm birth, cesarean delivery, and neonatal intensive care unit admission.⁴ Superimposed preeclampsia occurs in about 17% to 25% of pregnancies affected by chronic hypertension, compared with 3% to 5% of the general population.³

Historically, a higher treatment threshold of 160/110 mm Hg was preferred to avoid theoretical complications of low placental perfusion.² Practically, this often meant discontinuing antihypertensives at the onset of prenatal care if BP was well controlled. A few small trials previously demonstrated that tight BP goals reduced the risk for severe hypertension, but they did not show an improvement in pregnancy outcomes.^5-7 This larger RCT evaluated whether treatment of mild chronic hypertension in pregnancy at lower BP thresholds is associated with improved pregnancy outcomes without negative impact on fetal growth.

STUDY SUMMARY

Active BP treatment yielded better pregnancy outcomes

In a US multicenter, open-label RCT, 2419 pregnant patients with chronic hypertension and singleton fetuses at gestational age < 23 weeks were randomized to receive either active pharmacologic treatment with a BP goal of 140/90 mm Hg or standard treatment, in which BP medication was withheld unless BP reached 160/105 mm Hg (severe hypertension). If medication was initiated in the standard-treatment group, the goal was also 140/90 mm Hg. Exclusion criteria included severe hypertension or suspected intrauterine growth restriction at randomization, known secondary hypertension, certain high-risk comorbidities (eg, cardiac or renal disease), or a major fetal anomaly.

The American College of Obstetricians and Gynecologists and the Society for Maternal– Fetal Medicine have issued statements recommending a change in practice based on this trial.

First-line medications were labetalol or extended-release nifedipine in the majority of patients in the active-treatment group and in standard-treatment patients who developed severe hypertension. Patients were followed until 6 weeks after delivery. Intention­-to-treat analyses were performed. The primary outcome was a composite of fetal or neonatal death before 28 days of life, superimposed preeclampsia with severe features up to 2 weeks postpartum, placental abruption leading to delivery, and medically indicated preterm birth before 35 weeks’ gestation. Safety outcomes included birthweight < 10th and < 5th percentile for gestational age.

Primary outcome events occurred in 30.2% of the active-treatment group compared with 37% of the standard-treatment group (adjusted risk ratio [aRR] = 0.82; 95% CI, 0.74-0.92; number needed to treat [NNT] = 15). Preeclampsia with severe features (23.3% vs 29.1%; aRR = 0.80; 95% CI, 0.70-0.92) and medically indicated preterm birth before 35 weeks (12.2% vs 16.7%; aRR = 0.73; 95% CI, 0.6-0.89) occurred less often in the active-treatment group compared with the standard-treatment group. There were no differences in rates of placental abruption, fetal or neonatal death, or small-for-gestational-age infants.

WHAT’S NEW

Target BP of < 140/90 mm Hg reduced risk

This trial provides high-quality evidence that initiating or maintaining treatment at a nonsevere BP threshold (< 140/90 mm Hg) in pregnant patients with mild chronic hypertension reduces maternal and neonatal risk without increasing the risk for small-for-­gestational-age infants. The American College of Obstetricians and Gynecologists and the Society for Maternal–Fetal Medicine have issued statements recommending a change in practice based on this trial.^8,9

Continue to: CAVEATS

 

 

CAVEATS

Patient characteristics and medication choices were limited

This trial does not identify a BP goal for patients who are at highest risk for complications of hypertension or who already have been given a diagnosis of a growth-restricted fetus, as those patients were excluded.

Most patients in the trial who required medications received labetalol or extended-­release nifedipine. It is unclear if other medications would produce similar outcomes.

CHALLENGES TO IMPLEMENTATION

Limited challenges anticipated

There should be limited challenges to implementation.

ILLUSTRATIVE CASE

A 32-year-old primigravida at 10 weeks’ gestation presents for an initial prenatal visit. Medical history includes hypertension that is currently well controlled on labetalol 200 mg twice daily. The patient’s blood pressure (BP) at today’s visit is 125/80 mm Hg. Should labetalol be discontinued?

Chronic hypertension in pregnancy is hypertension that predates the pregnancy or with onset prior to 20 weeks’ gestation. Diagnostic criteria include systolic BP > 140 mm Hg or diastolic BP > 90 mm Hg, use of antihypertensive medications prior to pregnancy, or pregnancy-related hypertension persisting > 12 weeks postpartum.^2,3 Chronic hypertension affects 0.9% to 5% of pregnancies and is associated with increased risk for complications, such as superimposed preeclampsia, small-for-gestational-age infant, preterm birth, cesarean delivery, and neonatal intensive care unit admission.⁴ Superimposed preeclampsia occurs in about 17% to 25% of pregnancies affected by chronic hypertension, compared with 3% to 5% of the general population.³

Historically, a higher treatment threshold of 160/110 mm Hg was preferred to avoid theoretical complications of low placental perfusion.² Practically, this often meant discontinuing antihypertensives at the onset of prenatal care if BP was well controlled. A few small trials previously demonstrated that tight BP goals reduced the risk for severe hypertension, but they did not show an improvement in pregnancy outcomes.^5-7 This larger RCT evaluated whether treatment of mild chronic hypertension in pregnancy at lower BP thresholds is associated with improved pregnancy outcomes without negative impact on fetal growth.

STUDY SUMMARY

Active BP treatment yielded better pregnancy outcomes

In a US multicenter, open-label RCT, 2419 pregnant patients with chronic hypertension and singleton fetuses at gestational age < 23 weeks were randomized to receive either active pharmacologic treatment with a BP goal of 140/90 mm Hg or standard treatment, in which BP medication was withheld unless BP reached 160/105 mm Hg (severe hypertension). If medication was initiated in the standard-treatment group, the goal was also 140/90 mm Hg. Exclusion criteria included severe hypertension or suspected intrauterine growth restriction at randomization, known secondary hypertension, certain high-risk comorbidities (eg, cardiac or renal disease), or a major fetal anomaly.

The American College of Obstetricians and Gynecologists and the Society for Maternal– Fetal Medicine have issued statements recommending a change in practice based on this trial.

First-line medications were labetalol or extended-release nifedipine in the majority of patients in the active-treatment group and in standard-treatment patients who developed severe hypertension. Patients were followed until 6 weeks after delivery. Intention­-to-treat analyses were performed. The primary outcome was a composite of fetal or neonatal death before 28 days of life, superimposed preeclampsia with severe features up to 2 weeks postpartum, placental abruption leading to delivery, and medically indicated preterm birth before 35 weeks’ gestation. Safety outcomes included birthweight < 10th and < 5th percentile for gestational age.

Primary outcome events occurred in 30.2% of the active-treatment group compared with 37% of the standard-treatment group (adjusted risk ratio [aRR] = 0.82; 95% CI, 0.74-0.92; number needed to treat [NNT] = 15). Preeclampsia with severe features (23.3% vs 29.1%; aRR = 0.80; 95% CI, 0.70-0.92) and medically indicated preterm birth before 35 weeks (12.2% vs 16.7%; aRR = 0.73; 95% CI, 0.6-0.89) occurred less often in the active-treatment group compared with the standard-treatment group. There were no differences in rates of placental abruption, fetal or neonatal death, or small-for-gestational-age infants.

WHAT’S NEW

Target BP of < 140/90 mm Hg reduced risk

This trial provides high-quality evidence that initiating or maintaining treatment at a nonsevere BP threshold (< 140/90 mm Hg) in pregnant patients with mild chronic hypertension reduces maternal and neonatal risk without increasing the risk for small-for-­gestational-age infants. The American College of Obstetricians and Gynecologists and the Society for Maternal–Fetal Medicine have issued statements recommending a change in practice based on this trial.^8,9

Continue to: CAVEATS

 

 

CAVEATS

Patient characteristics and medication choices were limited

This trial does not identify a BP goal for patients who are at highest risk for complications of hypertension or who already have been given a diagnosis of a growth-restricted fetus, as those patients were excluded.

Most patients in the trial who required medications received labetalol or extended-­release nifedipine. It is unclear if other medications would produce similar outcomes.

CHALLENGES TO IMPLEMENTATION

Limited challenges anticipated

There should be limited challenges to implementation.

The US Preventive Services Task Force (USPSTF) had a productive year in 2022. In total, the USPSTF

• reviewed and made recommendations on 4 new topics
• re-assessed 19 previous recommendations on 11 topics
• made 24 separate recommendations, including 1 “A,” 3 “B,” 3 “C,” and 5 “D” recommendations and 12 “I” statements (see TABLE 1¹).

A note about grading. TABLE 2² outlines the USPSTF’s grade definitions and suggestions for practice. The importance of an “A” or “B” recommendation rests historically with the requirement in the Affordable Care Act (ACA) that all USPSTF-recommended services with either of these grades have to be provided by commercial health insurance plans with no co-pay or deductible applied. (The legal challenge in Texas to the ACA’s preventive care provision may change that.)

What’s new?

The USPSTF’s review of 4 new topics exceeds the entity’s output in each of the prior 4 years, when the Task Force was able to add only 1 or 2 topics annually. However, 3 of the 4 new topics in 2022 resulted in an insufficient evidence or “I” statement, which means there was not enough evidence to judge the relative benefits and harms of the intervention.

These 3 included screening for type 2 diabetes in children and adolescents younger than 18 years; screening for obstructive sleep apnea in the general adult population (ages ≥ 18 years); and screening for eating disorders in adolescents and adults. The fourth new topic, screening for anxiety in children and adolescents, resulted in a “B” recommendation and was described in a recent Practice Alert.³

Major revision to 1 prior recommendation

Only 1 of the 19 revisited recommendations resulted in a major revision: the use of daily aspirin for primary prevention of cardiovascular disease (CVD). Note that it does not apply to those who have established CVD, in whom the use of aspirin would be considered tertiary prevention or harm reduction.

In 2016, the USPSTF recommended (with a “B” grade) the use of daily low-dose aspirin for those ages 50 to 59 years who had a 10-year risk for a CVD event > 10%; no increased risk for bleeding; at least a 10-year life expectancy; and a willingness to take aspirin for 10 years. For those ages 60 to 69 years with a 10-year risk for a CVD event > 10%, the recommendation was a “C.” For those younger than 50 and older than 70, an “I” statement was issued.

In 2022, the USPSTF was much less enthusiastic about daily aspirin as a primary preventative.⁴ The recommendation is now a “C” for those ages 40 to 59 years who have a 10-year CVD risk ≥ 10%. Those most likely to benefit have a 10-year CVD risk > 15%.

Continue to: The recommendation pertains...

The recommendation pertains to the initiation of aspirin, not the continuation or discontinuation for those who have been using aspirin without complications. The ­USPSTF suggests that the dose of aspirin, if used, should be 81 mg and that it should not be continued past age 75 years. A more detailed discussion of this recommendation and some of its clinical considerations is contained in a recent Practice Alert.⁵

“D” is for “don’t”(with a few caveats)

Avoiding unnecessary or harmful testing and treatments is just as important as offering preventive services of proven benefit. Those practices listed in TABLE 1¹ with a “D” recommendation should be avoided in practice.

However, it is worth mentioning that, while postmenopausal hormone replacement therapy should not be prescribed for the prevention of chronic conditions, this does not mean it should not be used to alleviate postmenopausal vasomotor symptoms—albeit for a limited period of time.

Also, it is important to appreciate the difference between screening and diagnostic tests. When the USPSTF recommends for or against screening, they are referring to the practice in asymptomatic people. The recommendation does not pertain to diagnostic testing to confirm or rule out a condition in a person with symptoms suggestive of a condition. Thus, the recommendation against screening adults for chronic obstructive pulmonary disease applies only to those without symptoms.

Be selective with services graded “C” or “I”

The USPSTF recommendations that require the most clinical judgment and are the most difficult to implement are those with a “C.” Few individuals will benefit from these interventions, and those most likely to benefit usually are described in the clinical considerations that accompany the recommendation. These interventions are time consuming and may be subject to insurance co-pays and deductibles. All 3 “C” recommendations made in 2022 (see TABLE 1¹) pertained to the prevention of CVD, still the leading cause of death in the United States.

Continue it: As "I" statement is not the same...

An “I” statement is not the same as a recommendation against the service—but if the service is offered, both the physician and the patient should understand the uncertainty involved. The services the USPSTF has determined lack sufficient evidence of benefits and/or harms are often recommended by other­ organizations—and in fact, the use of the “I” statement distinguishes the USPSTF from other clinical guideline groups.

If good evidence does not exist, the ­USPSTF will not make a recommendation. This is the main reason that, when the USPSTF reevaluates a topic (about every 6 to 7 years), they seldom make significant changes to their previous recommendations. Good evidence tends to survive the test of time.

However, adherence to this standard can cause the USPSTF to lag behind other guideline producers for some commonly used interventions. This delay can be considered a detriment if the intervention eventually proves to be effective, but it is a benefit if the intervention proves to be nonbeneficial or even harmful.

Putting recommendations into best practice

Given the time constraints in primary care practice, the most efficient way of providing high-quality, clinical preventive services is by implementing USPSTF “A” and “B” recommendations, being very selective about who receives an intervention with a “C” recommendation or “I” statement, and avoiding interventions with a “D” recommendation. 

BREAKING NEWS

At press time, the USPSTF issued a draft recommendation statement that women begin receiving biennial mammograms starting at age 40 years (through age 74 years). For more, see: www.uspreventiveservicestaskforce.org/uspstf/draft-recommendation/breast-cancer-screening-adults#fullrecommendation start

The US Preventive Services Task Force (USPSTF) had a productive year in 2022. In total, the USPSTF

• reviewed and made recommendations on 4 new topics
• re-assessed 19 previous recommendations on 11 topics
• made 24 separate recommendations, including 1 “A,” 3 “B,” 3 “C,” and 5 “D” recommendations and 12 “I” statements (see TABLE 1¹).

A note about grading. TABLE 2² outlines the USPSTF’s grade definitions and suggestions for practice. The importance of an “A” or “B” recommendation rests historically with the requirement in the Affordable Care Act (ACA) that all USPSTF-recommended services with either of these grades have to be provided by commercial health insurance plans with no co-pay or deductible applied. (The legal challenge in Texas to the ACA’s preventive care provision may change that.)

What’s new?

The USPSTF’s review of 4 new topics exceeds the entity’s output in each of the prior 4 years, when the Task Force was able to add only 1 or 2 topics annually. However, 3 of the 4 new topics in 2022 resulted in an insufficient evidence or “I” statement, which means there was not enough evidence to judge the relative benefits and harms of the intervention.

These 3 included screening for type 2 diabetes in children and adolescents younger than 18 years; screening for obstructive sleep apnea in the general adult population (ages ≥ 18 years); and screening for eating disorders in adolescents and adults. The fourth new topic, screening for anxiety in children and adolescents, resulted in a “B” recommendation and was described in a recent Practice Alert.³

Major revision to 1 prior recommendation

Only 1 of the 19 revisited recommendations resulted in a major revision: the use of daily aspirin for primary prevention of cardiovascular disease (CVD). Note that it does not apply to those who have established CVD, in whom the use of aspirin would be considered tertiary prevention or harm reduction.

In 2016, the USPSTF recommended (with a “B” grade) the use of daily low-dose aspirin for those ages 50 to 59 years who had a 10-year risk for a CVD event > 10%; no increased risk for bleeding; at least a 10-year life expectancy; and a willingness to take aspirin for 10 years. For those ages 60 to 69 years with a 10-year risk for a CVD event > 10%, the recommendation was a “C.” For those younger than 50 and older than 70, an “I” statement was issued.

In 2022, the USPSTF was much less enthusiastic about daily aspirin as a primary preventative.⁴ The recommendation is now a “C” for those ages 40 to 59 years who have a 10-year CVD risk ≥ 10%. Those most likely to benefit have a 10-year CVD risk > 15%.

Continue to: The recommendation pertains...

The recommendation pertains to the initiation of aspirin, not the continuation or discontinuation for those who have been using aspirin without complications. The ­USPSTF suggests that the dose of aspirin, if used, should be 81 mg and that it should not be continued past age 75 years. A more detailed discussion of this recommendation and some of its clinical considerations is contained in a recent Practice Alert.⁵

“D” is for “don’t”(with a few caveats)

Avoiding unnecessary or harmful testing and treatments is just as important as offering preventive services of proven benefit. Those practices listed in TABLE 1¹ with a “D” recommendation should be avoided in practice.

However, it is worth mentioning that, while postmenopausal hormone replacement therapy should not be prescribed for the prevention of chronic conditions, this does not mean it should not be used to alleviate postmenopausal vasomotor symptoms—albeit for a limited period of time.

Also, it is important to appreciate the difference between screening and diagnostic tests. When the USPSTF recommends for or against screening, they are referring to the practice in asymptomatic people. The recommendation does not pertain to diagnostic testing to confirm or rule out a condition in a person with symptoms suggestive of a condition. Thus, the recommendation against screening adults for chronic obstructive pulmonary disease applies only to those without symptoms.

Be selective with services graded “C” or “I”

The USPSTF recommendations that require the most clinical judgment and are the most difficult to implement are those with a “C.” Few individuals will benefit from these interventions, and those most likely to benefit usually are described in the clinical considerations that accompany the recommendation. These interventions are time consuming and may be subject to insurance co-pays and deductibles. All 3 “C” recommendations made in 2022 (see TABLE 1¹) pertained to the prevention of CVD, still the leading cause of death in the United States.

Continue it: As "I" statement is not the same...

An “I” statement is not the same as a recommendation against the service—but if the service is offered, both the physician and the patient should understand the uncertainty involved. The services the USPSTF has determined lack sufficient evidence of benefits and/or harms are often recommended by other­ organizations—and in fact, the use of the “I” statement distinguishes the USPSTF from other clinical guideline groups.

If good evidence does not exist, the ­USPSTF will not make a recommendation. This is the main reason that, when the USPSTF reevaluates a topic (about every 6 to 7 years), they seldom make significant changes to their previous recommendations. Good evidence tends to survive the test of time.

However, adherence to this standard can cause the USPSTF to lag behind other guideline producers for some commonly used interventions. This delay can be considered a detriment if the intervention eventually proves to be effective, but it is a benefit if the intervention proves to be nonbeneficial or even harmful.

Putting recommendations into best practice

Given the time constraints in primary care practice, the most efficient way of providing high-quality, clinical preventive services is by implementing USPSTF “A” and “B” recommendations, being very selective about who receives an intervention with a “C” recommendation or “I” statement, and avoiding interventions with a “D” recommendation. 

BREAKING NEWS

At press time, the USPSTF issued a draft recommendation statement that women begin receiving biennial mammograms starting at age 40 years (through age 74 years). For more, see: www.uspreventiveservicestaskforce.org/uspstf/draft-recommendation/breast-cancer-screening-adults#fullrecommendation start

The US Preventive Services Task Force (USPSTF) had a productive year in 2022. In total, the USPSTF

• reviewed and made recommendations on 4 new topics
• re-assessed 19 previous recommendations on 11 topics
• made 24 separate recommendations, including 1 “A,” 3 “B,” 3 “C,” and 5 “D” recommendations and 12 “I” statements (see TABLE 1¹).

A note about grading. TABLE 2² outlines the USPSTF’s grade definitions and suggestions for practice. The importance of an “A” or “B” recommendation rests historically with the requirement in the Affordable Care Act (ACA) that all USPSTF-recommended services with either of these grades have to be provided by commercial health insurance plans with no co-pay or deductible applied. (The legal challenge in Texas to the ACA’s preventive care provision may change that.)

What’s new?

The USPSTF’s review of 4 new topics exceeds the entity’s output in each of the prior 4 years, when the Task Force was able to add only 1 or 2 topics annually. However, 3 of the 4 new topics in 2022 resulted in an insufficient evidence or “I” statement, which means there was not enough evidence to judge the relative benefits and harms of the intervention.

These 3 included screening for type 2 diabetes in children and adolescents younger than 18 years; screening for obstructive sleep apnea in the general adult population (ages ≥ 18 years); and screening for eating disorders in adolescents and adults. The fourth new topic, screening for anxiety in children and adolescents, resulted in a “B” recommendation and was described in a recent Practice Alert.³

Major revision to 1 prior recommendation

Only 1 of the 19 revisited recommendations resulted in a major revision: the use of daily aspirin for primary prevention of cardiovascular disease (CVD). Note that it does not apply to those who have established CVD, in whom the use of aspirin would be considered tertiary prevention or harm reduction.

In 2016, the USPSTF recommended (with a “B” grade) the use of daily low-dose aspirin for those ages 50 to 59 years who had a 10-year risk for a CVD event > 10%; no increased risk for bleeding; at least a 10-year life expectancy; and a willingness to take aspirin for 10 years. For those ages 60 to 69 years with a 10-year risk for a CVD event > 10%, the recommendation was a “C.” For those younger than 50 and older than 70, an “I” statement was issued.

In 2022, the USPSTF was much less enthusiastic about daily aspirin as a primary preventative.⁴ The recommendation is now a “C” for those ages 40 to 59 years who have a 10-year CVD risk ≥ 10%. Those most likely to benefit have a 10-year CVD risk > 15%.

Continue to: The recommendation pertains...

The recommendation pertains to the initiation of aspirin, not the continuation or discontinuation for those who have been using aspirin without complications. The ­USPSTF suggests that the dose of aspirin, if used, should be 81 mg and that it should not be continued past age 75 years. A more detailed discussion of this recommendation and some of its clinical considerations is contained in a recent Practice Alert.⁵

“D” is for “don’t”(with a few caveats)

Avoiding unnecessary or harmful testing and treatments is just as important as offering preventive services of proven benefit. Those practices listed in TABLE 1¹ with a “D” recommendation should be avoided in practice.

However, it is worth mentioning that, while postmenopausal hormone replacement therapy should not be prescribed for the prevention of chronic conditions, this does not mean it should not be used to alleviate postmenopausal vasomotor symptoms—albeit for a limited period of time.

Also, it is important to appreciate the difference between screening and diagnostic tests. When the USPSTF recommends for or against screening, they are referring to the practice in asymptomatic people. The recommendation does not pertain to diagnostic testing to confirm or rule out a condition in a person with symptoms suggestive of a condition. Thus, the recommendation against screening adults for chronic obstructive pulmonary disease applies only to those without symptoms.

Be selective with services graded “C” or “I”

The USPSTF recommendations that require the most clinical judgment and are the most difficult to implement are those with a “C.” Few individuals will benefit from these interventions, and those most likely to benefit usually are described in the clinical considerations that accompany the recommendation. These interventions are time consuming and may be subject to insurance co-pays and deductibles. All 3 “C” recommendations made in 2022 (see TABLE 1¹) pertained to the prevention of CVD, still the leading cause of death in the United States.

Continue it: As "I" statement is not the same...

An “I” statement is not the same as a recommendation against the service—but if the service is offered, both the physician and the patient should understand the uncertainty involved. The services the USPSTF has determined lack sufficient evidence of benefits and/or harms are often recommended by other­ organizations—and in fact, the use of the “I” statement distinguishes the USPSTF from other clinical guideline groups.

If good evidence does not exist, the ­USPSTF will not make a recommendation. This is the main reason that, when the USPSTF reevaluates a topic (about every 6 to 7 years), they seldom make significant changes to their previous recommendations. Good evidence tends to survive the test of time.

However, adherence to this standard can cause the USPSTF to lag behind other guideline producers for some commonly used interventions. This delay can be considered a detriment if the intervention eventually proves to be effective, but it is a benefit if the intervention proves to be nonbeneficial or even harmful.

Putting recommendations into best practice

Given the time constraints in primary care practice, the most efficient way of providing high-quality, clinical preventive services is by implementing USPSTF “A” and “B” recommendations, being very selective about who receives an intervention with a “C” recommendation or “I” statement, and avoiding interventions with a “D” recommendation. 

BREAKING NEWS

At press time, the USPSTF issued a draft recommendation statement that women begin receiving biennial mammograms starting at age 40 years (through age 74 years). For more, see: www.uspreventiveservicestaskforce.org/uspstf/draft-recommendation/breast-cancer-screening-adults#fullrecommendation start

Medication-assisted recovery (MAR)—the preferred terminology for the service formerly known as medication­-assisted treatment—entails a comprehensive set of interventions for managing opioid use disorder (OUD), including medications for opioid use disorder (MOUD). Despite the benefits of MAR—reducing opioid use, opioid-related mortality, and health care costs^1-3—only 11% of patients with a diagnosis of OUD received MOUD in 2020.³

When medication-assisted recovery services are rendered in primary care, treatment retention improves by 25%—highlighting a role for family medicine clinicians in treating OUD.

Primary care physicians, including family physicians, are well positioned to provide MAR across the patient’s lifespan. However, many family medicine clinicians do not possess the logistical knowledge or resources to implement this service.⁴ In this article, we describe options for, and barriers to, MAR and societal issues that have an impact on the care of these patients.

Pathophysiology of OUD

Opioids relieve pain by stimulating μ-opioid receptors and activating the brain’s reward system. These pleasurable effects motivate repeated use.⁵ Frequent opioid exposure causes neuroadaptation, tolerance, and dependence. For patients with OUD who are misusing illicit or prescription opioids, periods of abstinence following neuroadaptation lead to withdrawal symptoms that vary in intensity, depending on the drug, dose, and duration of use. Upregulated noradrenergic tone and dopamine deficiency manifest as numerous signs and symptoms of withdrawal, including⁵:

• Physiologic: secretory (diaphoresis, rhinorrhea, lacrimation, vomiting, diarrhea) and stimulatory (mydriasis, piloerection, hypertension, tachycardia, insomnia)
• Psychological: pain, cravings, dysphoria, anxiety.

A single episode of opioid withdrawal is not directly life-threatening, but untreated episodes can progressively amplify negative feedback and reinforce continued opioid use.⁶ Left untreated, withdrawal can be terminal.

Image: Copyright Joe Gorman

Medication-assisted recovery: Effective intervention

MAR services that integrate medical, behavioral, and psychosocial programs can reduce mortality from OUD 2-fold.^7,8 A meta-analysis found that, when MAR services are rendered in primary care, treatment retention improves by 25% (number needed to treat [NNT] = 6) and ongoing illicit opioid use is reduced by 50% (NNT = 6), relative to care at a specialty clinic⁹—highlighting a role for family medicine clinicians in treating OUD.

All 3 US Food and Drug Administration (FDA)–approved MOUD (methadone, buprenorphine, and naltrexone) reduce cravings; 2 (methadone and buprenorphine) mitigate withdrawal symptoms by activating the μ-opioid receptor; and naltrexone diminishes the reinforcing effects of use (TABLE^10-12). It is crucial to recognize the pharmacologic distinctions among MOUD because untreated withdrawal syndromes increase dropout from treatment programs and subsequent relapse.¹³

The Hx of medication-assisted recovery

To understand the landscape of MAR, it is important to understand the history of opioid treatment in the United States. In 1966, Congress passed the Narcotic Addiction Rehabilitation Act (NARA), which secured federal assistance by which state and local governments could develop drug treatment programs.¹⁴ NARA permitted legal offenders with OUD to be civilly committed to treatment programs, rather than prosecuted. However, limited resources and a burgeoning population led, instead, to low-cost outpatient programs saddled by strict requirements that lacked a basis for improving clinical outcomes.

Continue to: At the time NARA...

At the time NARA was passed by Congress, OUD was viewed—inaccurately—as a criminal problem, not a medical one. Subsequent legislation was crafted through that lens, which has placed a heavy burden on patients until today.¹⁴ Although medical understanding of OUD has advanced tremendously over the past 50 years, treatment remains siloed from mainstream medicine, even in primary care.

There is no one-size-fits-all approach to MAR, and relapse is common. Patient-specific factors and the availability of resources should be considered when designing the most individualized, advantageous plan for MAR.

Methadone

Background. Methadone has the most extensive history for treating OUD and consistently has demonstrated efficacy.¹³ A meta-analysis of randomized controlled trials comparing methadone to nonpharmacotherapy alone found that methadone improved treatment retention by an absolute 57% (NNT = 2).¹⁰

Methadone was approved by the FDA for detoxification and maintenance treatment in the early 1970s, although the Narcotic Addict Treatment Act (NATA) of 1974 restricted dispensing of maintenance treatment to highly regulated clinics known as opioid treatment programs (OTPs).¹⁴ NATA required the treating physician to register with the US Drug Enforcement Agency (DEA) and to comply with conservative dosing regimens and observed dosing.

Over time, regulations evolved to give the physician greater flexibility in developing a care plan, allowing “take-home” doses, and improving patients’ access to care. Although access to methadone for the treatment of OUD remains limited to federally certified OTPs, regulations facilitate incorporation of a whole-person approach to care, including counseling, individual and group therapy, and toxicology testing.⁷

Continue to: Clinical considerations

Clinical considerations. Methadone requires slow titration. For patients starting methadone as an outpatient, federal law¹⁵ limits the initial dose to 30 mg and requires physician documentation when the first-day total dosage exceeds 40 mg. This dosing constraint makes it challenging to provide care because a daily dosage ≥ 60 mg has been found to produce, first, higher program retention (relative risk = 1.36; 95% CI, 1.13-1.63) and, second, greater reduction in illicit opioid use (relative risk = 1.59; 95% CI, 1.16-2.18) than is seen in patients who receive a lower daily dosage.¹⁶

Due to a prolonged elimination half-life, methadone reaches steady-state in 3 to 5 days. Patients and their families should be educated that withdrawal symptoms might not feel fully managed in the first few days of therapy and that time is required to experience safely the regimen’s full effects.

Aggressive dose-titration during methadone induction can result in drug accumulation and respiratory depression. The risk for methadone-related mortality is highest in the first 2 weeks of therapy, mostly related to overdose potential if the drug is combined with other opioids.¹⁷

Buprenorphine

Background. The prescribing rate for buprenorphine, particularly in primary care, is accelerating.¹⁸ A meta-analysis of randomized controlled trials found that¹¹:

• compared to placebo, buprenorphine, at any dosage, improves treatment retention by an absolute 21% to 28% (NNT = 4-5)
• patients receiving high-dose buprenorphine (≥ 16 mg/d) had fewer evident cases of illicit opioid use.

Unlike methadone, buprenorphine exerts partial agonism at the μ-opioid receptor, resulting in a so-called ceiling effect that significantly reduces the adverse effect profile, including respiratory depression and euphoria, relative to a full-agonist opioid, such as methadone.¹⁹

Continue to: Whereas accessing methadone...

Whereas accessing methadone is limited to OTPs, buprenorphine is available for office-based treatment. By hosting OUD treatment and primary care in the same place, primary care physicians can provide comprehensive medical care including and beyond OUD, thereby improving retention and managing comorbidity.²⁰

Integrated models involving support staff—eg, nurses, behavioral health providers, and pharmacists—have produced the greatest success with office-based treatment models.²¹ Office-based treatment normalizes OUD as a chronic disease managed by the primary care physician, enabling concurrent harm-reduction strategies; medication reconciliation; and convenient, regular prescribing intervals (eg, every 30 days).²²
Nevertheless, access to buprenorphine is limited. Because buprenorphine is a controlled substance, the Ryan Haight Online Pharmacy Consumer Protection Act of 2008 prevents initial prescribing of buprenorphine without in-person evaluation. Telehealth consultations increased access to buprenorphine through temporary exceptions during the COVID-19 pandemic. However, revised rules and regulations for telehealth visits for these controlled substances are forthcoming from the DEA as temporary exceptions for telehealth consultations come to an end. Additionally, prescribing buprenorphine for OUD requires that the treating physician undergo specific training and obtain qualifications, which have evolved over time through federal legislation.

The Drug Addiction Treatment Act of 2000 (DATA 2000) authorized what is known as an X-waiver, which allows physicians to prescribe controlled substances for office-based treatment of OUD, provided that:

• they are registered to do so with the Substance Abuse and Mental Health Services Administration and the DEA
• they have had subspecialty training in addiction or completed an 8-hour training course
• they are able to refer patients to appropriate counseling and ancillary services.

DATA 2000 restricted patient panel sizes­ to 30 patients in the first year, expanding thereafter upon appropriate certification.

Although medical understanding of OUD has advanced tremendously over the past 50 years, treatment remains siloed from mainstream medicine, even in primary care.

The Comprehensive Addiction and Recovery Act of 2016 (CARA) and the Substance Use Disorder Prevention that Promotes Opioid Recovery and Treatment for Patients and Communities Act of 2018 (the SUPPORT Act) collectively extended prescribing authority for MOUD to other qualifying practitioners (eg, advanced practice clinicians). Despite these attempts to expand access to services, the overdose death rate has continued to increase.

Continue to: To further expand access to MAR...

To further expand access to MAR, the US Department of Health and Human Services updated its practice guidelines in April 2021, allowing clinicians to bypass X-waiver training requirements by applying for a notification-of-intent (NOI) buprenorphine waiver.^a However, clinicians are still limited to prescribing buprenorphine for 30 patients at a time. Clinicians who undergo complete X-waiver training may prescribe for 100 patients in the first year and, if eligible, 275 patients thereafter.

In addition, as a component of the Consolidation Appropriations Act of 2023, Congress passed the Mainstreaming Addiction Treatment Act of 2021, or MAT 2021, and Medication Access and Training Expansion Act of 2021, or MATE 2021. MAT eliminated the X-waiver, NOI, and restrictions on the number of patients for whom a provider could prescribe buprenorphine, under federal authority; however, restrictions within one’s state might limit the ability to prescribe buprenorphine. MATE 2021 is an educational requirement for licensing by the DEA (at application and renewal) that will require prescribers to complete 8 hours of training in substance use disorders starting in June 2023.

Patients and their families should be educated that withdrawal symptoms might not feel fully managed in the first few days of methadone therapy.

Use of the monthly injectable extended-release buprenorphine product^b is limited by an FDA Risk Evaluation and Mitigation Strategy (REMS) program, which requires specialized training and certification by the prescriber, distributor, and administering clinician. REMS reduces buprenorphine accessibility due to time, cost, and regulatory barriers; although such restrictions have been instituted with the patient’s safety in mind, any limitation to buprenorphine prescribing, apart from controlled substance licensure, serves only to limit access to a primary component of MAR.

Clinical considerations. Due to the competitive nature of buprenorphine and its high affinity for the μ-opioid receptor, the drug can displace other opioid agonists and precipitate acute withdrawal. The withdrawal experience can thereby condition fear and disfavor toward buprenorphine among patients.

It is vital, therefore, that (1) patients’ expectations for treatment be managed appropriately and (2) the treating physician be prepared to provide additional buprenorphine for adequate maintenance doses and utilize adjunct comfort agents (clonidine, nonsteroidal anti-inflammatory drugs, ondansetron) to manage acute withdrawal symptoms. Newer buprenorphine dosing strategies, such as micro-induction and macro-­induction, have emerged to curtail these risks.^23,24 This is an evolving area of MAR; newer low-threshold initiation strategies²⁵ (see “Low-threshold MOUD prescribing models,” in the text that follows) and evidence that supports micro-induction²⁶ might eliminate the practice of requiring active withdrawal for treatment.

Continue to: Regardless of the strategy...

Regardless of the strategy for dosing buprenorphine, it’s critical that patients be educated on how to initiate treatment outside a clinical setting, such as at home, where they occupy a familiar haven during a potentially uncomfortable time and can be as effective at initiation as they would be in a clinical setting, with no difference in precipitation of adverse effects.

At-home induction might be more appropriate for patients who are not yet in significant enough withdrawal while in the physician's office.²⁷ Guidance should be provided on dosing instructions, self-assessment of withdrawal­ symptoms, and, if applicable, patience with the slow-dissolving sublingual tablet or film formulation.

Naltrexone

Background. Naltrexone is available as an oral tablet and an extended-release, once-monthly intramuscular injection; the latter has demonstrated superiority in MAR.²⁸ Oral naltrexone has limited supporting evidence, is inferior to other MOUD options, and should not be used to treat OUD.⁷ Altogether, approval of naltrexone for OUD is controversial, due to potentially unethical trials and approval processes,²⁹ although a multicenter randomized controlled trial demonstrated the drug’s noninferiority with respect to treatment retention relative to buprenorphine.³⁰ Used over time, naltrexone does not relieve withdrawal symptoms but can reduce cravings.

Clinical considerations. There are numerous clinical barriers that limit the use of naltrexone.

First, patients should be abstinent from opioids for 7 to 14 days prior to starting therapy; usually, this means undergoing medically supervised withdrawal in a controlled environment. This is an obvious limitation for patients who are constrained financially—those who lack, or have inadequate, health insurance or are unable to be away from their job for an extended time.

Continue to: Second, because naltrexone...

Second, because naltrexone does not address withdrawal symptoms, supportive therapies should be incorporated into the treatment plan, including:

• clonidine for hyperadrenergic symptoms (anxiety, diaphoresis, hypertension)
• nonopioid analgesics for pain
• antiemetics, such as ondansetron and metoclopramide, for nausea or vomiting
• loperamide for diarrhea
• diphenhydramine for insomnia.

Third, patients taking naltrexone have a diminished response to opioids. This complicates pain management in the event of an emergent surgical procedure.

Last, when naltrexone wears off, patients are effectively opioid-naïve, which increases the risk for overdose in those who stop therapy abruptly.²⁹ The increased risk for overdose should be communicated to all patients with OUD who are being treated with naltrexone.

This nonopioid option is appealing to policymakers and is often prioritized in the criminal justice system; however, the decreased efficacy of naltrexone (compared to methadone and buprenorphine), potential for overdose, and challenges in initiating treatment are concerning and limit the drug’s use in many real-world settings.

Because naltrexone is not a controlled substance, regulations regarding maintaining inventory and distribution are more flexible.

Continue to: Overall, the cost-effectiveness...

Overall, the cost-effectiveness of intramuscular naltrexone is unclear. State-administered insurance programs vary in their requirements for coverage of naltrexone treatment.³¹

Comprehensive medication reconciliation is vital

Overall fragmentation of care within OTPs places patients at risk for adverse events, such as drug interactions.³² Under Title 42 of the US Code,³³ patients must provide written consent for an OTP provider to disclose their history of a substance use disorder. Allowing the patient to decide which medical providers can access their treatment records for an OUD benefits patient confidentiality but poses­ numerous issues worth exploring.

All prescribed controlled substances are recorded in the prescription drug monitoring program, or PDMP, a state-level electronic database accessible to health care professionals to inform prescribing decisions and identify drug interactions. The PDMP has substantially reduced opioid overprescribing and improved identification of patients at risk for overdose or misuse of opioids.

Buprenorphine, available for office-based treatment, has a so-called ceiling effect that reduces the adverse effect profile, including respiratory depression and euphoria.

Unlike all other controlled substances, however, prescriptions ordered by an OTP are not recorded in the PDMP (although there are recent exceptions to this scenario). Without such information, a physician might not have important information about the patient when making medical decisions—placing the patient at risk for harmful outcomes, such as drug–drug and drug–disease interactions.

For example: Methadone is associated with a prolonged QT interval,³⁴ increasing the risk for a fatal arrhythmia. Concurrent QT-prolonging medications, such as azithromycin and citalopram, further increase this risk.³⁵ Because methadone dispensing is isolated from the patient’s medical record, the clinician who prescribes MOUD has an incomplete patient history and could make a potentially fatal treatment decision.

Continue to: Diversion is unlikely

Diversion is unlikely

Health care providers often express concern about diversion in MOUD. However, misuse and diversion rates of methadone and buprenorphine have declined steadily since 2011, and, in fact, are actually lower than the diversion rate of prescription antibiotics.³⁶

Regardless, diversion of buprenorphine should not be a concern for physicians prescribing MOUD. Although a prescriber might worry about manipulation of the formulation of buprenorphine for intravenous administration, addition of naloxone to buprenorphine in tablet form diminishes the potential for overdose. Additionally, the ceiling effect of buprenorphine limits the likelihood of significant respiratory depression and euphoria.

Should buprenorphine reach a patient for whom it was not prescribed, it is highly unlikely that an overdose would result. Rather, the medication would protect against the effects of illicit opioids and relieve withdrawal symptoms. Most people with OUD who have misused buprenorphine have done so to relieve withdrawal symptoms,³⁷ not to experience intoxication.

Health care deserts

So-called health care deserts in parts of the United States are an ongoing problem that disproportionately affects lower-income and segregated Black and Hispanic communities³⁸—communities that shoulder the highest burden of OUD and OUD-related mortality³⁹ and whose populace is in greatest need of MAR. Even when health care is accessible in such a desert, some clinicians and pharmacies refuse to prescribe or dispense MOUD because of the accompanying stigma of OUD.

Prescribing buprenorphine for OUD requires that the treating physician undergo specific training, including subspecialty training in addiction or an 8-hour training course.

A MAR desert, like a pharmacy desert, is a geographic region—one without access to a MAR or an OTP provider, thereby preventing patients from reaching appropriate care; for some patients, having to travel to the nearest provider can render treatment inaccessible.⁴⁰

Continue to: Efforts are in place to identify...

Efforts are in place to identify areas at greatest need of OUD-related medical services, such as heat maps that identify areas of increased utilization of emergency medical services for opioid overdose. State-run programs have been implemented to increase access, such as the Illinois Helpline (https://helplineil.org) that provides support and resources for patients, friends, family, and providers.

Novel solutions

Key strategies to increase access to care and slow the opioid epidemic include low-threshold prescribing of MOUD and mobile OTPs.⁴¹

Low-threshold MOUD prescribing models. Adoption of one of these models in a medical practice that provides MAR might increase absolute enrollment. A low-threshold prescribing model involves⁴²:

• same-day treatment
• leniency with respect to abstinence periods and a concomitant substance use disorder
• enhanced accessibility to MOUD through nontraditional medical settings.

Do not use oral naltrexone to treat OUD; this route of administration has limited supporting evidence.

Low-threshold prescribing is flexible in regard to patients’ needs and bypasses many of the barriers discussed in this article. Impressive multicenter success has been achieved by the CA Bridge program in California (https://cabridge.org), including an increase in recognition of OUD, treatment initiations, and outpatient engagement.²⁵

The cost-effectiveness of low-threshold MOUD prescribing programs remains to be determined.

Mobile OTPs. In July 2021, the DEA authorized a mobile component to existing OTP registrants that is permitted to dispense methadone and buprenorphine. Mobile units are physically separate from the OTP but have similar functions, depending on available space. Services that cannot be provided on the mobile unit of an OTP must be available at its brick-and-mortar location.⁷ Logistically, OTP registrants no longer need a separate registration to implement a mobile unit, thus expanding care to patients in underserved or remote areas who often encounter barriers to access.⁴³

Conclusion

Understanding the distinct clinical and accessibility benefits and limitations among available MOUD is essential for prescribing clinicians. Accessing treatment is limited by federal regulation, stigma, and the existence of health care deserts that limit access to necessary care for patients with OUD. Newer harm-reduction models, such as low-threshold prescribing and mobile OTPs, represent progress, but many patients remain untreated.

a At buprenorphine.samhsa.gov/forms/select-practitioner-type.php

b Sold under the brand name Sublocade.

CORRESPONDENCE
Jennie B. Jarrett, PharmD, MMedEd, Department of Pharmacy Practice, University of Illinois Chicago College of Pharmacy, 833 South Wood Street (MC 886), Chicago, IL 60612; [email protected]

Medication-assisted recovery (MAR)—the preferred terminology for the service formerly known as medication­-assisted treatment—entails a comprehensive set of interventions for managing opioid use disorder (OUD), including medications for opioid use disorder (MOUD). Despite the benefits of MAR—reducing opioid use, opioid-related mortality, and health care costs^1-3—only 11% of patients with a diagnosis of OUD received MOUD in 2020.³

When medication-assisted recovery services are rendered in primary care, treatment retention improves by 25%—highlighting a role for family medicine clinicians in treating OUD.

Primary care physicians, including family physicians, are well positioned to provide MAR across the patient’s lifespan. However, many family medicine clinicians do not possess the logistical knowledge or resources to implement this service.⁴ In this article, we describe options for, and barriers to, MAR and societal issues that have an impact on the care of these patients.

Pathophysiology of OUD

Opioids relieve pain by stimulating μ-opioid receptors and activating the brain’s reward system. These pleasurable effects motivate repeated use.⁵ Frequent opioid exposure causes neuroadaptation, tolerance, and dependence. For patients with OUD who are misusing illicit or prescription opioids, periods of abstinence following neuroadaptation lead to withdrawal symptoms that vary in intensity, depending on the drug, dose, and duration of use. Upregulated noradrenergic tone and dopamine deficiency manifest as numerous signs and symptoms of withdrawal, including⁵:

• Physiologic: secretory (diaphoresis, rhinorrhea, lacrimation, vomiting, diarrhea) and stimulatory (mydriasis, piloerection, hypertension, tachycardia, insomnia)
• Psychological: pain, cravings, dysphoria, anxiety.

A single episode of opioid withdrawal is not directly life-threatening, but untreated episodes can progressively amplify negative feedback and reinforce continued opioid use.⁶ Left untreated, withdrawal can be terminal.

Image: Copyright Joe Gorman

Medication-assisted recovery: Effective intervention

MAR services that integrate medical, behavioral, and psychosocial programs can reduce mortality from OUD 2-fold.^7,8 A meta-analysis found that, when MAR services are rendered in primary care, treatment retention improves by 25% (number needed to treat [NNT] = 6) and ongoing illicit opioid use is reduced by 50% (NNT = 6), relative to care at a specialty clinic⁹—highlighting a role for family medicine clinicians in treating OUD.

All 3 US Food and Drug Administration (FDA)–approved MOUD (methadone, buprenorphine, and naltrexone) reduce cravings; 2 (methadone and buprenorphine) mitigate withdrawal symptoms by activating the μ-opioid receptor; and naltrexone diminishes the reinforcing effects of use (TABLE^10-12). It is crucial to recognize the pharmacologic distinctions among MOUD because untreated withdrawal syndromes increase dropout from treatment programs and subsequent relapse.¹³

The Hx of medication-assisted recovery

To understand the landscape of MAR, it is important to understand the history of opioid treatment in the United States. In 1966, Congress passed the Narcotic Addiction Rehabilitation Act (NARA), which secured federal assistance by which state and local governments could develop drug treatment programs.¹⁴ NARA permitted legal offenders with OUD to be civilly committed to treatment programs, rather than prosecuted. However, limited resources and a burgeoning population led, instead, to low-cost outpatient programs saddled by strict requirements that lacked a basis for improving clinical outcomes.

Continue to: At the time NARA...

At the time NARA was passed by Congress, OUD was viewed—inaccurately—as a criminal problem, not a medical one. Subsequent legislation was crafted through that lens, which has placed a heavy burden on patients until today.¹⁴ Although medical understanding of OUD has advanced tremendously over the past 50 years, treatment remains siloed from mainstream medicine, even in primary care.

There is no one-size-fits-all approach to MAR, and relapse is common. Patient-specific factors and the availability of resources should be considered when designing the most individualized, advantageous plan for MAR.

Methadone

Background. Methadone has the most extensive history for treating OUD and consistently has demonstrated efficacy.¹³ A meta-analysis of randomized controlled trials comparing methadone to nonpharmacotherapy alone found that methadone improved treatment retention by an absolute 57% (NNT = 2).¹⁰

Methadone was approved by the FDA for detoxification and maintenance treatment in the early 1970s, although the Narcotic Addict Treatment Act (NATA) of 1974 restricted dispensing of maintenance treatment to highly regulated clinics known as opioid treatment programs (OTPs).¹⁴ NATA required the treating physician to register with the US Drug Enforcement Agency (DEA) and to comply with conservative dosing regimens and observed dosing.

Over time, regulations evolved to give the physician greater flexibility in developing a care plan, allowing “take-home” doses, and improving patients’ access to care. Although access to methadone for the treatment of OUD remains limited to federally certified OTPs, regulations facilitate incorporation of a whole-person approach to care, including counseling, individual and group therapy, and toxicology testing.⁷

Continue to: Clinical considerations

Clinical considerations. Methadone requires slow titration. For patients starting methadone as an outpatient, federal law¹⁵ limits the initial dose to 30 mg and requires physician documentation when the first-day total dosage exceeds 40 mg. This dosing constraint makes it challenging to provide care because a daily dosage ≥ 60 mg has been found to produce, first, higher program retention (relative risk = 1.36; 95% CI, 1.13-1.63) and, second, greater reduction in illicit opioid use (relative risk = 1.59; 95% CI, 1.16-2.18) than is seen in patients who receive a lower daily dosage.¹⁶

Due to a prolonged elimination half-life, methadone reaches steady-state in 3 to 5 days. Patients and their families should be educated that withdrawal symptoms might not feel fully managed in the first few days of therapy and that time is required to experience safely the regimen’s full effects.

Aggressive dose-titration during methadone induction can result in drug accumulation and respiratory depression. The risk for methadone-related mortality is highest in the first 2 weeks of therapy, mostly related to overdose potential if the drug is combined with other opioids.¹⁷

Buprenorphine

Background. The prescribing rate for buprenorphine, particularly in primary care, is accelerating.¹⁸ A meta-analysis of randomized controlled trials found that¹¹:

• compared to placebo, buprenorphine, at any dosage, improves treatment retention by an absolute 21% to 28% (NNT = 4-5)
• patients receiving high-dose buprenorphine (≥ 16 mg/d) had fewer evident cases of illicit opioid use.

Unlike methadone, buprenorphine exerts partial agonism at the μ-opioid receptor, resulting in a so-called ceiling effect that significantly reduces the adverse effect profile, including respiratory depression and euphoria, relative to a full-agonist opioid, such as methadone.¹⁹

Continue to: Whereas accessing methadone...

Whereas accessing methadone is limited to OTPs, buprenorphine is available for office-based treatment. By hosting OUD treatment and primary care in the same place, primary care physicians can provide comprehensive medical care including and beyond OUD, thereby improving retention and managing comorbidity.²⁰

Integrated models involving support staff—eg, nurses, behavioral health providers, and pharmacists—have produced the greatest success with office-based treatment models.²¹ Office-based treatment normalizes OUD as a chronic disease managed by the primary care physician, enabling concurrent harm-reduction strategies; medication reconciliation; and convenient, regular prescribing intervals (eg, every 30 days).²²
Nevertheless, access to buprenorphine is limited. Because buprenorphine is a controlled substance, the Ryan Haight Online Pharmacy Consumer Protection Act of 2008 prevents initial prescribing of buprenorphine without in-person evaluation. Telehealth consultations increased access to buprenorphine through temporary exceptions during the COVID-19 pandemic. However, revised rules and regulations for telehealth visits for these controlled substances are forthcoming from the DEA as temporary exceptions for telehealth consultations come to an end. Additionally, prescribing buprenorphine for OUD requires that the treating physician undergo specific training and obtain qualifications, which have evolved over time through federal legislation.

The Drug Addiction Treatment Act of 2000 (DATA 2000) authorized what is known as an X-waiver, which allows physicians to prescribe controlled substances for office-based treatment of OUD, provided that:

• they are registered to do so with the Substance Abuse and Mental Health Services Administration and the DEA
• they have had subspecialty training in addiction or completed an 8-hour training course
• they are able to refer patients to appropriate counseling and ancillary services.

DATA 2000 restricted patient panel sizes­ to 30 patients in the first year, expanding thereafter upon appropriate certification.

Although medical understanding of OUD has advanced tremendously over the past 50 years, treatment remains siloed from mainstream medicine, even in primary care.

The Comprehensive Addiction and Recovery Act of 2016 (CARA) and the Substance Use Disorder Prevention that Promotes Opioid Recovery and Treatment for Patients and Communities Act of 2018 (the SUPPORT Act) collectively extended prescribing authority for MOUD to other qualifying practitioners (eg, advanced practice clinicians). Despite these attempts to expand access to services, the overdose death rate has continued to increase.

Continue to: To further expand access to MAR...

To further expand access to MAR, the US Department of Health and Human Services updated its practice guidelines in April 2021, allowing clinicians to bypass X-waiver training requirements by applying for a notification-of-intent (NOI) buprenorphine waiver.^a However, clinicians are still limited to prescribing buprenorphine for 30 patients at a time. Clinicians who undergo complete X-waiver training may prescribe for 100 patients in the first year and, if eligible, 275 patients thereafter.

In addition, as a component of the Consolidation Appropriations Act of 2023, Congress passed the Mainstreaming Addiction Treatment Act of 2021, or MAT 2021, and Medication Access and Training Expansion Act of 2021, or MATE 2021. MAT eliminated the X-waiver, NOI, and restrictions on the number of patients for whom a provider could prescribe buprenorphine, under federal authority; however, restrictions within one’s state might limit the ability to prescribe buprenorphine. MATE 2021 is an educational requirement for licensing by the DEA (at application and renewal) that will require prescribers to complete 8 hours of training in substance use disorders starting in June 2023.

Patients and their families should be educated that withdrawal symptoms might not feel fully managed in the first few days of methadone therapy.

Use of the monthly injectable extended-release buprenorphine product^b is limited by an FDA Risk Evaluation and Mitigation Strategy (REMS) program, which requires specialized training and certification by the prescriber, distributor, and administering clinician. REMS reduces buprenorphine accessibility due to time, cost, and regulatory barriers; although such restrictions have been instituted with the patient’s safety in mind, any limitation to buprenorphine prescribing, apart from controlled substance licensure, serves only to limit access to a primary component of MAR.

Clinical considerations. Due to the competitive nature of buprenorphine and its high affinity for the μ-opioid receptor, the drug can displace other opioid agonists and precipitate acute withdrawal. The withdrawal experience can thereby condition fear and disfavor toward buprenorphine among patients.

It is vital, therefore, that (1) patients’ expectations for treatment be managed appropriately and (2) the treating physician be prepared to provide additional buprenorphine for adequate maintenance doses and utilize adjunct comfort agents (clonidine, nonsteroidal anti-inflammatory drugs, ondansetron) to manage acute withdrawal symptoms. Newer buprenorphine dosing strategies, such as micro-induction and macro-­induction, have emerged to curtail these risks.^23,24 This is an evolving area of MAR; newer low-threshold initiation strategies²⁵ (see “Low-threshold MOUD prescribing models,” in the text that follows) and evidence that supports micro-induction²⁶ might eliminate the practice of requiring active withdrawal for treatment.

Continue to: Regardless of the strategy...

Regardless of the strategy for dosing buprenorphine, it’s critical that patients be educated on how to initiate treatment outside a clinical setting, such as at home, where they occupy a familiar haven during a potentially uncomfortable time and can be as effective at initiation as they would be in a clinical setting, with no difference in precipitation of adverse effects.

At-home induction might be more appropriate for patients who are not yet in significant enough withdrawal while in the physician's office.²⁷ Guidance should be provided on dosing instructions, self-assessment of withdrawal­ symptoms, and, if applicable, patience with the slow-dissolving sublingual tablet or film formulation.

Naltrexone

Background. Naltrexone is available as an oral tablet and an extended-release, once-monthly intramuscular injection; the latter has demonstrated superiority in MAR.²⁸ Oral naltrexone has limited supporting evidence, is inferior to other MOUD options, and should not be used to treat OUD.⁷ Altogether, approval of naltrexone for OUD is controversial, due to potentially unethical trials and approval processes,²⁹ although a multicenter randomized controlled trial demonstrated the drug’s noninferiority with respect to treatment retention relative to buprenorphine.³⁰ Used over time, naltrexone does not relieve withdrawal symptoms but can reduce cravings.

Clinical considerations. There are numerous clinical barriers that limit the use of naltrexone.

First, patients should be abstinent from opioids for 7 to 14 days prior to starting therapy; usually, this means undergoing medically supervised withdrawal in a controlled environment. This is an obvious limitation for patients who are constrained financially—those who lack, or have inadequate, health insurance or are unable to be away from their job for an extended time.

Continue to: Second, because naltrexone...

Second, because naltrexone does not address withdrawal symptoms, supportive therapies should be incorporated into the treatment plan, including:

• clonidine for hyperadrenergic symptoms (anxiety, diaphoresis, hypertension)
• nonopioid analgesics for pain
• antiemetics, such as ondansetron and metoclopramide, for nausea or vomiting
• loperamide for diarrhea
• diphenhydramine for insomnia.

Third, patients taking naltrexone have a diminished response to opioids. This complicates pain management in the event of an emergent surgical procedure.

Last, when naltrexone wears off, patients are effectively opioid-naïve, which increases the risk for overdose in those who stop therapy abruptly.²⁹ The increased risk for overdose should be communicated to all patients with OUD who are being treated with naltrexone.

This nonopioid option is appealing to policymakers and is often prioritized in the criminal justice system; however, the decreased efficacy of naltrexone (compared to methadone and buprenorphine), potential for overdose, and challenges in initiating treatment are concerning and limit the drug’s use in many real-world settings.

Because naltrexone is not a controlled substance, regulations regarding maintaining inventory and distribution are more flexible.

Continue to: Overall, the cost-effectiveness...

Overall, the cost-effectiveness of intramuscular naltrexone is unclear. State-administered insurance programs vary in their requirements for coverage of naltrexone treatment.³¹

Comprehensive medication reconciliation is vital

Overall fragmentation of care within OTPs places patients at risk for adverse events, such as drug interactions.³² Under Title 42 of the US Code,³³ patients must provide written consent for an OTP provider to disclose their history of a substance use disorder. Allowing the patient to decide which medical providers can access their treatment records for an OUD benefits patient confidentiality but poses­ numerous issues worth exploring.

All prescribed controlled substances are recorded in the prescription drug monitoring program, or PDMP, a state-level electronic database accessible to health care professionals to inform prescribing decisions and identify drug interactions. The PDMP has substantially reduced opioid overprescribing and improved identification of patients at risk for overdose or misuse of opioids.

Buprenorphine, available for office-based treatment, has a so-called ceiling effect that reduces the adverse effect profile, including respiratory depression and euphoria.

Unlike all other controlled substances, however, prescriptions ordered by an OTP are not recorded in the PDMP (although there are recent exceptions to this scenario). Without such information, a physician might not have important information about the patient when making medical decisions—placing the patient at risk for harmful outcomes, such as drug–drug and drug–disease interactions.

For example: Methadone is associated with a prolonged QT interval,³⁴ increasing the risk for a fatal arrhythmia. Concurrent QT-prolonging medications, such as azithromycin and citalopram, further increase this risk.³⁵ Because methadone dispensing is isolated from the patient’s medical record, the clinician who prescribes MOUD has an incomplete patient history and could make a potentially fatal treatment decision.

Continue to: Diversion is unlikely

Diversion is unlikely

Health care providers often express concern about diversion in MOUD. However, misuse and diversion rates of methadone and buprenorphine have declined steadily since 2011, and, in fact, are actually lower than the diversion rate of prescription antibiotics.³⁶

Regardless, diversion of buprenorphine should not be a concern for physicians prescribing MOUD. Although a prescriber might worry about manipulation of the formulation of buprenorphine for intravenous administration, addition of naloxone to buprenorphine in tablet form diminishes the potential for overdose. Additionally, the ceiling effect of buprenorphine limits the likelihood of significant respiratory depression and euphoria.

Should buprenorphine reach a patient for whom it was not prescribed, it is highly unlikely that an overdose would result. Rather, the medication would protect against the effects of illicit opioids and relieve withdrawal symptoms. Most people with OUD who have misused buprenorphine have done so to relieve withdrawal symptoms,³⁷ not to experience intoxication.

Health care deserts

So-called health care deserts in parts of the United States are an ongoing problem that disproportionately affects lower-income and segregated Black and Hispanic communities³⁸—communities that shoulder the highest burden of OUD and OUD-related mortality³⁹ and whose populace is in greatest need of MAR. Even when health care is accessible in such a desert, some clinicians and pharmacies refuse to prescribe or dispense MOUD because of the accompanying stigma of OUD.

Prescribing buprenorphine for OUD requires that the treating physician undergo specific training, including subspecialty training in addiction or an 8-hour training course.

A MAR desert, like a pharmacy desert, is a geographic region—one without access to a MAR or an OTP provider, thereby preventing patients from reaching appropriate care; for some patients, having to travel to the nearest provider can render treatment inaccessible.⁴⁰

Continue to: Efforts are in place to identify...

Efforts are in place to identify areas at greatest need of OUD-related medical services, such as heat maps that identify areas of increased utilization of emergency medical services for opioid overdose. State-run programs have been implemented to increase access, such as the Illinois Helpline (https://helplineil.org) that provides support and resources for patients, friends, family, and providers.

Novel solutions

Key strategies to increase access to care and slow the opioid epidemic include low-threshold prescribing of MOUD and mobile OTPs.⁴¹

Low-threshold MOUD prescribing models. Adoption of one of these models in a medical practice that provides MAR might increase absolute enrollment. A low-threshold prescribing model involves⁴²:

• same-day treatment
• leniency with respect to abstinence periods and a concomitant substance use disorder
• enhanced accessibility to MOUD through nontraditional medical settings.

Do not use oral naltrexone to treat OUD; this route of administration has limited supporting evidence.

Low-threshold prescribing is flexible in regard to patients’ needs and bypasses many of the barriers discussed in this article. Impressive multicenter success has been achieved by the CA Bridge program in California (https://cabridge.org), including an increase in recognition of OUD, treatment initiations, and outpatient engagement.²⁵

The cost-effectiveness of low-threshold MOUD prescribing programs remains to be determined.

Mobile OTPs. In July 2021, the DEA authorized a mobile component to existing OTP registrants that is permitted to dispense methadone and buprenorphine. Mobile units are physically separate from the OTP but have similar functions, depending on available space. Services that cannot be provided on the mobile unit of an OTP must be available at its brick-and-mortar location.⁷ Logistically, OTP registrants no longer need a separate registration to implement a mobile unit, thus expanding care to patients in underserved or remote areas who often encounter barriers to access.⁴³

Conclusion

Understanding the distinct clinical and accessibility benefits and limitations among available MOUD is essential for prescribing clinicians. Accessing treatment is limited by federal regulation, stigma, and the existence of health care deserts that limit access to necessary care for patients with OUD. Newer harm-reduction models, such as low-threshold prescribing and mobile OTPs, represent progress, but many patients remain untreated.

a At buprenorphine.samhsa.gov/forms/select-practitioner-type.php

b Sold under the brand name Sublocade.

CORRESPONDENCE
Jennie B. Jarrett, PharmD, MMedEd, Department of Pharmacy Practice, University of Illinois Chicago College of Pharmacy, 833 South Wood Street (MC 886), Chicago, IL 60612; [email protected]

Medication-assisted recovery (MAR)—the preferred terminology for the service formerly known as medication­-assisted treatment—entails a comprehensive set of interventions for managing opioid use disorder (OUD), including medications for opioid use disorder (MOUD). Despite the benefits of MAR—reducing opioid use, opioid-related mortality, and health care costs^1-3—only 11% of patients with a diagnosis of OUD received MOUD in 2020.³

When medication-assisted recovery services are rendered in primary care, treatment retention improves by 25%—highlighting a role for family medicine clinicians in treating OUD.

Primary care physicians, including family physicians, are well positioned to provide MAR across the patient’s lifespan. However, many family medicine clinicians do not possess the logistical knowledge or resources to implement this service.⁴ In this article, we describe options for, and barriers to, MAR and societal issues that have an impact on the care of these patients.

Pathophysiology of OUD

Opioids relieve pain by stimulating μ-opioid receptors and activating the brain’s reward system. These pleasurable effects motivate repeated use.⁵ Frequent opioid exposure causes neuroadaptation, tolerance, and dependence. For patients with OUD who are misusing illicit or prescription opioids, periods of abstinence following neuroadaptation lead to withdrawal symptoms that vary in intensity, depending on the drug, dose, and duration of use. Upregulated noradrenergic tone and dopamine deficiency manifest as numerous signs and symptoms of withdrawal, including⁵:

• Physiologic: secretory (diaphoresis, rhinorrhea, lacrimation, vomiting, diarrhea) and stimulatory (mydriasis, piloerection, hypertension, tachycardia, insomnia)
• Psychological: pain, cravings, dysphoria, anxiety.

A single episode of opioid withdrawal is not directly life-threatening, but untreated episodes can progressively amplify negative feedback and reinforce continued opioid use.⁶ Left untreated, withdrawal can be terminal.

Image: Copyright Joe Gorman

Medication-assisted recovery: Effective intervention

MAR services that integrate medical, behavioral, and psychosocial programs can reduce mortality from OUD 2-fold.^7,8 A meta-analysis found that, when MAR services are rendered in primary care, treatment retention improves by 25% (number needed to treat [NNT] = 6) and ongoing illicit opioid use is reduced by 50% (NNT = 6), relative to care at a specialty clinic⁹—highlighting a role for family medicine clinicians in treating OUD.

All 3 US Food and Drug Administration (FDA)–approved MOUD (methadone, buprenorphine, and naltrexone) reduce cravings; 2 (methadone and buprenorphine) mitigate withdrawal symptoms by activating the μ-opioid receptor; and naltrexone diminishes the reinforcing effects of use (TABLE^10-12). It is crucial to recognize the pharmacologic distinctions among MOUD because untreated withdrawal syndromes increase dropout from treatment programs and subsequent relapse.¹³

The Hx of medication-assisted recovery

To understand the landscape of MAR, it is important to understand the history of opioid treatment in the United States. In 1966, Congress passed the Narcotic Addiction Rehabilitation Act (NARA), which secured federal assistance by which state and local governments could develop drug treatment programs.¹⁴ NARA permitted legal offenders with OUD to be civilly committed to treatment programs, rather than prosecuted. However, limited resources and a burgeoning population led, instead, to low-cost outpatient programs saddled by strict requirements that lacked a basis for improving clinical outcomes.

Continue to: At the time NARA...

At the time NARA was passed by Congress, OUD was viewed—inaccurately—as a criminal problem, not a medical one. Subsequent legislation was crafted through that lens, which has placed a heavy burden on patients until today.¹⁴ Although medical understanding of OUD has advanced tremendously over the past 50 years, treatment remains siloed from mainstream medicine, even in primary care.

There is no one-size-fits-all approach to MAR, and relapse is common. Patient-specific factors and the availability of resources should be considered when designing the most individualized, advantageous plan for MAR.

Methadone

Background. Methadone has the most extensive history for treating OUD and consistently has demonstrated efficacy.¹³ A meta-analysis of randomized controlled trials comparing methadone to nonpharmacotherapy alone found that methadone improved treatment retention by an absolute 57% (NNT = 2).¹⁰

Methadone was approved by the FDA for detoxification and maintenance treatment in the early 1970s, although the Narcotic Addict Treatment Act (NATA) of 1974 restricted dispensing of maintenance treatment to highly regulated clinics known as opioid treatment programs (OTPs).¹⁴ NATA required the treating physician to register with the US Drug Enforcement Agency (DEA) and to comply with conservative dosing regimens and observed dosing.

Over time, regulations evolved to give the physician greater flexibility in developing a care plan, allowing “take-home” doses, and improving patients’ access to care. Although access to methadone for the treatment of OUD remains limited to federally certified OTPs, regulations facilitate incorporation of a whole-person approach to care, including counseling, individual and group therapy, and toxicology testing.⁷

Continue to: Clinical considerations

Clinical considerations. Methadone requires slow titration. For patients starting methadone as an outpatient, federal law¹⁵ limits the initial dose to 30 mg and requires physician documentation when the first-day total dosage exceeds 40 mg. This dosing constraint makes it challenging to provide care because a daily dosage ≥ 60 mg has been found to produce, first, higher program retention (relative risk = 1.36; 95% CI, 1.13-1.63) and, second, greater reduction in illicit opioid use (relative risk = 1.59; 95% CI, 1.16-2.18) than is seen in patients who receive a lower daily dosage.¹⁶

Due to a prolonged elimination half-life, methadone reaches steady-state in 3 to 5 days. Patients and their families should be educated that withdrawal symptoms might not feel fully managed in the first few days of therapy and that time is required to experience safely the regimen’s full effects.

Aggressive dose-titration during methadone induction can result in drug accumulation and respiratory depression. The risk for methadone-related mortality is highest in the first 2 weeks of therapy, mostly related to overdose potential if the drug is combined with other opioids.¹⁷

Buprenorphine

Background. The prescribing rate for buprenorphine, particularly in primary care, is accelerating.¹⁸ A meta-analysis of randomized controlled trials found that¹¹:

• compared to placebo, buprenorphine, at any dosage, improves treatment retention by an absolute 21% to 28% (NNT = 4-5)
• patients receiving high-dose buprenorphine (≥ 16 mg/d) had fewer evident cases of illicit opioid use.

Unlike methadone, buprenorphine exerts partial agonism at the μ-opioid receptor, resulting in a so-called ceiling effect that significantly reduces the adverse effect profile, including respiratory depression and euphoria, relative to a full-agonist opioid, such as methadone.¹⁹

Continue to: Whereas accessing methadone...

Whereas accessing methadone is limited to OTPs, buprenorphine is available for office-based treatment. By hosting OUD treatment and primary care in the same place, primary care physicians can provide comprehensive medical care including and beyond OUD, thereby improving retention and managing comorbidity.²⁰

Integrated models involving support staff—eg, nurses, behavioral health providers, and pharmacists—have produced the greatest success with office-based treatment models.²¹ Office-based treatment normalizes OUD as a chronic disease managed by the primary care physician, enabling concurrent harm-reduction strategies; medication reconciliation; and convenient, regular prescribing intervals (eg, every 30 days).²²
Nevertheless, access to buprenorphine is limited. Because buprenorphine is a controlled substance, the Ryan Haight Online Pharmacy Consumer Protection Act of 2008 prevents initial prescribing of buprenorphine without in-person evaluation. Telehealth consultations increased access to buprenorphine through temporary exceptions during the COVID-19 pandemic. However, revised rules and regulations for telehealth visits for these controlled substances are forthcoming from the DEA as temporary exceptions for telehealth consultations come to an end. Additionally, prescribing buprenorphine for OUD requires that the treating physician undergo specific training and obtain qualifications, which have evolved over time through federal legislation.

The Drug Addiction Treatment Act of 2000 (DATA 2000) authorized what is known as an X-waiver, which allows physicians to prescribe controlled substances for office-based treatment of OUD, provided that:

• they are registered to do so with the Substance Abuse and Mental Health Services Administration and the DEA
• they have had subspecialty training in addiction or completed an 8-hour training course
• they are able to refer patients to appropriate counseling and ancillary services.

DATA 2000 restricted patient panel sizes­ to 30 patients in the first year, expanding thereafter upon appropriate certification.

Although medical understanding of OUD has advanced tremendously over the past 50 years, treatment remains siloed from mainstream medicine, even in primary care.

The Comprehensive Addiction and Recovery Act of 2016 (CARA) and the Substance Use Disorder Prevention that Promotes Opioid Recovery and Treatment for Patients and Communities Act of 2018 (the SUPPORT Act) collectively extended prescribing authority for MOUD to other qualifying practitioners (eg, advanced practice clinicians). Despite these attempts to expand access to services, the overdose death rate has continued to increase.

Continue to: To further expand access to MAR...

To further expand access to MAR, the US Department of Health and Human Services updated its practice guidelines in April 2021, allowing clinicians to bypass X-waiver training requirements by applying for a notification-of-intent (NOI) buprenorphine waiver.^a However, clinicians are still limited to prescribing buprenorphine for 30 patients at a time. Clinicians who undergo complete X-waiver training may prescribe for 100 patients in the first year and, if eligible, 275 patients thereafter.

In addition, as a component of the Consolidation Appropriations Act of 2023, Congress passed the Mainstreaming Addiction Treatment Act of 2021, or MAT 2021, and Medication Access and Training Expansion Act of 2021, or MATE 2021. MAT eliminated the X-waiver, NOI, and restrictions on the number of patients for whom a provider could prescribe buprenorphine, under federal authority; however, restrictions within one’s state might limit the ability to prescribe buprenorphine. MATE 2021 is an educational requirement for licensing by the DEA (at application and renewal) that will require prescribers to complete 8 hours of training in substance use disorders starting in June 2023.

Patients and their families should be educated that withdrawal symptoms might not feel fully managed in the first few days of methadone therapy.

Use of the monthly injectable extended-release buprenorphine product^b is limited by an FDA Risk Evaluation and Mitigation Strategy (REMS) program, which requires specialized training and certification by the prescriber, distributor, and administering clinician. REMS reduces buprenorphine accessibility due to time, cost, and regulatory barriers; although such restrictions have been instituted with the patient’s safety in mind, any limitation to buprenorphine prescribing, apart from controlled substance licensure, serves only to limit access to a primary component of MAR.

Clinical considerations. Due to the competitive nature of buprenorphine and its high affinity for the μ-opioid receptor, the drug can displace other opioid agonists and precipitate acute withdrawal. The withdrawal experience can thereby condition fear and disfavor toward buprenorphine among patients.

It is vital, therefore, that (1) patients’ expectations for treatment be managed appropriately and (2) the treating physician be prepared to provide additional buprenorphine for adequate maintenance doses and utilize adjunct comfort agents (clonidine, nonsteroidal anti-inflammatory drugs, ondansetron) to manage acute withdrawal symptoms. Newer buprenorphine dosing strategies, such as micro-induction and macro-­induction, have emerged to curtail these risks.^23,24 This is an evolving area of MAR; newer low-threshold initiation strategies²⁵ (see “Low-threshold MOUD prescribing models,” in the text that follows) and evidence that supports micro-induction²⁶ might eliminate the practice of requiring active withdrawal for treatment.

Continue to: Regardless of the strategy...

Regardless of the strategy for dosing buprenorphine, it’s critical that patients be educated on how to initiate treatment outside a clinical setting, such as at home, where they occupy a familiar haven during a potentially uncomfortable time and can be as effective at initiation as they would be in a clinical setting, with no difference in precipitation of adverse effects.

At-home induction might be more appropriate for patients who are not yet in significant enough withdrawal while in the physician's office.²⁷ Guidance should be provided on dosing instructions, self-assessment of withdrawal­ symptoms, and, if applicable, patience with the slow-dissolving sublingual tablet or film formulation.

Naltrexone

Background. Naltrexone is available as an oral tablet and an extended-release, once-monthly intramuscular injection; the latter has demonstrated superiority in MAR.²⁸ Oral naltrexone has limited supporting evidence, is inferior to other MOUD options, and should not be used to treat OUD.⁷ Altogether, approval of naltrexone for OUD is controversial, due to potentially unethical trials and approval processes,²⁹ although a multicenter randomized controlled trial demonstrated the drug’s noninferiority with respect to treatment retention relative to buprenorphine.³⁰ Used over time, naltrexone does not relieve withdrawal symptoms but can reduce cravings.

Clinical considerations. There are numerous clinical barriers that limit the use of naltrexone.

First, patients should be abstinent from opioids for 7 to 14 days prior to starting therapy; usually, this means undergoing medically supervised withdrawal in a controlled environment. This is an obvious limitation for patients who are constrained financially—those who lack, or have inadequate, health insurance or are unable to be away from their job for an extended time.

Continue to: Second, because naltrexone...

Second, because naltrexone does not address withdrawal symptoms, supportive therapies should be incorporated into the treatment plan, including:

• clonidine for hyperadrenergic symptoms (anxiety, diaphoresis, hypertension)
• nonopioid analgesics for pain
• antiemetics, such as ondansetron and metoclopramide, for nausea or vomiting
• loperamide for diarrhea
• diphenhydramine for insomnia.

Third, patients taking naltrexone have a diminished response to opioids. This complicates pain management in the event of an emergent surgical procedure.

Last, when naltrexone wears off, patients are effectively opioid-naïve, which increases the risk for overdose in those who stop therapy abruptly.²⁹ The increased risk for overdose should be communicated to all patients with OUD who are being treated with naltrexone.

This nonopioid option is appealing to policymakers and is often prioritized in the criminal justice system; however, the decreased efficacy of naltrexone (compared to methadone and buprenorphine), potential for overdose, and challenges in initiating treatment are concerning and limit the drug’s use in many real-world settings.

Because naltrexone is not a controlled substance, regulations regarding maintaining inventory and distribution are more flexible.

Continue to: Overall, the cost-effectiveness...

Overall, the cost-effectiveness of intramuscular naltrexone is unclear. State-administered insurance programs vary in their requirements for coverage of naltrexone treatment.³¹

Comprehensive medication reconciliation is vital

Overall fragmentation of care within OTPs places patients at risk for adverse events, such as drug interactions.³² Under Title 42 of the US Code,³³ patients must provide written consent for an OTP provider to disclose their history of a substance use disorder. Allowing the patient to decide which medical providers can access their treatment records for an OUD benefits patient confidentiality but poses­ numerous issues worth exploring.

All prescribed controlled substances are recorded in the prescription drug monitoring program, or PDMP, a state-level electronic database accessible to health care professionals to inform prescribing decisions and identify drug interactions. The PDMP has substantially reduced opioid overprescribing and improved identification of patients at risk for overdose or misuse of opioids.

Buprenorphine, available for office-based treatment, has a so-called ceiling effect that reduces the adverse effect profile, including respiratory depression and euphoria.

Unlike all other controlled substances, however, prescriptions ordered by an OTP are not recorded in the PDMP (although there are recent exceptions to this scenario). Without such information, a physician might not have important information about the patient when making medical decisions—placing the patient at risk for harmful outcomes, such as drug–drug and drug–disease interactions.

For example: Methadone is associated with a prolonged QT interval,³⁴ increasing the risk for a fatal arrhythmia. Concurrent QT-prolonging medications, such as azithromycin and citalopram, further increase this risk.³⁵ Because methadone dispensing is isolated from the patient’s medical record, the clinician who prescribes MOUD has an incomplete patient history and could make a potentially fatal treatment decision.

Continue to: Diversion is unlikely

Diversion is unlikely

Health care providers often express concern about diversion in MOUD. However, misuse and diversion rates of methadone and buprenorphine have declined steadily since 2011, and, in fact, are actually lower than the diversion rate of prescription antibiotics.³⁶

Regardless, diversion of buprenorphine should not be a concern for physicians prescribing MOUD. Although a prescriber might worry about manipulation of the formulation of buprenorphine for intravenous administration, addition of naloxone to buprenorphine in tablet form diminishes the potential for overdose. Additionally, the ceiling effect of buprenorphine limits the likelihood of significant respiratory depression and euphoria.

Should buprenorphine reach a patient for whom it was not prescribed, it is highly unlikely that an overdose would result. Rather, the medication would protect against the effects of illicit opioids and relieve withdrawal symptoms. Most people with OUD who have misused buprenorphine have done so to relieve withdrawal symptoms,³⁷ not to experience intoxication.

Health care deserts

So-called health care deserts in parts of the United States are an ongoing problem that disproportionately affects lower-income and segregated Black and Hispanic communities³⁸—communities that shoulder the highest burden of OUD and OUD-related mortality³⁹ and whose populace is in greatest need of MAR. Even when health care is accessible in such a desert, some clinicians and pharmacies refuse to prescribe or dispense MOUD because of the accompanying stigma of OUD.

Prescribing buprenorphine for OUD requires that the treating physician undergo specific training, including subspecialty training in addiction or an 8-hour training course.

A MAR desert, like a pharmacy desert, is a geographic region—one without access to a MAR or an OTP provider, thereby preventing patients from reaching appropriate care; for some patients, having to travel to the nearest provider can render treatment inaccessible.⁴⁰

Continue to: Efforts are in place to identify...

Efforts are in place to identify areas at greatest need of OUD-related medical services, such as heat maps that identify areas of increased utilization of emergency medical services for opioid overdose. State-run programs have been implemented to increase access, such as the Illinois Helpline (https://helplineil.org) that provides support and resources for patients, friends, family, and providers.

Novel solutions

Key strategies to increase access to care and slow the opioid epidemic include low-threshold prescribing of MOUD and mobile OTPs.⁴¹

Low-threshold MOUD prescribing models. Adoption of one of these models in a medical practice that provides MAR might increase absolute enrollment. A low-threshold prescribing model involves⁴²:

• same-day treatment
• leniency with respect to abstinence periods and a concomitant substance use disorder
• enhanced accessibility to MOUD through nontraditional medical settings.

Do not use oral naltrexone to treat OUD; this route of administration has limited supporting evidence.

Low-threshold prescribing is flexible in regard to patients’ needs and bypasses many of the barriers discussed in this article. Impressive multicenter success has been achieved by the CA Bridge program in California (https://cabridge.org), including an increase in recognition of OUD, treatment initiations, and outpatient engagement.²⁵

The cost-effectiveness of low-threshold MOUD prescribing programs remains to be determined.

Mobile OTPs. In July 2021, the DEA authorized a mobile component to existing OTP registrants that is permitted to dispense methadone and buprenorphine. Mobile units are physically separate from the OTP but have similar functions, depending on available space. Services that cannot be provided on the mobile unit of an OTP must be available at its brick-and-mortar location.⁷ Logistically, OTP registrants no longer need a separate registration to implement a mobile unit, thus expanding care to patients in underserved or remote areas who often encounter barriers to access.⁴³

Conclusion

Understanding the distinct clinical and accessibility benefits and limitations among available MOUD is essential for prescribing clinicians. Accessing treatment is limited by federal regulation, stigma, and the existence of health care deserts that limit access to necessary care for patients with OUD. Newer harm-reduction models, such as low-threshold prescribing and mobile OTPs, represent progress, but many patients remain untreated.

a At buprenorphine.samhsa.gov/forms/select-practitioner-type.php

b Sold under the brand name Sublocade.

CORRESPONDENCE
Jennie B. Jarrett, PharmD, MMedEd, Department of Pharmacy Practice, University of Illinois Chicago College of Pharmacy, 833 South Wood Street (MC 886), Chicago, IL 60612; [email protected]

The media is filled with stories about the opioid crisis. We have all heard the horror stories of addiction and overdose, as well as “pill mill” doctors. In fact, more than 932,000 people have died of drug overdose since 1999 and, in recent years, approximately 75% of drug overdoses involved opioids.

Yet, they still have their place in the treatment of pain. It has been estimated that approximately 37% of all opioid prescriptions are written by primary care doctors, so it is essential that we doctors know appropriate prescribing guidelines.

The CDC updated the 2016 guidelines for prescribing opioids for pain in 2022. They cover when to initiate prescribing of opioids, selecting appropriate opioids and doses, and deciding the duration of therapy. The guidelines do a great job providing evidence-based recommendations while at the same time keeping the problems with opioids in the picture.

For primary care doctors, pain is one of the most common complaints we see – from broken bones to low back pain to cancer pain. It is important to note that the current guidelines exclude pain from sickle cell disease, cancer-related pain, palliative care, and end-of-life care. The guidelines apply to acute, subacute, and chronic pain. Pain is a complex symptom and often needs a multipronged approach. We make a mistake if we just prescribe a pain medication without understanding the root cause of the pain.

The guidelines suggest starting with nonopioid medications and incorporating nonmedicinal modes of treatments, such as physical therapy, as well. Opioids should be started at the lowest dose and for the shortest duration. Immediate-release medications are preferred over long-acting or extended-release ones. The patient should always be informed of the risks and benefits.

While the guidelines do a great job recommending how to prescribe opioids, they do not go into any depth discussing other treatment options. Perhaps knowledge of other treatment modalities would help primary care physicians avoid opioid prescribing. When treating our patients, it is important to educate them on how to manage their own symptoms.

The guidelines also advise tapering patients who may have been on high-dose opioids for long periods of time. Doctors know this is a very difficult task. However, resources to help with this are often lacking. For example, rehab may not be covered under a patient’s insurance, or it may be cheaper to take an opioid than to go to physical therapy. Although the recommendation is to taper, community assets may not support this. Guidelines are one thing, but the rest of the health care system needs to catch up to them and make them practical.

Primary care doctors often utilize our physical medicine, rehabilitation, and pain management specialists to assist in managing our patients’ pain. Here too, access to this resource is often difficult to come by. Depending on a patient’s insurance, it can take months to get an appointment.

In general, the current guidelines offer 12 key recommendations when prescribing opioids. They are a great reference; however, we need more real-life tools. For many of us in primary care, these guidelines support what we’ve been doing all along.

Primary care doctors will surely play a huge role in addressing the opioid crisis. We can prescribe opioids appropriately, but it doesn’t erase the problems of those patients who were overprescribed in the past. Many still seek out these medications whether for monetary reasons or just for the high. It is often easy to blame the patient but the one in control is the one with the prescription pad. Yet, it is important to remember that many of these patients are in real pain and need help.

Often, it is simpler to just prescribe a pain medication than it is to explain why one is not appropriate. As primary care doctors, we need to be effective ambassadors of appropriate opioid prescribing and often that means doing the hard thing and saying no to a patient.

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J.

[email protected]

The media is filled with stories about the opioid crisis. We have all heard the horror stories of addiction and overdose, as well as “pill mill” doctors. In fact, more than 932,000 people have died of drug overdose since 1999 and, in recent years, approximately 75% of drug overdoses involved opioids.

Yet, they still have their place in the treatment of pain. It has been estimated that approximately 37% of all opioid prescriptions are written by primary care doctors, so it is essential that we doctors know appropriate prescribing guidelines.

The CDC updated the 2016 guidelines for prescribing opioids for pain in 2022. They cover when to initiate prescribing of opioids, selecting appropriate opioids and doses, and deciding the duration of therapy. The guidelines do a great job providing evidence-based recommendations while at the same time keeping the problems with opioids in the picture.

For primary care doctors, pain is one of the most common complaints we see – from broken bones to low back pain to cancer pain. It is important to note that the current guidelines exclude pain from sickle cell disease, cancer-related pain, palliative care, and end-of-life care. The guidelines apply to acute, subacute, and chronic pain. Pain is a complex symptom and often needs a multipronged approach. We make a mistake if we just prescribe a pain medication without understanding the root cause of the pain.

The guidelines suggest starting with nonopioid medications and incorporating nonmedicinal modes of treatments, such as physical therapy, as well. Opioids should be started at the lowest dose and for the shortest duration. Immediate-release medications are preferred over long-acting or extended-release ones. The patient should always be informed of the risks and benefits.

While the guidelines do a great job recommending how to prescribe opioids, they do not go into any depth discussing other treatment options. Perhaps knowledge of other treatment modalities would help primary care physicians avoid opioid prescribing. When treating our patients, it is important to educate them on how to manage their own symptoms.

The guidelines also advise tapering patients who may have been on high-dose opioids for long periods of time. Doctors know this is a very difficult task. However, resources to help with this are often lacking. For example, rehab may not be covered under a patient’s insurance, or it may be cheaper to take an opioid than to go to physical therapy. Although the recommendation is to taper, community assets may not support this. Guidelines are one thing, but the rest of the health care system needs to catch up to them and make them practical.

Primary care doctors often utilize our physical medicine, rehabilitation, and pain management specialists to assist in managing our patients’ pain. Here too, access to this resource is often difficult to come by. Depending on a patient’s insurance, it can take months to get an appointment.

In general, the current guidelines offer 12 key recommendations when prescribing opioids. They are a great reference; however, we need more real-life tools. For many of us in primary care, these guidelines support what we’ve been doing all along.

Primary care doctors will surely play a huge role in addressing the opioid crisis. We can prescribe opioids appropriately, but it doesn’t erase the problems of those patients who were overprescribed in the past. Many still seek out these medications whether for monetary reasons or just for the high. It is often easy to blame the patient but the one in control is the one with the prescription pad. Yet, it is important to remember that many of these patients are in real pain and need help.

Often, it is simpler to just prescribe a pain medication than it is to explain why one is not appropriate. As primary care doctors, we need to be effective ambassadors of appropriate opioid prescribing and often that means doing the hard thing and saying no to a patient.

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J.

[email protected]

The media is filled with stories about the opioid crisis. We have all heard the horror stories of addiction and overdose, as well as “pill mill” doctors. In fact, more than 932,000 people have died of drug overdose since 1999 and, in recent years, approximately 75% of drug overdoses involved opioids.

Yet, they still have their place in the treatment of pain. It has been estimated that approximately 37% of all opioid prescriptions are written by primary care doctors, so it is essential that we doctors know appropriate prescribing guidelines.

The CDC updated the 2016 guidelines for prescribing opioids for pain in 2022. They cover when to initiate prescribing of opioids, selecting appropriate opioids and doses, and deciding the duration of therapy. The guidelines do a great job providing evidence-based recommendations while at the same time keeping the problems with opioids in the picture.

For primary care doctors, pain is one of the most common complaints we see – from broken bones to low back pain to cancer pain. It is important to note that the current guidelines exclude pain from sickle cell disease, cancer-related pain, palliative care, and end-of-life care. The guidelines apply to acute, subacute, and chronic pain. Pain is a complex symptom and often needs a multipronged approach. We make a mistake if we just prescribe a pain medication without understanding the root cause of the pain.

The guidelines suggest starting with nonopioid medications and incorporating nonmedicinal modes of treatments, such as physical therapy, as well. Opioids should be started at the lowest dose and for the shortest duration. Immediate-release medications are preferred over long-acting or extended-release ones. The patient should always be informed of the risks and benefits.

While the guidelines do a great job recommending how to prescribe opioids, they do not go into any depth discussing other treatment options. Perhaps knowledge of other treatment modalities would help primary care physicians avoid opioid prescribing. When treating our patients, it is important to educate them on how to manage their own symptoms.

The guidelines also advise tapering patients who may have been on high-dose opioids for long periods of time. Doctors know this is a very difficult task. However, resources to help with this are often lacking. For example, rehab may not be covered under a patient’s insurance, or it may be cheaper to take an opioid than to go to physical therapy. Although the recommendation is to taper, community assets may not support this. Guidelines are one thing, but the rest of the health care system needs to catch up to them and make them practical.

Primary care doctors often utilize our physical medicine, rehabilitation, and pain management specialists to assist in managing our patients’ pain. Here too, access to this resource is often difficult to come by. Depending on a patient’s insurance, it can take months to get an appointment.

In general, the current guidelines offer 12 key recommendations when prescribing opioids. They are a great reference; however, we need more real-life tools. For many of us in primary care, these guidelines support what we’ve been doing all along.

Primary care doctors will surely play a huge role in addressing the opioid crisis. We can prescribe opioids appropriately, but it doesn’t erase the problems of those patients who were overprescribed in the past. Many still seek out these medications whether for monetary reasons or just for the high. It is often easy to blame the patient but the one in control is the one with the prescription pad. Yet, it is important to remember that many of these patients are in real pain and need help.

Often, it is simpler to just prescribe a pain medication than it is to explain why one is not appropriate. As primary care doctors, we need to be effective ambassadors of appropriate opioid prescribing and often that means doing the hard thing and saying no to a patient.

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J.

[email protected]