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Golimumab approval extended to polyarticular-course JIA and juvenile PsA
after the Food and Drug Administration approved the tumor necrosis factor inhibitor for these indications on Sept. 30, according to an announcement from its manufacturer, Janssen.
Results from the open-label, single-arm, multicenter, phase 3, GO-VIVA clinical trial formed the basis for the agency’s approval of IV golimumab. GO-VIVA was conducted in 127 patients aged 2-17 years with JIA with arthritis in five or more joints (despite receiving treatment with methotrexate for at least 2 months) as part of a postmarketing requirement under the Pediatric Research Equity Act after the intravenous formulation of the biologic was approved for adults with rheumatoid arthritis in 2013. It demonstrated that pediatric patients had a level of pharmacokinetic exposure to golimumab that was similar to what was observed in two pivotal phase 3 trials in adults with moderately to severely active RA and active PsA, as well as efficacy that was generally consistent with responses seen in adult patients with RA, the manufacturer said.
Besides RA, intravenous golimumab was previously approved for adults with PsA and ankylosing spondylitis. As opposed to the IV dosing for adults with RA, PsA, and ankylosing spondylitis at 2 mg/kg infused over 30 minutes at weeks 0 and 4, and every 8 weeks thereafter, dosing for pediatric patients with pJIA and PsA is based on body surface area at 80 mg/m2, also given as an IV infusion over 30 minutes at weeks 0 and 4, and every 8 weeks thereafter.
The adverse reactions observed in GO-VIVA were consistent with the established safety profile of intravenous golimumab in adult patients with RA and PsA, according to Janssen.
The full prescribing information for intravenous golimumab can be found on the FDA website.
after the Food and Drug Administration approved the tumor necrosis factor inhibitor for these indications on Sept. 30, according to an announcement from its manufacturer, Janssen.
Results from the open-label, single-arm, multicenter, phase 3, GO-VIVA clinical trial formed the basis for the agency’s approval of IV golimumab. GO-VIVA was conducted in 127 patients aged 2-17 years with JIA with arthritis in five or more joints (despite receiving treatment with methotrexate for at least 2 months) as part of a postmarketing requirement under the Pediatric Research Equity Act after the intravenous formulation of the biologic was approved for adults with rheumatoid arthritis in 2013. It demonstrated that pediatric patients had a level of pharmacokinetic exposure to golimumab that was similar to what was observed in two pivotal phase 3 trials in adults with moderately to severely active RA and active PsA, as well as efficacy that was generally consistent with responses seen in adult patients with RA, the manufacturer said.
Besides RA, intravenous golimumab was previously approved for adults with PsA and ankylosing spondylitis. As opposed to the IV dosing for adults with RA, PsA, and ankylosing spondylitis at 2 mg/kg infused over 30 minutes at weeks 0 and 4, and every 8 weeks thereafter, dosing for pediatric patients with pJIA and PsA is based on body surface area at 80 mg/m2, also given as an IV infusion over 30 minutes at weeks 0 and 4, and every 8 weeks thereafter.
The adverse reactions observed in GO-VIVA were consistent with the established safety profile of intravenous golimumab in adult patients with RA and PsA, according to Janssen.
The full prescribing information for intravenous golimumab can be found on the FDA website.
after the Food and Drug Administration approved the tumor necrosis factor inhibitor for these indications on Sept. 30, according to an announcement from its manufacturer, Janssen.
Results from the open-label, single-arm, multicenter, phase 3, GO-VIVA clinical trial formed the basis for the agency’s approval of IV golimumab. GO-VIVA was conducted in 127 patients aged 2-17 years with JIA with arthritis in five or more joints (despite receiving treatment with methotrexate for at least 2 months) as part of a postmarketing requirement under the Pediatric Research Equity Act after the intravenous formulation of the biologic was approved for adults with rheumatoid arthritis in 2013. It demonstrated that pediatric patients had a level of pharmacokinetic exposure to golimumab that was similar to what was observed in two pivotal phase 3 trials in adults with moderately to severely active RA and active PsA, as well as efficacy that was generally consistent with responses seen in adult patients with RA, the manufacturer said.
Besides RA, intravenous golimumab was previously approved for adults with PsA and ankylosing spondylitis. As opposed to the IV dosing for adults with RA, PsA, and ankylosing spondylitis at 2 mg/kg infused over 30 minutes at weeks 0 and 4, and every 8 weeks thereafter, dosing for pediatric patients with pJIA and PsA is based on body surface area at 80 mg/m2, also given as an IV infusion over 30 minutes at weeks 0 and 4, and every 8 weeks thereafter.
The adverse reactions observed in GO-VIVA were consistent with the established safety profile of intravenous golimumab in adult patients with RA and PsA, according to Janssen.
The full prescribing information for intravenous golimumab can be found on the FDA website.
Tailoring cosmetic procedures for skin of color patients minimize risks
Based on the fact that hyperpigmentation and other adverse events associated with cosmetic dermatologic procedures are relevant to skin type, not racial identification, individualized strategies to minimize the risk of potential adverse events are always appropriate, according to an expert speaking at the virtual Skin of Color Update 2020.
There are many highly effective interventions that employ lasers, chemical peels, and topical agents to achieve excellent cosmetic results in darker skin, but results are highly dependent on first understanding the relative risks and treatment goals, Cheryl Burgess, MD, president and founder of the Center for Dermatology and Dermatologic Surgery, Washington, D.C., said at the meeting.
She stressed the importance of educating patients that “all cosmetic procedures are not for skin of color.” Her approach is to engage patients on what they are trying to accomplish and then seeking a solution that tailors treatment to skin type based on the Fitzpatrick scale, the Roberts Hyperpigmentation Scale, or other guidance.
“There are so many different methods that we can use, and these are not necessarily the ones that patients have read about in a magazine,” Dr. Burgess said.
Intense pulsed laser (IPL) for hair removal is an example. This technique is not appropriate in patients with Fitzpatrick skin type IV or higher, according to Dr. Burgess, who presented a case example of a bad outcome. In this case, a patient came to her for treatment after exposure to IPL resulted in first- and second-degree burns complicated by extensive hypopigmentation.
Ultimately, the solution in this case involved more laser therapy, but this time a strategy was selected appropriate to skin of color.
“It is hard to suggest to a patient that we are going to use a laser device” when the problem was caused by a laser, Dr. Burgess observed, but properly selected lasers are effective and should be considered in patients with dark skin.
In this case, triple cream containing 6% hydroquinone was the first step towards resolving the hyperpigmentation. Jessner’s peel was also applied to increase penetration.
Laser treatment using two different types of devices was also employed: A 1,927-nm thulium-fractionated erbium glass laser and a 650-microsecond 1,064-nm Nd:YAG laser. The excellent resolution of the hyperpigmentation demonstrates that lasers are effective in dark skin when used appropriately, she noted.
Dr. Burgess emphasized that tailored therapy is not just relevant to Black patients. She cited data indicating that the proportion of multiracial individuals in the United States is increasing, and when tailoring cosmetic procedures, she recommended considering skin characteristics, not just skin color.
Relative to white skin, pigmented skin typically has greater elasticity, greater amounts of collagen, and greater oil content. Importantly, darker skin has a greater propensity to darkening as a result of injury, she said.
In a review of the hyperpigmentation process that follows injury or other insults, Dr. Burgess reported that only three occur inside the melanocyte. There are now topically applied agents to intervene at many of these steps, including hydroquinone to reduce up-regulation of tyrosinase enzymes, and cysteamine to inhibit conversion of DOPA to dopaquinone. All of these, often used in combination, offer potential benefit in skin of color.
However, “you must understand skin of color,” Dr. Burgess emphasized. For example, most hyaluronic acid dermal fillers can be considered in patients with Fitzpatrick skin types IV or higher with low risks for hypo- or hyperpigmentation, scarring, or keloid formation, but technique is important.
“There is more postinflammatory hyperpigmentation with serial or multiple puncture injection techniques” in dark skin relative to lighter skin, according to Dr. Burgess. She recommended reducing this risk with relatively slow injection times.
When in doubt about the result with any cosmetic procedure, test spots are a reasonable strategy, Dr. Burgess said. When there is concern about risk for adverse events, she recommended using low doses and longer intervals between treatments than might otherwise be considered. Patients should participate in understanding the rationale for selecting one approach over another.
It helps for patients to know that “the desired outcome may take many more sessions than what they read about in that we might have to consider conservative measures in order to ensure that we accomplish the cosmetic effect than they want,” she said.
It is critical that clinicians who perform laser or other cosmetic procedures on darker skin be aware of these precautions, agreed Eliot F. Battle Jr., MD, CEO and cofounder of Cultura Dermatology and Laser Center, Washington, D.C. “Over the past 20 years, we have improved lasers that can safely and effectively treat patients with skin of color, but we still have a way to go,” he said at the meeting. Darker skin behaves differently in response to this energy.
“The pigment in the skin of patients of color competes for the laser light, which can cause heat-related side effects, like blistering and pigmentary changes. Skin of color also has an increased incidence of scarring and unwanted pigmentary changes from laser treatments that create irritation and inflammation,” he explained.
It is important to be aware of these differences, but practitioners also “need to treat conservatively to minimize these unwanted side effects,” Dr. Battle said.
Dr. Burgess reported financial relationships with Allergan, Merz Aesthetics, Revance Therapeutics, and Galderma. Dr. Battle had no commercial disclosures.
Based on the fact that hyperpigmentation and other adverse events associated with cosmetic dermatologic procedures are relevant to skin type, not racial identification, individualized strategies to minimize the risk of potential adverse events are always appropriate, according to an expert speaking at the virtual Skin of Color Update 2020.
There are many highly effective interventions that employ lasers, chemical peels, and topical agents to achieve excellent cosmetic results in darker skin, but results are highly dependent on first understanding the relative risks and treatment goals, Cheryl Burgess, MD, president and founder of the Center for Dermatology and Dermatologic Surgery, Washington, D.C., said at the meeting.
She stressed the importance of educating patients that “all cosmetic procedures are not for skin of color.” Her approach is to engage patients on what they are trying to accomplish and then seeking a solution that tailors treatment to skin type based on the Fitzpatrick scale, the Roberts Hyperpigmentation Scale, or other guidance.
“There are so many different methods that we can use, and these are not necessarily the ones that patients have read about in a magazine,” Dr. Burgess said.
Intense pulsed laser (IPL) for hair removal is an example. This technique is not appropriate in patients with Fitzpatrick skin type IV or higher, according to Dr. Burgess, who presented a case example of a bad outcome. In this case, a patient came to her for treatment after exposure to IPL resulted in first- and second-degree burns complicated by extensive hypopigmentation.
Ultimately, the solution in this case involved more laser therapy, but this time a strategy was selected appropriate to skin of color.
“It is hard to suggest to a patient that we are going to use a laser device” when the problem was caused by a laser, Dr. Burgess observed, but properly selected lasers are effective and should be considered in patients with dark skin.
In this case, triple cream containing 6% hydroquinone was the first step towards resolving the hyperpigmentation. Jessner’s peel was also applied to increase penetration.
Laser treatment using two different types of devices was also employed: A 1,927-nm thulium-fractionated erbium glass laser and a 650-microsecond 1,064-nm Nd:YAG laser. The excellent resolution of the hyperpigmentation demonstrates that lasers are effective in dark skin when used appropriately, she noted.
Dr. Burgess emphasized that tailored therapy is not just relevant to Black patients. She cited data indicating that the proportion of multiracial individuals in the United States is increasing, and when tailoring cosmetic procedures, she recommended considering skin characteristics, not just skin color.
Relative to white skin, pigmented skin typically has greater elasticity, greater amounts of collagen, and greater oil content. Importantly, darker skin has a greater propensity to darkening as a result of injury, she said.
In a review of the hyperpigmentation process that follows injury or other insults, Dr. Burgess reported that only three occur inside the melanocyte. There are now topically applied agents to intervene at many of these steps, including hydroquinone to reduce up-regulation of tyrosinase enzymes, and cysteamine to inhibit conversion of DOPA to dopaquinone. All of these, often used in combination, offer potential benefit in skin of color.
However, “you must understand skin of color,” Dr. Burgess emphasized. For example, most hyaluronic acid dermal fillers can be considered in patients with Fitzpatrick skin types IV or higher with low risks for hypo- or hyperpigmentation, scarring, or keloid formation, but technique is important.
“There is more postinflammatory hyperpigmentation with serial or multiple puncture injection techniques” in dark skin relative to lighter skin, according to Dr. Burgess. She recommended reducing this risk with relatively slow injection times.
When in doubt about the result with any cosmetic procedure, test spots are a reasonable strategy, Dr. Burgess said. When there is concern about risk for adverse events, she recommended using low doses and longer intervals between treatments than might otherwise be considered. Patients should participate in understanding the rationale for selecting one approach over another.
It helps for patients to know that “the desired outcome may take many more sessions than what they read about in that we might have to consider conservative measures in order to ensure that we accomplish the cosmetic effect than they want,” she said.
It is critical that clinicians who perform laser or other cosmetic procedures on darker skin be aware of these precautions, agreed Eliot F. Battle Jr., MD, CEO and cofounder of Cultura Dermatology and Laser Center, Washington, D.C. “Over the past 20 years, we have improved lasers that can safely and effectively treat patients with skin of color, but we still have a way to go,” he said at the meeting. Darker skin behaves differently in response to this energy.
“The pigment in the skin of patients of color competes for the laser light, which can cause heat-related side effects, like blistering and pigmentary changes. Skin of color also has an increased incidence of scarring and unwanted pigmentary changes from laser treatments that create irritation and inflammation,” he explained.
It is important to be aware of these differences, but practitioners also “need to treat conservatively to minimize these unwanted side effects,” Dr. Battle said.
Dr. Burgess reported financial relationships with Allergan, Merz Aesthetics, Revance Therapeutics, and Galderma. Dr. Battle had no commercial disclosures.
Based on the fact that hyperpigmentation and other adverse events associated with cosmetic dermatologic procedures are relevant to skin type, not racial identification, individualized strategies to minimize the risk of potential adverse events are always appropriate, according to an expert speaking at the virtual Skin of Color Update 2020.
There are many highly effective interventions that employ lasers, chemical peels, and topical agents to achieve excellent cosmetic results in darker skin, but results are highly dependent on first understanding the relative risks and treatment goals, Cheryl Burgess, MD, president and founder of the Center for Dermatology and Dermatologic Surgery, Washington, D.C., said at the meeting.
She stressed the importance of educating patients that “all cosmetic procedures are not for skin of color.” Her approach is to engage patients on what they are trying to accomplish and then seeking a solution that tailors treatment to skin type based on the Fitzpatrick scale, the Roberts Hyperpigmentation Scale, or other guidance.
“There are so many different methods that we can use, and these are not necessarily the ones that patients have read about in a magazine,” Dr. Burgess said.
Intense pulsed laser (IPL) for hair removal is an example. This technique is not appropriate in patients with Fitzpatrick skin type IV or higher, according to Dr. Burgess, who presented a case example of a bad outcome. In this case, a patient came to her for treatment after exposure to IPL resulted in first- and second-degree burns complicated by extensive hypopigmentation.
Ultimately, the solution in this case involved more laser therapy, but this time a strategy was selected appropriate to skin of color.
“It is hard to suggest to a patient that we are going to use a laser device” when the problem was caused by a laser, Dr. Burgess observed, but properly selected lasers are effective and should be considered in patients with dark skin.
In this case, triple cream containing 6% hydroquinone was the first step towards resolving the hyperpigmentation. Jessner’s peel was also applied to increase penetration.
Laser treatment using two different types of devices was also employed: A 1,927-nm thulium-fractionated erbium glass laser and a 650-microsecond 1,064-nm Nd:YAG laser. The excellent resolution of the hyperpigmentation demonstrates that lasers are effective in dark skin when used appropriately, she noted.
Dr. Burgess emphasized that tailored therapy is not just relevant to Black patients. She cited data indicating that the proportion of multiracial individuals in the United States is increasing, and when tailoring cosmetic procedures, she recommended considering skin characteristics, not just skin color.
Relative to white skin, pigmented skin typically has greater elasticity, greater amounts of collagen, and greater oil content. Importantly, darker skin has a greater propensity to darkening as a result of injury, she said.
In a review of the hyperpigmentation process that follows injury or other insults, Dr. Burgess reported that only three occur inside the melanocyte. There are now topically applied agents to intervene at many of these steps, including hydroquinone to reduce up-regulation of tyrosinase enzymes, and cysteamine to inhibit conversion of DOPA to dopaquinone. All of these, often used in combination, offer potential benefit in skin of color.
However, “you must understand skin of color,” Dr. Burgess emphasized. For example, most hyaluronic acid dermal fillers can be considered in patients with Fitzpatrick skin types IV or higher with low risks for hypo- or hyperpigmentation, scarring, or keloid formation, but technique is important.
“There is more postinflammatory hyperpigmentation with serial or multiple puncture injection techniques” in dark skin relative to lighter skin, according to Dr. Burgess. She recommended reducing this risk with relatively slow injection times.
When in doubt about the result with any cosmetic procedure, test spots are a reasonable strategy, Dr. Burgess said. When there is concern about risk for adverse events, she recommended using low doses and longer intervals between treatments than might otherwise be considered. Patients should participate in understanding the rationale for selecting one approach over another.
It helps for patients to know that “the desired outcome may take many more sessions than what they read about in that we might have to consider conservative measures in order to ensure that we accomplish the cosmetic effect than they want,” she said.
It is critical that clinicians who perform laser or other cosmetic procedures on darker skin be aware of these precautions, agreed Eliot F. Battle Jr., MD, CEO and cofounder of Cultura Dermatology and Laser Center, Washington, D.C. “Over the past 20 years, we have improved lasers that can safely and effectively treat patients with skin of color, but we still have a way to go,” he said at the meeting. Darker skin behaves differently in response to this energy.
“The pigment in the skin of patients of color competes for the laser light, which can cause heat-related side effects, like blistering and pigmentary changes. Skin of color also has an increased incidence of scarring and unwanted pigmentary changes from laser treatments that create irritation and inflammation,” he explained.
It is important to be aware of these differences, but practitioners also “need to treat conservatively to minimize these unwanted side effects,” Dr. Battle said.
Dr. Burgess reported financial relationships with Allergan, Merz Aesthetics, Revance Therapeutics, and Galderma. Dr. Battle had no commercial disclosures.
FROM SOC 2020
High-dose TRT: A new standard of care for LS-SCLC?
In a phase 2 trial, the 2-year overall survival rate was 51.3% when twice-daily TRT was given at a dose of 45 Gy in 30 fractions and 75% when it was given at a dose of 60 Gy in 40 fractions in patients with LS-SCLC. The two treatment arms had similar safety and quality of life outcomes.
The higher dose “did not add toxicity,” a significant concern with higher radiation doses, said Bjorn Gronberg, MD, PhD, of the Norwegian University of Science and Technology in Trondheim, when presenting this study at the European Society for Medical Oncology Virtual Congress 2020.
However, the discussant for this study pointed out several limitations of the trial and concluded that the 45 Gy dose should remain the standard of care.
Dr. Gonberg explained that concurrent platinum/etoposide (PE) chemotherapy and TRT is the standard treatment for LS-SCLC, and the most recommended schedule for TRT is twice daily at 45 Gy in 30 fractions. He noted, however, that “there’s clearly a need for better treatment” because less than 30% of patients are cured.
“We hypothesized that increasing the dose of radiotherapy might improve survival,” he said.
Study details
Dr. Gonberg and colleagues conducted a phase 2 trial of patients with stage I-III SCLC confined to one hemithorax plus regional lymph nodes. The trial enrolled 176 patients and randomized 170 of them.
The patients received four courses of PE 3 weeks apart. For TRT, 81 patients were randomized to 45 Gy in 30 fractions, and 89 patients were randomized to 60 Gy in 40 fractions, with 10 fractions per week starting with the second PE course.
All patients who responded to chemoradiotherapy were offered prophylactic cranial irradiation at 25 Gy in 10 fractions or 30 Gy in 15 fractions.
Baseline characteristics were well balanced between the treatment arms. The median age was 65 years in both arms, and most patients were women (60.5% in the 45 Gy arm and 56% in the 60 Gy arm).
The mean number of chemotherapy courses was 3.8 in each arm, about 85% of patients received prophylactic cranial radiation, and roughly half received second-line chemotherapy. Overall, 73 patients completed TRT in the 45 Gy arm, and 81 completed TRT in the 60 Gy arm.
Efficacy
There was no significant difference in overall response rate between the treatment arms. It was 81.6% in the 45 Gy arm and 82.1% in the 60 Gy arm (P = .81).
Similarly, there was no significant difference in progression-free survival. The median progression-free survival was 11.1 months in the lower-dose arm and 18.7 months in the higher-dose arm (P = .22).
Still, there was a significant difference in overall survival between the arms. The 2-year overall survival rate was 51.3% in the lower-dose arm and 75% in the higher-dose arm (P = .002). The median overall survival was 24 months and 37.2 months, respectively (P = .034).
Discussant Corinne Faivre-Finn, MD, PhD, of the University of Manchester (England), cautioned that the lower-dose arm appeared to underperform, compared with prior research.
Additionally, “the survival curves separate at about 9 months, [with a] significant difference at 2 years, but the survival curves are coming back together at around 5 years, and that shows that there is a small difference in terms of long-term cure,” she said.
Safety
There were no significant differences in toxicity between the treatment arms.
Dr. Gronberg noted that esophagitis is considered the main dose-limiting toxicity with TRT, but there was no difference in incidence between the two arms (P = .916). Grade 3 esophagitis occurred in 18.4% of patients in the lower-dose arm and 19% of those in the higher-dose arm. There was no grade 4 esophagitis.
Rates of grade 3 and 4 neutropenic infections were higher in the lower-dose arm than in the higher-dose arm, but the difference was not statistically significant (P = .08).
There were also no significant differences in quality of life surveys that patients filled out periodically from baseline until week 52.
“Not so surprisingly,” Dr. Gronberg said, dysphagia was more common at the end of TRT. However, patients had recovered to baseline levels at week 22.
“There’s no difference in the maximum dysphagia reported between the treatment arms, but ... patients in the high-dose arm needed longer time to recover from dysphagia,” Dr. Gronberg said.
Scores for dyspnea, physical function, and global quality of life were similar between the treatment arms.
The similar toxicity between the arms “is quite puzzling,” Dr. Faivre-Finn said, given the 33% increase in radiation dose in the experimental arm. She said this “probably points out an imbalance in some of the factors” between the groups, including tumor volume and doses to organs at risk, which were not reported.
“There are some important missing data, in terms of interpretation of results,” she said.
Given the limitations, and the fact that the study population was relatively small, Dr. Faivre-Finn said “the results cannot be considered definitive and practice changing,” pending additional study.
“So my final conclusion is that twice-a-day radiotherapy at a dose of 45 Gy remains the standard of care, as recommended in the recently published ASTRO [American Society for Radiation Oncology] guidelines,” Dr. Faivre-Finn said.
The study was funded by the Norwegian Cancer Society, the Nordic Cancer Union, and the Norwegian University of Science and Technology. Dr. Gronberg disclosed relationships with Pfizer, Roche, Eli Lilly, and other companies. Dr. Faivre-Finn disclosed relationships with AstraZeneca, Merck, Pfizer, Elekta, and Boehringer Ingelheim.
SOURCE: Gronberg B et al. ESMO 2020, Abstract 1783O.
In a phase 2 trial, the 2-year overall survival rate was 51.3% when twice-daily TRT was given at a dose of 45 Gy in 30 fractions and 75% when it was given at a dose of 60 Gy in 40 fractions in patients with LS-SCLC. The two treatment arms had similar safety and quality of life outcomes.
The higher dose “did not add toxicity,” a significant concern with higher radiation doses, said Bjorn Gronberg, MD, PhD, of the Norwegian University of Science and Technology in Trondheim, when presenting this study at the European Society for Medical Oncology Virtual Congress 2020.
However, the discussant for this study pointed out several limitations of the trial and concluded that the 45 Gy dose should remain the standard of care.
Dr. Gonberg explained that concurrent platinum/etoposide (PE) chemotherapy and TRT is the standard treatment for LS-SCLC, and the most recommended schedule for TRT is twice daily at 45 Gy in 30 fractions. He noted, however, that “there’s clearly a need for better treatment” because less than 30% of patients are cured.
“We hypothesized that increasing the dose of radiotherapy might improve survival,” he said.
Study details
Dr. Gonberg and colleagues conducted a phase 2 trial of patients with stage I-III SCLC confined to one hemithorax plus regional lymph nodes. The trial enrolled 176 patients and randomized 170 of them.
The patients received four courses of PE 3 weeks apart. For TRT, 81 patients were randomized to 45 Gy in 30 fractions, and 89 patients were randomized to 60 Gy in 40 fractions, with 10 fractions per week starting with the second PE course.
All patients who responded to chemoradiotherapy were offered prophylactic cranial irradiation at 25 Gy in 10 fractions or 30 Gy in 15 fractions.
Baseline characteristics were well balanced between the treatment arms. The median age was 65 years in both arms, and most patients were women (60.5% in the 45 Gy arm and 56% in the 60 Gy arm).
The mean number of chemotherapy courses was 3.8 in each arm, about 85% of patients received prophylactic cranial radiation, and roughly half received second-line chemotherapy. Overall, 73 patients completed TRT in the 45 Gy arm, and 81 completed TRT in the 60 Gy arm.
Efficacy
There was no significant difference in overall response rate between the treatment arms. It was 81.6% in the 45 Gy arm and 82.1% in the 60 Gy arm (P = .81).
Similarly, there was no significant difference in progression-free survival. The median progression-free survival was 11.1 months in the lower-dose arm and 18.7 months in the higher-dose arm (P = .22).
Still, there was a significant difference in overall survival between the arms. The 2-year overall survival rate was 51.3% in the lower-dose arm and 75% in the higher-dose arm (P = .002). The median overall survival was 24 months and 37.2 months, respectively (P = .034).
Discussant Corinne Faivre-Finn, MD, PhD, of the University of Manchester (England), cautioned that the lower-dose arm appeared to underperform, compared with prior research.
Additionally, “the survival curves separate at about 9 months, [with a] significant difference at 2 years, but the survival curves are coming back together at around 5 years, and that shows that there is a small difference in terms of long-term cure,” she said.
Safety
There were no significant differences in toxicity between the treatment arms.
Dr. Gronberg noted that esophagitis is considered the main dose-limiting toxicity with TRT, but there was no difference in incidence between the two arms (P = .916). Grade 3 esophagitis occurred in 18.4% of patients in the lower-dose arm and 19% of those in the higher-dose arm. There was no grade 4 esophagitis.
Rates of grade 3 and 4 neutropenic infections were higher in the lower-dose arm than in the higher-dose arm, but the difference was not statistically significant (P = .08).
There were also no significant differences in quality of life surveys that patients filled out periodically from baseline until week 52.
“Not so surprisingly,” Dr. Gronberg said, dysphagia was more common at the end of TRT. However, patients had recovered to baseline levels at week 22.
“There’s no difference in the maximum dysphagia reported between the treatment arms, but ... patients in the high-dose arm needed longer time to recover from dysphagia,” Dr. Gronberg said.
Scores for dyspnea, physical function, and global quality of life were similar between the treatment arms.
The similar toxicity between the arms “is quite puzzling,” Dr. Faivre-Finn said, given the 33% increase in radiation dose in the experimental arm. She said this “probably points out an imbalance in some of the factors” between the groups, including tumor volume and doses to organs at risk, which were not reported.
“There are some important missing data, in terms of interpretation of results,” she said.
Given the limitations, and the fact that the study population was relatively small, Dr. Faivre-Finn said “the results cannot be considered definitive and practice changing,” pending additional study.
“So my final conclusion is that twice-a-day radiotherapy at a dose of 45 Gy remains the standard of care, as recommended in the recently published ASTRO [American Society for Radiation Oncology] guidelines,” Dr. Faivre-Finn said.
The study was funded by the Norwegian Cancer Society, the Nordic Cancer Union, and the Norwegian University of Science and Technology. Dr. Gronberg disclosed relationships with Pfizer, Roche, Eli Lilly, and other companies. Dr. Faivre-Finn disclosed relationships with AstraZeneca, Merck, Pfizer, Elekta, and Boehringer Ingelheim.
SOURCE: Gronberg B et al. ESMO 2020, Abstract 1783O.
In a phase 2 trial, the 2-year overall survival rate was 51.3% when twice-daily TRT was given at a dose of 45 Gy in 30 fractions and 75% when it was given at a dose of 60 Gy in 40 fractions in patients with LS-SCLC. The two treatment arms had similar safety and quality of life outcomes.
The higher dose “did not add toxicity,” a significant concern with higher radiation doses, said Bjorn Gronberg, MD, PhD, of the Norwegian University of Science and Technology in Trondheim, when presenting this study at the European Society for Medical Oncology Virtual Congress 2020.
However, the discussant for this study pointed out several limitations of the trial and concluded that the 45 Gy dose should remain the standard of care.
Dr. Gonberg explained that concurrent platinum/etoposide (PE) chemotherapy and TRT is the standard treatment for LS-SCLC, and the most recommended schedule for TRT is twice daily at 45 Gy in 30 fractions. He noted, however, that “there’s clearly a need for better treatment” because less than 30% of patients are cured.
“We hypothesized that increasing the dose of radiotherapy might improve survival,” he said.
Study details
Dr. Gonberg and colleagues conducted a phase 2 trial of patients with stage I-III SCLC confined to one hemithorax plus regional lymph nodes. The trial enrolled 176 patients and randomized 170 of them.
The patients received four courses of PE 3 weeks apart. For TRT, 81 patients were randomized to 45 Gy in 30 fractions, and 89 patients were randomized to 60 Gy in 40 fractions, with 10 fractions per week starting with the second PE course.
All patients who responded to chemoradiotherapy were offered prophylactic cranial irradiation at 25 Gy in 10 fractions or 30 Gy in 15 fractions.
Baseline characteristics were well balanced between the treatment arms. The median age was 65 years in both arms, and most patients were women (60.5% in the 45 Gy arm and 56% in the 60 Gy arm).
The mean number of chemotherapy courses was 3.8 in each arm, about 85% of patients received prophylactic cranial radiation, and roughly half received second-line chemotherapy. Overall, 73 patients completed TRT in the 45 Gy arm, and 81 completed TRT in the 60 Gy arm.
Efficacy
There was no significant difference in overall response rate between the treatment arms. It was 81.6% in the 45 Gy arm and 82.1% in the 60 Gy arm (P = .81).
Similarly, there was no significant difference in progression-free survival. The median progression-free survival was 11.1 months in the lower-dose arm and 18.7 months in the higher-dose arm (P = .22).
Still, there was a significant difference in overall survival between the arms. The 2-year overall survival rate was 51.3% in the lower-dose arm and 75% in the higher-dose arm (P = .002). The median overall survival was 24 months and 37.2 months, respectively (P = .034).
Discussant Corinne Faivre-Finn, MD, PhD, of the University of Manchester (England), cautioned that the lower-dose arm appeared to underperform, compared with prior research.
Additionally, “the survival curves separate at about 9 months, [with a] significant difference at 2 years, but the survival curves are coming back together at around 5 years, and that shows that there is a small difference in terms of long-term cure,” she said.
Safety
There were no significant differences in toxicity between the treatment arms.
Dr. Gronberg noted that esophagitis is considered the main dose-limiting toxicity with TRT, but there was no difference in incidence between the two arms (P = .916). Grade 3 esophagitis occurred in 18.4% of patients in the lower-dose arm and 19% of those in the higher-dose arm. There was no grade 4 esophagitis.
Rates of grade 3 and 4 neutropenic infections were higher in the lower-dose arm than in the higher-dose arm, but the difference was not statistically significant (P = .08).
There were also no significant differences in quality of life surveys that patients filled out periodically from baseline until week 52.
“Not so surprisingly,” Dr. Gronberg said, dysphagia was more common at the end of TRT. However, patients had recovered to baseline levels at week 22.
“There’s no difference in the maximum dysphagia reported between the treatment arms, but ... patients in the high-dose arm needed longer time to recover from dysphagia,” Dr. Gronberg said.
Scores for dyspnea, physical function, and global quality of life were similar between the treatment arms.
The similar toxicity between the arms “is quite puzzling,” Dr. Faivre-Finn said, given the 33% increase in radiation dose in the experimental arm. She said this “probably points out an imbalance in some of the factors” between the groups, including tumor volume and doses to organs at risk, which were not reported.
“There are some important missing data, in terms of interpretation of results,” she said.
Given the limitations, and the fact that the study population was relatively small, Dr. Faivre-Finn said “the results cannot be considered definitive and practice changing,” pending additional study.
“So my final conclusion is that twice-a-day radiotherapy at a dose of 45 Gy remains the standard of care, as recommended in the recently published ASTRO [American Society for Radiation Oncology] guidelines,” Dr. Faivre-Finn said.
The study was funded by the Norwegian Cancer Society, the Nordic Cancer Union, and the Norwegian University of Science and Technology. Dr. Gronberg disclosed relationships with Pfizer, Roche, Eli Lilly, and other companies. Dr. Faivre-Finn disclosed relationships with AstraZeneca, Merck, Pfizer, Elekta, and Boehringer Ingelheim.
SOURCE: Gronberg B et al. ESMO 2020, Abstract 1783O.
FROM ESMO 2020
HPV vaccine shown to substantially reduce cervical cancer risk
It’s been shown that the vaccine (Gardasil) helps prevent genital warts and high-grade cervical lesions, but until now, data on the ability of the vaccine to prevent cervical cancer, although widely assumed, had been lacking.
“Our results extend [the] knowledge base by showing that quadrivalent HPV vaccination is also associated with a substantially reduced risk of invasive cervical cancer, which is the ultimate intent of HPV vaccination programs,” said investigators led by Jiayao Lei, PhD, a researcher in the department of medical epidemiology and biostatistics at the Karolinska Institute, Stockholm.
The study was published online Oct. 1 in the New England Journal of Medicine.
“This work provides evidence of actual cancer prevention,” commented Diane Harper, MD, an HPV expert and professor in the departments of family medicine and obstetrics & gynecology at the University of Michigan, Ann Arbor. She was the principal investigator on the original Gardasil trial.
This study “shows that the quadrivalent HPV vaccine provides prevention from the sexually transmitted HPV infection that actually reduces the incidence of cervical cancer in young women up to 30 years of age,” she said when approached for comment.
However, she also added a note of caution. These new results show “that vaccinated women still develop cervical cancer, but at a slower rate. This makes the connection between early-age vaccination and continued adult life screening incredibly important,” Dr. Harper said in an interview
Cervical cancer was diagnosed in 19 of the 527,871 women (0.004%) who had received at least one dose of the vaccine versus 538 among the 1,145,112 women (0.05%) who had not.
The cumulative incidence was 47 cases per 100,000 vaccinated women and 94 cases per 100,000 unvaccinated women. The cervical cancer incidence rate ratio for the comparison of vaccinated versus unvaccinated women was 0.37 (95% confidence interval, 0.21-0.57).
The risk reduction was even greater among women who had been vaccinated before the age of 17, with a cumulative incidence of 4 versus 54 cases per 100,000 for women vaccinated after age 17. The incidence rate ratio was 0.12 (95% CI, 0.00-0.34) for women who had been vaccinated before age 17 versus 0.47 (95% CI, 0.27-0.75) among those vaccinated from age 17 to 30 years.
Overall, “the risk of cervical cancer among participants who had initiated vaccination before the age of 17 years was 88% lower than among those who had never been vaccinated,” the investigators noted.
These results “support the recommendation to administer quadrivalent HPV vaccine before exposure to HPV infection to achieve the most substantial benefit,” the investigators wrote.
Details of the Swedish review
For their review, Dr. Lei and colleagues used several Swedish demographic and health registries to connect vaccination status to incident cervical cancers, using the personal identification numbers Sweden issues to residents.
Participants were followed starting either on their 10th birthday or on Jan. 1, 2006, whichever came later. They were followed until, among other things, diagnosis of invasive cervical cancer; their 31st birthday; or until Dec. 31, 2017, whichever came first.
The quadrivalent HPV vaccine, approved in Sweden in 2006, was used almost exclusively during the study period. Participants were considered vaccinated if they had received only one shot, but the investigators set out to analyze a relationship between the incidence of invasive cervical cancer and the number of shots given.
Among other things, the team controlled for age at follow-up, calendar year, county of residence, maternal disease history, and parental characteristics, including education and household income.
The investigators commented that it’s possible that HPV-vaccinated women could have been generally healthier than unvaccinated women and so would have been at lower risk for cervical cancer.
“Confounding by lifestyle and health factors in the women (such as smoking status, sexual activity, oral contraceptive use, and obesity) cannot be excluded; these factors are known to be associated with a risk of cervical cancer,” the investigators wrote.
HPV is also associated with other types of cancer, including anal and oropharyngeal cancers. But these cancers develop over a longer period than cervical cancer.
Dr. Harper noted that the “probability of HPV 16 cancer by time since infection peaks at 40 years after infection for anal cancers and nearly 50 years after infection for oropharyngeal cancers. This means that registries, such as in Sweden, for the next 40 years will record the evidence to say whether HPV vaccination lasts long enough to prevent [these] other HPV 16–associated cancers occurring at a much later time in life.”
The work was funded by the Swedish Foundation for Strategic Research, the Swedish Cancer Society, and the Swedish Research Council and by the China Scholarship Council. Dr. Lei and two other investigators reported HPV vaccine research funding from Merck, the maker of Gardasil. Harper disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
It’s been shown that the vaccine (Gardasil) helps prevent genital warts and high-grade cervical lesions, but until now, data on the ability of the vaccine to prevent cervical cancer, although widely assumed, had been lacking.
“Our results extend [the] knowledge base by showing that quadrivalent HPV vaccination is also associated with a substantially reduced risk of invasive cervical cancer, which is the ultimate intent of HPV vaccination programs,” said investigators led by Jiayao Lei, PhD, a researcher in the department of medical epidemiology and biostatistics at the Karolinska Institute, Stockholm.
The study was published online Oct. 1 in the New England Journal of Medicine.
“This work provides evidence of actual cancer prevention,” commented Diane Harper, MD, an HPV expert and professor in the departments of family medicine and obstetrics & gynecology at the University of Michigan, Ann Arbor. She was the principal investigator on the original Gardasil trial.
This study “shows that the quadrivalent HPV vaccine provides prevention from the sexually transmitted HPV infection that actually reduces the incidence of cervical cancer in young women up to 30 years of age,” she said when approached for comment.
However, she also added a note of caution. These new results show “that vaccinated women still develop cervical cancer, but at a slower rate. This makes the connection between early-age vaccination and continued adult life screening incredibly important,” Dr. Harper said in an interview
Cervical cancer was diagnosed in 19 of the 527,871 women (0.004%) who had received at least one dose of the vaccine versus 538 among the 1,145,112 women (0.05%) who had not.
The cumulative incidence was 47 cases per 100,000 vaccinated women and 94 cases per 100,000 unvaccinated women. The cervical cancer incidence rate ratio for the comparison of vaccinated versus unvaccinated women was 0.37 (95% confidence interval, 0.21-0.57).
The risk reduction was even greater among women who had been vaccinated before the age of 17, with a cumulative incidence of 4 versus 54 cases per 100,000 for women vaccinated after age 17. The incidence rate ratio was 0.12 (95% CI, 0.00-0.34) for women who had been vaccinated before age 17 versus 0.47 (95% CI, 0.27-0.75) among those vaccinated from age 17 to 30 years.
Overall, “the risk of cervical cancer among participants who had initiated vaccination before the age of 17 years was 88% lower than among those who had never been vaccinated,” the investigators noted.
These results “support the recommendation to administer quadrivalent HPV vaccine before exposure to HPV infection to achieve the most substantial benefit,” the investigators wrote.
Details of the Swedish review
For their review, Dr. Lei and colleagues used several Swedish demographic and health registries to connect vaccination status to incident cervical cancers, using the personal identification numbers Sweden issues to residents.
Participants were followed starting either on their 10th birthday or on Jan. 1, 2006, whichever came later. They were followed until, among other things, diagnosis of invasive cervical cancer; their 31st birthday; or until Dec. 31, 2017, whichever came first.
The quadrivalent HPV vaccine, approved in Sweden in 2006, was used almost exclusively during the study period. Participants were considered vaccinated if they had received only one shot, but the investigators set out to analyze a relationship between the incidence of invasive cervical cancer and the number of shots given.
Among other things, the team controlled for age at follow-up, calendar year, county of residence, maternal disease history, and parental characteristics, including education and household income.
The investigators commented that it’s possible that HPV-vaccinated women could have been generally healthier than unvaccinated women and so would have been at lower risk for cervical cancer.
“Confounding by lifestyle and health factors in the women (such as smoking status, sexual activity, oral contraceptive use, and obesity) cannot be excluded; these factors are known to be associated with a risk of cervical cancer,” the investigators wrote.
HPV is also associated with other types of cancer, including anal and oropharyngeal cancers. But these cancers develop over a longer period than cervical cancer.
Dr. Harper noted that the “probability of HPV 16 cancer by time since infection peaks at 40 years after infection for anal cancers and nearly 50 years after infection for oropharyngeal cancers. This means that registries, such as in Sweden, for the next 40 years will record the evidence to say whether HPV vaccination lasts long enough to prevent [these] other HPV 16–associated cancers occurring at a much later time in life.”
The work was funded by the Swedish Foundation for Strategic Research, the Swedish Cancer Society, and the Swedish Research Council and by the China Scholarship Council. Dr. Lei and two other investigators reported HPV vaccine research funding from Merck, the maker of Gardasil. Harper disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
It’s been shown that the vaccine (Gardasil) helps prevent genital warts and high-grade cervical lesions, but until now, data on the ability of the vaccine to prevent cervical cancer, although widely assumed, had been lacking.
“Our results extend [the] knowledge base by showing that quadrivalent HPV vaccination is also associated with a substantially reduced risk of invasive cervical cancer, which is the ultimate intent of HPV vaccination programs,” said investigators led by Jiayao Lei, PhD, a researcher in the department of medical epidemiology and biostatistics at the Karolinska Institute, Stockholm.
The study was published online Oct. 1 in the New England Journal of Medicine.
“This work provides evidence of actual cancer prevention,” commented Diane Harper, MD, an HPV expert and professor in the departments of family medicine and obstetrics & gynecology at the University of Michigan, Ann Arbor. She was the principal investigator on the original Gardasil trial.
This study “shows that the quadrivalent HPV vaccine provides prevention from the sexually transmitted HPV infection that actually reduces the incidence of cervical cancer in young women up to 30 years of age,” she said when approached for comment.
However, she also added a note of caution. These new results show “that vaccinated women still develop cervical cancer, but at a slower rate. This makes the connection between early-age vaccination and continued adult life screening incredibly important,” Dr. Harper said in an interview
Cervical cancer was diagnosed in 19 of the 527,871 women (0.004%) who had received at least one dose of the vaccine versus 538 among the 1,145,112 women (0.05%) who had not.
The cumulative incidence was 47 cases per 100,000 vaccinated women and 94 cases per 100,000 unvaccinated women. The cervical cancer incidence rate ratio for the comparison of vaccinated versus unvaccinated women was 0.37 (95% confidence interval, 0.21-0.57).
The risk reduction was even greater among women who had been vaccinated before the age of 17, with a cumulative incidence of 4 versus 54 cases per 100,000 for women vaccinated after age 17. The incidence rate ratio was 0.12 (95% CI, 0.00-0.34) for women who had been vaccinated before age 17 versus 0.47 (95% CI, 0.27-0.75) among those vaccinated from age 17 to 30 years.
Overall, “the risk of cervical cancer among participants who had initiated vaccination before the age of 17 years was 88% lower than among those who had never been vaccinated,” the investigators noted.
These results “support the recommendation to administer quadrivalent HPV vaccine before exposure to HPV infection to achieve the most substantial benefit,” the investigators wrote.
Details of the Swedish review
For their review, Dr. Lei and colleagues used several Swedish demographic and health registries to connect vaccination status to incident cervical cancers, using the personal identification numbers Sweden issues to residents.
Participants were followed starting either on their 10th birthday or on Jan. 1, 2006, whichever came later. They were followed until, among other things, diagnosis of invasive cervical cancer; their 31st birthday; or until Dec. 31, 2017, whichever came first.
The quadrivalent HPV vaccine, approved in Sweden in 2006, was used almost exclusively during the study period. Participants were considered vaccinated if they had received only one shot, but the investigators set out to analyze a relationship between the incidence of invasive cervical cancer and the number of shots given.
Among other things, the team controlled for age at follow-up, calendar year, county of residence, maternal disease history, and parental characteristics, including education and household income.
The investigators commented that it’s possible that HPV-vaccinated women could have been generally healthier than unvaccinated women and so would have been at lower risk for cervical cancer.
“Confounding by lifestyle and health factors in the women (such as smoking status, sexual activity, oral contraceptive use, and obesity) cannot be excluded; these factors are known to be associated with a risk of cervical cancer,” the investigators wrote.
HPV is also associated with other types of cancer, including anal and oropharyngeal cancers. But these cancers develop over a longer period than cervical cancer.
Dr. Harper noted that the “probability of HPV 16 cancer by time since infection peaks at 40 years after infection for anal cancers and nearly 50 years after infection for oropharyngeal cancers. This means that registries, such as in Sweden, for the next 40 years will record the evidence to say whether HPV vaccination lasts long enough to prevent [these] other HPV 16–associated cancers occurring at a much later time in life.”
The work was funded by the Swedish Foundation for Strategic Research, the Swedish Cancer Society, and the Swedish Research Council and by the China Scholarship Council. Dr. Lei and two other investigators reported HPV vaccine research funding from Merck, the maker of Gardasil. Harper disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Real-world safety, efficacy found for fecal transplants
Fecal microbiota transplantation (FMT) appears safe and effective as a treatment for most Clostridioides difficile infections as it is currently being administered, researchers say.
“We actually didn’t see any infections that were definitely transmissible via fecal transplant,” Colleen Kelly, MD, an associate professor of medicine at Brown University, Providence, R.I., said in an interview.
The findings, published online Oct. 1 in the journal Gastroenterology, come from the American Gastroenterological Association (AGA) NIH-funded FMT National Registry and could allay concerns about a treatment that has yet to gain full approval by the Food and Drug Administration, despite successful clinical trials.
C. diff infections are common and increasing in the United States, often can’t be cured with conventional treatments such as antibiotics, and can be deadly.
Transplanting fecal matter from a donor to the patient appears to work by restoring beneficial microorganisms to the patient’s gut. The procedure is also under investigation for a wide range of other ailments, from irritable bowel syndrome to mood disorders.
But much remains unknown. Researchers have counted a thousand bacterial species along with viruses, bacteriophages, archaea, and fungi in the human gut that interact in complex ways, not all of them beneficial.
The FDA has not enforced regulations that would prohibit the procedure, but in March, it warned about infections with enteropathogenic Escherichia coli and Shiga toxin–producing E. coli following fecal transplants.
As a result of these reports, and the theoretical risk of spreading SARS-CoV-2, OpenBiome, the largest stool bank in the United States, has suspended shipments except for emergency orders, and asked clinicians to quarantine any of its products they already have on hand.
In the meantime, long-term effects of the treatment have not been well documented. And clinical trials have excluded patients who might benefit, such as those who have been immunocompromised or have inflammatory bowel disease.
National registry follows patients outside clinical trials
To better understand how patients fare outside these trials, AGA and other organizations developed a national registry, funded by a grant from the National Institute of Allergy and Infectious Diseases.
The current report summarizes results on 259 patients enrolled between Dec. 5, 2017, and Sept. 2, 2019 at 20 sites.
At baseline, 44% of these patients suffered moderate and 36% mild C. diff infections. The duration of the diagnosis ranged from less than 1 week to 9 years, with a median duration of 20 weeks. They ranged from 1 to 15 episodes with a mean of 3.5.
Almost all had received vancomycin, and 62% had at least two courses. About 40% had received metronidazole and 28% had received fidaxomicin.
Almost all participants received stool from an unknown donor, mostly from stool banks, with OpenBiome accounting for 67%. About 85% of the transplants were administered through colonoscopy and 6% by upper endoscopy.
Out of 222 patients who returned for a 1-month follow-up, 90% met the investigators’ definition of cure: resolution of diarrhea without need for further anti–C. diff therapy. About 98% received only one transplant. An intent to treat analysis produced a cure rate of 86%.
Results were good in patients with comorbidities, including 12% who had irritable bowel syndrome, 9% who had ulcerative colitis, and 7% who had Crohn’s disease, Dr. Kelly said. “I hope everybody sees the importance of it. In these patients that are more complicated, who may have underlying comorbidities, who may not have been in the clinical trials, it looks effective in that group, and also incredibly safe.”
She added that the risk of transmitting SARS-CoV-2 is minor. “I think it would be a very, very unlikely way for someone to get a respiratory pathogen.”
Of the 112 participants who were cured at 1 month and returned for follow-up after 6 months, 4 developed recurrent C. diff infection. Eleven patients who were not cured in the first month returned after 6 months. Of these, seven were reported cured at this later follow-up.
Three complications occurred as result of the procedure: one colonoscopic perforation and two episodes of gastrointestinal bleeding.
About 45% of participants reported at least one symptom, with diarrhea not related to C. difficile the most common, followed by abdominal pain, bloating, and constipation.
Eleven patients suffered infections, including two which the investigators thought might be related to the procedure: Bacteroides fragilis in one participant with severe diarrhea, and enteropathogenic E. coli in another with loose stools. Other infections included four urinary tract infections, three cases of pneumonia, one E. coli bacteremia and one tooth infection.
Within a month of the procedure, 27 patients were hospitalized, with 3 of these cases considered possibly related to the procedure.
Findings may not apply to all clinical settings
Vincent B. Young, MD, PhD, a professor of medicine and infectious diseases at the University of Michigan, Ann Arbor, pointed out that the findings might not apply to all clinical settings. The participating clinicians were almost all gastroenterologists working in academic centers.
“Most of them are not Joe Doctor at the doctor’s office,” said Dr. Young, who was not involved with the study. Clinicians in other specialties, such as infectious diseases, might be more inclined to administer fecal transplants through capsules rather than colonoscopies.
And he added that the study does not address effects of the transplant that might develop over years. “Some people talk about how changes in the microbiota lead to increased risk for long-term complications, things like cancer or heart disease. You’re not going to see those in 6 months.”
Also, the study didn’t yield any findings on indications other than C. diff. “In no way, shape, or form does it mean you can use it for autism, depression, heart disease, or [irritable bowel syndrome],” he said.
Still, he said, the study “confirms the fact that fecal cell transplantation is an effective treatment for recurrent C. diff infection when administered as they administered it.”
The National Institute of Allergy and Infectious Diseases funded the registry. Dr. Kelly reported a relationship with Finch Therapeutics. Dr. Young reports financial relationships with Vedanta Biosciences and Bio-K+.
This story was updated on Oct. 4, 2020.
A version of this article originally appeared on Medscape.com.
Fecal microbiota transplantation (FMT) appears safe and effective as a treatment for most Clostridioides difficile infections as it is currently being administered, researchers say.
“We actually didn’t see any infections that were definitely transmissible via fecal transplant,” Colleen Kelly, MD, an associate professor of medicine at Brown University, Providence, R.I., said in an interview.
The findings, published online Oct. 1 in the journal Gastroenterology, come from the American Gastroenterological Association (AGA) NIH-funded FMT National Registry and could allay concerns about a treatment that has yet to gain full approval by the Food and Drug Administration, despite successful clinical trials.
C. diff infections are common and increasing in the United States, often can’t be cured with conventional treatments such as antibiotics, and can be deadly.
Transplanting fecal matter from a donor to the patient appears to work by restoring beneficial microorganisms to the patient’s gut. The procedure is also under investigation for a wide range of other ailments, from irritable bowel syndrome to mood disorders.
But much remains unknown. Researchers have counted a thousand bacterial species along with viruses, bacteriophages, archaea, and fungi in the human gut that interact in complex ways, not all of them beneficial.
The FDA has not enforced regulations that would prohibit the procedure, but in March, it warned about infections with enteropathogenic Escherichia coli and Shiga toxin–producing E. coli following fecal transplants.
As a result of these reports, and the theoretical risk of spreading SARS-CoV-2, OpenBiome, the largest stool bank in the United States, has suspended shipments except for emergency orders, and asked clinicians to quarantine any of its products they already have on hand.
In the meantime, long-term effects of the treatment have not been well documented. And clinical trials have excluded patients who might benefit, such as those who have been immunocompromised or have inflammatory bowel disease.
National registry follows patients outside clinical trials
To better understand how patients fare outside these trials, AGA and other organizations developed a national registry, funded by a grant from the National Institute of Allergy and Infectious Diseases.
The current report summarizes results on 259 patients enrolled between Dec. 5, 2017, and Sept. 2, 2019 at 20 sites.
At baseline, 44% of these patients suffered moderate and 36% mild C. diff infections. The duration of the diagnosis ranged from less than 1 week to 9 years, with a median duration of 20 weeks. They ranged from 1 to 15 episodes with a mean of 3.5.
Almost all had received vancomycin, and 62% had at least two courses. About 40% had received metronidazole and 28% had received fidaxomicin.
Almost all participants received stool from an unknown donor, mostly from stool banks, with OpenBiome accounting for 67%. About 85% of the transplants were administered through colonoscopy and 6% by upper endoscopy.
Out of 222 patients who returned for a 1-month follow-up, 90% met the investigators’ definition of cure: resolution of diarrhea without need for further anti–C. diff therapy. About 98% received only one transplant. An intent to treat analysis produced a cure rate of 86%.
Results were good in patients with comorbidities, including 12% who had irritable bowel syndrome, 9% who had ulcerative colitis, and 7% who had Crohn’s disease, Dr. Kelly said. “I hope everybody sees the importance of it. In these patients that are more complicated, who may have underlying comorbidities, who may not have been in the clinical trials, it looks effective in that group, and also incredibly safe.”
She added that the risk of transmitting SARS-CoV-2 is minor. “I think it would be a very, very unlikely way for someone to get a respiratory pathogen.”
Of the 112 participants who were cured at 1 month and returned for follow-up after 6 months, 4 developed recurrent C. diff infection. Eleven patients who were not cured in the first month returned after 6 months. Of these, seven were reported cured at this later follow-up.
Three complications occurred as result of the procedure: one colonoscopic perforation and two episodes of gastrointestinal bleeding.
About 45% of participants reported at least one symptom, with diarrhea not related to C. difficile the most common, followed by abdominal pain, bloating, and constipation.
Eleven patients suffered infections, including two which the investigators thought might be related to the procedure: Bacteroides fragilis in one participant with severe diarrhea, and enteropathogenic E. coli in another with loose stools. Other infections included four urinary tract infections, three cases of pneumonia, one E. coli bacteremia and one tooth infection.
Within a month of the procedure, 27 patients were hospitalized, with 3 of these cases considered possibly related to the procedure.
Findings may not apply to all clinical settings
Vincent B. Young, MD, PhD, a professor of medicine and infectious diseases at the University of Michigan, Ann Arbor, pointed out that the findings might not apply to all clinical settings. The participating clinicians were almost all gastroenterologists working in academic centers.
“Most of them are not Joe Doctor at the doctor’s office,” said Dr. Young, who was not involved with the study. Clinicians in other specialties, such as infectious diseases, might be more inclined to administer fecal transplants through capsules rather than colonoscopies.
And he added that the study does not address effects of the transplant that might develop over years. “Some people talk about how changes in the microbiota lead to increased risk for long-term complications, things like cancer or heart disease. You’re not going to see those in 6 months.”
Also, the study didn’t yield any findings on indications other than C. diff. “In no way, shape, or form does it mean you can use it for autism, depression, heart disease, or [irritable bowel syndrome],” he said.
Still, he said, the study “confirms the fact that fecal cell transplantation is an effective treatment for recurrent C. diff infection when administered as they administered it.”
The National Institute of Allergy and Infectious Diseases funded the registry. Dr. Kelly reported a relationship with Finch Therapeutics. Dr. Young reports financial relationships with Vedanta Biosciences and Bio-K+.
This story was updated on Oct. 4, 2020.
A version of this article originally appeared on Medscape.com.
Fecal microbiota transplantation (FMT) appears safe and effective as a treatment for most Clostridioides difficile infections as it is currently being administered, researchers say.
“We actually didn’t see any infections that were definitely transmissible via fecal transplant,” Colleen Kelly, MD, an associate professor of medicine at Brown University, Providence, R.I., said in an interview.
The findings, published online Oct. 1 in the journal Gastroenterology, come from the American Gastroenterological Association (AGA) NIH-funded FMT National Registry and could allay concerns about a treatment that has yet to gain full approval by the Food and Drug Administration, despite successful clinical trials.
C. diff infections are common and increasing in the United States, often can’t be cured with conventional treatments such as antibiotics, and can be deadly.
Transplanting fecal matter from a donor to the patient appears to work by restoring beneficial microorganisms to the patient’s gut. The procedure is also under investigation for a wide range of other ailments, from irritable bowel syndrome to mood disorders.
But much remains unknown. Researchers have counted a thousand bacterial species along with viruses, bacteriophages, archaea, and fungi in the human gut that interact in complex ways, not all of them beneficial.
The FDA has not enforced regulations that would prohibit the procedure, but in March, it warned about infections with enteropathogenic Escherichia coli and Shiga toxin–producing E. coli following fecal transplants.
As a result of these reports, and the theoretical risk of spreading SARS-CoV-2, OpenBiome, the largest stool bank in the United States, has suspended shipments except for emergency orders, and asked clinicians to quarantine any of its products they already have on hand.
In the meantime, long-term effects of the treatment have not been well documented. And clinical trials have excluded patients who might benefit, such as those who have been immunocompromised or have inflammatory bowel disease.
National registry follows patients outside clinical trials
To better understand how patients fare outside these trials, AGA and other organizations developed a national registry, funded by a grant from the National Institute of Allergy and Infectious Diseases.
The current report summarizes results on 259 patients enrolled between Dec. 5, 2017, and Sept. 2, 2019 at 20 sites.
At baseline, 44% of these patients suffered moderate and 36% mild C. diff infections. The duration of the diagnosis ranged from less than 1 week to 9 years, with a median duration of 20 weeks. They ranged from 1 to 15 episodes with a mean of 3.5.
Almost all had received vancomycin, and 62% had at least two courses. About 40% had received metronidazole and 28% had received fidaxomicin.
Almost all participants received stool from an unknown donor, mostly from stool banks, with OpenBiome accounting for 67%. About 85% of the transplants were administered through colonoscopy and 6% by upper endoscopy.
Out of 222 patients who returned for a 1-month follow-up, 90% met the investigators’ definition of cure: resolution of diarrhea without need for further anti–C. diff therapy. About 98% received only one transplant. An intent to treat analysis produced a cure rate of 86%.
Results were good in patients with comorbidities, including 12% who had irritable bowel syndrome, 9% who had ulcerative colitis, and 7% who had Crohn’s disease, Dr. Kelly said. “I hope everybody sees the importance of it. In these patients that are more complicated, who may have underlying comorbidities, who may not have been in the clinical trials, it looks effective in that group, and also incredibly safe.”
She added that the risk of transmitting SARS-CoV-2 is minor. “I think it would be a very, very unlikely way for someone to get a respiratory pathogen.”
Of the 112 participants who were cured at 1 month and returned for follow-up after 6 months, 4 developed recurrent C. diff infection. Eleven patients who were not cured in the first month returned after 6 months. Of these, seven were reported cured at this later follow-up.
Three complications occurred as result of the procedure: one colonoscopic perforation and two episodes of gastrointestinal bleeding.
About 45% of participants reported at least one symptom, with diarrhea not related to C. difficile the most common, followed by abdominal pain, bloating, and constipation.
Eleven patients suffered infections, including two which the investigators thought might be related to the procedure: Bacteroides fragilis in one participant with severe diarrhea, and enteropathogenic E. coli in another with loose stools. Other infections included four urinary tract infections, three cases of pneumonia, one E. coli bacteremia and one tooth infection.
Within a month of the procedure, 27 patients were hospitalized, with 3 of these cases considered possibly related to the procedure.
Findings may not apply to all clinical settings
Vincent B. Young, MD, PhD, a professor of medicine and infectious diseases at the University of Michigan, Ann Arbor, pointed out that the findings might not apply to all clinical settings. The participating clinicians were almost all gastroenterologists working in academic centers.
“Most of them are not Joe Doctor at the doctor’s office,” said Dr. Young, who was not involved with the study. Clinicians in other specialties, such as infectious diseases, might be more inclined to administer fecal transplants through capsules rather than colonoscopies.
And he added that the study does not address effects of the transplant that might develop over years. “Some people talk about how changes in the microbiota lead to increased risk for long-term complications, things like cancer or heart disease. You’re not going to see those in 6 months.”
Also, the study didn’t yield any findings on indications other than C. diff. “In no way, shape, or form does it mean you can use it for autism, depression, heart disease, or [irritable bowel syndrome],” he said.
Still, he said, the study “confirms the fact that fecal cell transplantation is an effective treatment for recurrent C. diff infection when administered as they administered it.”
The National Institute of Allergy and Infectious Diseases funded the registry. Dr. Kelly reported a relationship with Finch Therapeutics. Dr. Young reports financial relationships with Vedanta Biosciences and Bio-K+.
This story was updated on Oct. 4, 2020.
A version of this article originally appeared on Medscape.com.
Mental illness tied to increased mortality in COVID-19
A psychiatric diagnosis for patients hospitalized with COVID-19 is linked to a significantly increased risk for death, new research shows.
Investigators found that patients who were hospitalized with COVID-19 and who had been diagnosed with a psychiatric disorder had a 50% increased risk for a COVID-related death in comparison with COVID-19 patients who had not received a psychiatric diagnosis.
“Pay attention and potentially address/treat a prior psychiatric diagnosis if a patient is hospitalized for COVID-19, as this risk factor can impact the patient’s outcome – death – while in the hospital,” lead investigator Luming Li, MD, assistant professor of psychiatry and associate medical director of quality improvement, Yale New Haven Psychiatric Hospital, New Haven, Conn., said in an interview.
The study was published Sept. 30 in JAMA Network Open.
Negative impact
“We were interested to learn more about the impact of psychiatric diagnoses on COVID-19 mortality, as prior large cohort studies included neurological and other medical conditions but did not assess for a priori psychiatric diagnoses,” said Dr. Li.
“We know from the literature that prior psychiatric diagnoses can have a negative impact on the outcomes of medical conditions, and therefore we tested our hypothesis on a cohort of patients who were hospitalized with COVID-19,” she added.
To investigate, the researchers analyzed data on 1,685 patients hospitalized with COVID-19 between Feb. 15 and April 25, 2020, and whose cases were followed to May 27, 2020. The patients (mean age, 65.2 years; 52.6% men) were drawn from the Yale New Haven Health System.
The median follow-up period was 8 days (interquartile range, 4-16 days) .
Of these patients, 28% had received a psychiatric diagnosis prior to hospitalization. (i.e., cancer, cerebrovascular disease, heart failure, diabetes, kidney disease, liver disease, MI, and/or HIV).
Psychiatric diagnoses were defined in accordance with ICD codes that included mental and behavioral health, Alzheimer’s disease, and self-injury.
Vulnerability to stress
In the unadjusted model, the risk for COVID-19–related hospital death was greater for those who had received any psychiatric diagnosis, compared with those had not (hazard ratio, 2.3; 95% CI, 1.8-2.9; P < .001).
In the adjusted model that controlled for demographic characteristics, other medical comorbidities, and hospital location, the mortality risk somewhat decreased but still remained significantly higher (HR, 1.5; 95% CI, 1.1-1.9; P = .003).
Dr. Li noted a number of factors that might account for the higher mortality rate among psychiatric patients who had COVID-19 in comparison with COVD-19 patients who did not have a psychiatric disorder. These included “potential inflammatory and stress responses that the body experiences related to prior psychiatric conditions,” she said.
Having been previously diagnosed with a psychiatric disorder may also “reflect existing neurochemical differences, compared to those who do not have a prior psychiatric diagnosis, [and] these differences may make the population with the prior psychiatric diagnosis more vulnerable to respond to an acute stressor such as COVID-19,” she said.
Quality care
Harold Pincus, MD, professor and vice chair of the department of psychiatry at Columbia University, New York, said it “adds to the fairly well-known and well-established phenomenon that people with mental illnesses have a high risk of all sorts of morbidity and mortality for non–mental health conditions.”
The researchers “adjusted for various expected [mortality] risks that would be independent of the presence of COVID-19,” so “there was something else going on associated with mortality,” said Dr. Pincus, who is also codirector of the Irving Institute for Clinical and Translation Research. He was not involved with the study.
Beyond the possibility of “some basic immunologic process affected by the presence of a mental disorder,” it is possible that the vulnerability is “related to access to quality care for the comorbid general condition that is not being effectively treated,” he said.
“The take-home message is that people with mental disorders are at higher risk for death, and we need to make sure that, irrespective of COVID-19, they get adequate preventive and chronic-disease care, which would be the most effective way to intervene and protect the impact of a serious disease like COVID-19,” he noted. This would include being appropriately vaccinated and receiving preventive healthcare to reduce smoking and encourage weight loss.
No source of funding for the study was provided. Dr. Li reported receiving grants from a Health and Aging Policy Fellowship during the conduct of the study. Dr. Pincus reported no relevant financial relationships.
A psychiatric diagnosis for patients hospitalized with COVID-19 is linked to a significantly increased risk for death, new research shows.
Investigators found that patients who were hospitalized with COVID-19 and who had been diagnosed with a psychiatric disorder had a 50% increased risk for a COVID-related death in comparison with COVID-19 patients who had not received a psychiatric diagnosis.
“Pay attention and potentially address/treat a prior psychiatric diagnosis if a patient is hospitalized for COVID-19, as this risk factor can impact the patient’s outcome – death – while in the hospital,” lead investigator Luming Li, MD, assistant professor of psychiatry and associate medical director of quality improvement, Yale New Haven Psychiatric Hospital, New Haven, Conn., said in an interview.
The study was published Sept. 30 in JAMA Network Open.
Negative impact
“We were interested to learn more about the impact of psychiatric diagnoses on COVID-19 mortality, as prior large cohort studies included neurological and other medical conditions but did not assess for a priori psychiatric diagnoses,” said Dr. Li.
“We know from the literature that prior psychiatric diagnoses can have a negative impact on the outcomes of medical conditions, and therefore we tested our hypothesis on a cohort of patients who were hospitalized with COVID-19,” she added.
To investigate, the researchers analyzed data on 1,685 patients hospitalized with COVID-19 between Feb. 15 and April 25, 2020, and whose cases were followed to May 27, 2020. The patients (mean age, 65.2 years; 52.6% men) were drawn from the Yale New Haven Health System.
The median follow-up period was 8 days (interquartile range, 4-16 days) .
Of these patients, 28% had received a psychiatric diagnosis prior to hospitalization. (i.e., cancer, cerebrovascular disease, heart failure, diabetes, kidney disease, liver disease, MI, and/or HIV).
Psychiatric diagnoses were defined in accordance with ICD codes that included mental and behavioral health, Alzheimer’s disease, and self-injury.
Vulnerability to stress
In the unadjusted model, the risk for COVID-19–related hospital death was greater for those who had received any psychiatric diagnosis, compared with those had not (hazard ratio, 2.3; 95% CI, 1.8-2.9; P < .001).
In the adjusted model that controlled for demographic characteristics, other medical comorbidities, and hospital location, the mortality risk somewhat decreased but still remained significantly higher (HR, 1.5; 95% CI, 1.1-1.9; P = .003).
Dr. Li noted a number of factors that might account for the higher mortality rate among psychiatric patients who had COVID-19 in comparison with COVD-19 patients who did not have a psychiatric disorder. These included “potential inflammatory and stress responses that the body experiences related to prior psychiatric conditions,” she said.
Having been previously diagnosed with a psychiatric disorder may also “reflect existing neurochemical differences, compared to those who do not have a prior psychiatric diagnosis, [and] these differences may make the population with the prior psychiatric diagnosis more vulnerable to respond to an acute stressor such as COVID-19,” she said.
Quality care
Harold Pincus, MD, professor and vice chair of the department of psychiatry at Columbia University, New York, said it “adds to the fairly well-known and well-established phenomenon that people with mental illnesses have a high risk of all sorts of morbidity and mortality for non–mental health conditions.”
The researchers “adjusted for various expected [mortality] risks that would be independent of the presence of COVID-19,” so “there was something else going on associated with mortality,” said Dr. Pincus, who is also codirector of the Irving Institute for Clinical and Translation Research. He was not involved with the study.
Beyond the possibility of “some basic immunologic process affected by the presence of a mental disorder,” it is possible that the vulnerability is “related to access to quality care for the comorbid general condition that is not being effectively treated,” he said.
“The take-home message is that people with mental disorders are at higher risk for death, and we need to make sure that, irrespective of COVID-19, they get adequate preventive and chronic-disease care, which would be the most effective way to intervene and protect the impact of a serious disease like COVID-19,” he noted. This would include being appropriately vaccinated and receiving preventive healthcare to reduce smoking and encourage weight loss.
No source of funding for the study was provided. Dr. Li reported receiving grants from a Health and Aging Policy Fellowship during the conduct of the study. Dr. Pincus reported no relevant financial relationships.
A psychiatric diagnosis for patients hospitalized with COVID-19 is linked to a significantly increased risk for death, new research shows.
Investigators found that patients who were hospitalized with COVID-19 and who had been diagnosed with a psychiatric disorder had a 50% increased risk for a COVID-related death in comparison with COVID-19 patients who had not received a psychiatric diagnosis.
“Pay attention and potentially address/treat a prior psychiatric diagnosis if a patient is hospitalized for COVID-19, as this risk factor can impact the patient’s outcome – death – while in the hospital,” lead investigator Luming Li, MD, assistant professor of psychiatry and associate medical director of quality improvement, Yale New Haven Psychiatric Hospital, New Haven, Conn., said in an interview.
The study was published Sept. 30 in JAMA Network Open.
Negative impact
“We were interested to learn more about the impact of psychiatric diagnoses on COVID-19 mortality, as prior large cohort studies included neurological and other medical conditions but did not assess for a priori psychiatric diagnoses,” said Dr. Li.
“We know from the literature that prior psychiatric diagnoses can have a negative impact on the outcomes of medical conditions, and therefore we tested our hypothesis on a cohort of patients who were hospitalized with COVID-19,” she added.
To investigate, the researchers analyzed data on 1,685 patients hospitalized with COVID-19 between Feb. 15 and April 25, 2020, and whose cases were followed to May 27, 2020. The patients (mean age, 65.2 years; 52.6% men) were drawn from the Yale New Haven Health System.
The median follow-up period was 8 days (interquartile range, 4-16 days) .
Of these patients, 28% had received a psychiatric diagnosis prior to hospitalization. (i.e., cancer, cerebrovascular disease, heart failure, diabetes, kidney disease, liver disease, MI, and/or HIV).
Psychiatric diagnoses were defined in accordance with ICD codes that included mental and behavioral health, Alzheimer’s disease, and self-injury.
Vulnerability to stress
In the unadjusted model, the risk for COVID-19–related hospital death was greater for those who had received any psychiatric diagnosis, compared with those had not (hazard ratio, 2.3; 95% CI, 1.8-2.9; P < .001).
In the adjusted model that controlled for demographic characteristics, other medical comorbidities, and hospital location, the mortality risk somewhat decreased but still remained significantly higher (HR, 1.5; 95% CI, 1.1-1.9; P = .003).
Dr. Li noted a number of factors that might account for the higher mortality rate among psychiatric patients who had COVID-19 in comparison with COVD-19 patients who did not have a psychiatric disorder. These included “potential inflammatory and stress responses that the body experiences related to prior psychiatric conditions,” she said.
Having been previously diagnosed with a psychiatric disorder may also “reflect existing neurochemical differences, compared to those who do not have a prior psychiatric diagnosis, [and] these differences may make the population with the prior psychiatric diagnosis more vulnerable to respond to an acute stressor such as COVID-19,” she said.
Quality care
Harold Pincus, MD, professor and vice chair of the department of psychiatry at Columbia University, New York, said it “adds to the fairly well-known and well-established phenomenon that people with mental illnesses have a high risk of all sorts of morbidity and mortality for non–mental health conditions.”
The researchers “adjusted for various expected [mortality] risks that would be independent of the presence of COVID-19,” so “there was something else going on associated with mortality,” said Dr. Pincus, who is also codirector of the Irving Institute for Clinical and Translation Research. He was not involved with the study.
Beyond the possibility of “some basic immunologic process affected by the presence of a mental disorder,” it is possible that the vulnerability is “related to access to quality care for the comorbid general condition that is not being effectively treated,” he said.
“The take-home message is that people with mental disorders are at higher risk for death, and we need to make sure that, irrespective of COVID-19, they get adequate preventive and chronic-disease care, which would be the most effective way to intervene and protect the impact of a serious disease like COVID-19,” he noted. This would include being appropriately vaccinated and receiving preventive healthcare to reduce smoking and encourage weight loss.
No source of funding for the study was provided. Dr. Li reported receiving grants from a Health and Aging Policy Fellowship during the conduct of the study. Dr. Pincus reported no relevant financial relationships.
Highlights in Disease-Modifying Therapies From ECTRIMS2020
Dr Patricia Coyle from Stony Brook University Medical Center in New York highlights new data on disease-modifying therapies (DMTs) from the 8th Joint ACTRIMS-ECTRIMS Meeting, MSVirtual2020.
Focusing on relapsing-remitting multiple sclerosis (RRMS), Dr Coyle discusses new research that further explores the efficacy and rebound effects of DMTs, 24 of which are approved in the United States for this patient population.
She reports on results from a database study comparing DMTs vs moderate-efficacy drugs and escalating treatment in the first-line setting, a cohort of pediatric patients receiving adult-approved teriflunomide, and an exploration of fingolimod rebound syndrome.
INFORMATION FROM INDUSTRY
Resources
Have You Seen the Head-to-Head Efficacy Data for ZEPOSIA® (ozanimod)?
Clinical Trial Safety Findings for an S1P Therapy
Discover How to Start Appropriate Patients on an S1P
US-ZEP-20-0997 10/20
Patricia K. Coyle, MD, Professor, Interim Chair, Director, Multiple Sclerosis Comprehensive Care Center, Department of Neurology, Stony Brook University Medical Center, Stony Brook, New York
Dr Patricia Coyle from Stony Brook University Medical Center in New York highlights new data on disease-modifying therapies (DMTs) from the 8th Joint ACTRIMS-ECTRIMS Meeting, MSVirtual2020.
Focusing on relapsing-remitting multiple sclerosis (RRMS), Dr Coyle discusses new research that further explores the efficacy and rebound effects of DMTs, 24 of which are approved in the United States for this patient population.
She reports on results from a database study comparing DMTs vs moderate-efficacy drugs and escalating treatment in the first-line setting, a cohort of pediatric patients receiving adult-approved teriflunomide, and an exploration of fingolimod rebound syndrome.
INFORMATION FROM INDUSTRY
Resources
Have You Seen the Head-to-Head Efficacy Data for ZEPOSIA® (ozanimod)?
Clinical Trial Safety Findings for an S1P Therapy
Discover How to Start Appropriate Patients on an S1P
US-ZEP-20-0997 10/20
Patricia K. Coyle, MD, Professor, Interim Chair, Director, Multiple Sclerosis Comprehensive Care Center, Department of Neurology, Stony Brook University Medical Center, Stony Brook, New York
Dr Patricia Coyle from Stony Brook University Medical Center in New York highlights new data on disease-modifying therapies (DMTs) from the 8th Joint ACTRIMS-ECTRIMS Meeting, MSVirtual2020.
Focusing on relapsing-remitting multiple sclerosis (RRMS), Dr Coyle discusses new research that further explores the efficacy and rebound effects of DMTs, 24 of which are approved in the United States for this patient population.
She reports on results from a database study comparing DMTs vs moderate-efficacy drugs and escalating treatment in the first-line setting, a cohort of pediatric patients receiving adult-approved teriflunomide, and an exploration of fingolimod rebound syndrome.
INFORMATION FROM INDUSTRY
Resources
Have You Seen the Head-to-Head Efficacy Data for ZEPOSIA® (ozanimod)?
Clinical Trial Safety Findings for an S1P Therapy
Discover How to Start Appropriate Patients on an S1P
US-ZEP-20-0997 10/20
Patricia K. Coyle, MD, Professor, Interim Chair, Director, Multiple Sclerosis Comprehensive Care Center, Department of Neurology, Stony Brook University Medical Center, Stony Brook, New York
Endoscopic drainage of pancreatic fluid collections
Pancreatic fluid collections (PFCs) are common after acute pancreatitis but almost always resolve spontaneously. Persistent collections that cause symptoms, become infected, and/or compress vital structures require treatment. Open surgery had traditionally been considered the standard method for this indication;1 Given its inherently less invasive nature, endoscopic transmural drainage (ETMD) has become a mainstay of this step-up philosophy – it is now the dominant strategy for pseudocyst drainage and, on the basis of emerging randomized trial data, compares very favorably with surgery for the treatment of walled-off necrosis (WON).
According to the step-up approach, the initial treatment of symptomatic and/or infected collections that are within 4 weeks of an attack of pancreatitis involves conservative management because the wall of the collection is typically immature; the systemic inflammation may be significantly exacerbated by definitive drainage, particularly surgery. In this early phase, failure of conservative management is addressed by percutaneous catheter placement, stepping up to a minimally invasive operation if the response to percutaneous drainage and antibiotics is insufficient.
Collections that are at least 4 weeks from the onset of acute pancreatitis are considered mature and termed pseudocysts or WONs depending on whether they contain pure fluid or necrotic tissue. In this phase, endoscopic treatment plays a primary management role because these collections are generally adherent to the stomach or duodenal wall and their capsule is organized enough to withstand endoscopic intervention. If treatment can be held off until this phase, then percutaneous and surgical drainage can often be avoided.
In practice, the 4-week rule holds true for most, but not all, PFCs. ETMD can be performed in some particularly mature collections prior to 4 weeks if the indication is strong and the collection appears to have a mature wall. However, the potential for cyst wall perforation is higher and should be considered in the risk-benefit discussion. Conversely, some collections beyond 4 weeks lack an adequately organized wall and require additional time for maturation.
While endoscopic drainage of pseudocysts has essentially supplanted surgery, the management of WON is more complex and remains multidisciplinary. Two recent randomized trials demonstrated no difference in major complications and/or death between a surgical and endoscopic step-up strategy for WON.2,3 Rates of pancreatic fistulae, hospital stay, and overall treatment costs, however, favored endoscopy. Nevertheless, defining the ideal strategy for many of these patients with complexity requires multidisciplinary discussion. Surgery continues to play a primary role in several scenarios, including collections that are not close to the upper GI tract, those that are particularly complex and extend caudally, and situations in which the endoscopic progress is too slow.
The three most important questions when deciding to embark on ETMD are: (1) whether drainage is indicated (that is, is the patient symptomatic or is there evidence that the PFC is infected?), (2) whether the wall of the collection is adequately mature and apposed to the GI tract wall; and (3) whether the collection contains necrosis? This last question has critical implications in the technical approach to drainage. While CT scan with IV contrast is accurate for assessing wall maturity, it is inadequate to evaluate the presence or quantity of necrosum. Transabdominal ultrasound, endoscopic ultrasound, and MRI (on a T2 sequence) are all superior for this purpose. MRI has the additional benefit of assessing the pancreatic duct integrity, which may influence subsequent management.
Pseudocysts can be managed by cyst-gastrostomy or cyst-duodenostomy alone, whereas most WONs require the additional step of endoscopic necrosectomy – the process of entering the cyst cavity to mechanically debride necrotic tissue. Because of a higher rate of technical success, endoscopic ultrasound–directed creation of the transmural drainage pathway has become standard practice. In addition, it is likely safer, allowing for the identification and avoidance of interceding vessels and other vital structures. The role of endoscopic retrograde cholangiopancreatography with pancreatic stent placement as primary therapy for PFCs is limited to the drainage of small collections (<5 cm), for which it is the preferred treatment strategy. It is as effective as ETMD, which may not be feasible or safe for small PFCs.
Plastic double-pigtail stents have traditionally been used to maintain the transmural tract for both pseudocyst and WON. Recently, however, metallic stents have become more popular. Fully covered biliary self-expanding metallic stents (SEMS) are easier to place, have a larger lumen, and are associated with improved outcomes, compared with plastic stents in observational studies of pseudocyst drainage. Lumen-apposing metallic stents (LAMS) have become the preferred prosthesis for WON drainage given the ability to near-simultaneously establish access and deploy the stent, as well as their much larger caliber lumen which permits seamless entry into the cavity with an endoscope. Based on ease and efficiency of use, LAMS are also commonly employed for pseudocyst drainage, although entry into the cavity is unnecessary.
Plastic stents have been shown to be more cost effective than LAMS for pseudocyst drainage, although the economics around biliary SEMS in this context have not been explored. Robust comparative effectiveness data defining the optimal prostheses for pseudocysts are needed. The literature comparing LAMS to plastic stents for the management of WON is mixed. Studies have shown LAMS to be more cost effective, but a small randomized trial demonstrated no difference in clinical success or in the number of procedures to achieve WON resolution.4 We generally favor LAMS for WON since large-caliber balloon dilation of the tract seems safer within the lumen of the LAMS (which could seal small perforations and tamponade bleeding vessels) than within a freshly created tract.
Secondary infection of the cavity, usually because of stent occlusion, and bleeding are the most common complications of ETMD. Even in the absence of stent occlusion, contamination of the collection after ETMD is ubiquitous and, as such, we prescribe prophylactic antibiotics for 1-2 weeks after the procedure, although this practice is not evidence based. Hemorrhage appears to be increasing in frequency with the diffusion of LAMS; this has been postulated to be due to particularly rapid cyst cavity collapse resulting in erosion of the stent into contralateral cyst wall vessels. CT angiography followed by an embolization procedure for a possible pseudoaneurysm is the mainstay of treatment. Serious venous bleeding is more challenging to address because angiographic options are limited.
Despite tremendous recent advances, several important controversies in the endoscopic management of PFCs persist. The optimal prosthesis, the importance of first-session endoscopic necroscopy (compared with stepping up to endoscopic necroscopy only if necessary), the roles of adjunctive drain placement and chemical debridement (such as hydrogen peroxide), the need for concomitant pancreatic stent placement, and the preferred long-term management of a disconnected pancreatic duct are areas for which additional research is sorely needed. We further discuss these questions and many additional technical considerations pertaining to endoscopic drainage in a recent review.5
In summary, endoscopic transmural drainage of mature PFCs is effective and safe. Existing evidence supports its use as the favored treatment modality in appropriate candidates and has rendered it a mainstay of the therapeutic armamentarium for this disease. Further studies are needed to address critical unanswered questions and to develop a uniform endoscopic management paradigm.
References
1. van Santvoort HC et al. N Engl J Med. 2010;362(16):1491-502.
2. van Brunschot S et al. Lancet. 2018;391(10115):51-8.
3. Bang JY et al. Gastroenterology. 2019;156(4):1027-40.
4. Bang JY et al. Gut. 2019;68(7):1200-9.
5. Elmunzer BJ. Clin Gastroenterol Hepatol. 2018;16(12):1851-63.
Dr. Moran is assistant professor of medicine, division of gastroenterology and hepatology, Medical University of South Carolina, Charleston; Dr. Elmunzer is the Peter Cotton Professor of Medicine and Endoscopic Innovation, division of gastroenterology and hepatology, Medical University of South Carolina. The authors have no conflicts of interest pertaining to this review.
Pancreatic fluid collections (PFCs) are common after acute pancreatitis but almost always resolve spontaneously. Persistent collections that cause symptoms, become infected, and/or compress vital structures require treatment. Open surgery had traditionally been considered the standard method for this indication;1 Given its inherently less invasive nature, endoscopic transmural drainage (ETMD) has become a mainstay of this step-up philosophy – it is now the dominant strategy for pseudocyst drainage and, on the basis of emerging randomized trial data, compares very favorably with surgery for the treatment of walled-off necrosis (WON).
According to the step-up approach, the initial treatment of symptomatic and/or infected collections that are within 4 weeks of an attack of pancreatitis involves conservative management because the wall of the collection is typically immature; the systemic inflammation may be significantly exacerbated by definitive drainage, particularly surgery. In this early phase, failure of conservative management is addressed by percutaneous catheter placement, stepping up to a minimally invasive operation if the response to percutaneous drainage and antibiotics is insufficient.
Collections that are at least 4 weeks from the onset of acute pancreatitis are considered mature and termed pseudocysts or WONs depending on whether they contain pure fluid or necrotic tissue. In this phase, endoscopic treatment plays a primary management role because these collections are generally adherent to the stomach or duodenal wall and their capsule is organized enough to withstand endoscopic intervention. If treatment can be held off until this phase, then percutaneous and surgical drainage can often be avoided.
In practice, the 4-week rule holds true for most, but not all, PFCs. ETMD can be performed in some particularly mature collections prior to 4 weeks if the indication is strong and the collection appears to have a mature wall. However, the potential for cyst wall perforation is higher and should be considered in the risk-benefit discussion. Conversely, some collections beyond 4 weeks lack an adequately organized wall and require additional time for maturation.
While endoscopic drainage of pseudocysts has essentially supplanted surgery, the management of WON is more complex and remains multidisciplinary. Two recent randomized trials demonstrated no difference in major complications and/or death between a surgical and endoscopic step-up strategy for WON.2,3 Rates of pancreatic fistulae, hospital stay, and overall treatment costs, however, favored endoscopy. Nevertheless, defining the ideal strategy for many of these patients with complexity requires multidisciplinary discussion. Surgery continues to play a primary role in several scenarios, including collections that are not close to the upper GI tract, those that are particularly complex and extend caudally, and situations in which the endoscopic progress is too slow.
The three most important questions when deciding to embark on ETMD are: (1) whether drainage is indicated (that is, is the patient symptomatic or is there evidence that the PFC is infected?), (2) whether the wall of the collection is adequately mature and apposed to the GI tract wall; and (3) whether the collection contains necrosis? This last question has critical implications in the technical approach to drainage. While CT scan with IV contrast is accurate for assessing wall maturity, it is inadequate to evaluate the presence or quantity of necrosum. Transabdominal ultrasound, endoscopic ultrasound, and MRI (on a T2 sequence) are all superior for this purpose. MRI has the additional benefit of assessing the pancreatic duct integrity, which may influence subsequent management.
Pseudocysts can be managed by cyst-gastrostomy or cyst-duodenostomy alone, whereas most WONs require the additional step of endoscopic necrosectomy – the process of entering the cyst cavity to mechanically debride necrotic tissue. Because of a higher rate of technical success, endoscopic ultrasound–directed creation of the transmural drainage pathway has become standard practice. In addition, it is likely safer, allowing for the identification and avoidance of interceding vessels and other vital structures. The role of endoscopic retrograde cholangiopancreatography with pancreatic stent placement as primary therapy for PFCs is limited to the drainage of small collections (<5 cm), for which it is the preferred treatment strategy. It is as effective as ETMD, which may not be feasible or safe for small PFCs.
Plastic double-pigtail stents have traditionally been used to maintain the transmural tract for both pseudocyst and WON. Recently, however, metallic stents have become more popular. Fully covered biliary self-expanding metallic stents (SEMS) are easier to place, have a larger lumen, and are associated with improved outcomes, compared with plastic stents in observational studies of pseudocyst drainage. Lumen-apposing metallic stents (LAMS) have become the preferred prosthesis for WON drainage given the ability to near-simultaneously establish access and deploy the stent, as well as their much larger caliber lumen which permits seamless entry into the cavity with an endoscope. Based on ease and efficiency of use, LAMS are also commonly employed for pseudocyst drainage, although entry into the cavity is unnecessary.
Plastic stents have been shown to be more cost effective than LAMS for pseudocyst drainage, although the economics around biliary SEMS in this context have not been explored. Robust comparative effectiveness data defining the optimal prostheses for pseudocysts are needed. The literature comparing LAMS to plastic stents for the management of WON is mixed. Studies have shown LAMS to be more cost effective, but a small randomized trial demonstrated no difference in clinical success or in the number of procedures to achieve WON resolution.4 We generally favor LAMS for WON since large-caliber balloon dilation of the tract seems safer within the lumen of the LAMS (which could seal small perforations and tamponade bleeding vessels) than within a freshly created tract.
Secondary infection of the cavity, usually because of stent occlusion, and bleeding are the most common complications of ETMD. Even in the absence of stent occlusion, contamination of the collection after ETMD is ubiquitous and, as such, we prescribe prophylactic antibiotics for 1-2 weeks after the procedure, although this practice is not evidence based. Hemorrhage appears to be increasing in frequency with the diffusion of LAMS; this has been postulated to be due to particularly rapid cyst cavity collapse resulting in erosion of the stent into contralateral cyst wall vessels. CT angiography followed by an embolization procedure for a possible pseudoaneurysm is the mainstay of treatment. Serious venous bleeding is more challenging to address because angiographic options are limited.
Despite tremendous recent advances, several important controversies in the endoscopic management of PFCs persist. The optimal prosthesis, the importance of first-session endoscopic necroscopy (compared with stepping up to endoscopic necroscopy only if necessary), the roles of adjunctive drain placement and chemical debridement (such as hydrogen peroxide), the need for concomitant pancreatic stent placement, and the preferred long-term management of a disconnected pancreatic duct are areas for which additional research is sorely needed. We further discuss these questions and many additional technical considerations pertaining to endoscopic drainage in a recent review.5
In summary, endoscopic transmural drainage of mature PFCs is effective and safe. Existing evidence supports its use as the favored treatment modality in appropriate candidates and has rendered it a mainstay of the therapeutic armamentarium for this disease. Further studies are needed to address critical unanswered questions and to develop a uniform endoscopic management paradigm.
References
1. van Santvoort HC et al. N Engl J Med. 2010;362(16):1491-502.
2. van Brunschot S et al. Lancet. 2018;391(10115):51-8.
3. Bang JY et al. Gastroenterology. 2019;156(4):1027-40.
4. Bang JY et al. Gut. 2019;68(7):1200-9.
5. Elmunzer BJ. Clin Gastroenterol Hepatol. 2018;16(12):1851-63.
Dr. Moran is assistant professor of medicine, division of gastroenterology and hepatology, Medical University of South Carolina, Charleston; Dr. Elmunzer is the Peter Cotton Professor of Medicine and Endoscopic Innovation, division of gastroenterology and hepatology, Medical University of South Carolina. The authors have no conflicts of interest pertaining to this review.
Pancreatic fluid collections (PFCs) are common after acute pancreatitis but almost always resolve spontaneously. Persistent collections that cause symptoms, become infected, and/or compress vital structures require treatment. Open surgery had traditionally been considered the standard method for this indication;1 Given its inherently less invasive nature, endoscopic transmural drainage (ETMD) has become a mainstay of this step-up philosophy – it is now the dominant strategy for pseudocyst drainage and, on the basis of emerging randomized trial data, compares very favorably with surgery for the treatment of walled-off necrosis (WON).
According to the step-up approach, the initial treatment of symptomatic and/or infected collections that are within 4 weeks of an attack of pancreatitis involves conservative management because the wall of the collection is typically immature; the systemic inflammation may be significantly exacerbated by definitive drainage, particularly surgery. In this early phase, failure of conservative management is addressed by percutaneous catheter placement, stepping up to a minimally invasive operation if the response to percutaneous drainage and antibiotics is insufficient.
Collections that are at least 4 weeks from the onset of acute pancreatitis are considered mature and termed pseudocysts or WONs depending on whether they contain pure fluid or necrotic tissue. In this phase, endoscopic treatment plays a primary management role because these collections are generally adherent to the stomach or duodenal wall and their capsule is organized enough to withstand endoscopic intervention. If treatment can be held off until this phase, then percutaneous and surgical drainage can often be avoided.
In practice, the 4-week rule holds true for most, but not all, PFCs. ETMD can be performed in some particularly mature collections prior to 4 weeks if the indication is strong and the collection appears to have a mature wall. However, the potential for cyst wall perforation is higher and should be considered in the risk-benefit discussion. Conversely, some collections beyond 4 weeks lack an adequately organized wall and require additional time for maturation.
While endoscopic drainage of pseudocysts has essentially supplanted surgery, the management of WON is more complex and remains multidisciplinary. Two recent randomized trials demonstrated no difference in major complications and/or death between a surgical and endoscopic step-up strategy for WON.2,3 Rates of pancreatic fistulae, hospital stay, and overall treatment costs, however, favored endoscopy. Nevertheless, defining the ideal strategy for many of these patients with complexity requires multidisciplinary discussion. Surgery continues to play a primary role in several scenarios, including collections that are not close to the upper GI tract, those that are particularly complex and extend caudally, and situations in which the endoscopic progress is too slow.
The three most important questions when deciding to embark on ETMD are: (1) whether drainage is indicated (that is, is the patient symptomatic or is there evidence that the PFC is infected?), (2) whether the wall of the collection is adequately mature and apposed to the GI tract wall; and (3) whether the collection contains necrosis? This last question has critical implications in the technical approach to drainage. While CT scan with IV contrast is accurate for assessing wall maturity, it is inadequate to evaluate the presence or quantity of necrosum. Transabdominal ultrasound, endoscopic ultrasound, and MRI (on a T2 sequence) are all superior for this purpose. MRI has the additional benefit of assessing the pancreatic duct integrity, which may influence subsequent management.
Pseudocysts can be managed by cyst-gastrostomy or cyst-duodenostomy alone, whereas most WONs require the additional step of endoscopic necrosectomy – the process of entering the cyst cavity to mechanically debride necrotic tissue. Because of a higher rate of technical success, endoscopic ultrasound–directed creation of the transmural drainage pathway has become standard practice. In addition, it is likely safer, allowing for the identification and avoidance of interceding vessels and other vital structures. The role of endoscopic retrograde cholangiopancreatography with pancreatic stent placement as primary therapy for PFCs is limited to the drainage of small collections (<5 cm), for which it is the preferred treatment strategy. It is as effective as ETMD, which may not be feasible or safe for small PFCs.
Plastic double-pigtail stents have traditionally been used to maintain the transmural tract for both pseudocyst and WON. Recently, however, metallic stents have become more popular. Fully covered biliary self-expanding metallic stents (SEMS) are easier to place, have a larger lumen, and are associated with improved outcomes, compared with plastic stents in observational studies of pseudocyst drainage. Lumen-apposing metallic stents (LAMS) have become the preferred prosthesis for WON drainage given the ability to near-simultaneously establish access and deploy the stent, as well as their much larger caliber lumen which permits seamless entry into the cavity with an endoscope. Based on ease and efficiency of use, LAMS are also commonly employed for pseudocyst drainage, although entry into the cavity is unnecessary.
Plastic stents have been shown to be more cost effective than LAMS for pseudocyst drainage, although the economics around biliary SEMS in this context have not been explored. Robust comparative effectiveness data defining the optimal prostheses for pseudocysts are needed. The literature comparing LAMS to plastic stents for the management of WON is mixed. Studies have shown LAMS to be more cost effective, but a small randomized trial demonstrated no difference in clinical success or in the number of procedures to achieve WON resolution.4 We generally favor LAMS for WON since large-caliber balloon dilation of the tract seems safer within the lumen of the LAMS (which could seal small perforations and tamponade bleeding vessels) than within a freshly created tract.
Secondary infection of the cavity, usually because of stent occlusion, and bleeding are the most common complications of ETMD. Even in the absence of stent occlusion, contamination of the collection after ETMD is ubiquitous and, as such, we prescribe prophylactic antibiotics for 1-2 weeks after the procedure, although this practice is not evidence based. Hemorrhage appears to be increasing in frequency with the diffusion of LAMS; this has been postulated to be due to particularly rapid cyst cavity collapse resulting in erosion of the stent into contralateral cyst wall vessels. CT angiography followed by an embolization procedure for a possible pseudoaneurysm is the mainstay of treatment. Serious venous bleeding is more challenging to address because angiographic options are limited.
Despite tremendous recent advances, several important controversies in the endoscopic management of PFCs persist. The optimal prosthesis, the importance of first-session endoscopic necroscopy (compared with stepping up to endoscopic necroscopy only if necessary), the roles of adjunctive drain placement and chemical debridement (such as hydrogen peroxide), the need for concomitant pancreatic stent placement, and the preferred long-term management of a disconnected pancreatic duct are areas for which additional research is sorely needed. We further discuss these questions and many additional technical considerations pertaining to endoscopic drainage in a recent review.5
In summary, endoscopic transmural drainage of mature PFCs is effective and safe. Existing evidence supports its use as the favored treatment modality in appropriate candidates and has rendered it a mainstay of the therapeutic armamentarium for this disease. Further studies are needed to address critical unanswered questions and to develop a uniform endoscopic management paradigm.
References
1. van Santvoort HC et al. N Engl J Med. 2010;362(16):1491-502.
2. van Brunschot S et al. Lancet. 2018;391(10115):51-8.
3. Bang JY et al. Gastroenterology. 2019;156(4):1027-40.
4. Bang JY et al. Gut. 2019;68(7):1200-9.
5. Elmunzer BJ. Clin Gastroenterol Hepatol. 2018;16(12):1851-63.
Dr. Moran is assistant professor of medicine, division of gastroenterology and hepatology, Medical University of South Carolina, Charleston; Dr. Elmunzer is the Peter Cotton Professor of Medicine and Endoscopic Innovation, division of gastroenterology and hepatology, Medical University of South Carolina. The authors have no conflicts of interest pertaining to this review.
New treatment options show promise for centrifugal cicatricial alopecia
according to a review of current strategies for this challenging disease, delivered at the virtual Skin of Color Update 2020.
Two case reports of favorable results with topical metformin were published earlier this year. A subsequent case in which metformin provided a major improvement in quality of life has provided further encouragement, according to Crystal Aguh, MD, director of the ethnic skin program at Johns Hopkins University, Baltimore.
In the subsequent case, there was complete scalp coverage, allowing the patient to no longer use a wig, which is “tough to achieve in patients with advanced disease,” Dr. Aguh said.
In the two published cases, 10% metformin compounded in Lipoderm (PCCA) produced notable hair growth within 6 months. Dr. Aguh said that the case studies were prompted by experimental evidence associating metformin with an antifibrotic effect.
This finding is potentially important. Most current treatments for CCCA are based on anti-inflammatory activity, according to Dr. Aguh, but fibrosis is strongly implicated in the pathogenesis of CCCA. Of several lines of evidence, one is the association between CCCA and other fibrosing conditions.
For example, women with CCCA “are several times more likely to have uterine fibroids than women without CCCA,” said Dr. Aguh, citing a study that she published in 2018. She suggested that there is an urgent need for new treatment options because of the “often-disappointing” responses to current standard therapies.
In the CCCA cases treated so far, topical metformin has been well tolerated, which is attributed to the low level of systemic absorption. No nausea or other gastrointestinal side effects common to oral metformin have been so far observed in Dr. Aguh’s cases.
“Some patients experience scalp dryness or irritation,” she said, but added that a light coating of emollient typically relieves this complaint.
Despite the promising results, topical metformin “is not a silver bullet,” Dr. Aguh cautioned. She estimated that only 10%-15% of patients respond, but this treatment can be considered “as an adjunctive option to avoid another round of intralesional steroids.”
Platelet-rich plasma (PRP) is another option that has demonstrated promise in a published case report for which Dr. Aguh served as a coauthor. In this series of two patients, only one had CCCA. The other had lichen planopilaris, but both patients experienced hair regrowth after failing standard therapies.
When treating alopecia with PRP, Dr. Aguh typically offers three or four sessions spaced 4 weeks apart. She does not start other treatments at the same time, but she does not discontinue topical treatments that patients are already taking, including topical minoxidil.
Again, like topical metformin, PRP is reasonably considered in patients who have failed standard therapies, according to Dr. Aguh. She cautioned that responses are not permanent. Patients who respond typically require retreatment a year or more later, but good responses have been seen after retreatment.
Appropriate hair care can help. Dr. Aguh recounted a case in which a patient with presumed CCCA was referred after failing intralesional triamcinolone injections. Ultimately, the patient was diagnosed with acquired trichorrhexis nodosa, but the large clinical improvements gained from better hair care practices, including avoidance of chemical relaxants and thermal styling, are relevant to CCCA, as well as other conditions resulting in hair loss.
In a book written by Dr. Aguh, titled “90 Days to Beautiful Hair,” strategies for better hair care practices include advice to reduce tension on hair follicles.
The role of increased traction is an issue in CCCA, agreed Amy McMichael, MD, chair of the department of dermatology, Wake Forest University, Winston-Salem, N.C. Although she provided data at the meeting suggesting that CCCA is a fibrosing disease linked to genetic susceptibility, she said there is also a “strong association” between the severity of CCCA and extensions, hair weaving, and other tension-associated hairstyles.
While there is an urgent need to develop therapies that address the underlying pathophysiology of CCCA, she concurred that patients with this or other conditions associated with hair loss, such as seborrheic dermatitis or frontal fibrosing alopecia, should not ignore appropriate hair care.
Dr. Aguh has financial relationships with LEO Pharma and UCB Pharma. Dr. McMichael’s disclosures included serving as an investigator and/or consultant for companies that included Allergan, Procter & Gamble, Nutrafol, Johnson & Johnson, and Aclaris.
according to a review of current strategies for this challenging disease, delivered at the virtual Skin of Color Update 2020.
Two case reports of favorable results with topical metformin were published earlier this year. A subsequent case in which metformin provided a major improvement in quality of life has provided further encouragement, according to Crystal Aguh, MD, director of the ethnic skin program at Johns Hopkins University, Baltimore.
In the subsequent case, there was complete scalp coverage, allowing the patient to no longer use a wig, which is “tough to achieve in patients with advanced disease,” Dr. Aguh said.
In the two published cases, 10% metformin compounded in Lipoderm (PCCA) produced notable hair growth within 6 months. Dr. Aguh said that the case studies were prompted by experimental evidence associating metformin with an antifibrotic effect.
This finding is potentially important. Most current treatments for CCCA are based on anti-inflammatory activity, according to Dr. Aguh, but fibrosis is strongly implicated in the pathogenesis of CCCA. Of several lines of evidence, one is the association between CCCA and other fibrosing conditions.
For example, women with CCCA “are several times more likely to have uterine fibroids than women without CCCA,” said Dr. Aguh, citing a study that she published in 2018. She suggested that there is an urgent need for new treatment options because of the “often-disappointing” responses to current standard therapies.
In the CCCA cases treated so far, topical metformin has been well tolerated, which is attributed to the low level of systemic absorption. No nausea or other gastrointestinal side effects common to oral metformin have been so far observed in Dr. Aguh’s cases.
“Some patients experience scalp dryness or irritation,” she said, but added that a light coating of emollient typically relieves this complaint.
Despite the promising results, topical metformin “is not a silver bullet,” Dr. Aguh cautioned. She estimated that only 10%-15% of patients respond, but this treatment can be considered “as an adjunctive option to avoid another round of intralesional steroids.”
Platelet-rich plasma (PRP) is another option that has demonstrated promise in a published case report for which Dr. Aguh served as a coauthor. In this series of two patients, only one had CCCA. The other had lichen planopilaris, but both patients experienced hair regrowth after failing standard therapies.
When treating alopecia with PRP, Dr. Aguh typically offers three or four sessions spaced 4 weeks apart. She does not start other treatments at the same time, but she does not discontinue topical treatments that patients are already taking, including topical minoxidil.
Again, like topical metformin, PRP is reasonably considered in patients who have failed standard therapies, according to Dr. Aguh. She cautioned that responses are not permanent. Patients who respond typically require retreatment a year or more later, but good responses have been seen after retreatment.
Appropriate hair care can help. Dr. Aguh recounted a case in which a patient with presumed CCCA was referred after failing intralesional triamcinolone injections. Ultimately, the patient was diagnosed with acquired trichorrhexis nodosa, but the large clinical improvements gained from better hair care practices, including avoidance of chemical relaxants and thermal styling, are relevant to CCCA, as well as other conditions resulting in hair loss.
In a book written by Dr. Aguh, titled “90 Days to Beautiful Hair,” strategies for better hair care practices include advice to reduce tension on hair follicles.
The role of increased traction is an issue in CCCA, agreed Amy McMichael, MD, chair of the department of dermatology, Wake Forest University, Winston-Salem, N.C. Although she provided data at the meeting suggesting that CCCA is a fibrosing disease linked to genetic susceptibility, she said there is also a “strong association” between the severity of CCCA and extensions, hair weaving, and other tension-associated hairstyles.
While there is an urgent need to develop therapies that address the underlying pathophysiology of CCCA, she concurred that patients with this or other conditions associated with hair loss, such as seborrheic dermatitis or frontal fibrosing alopecia, should not ignore appropriate hair care.
Dr. Aguh has financial relationships with LEO Pharma and UCB Pharma. Dr. McMichael’s disclosures included serving as an investigator and/or consultant for companies that included Allergan, Procter & Gamble, Nutrafol, Johnson & Johnson, and Aclaris.
according to a review of current strategies for this challenging disease, delivered at the virtual Skin of Color Update 2020.
Two case reports of favorable results with topical metformin were published earlier this year. A subsequent case in which metformin provided a major improvement in quality of life has provided further encouragement, according to Crystal Aguh, MD, director of the ethnic skin program at Johns Hopkins University, Baltimore.
In the subsequent case, there was complete scalp coverage, allowing the patient to no longer use a wig, which is “tough to achieve in patients with advanced disease,” Dr. Aguh said.
In the two published cases, 10% metformin compounded in Lipoderm (PCCA) produced notable hair growth within 6 months. Dr. Aguh said that the case studies were prompted by experimental evidence associating metformin with an antifibrotic effect.
This finding is potentially important. Most current treatments for CCCA are based on anti-inflammatory activity, according to Dr. Aguh, but fibrosis is strongly implicated in the pathogenesis of CCCA. Of several lines of evidence, one is the association between CCCA and other fibrosing conditions.
For example, women with CCCA “are several times more likely to have uterine fibroids than women without CCCA,” said Dr. Aguh, citing a study that she published in 2018. She suggested that there is an urgent need for new treatment options because of the “often-disappointing” responses to current standard therapies.
In the CCCA cases treated so far, topical metformin has been well tolerated, which is attributed to the low level of systemic absorption. No nausea or other gastrointestinal side effects common to oral metformin have been so far observed in Dr. Aguh’s cases.
“Some patients experience scalp dryness or irritation,” she said, but added that a light coating of emollient typically relieves this complaint.
Despite the promising results, topical metformin “is not a silver bullet,” Dr. Aguh cautioned. She estimated that only 10%-15% of patients respond, but this treatment can be considered “as an adjunctive option to avoid another round of intralesional steroids.”
Platelet-rich plasma (PRP) is another option that has demonstrated promise in a published case report for which Dr. Aguh served as a coauthor. In this series of two patients, only one had CCCA. The other had lichen planopilaris, but both patients experienced hair regrowth after failing standard therapies.
When treating alopecia with PRP, Dr. Aguh typically offers three or four sessions spaced 4 weeks apart. She does not start other treatments at the same time, but she does not discontinue topical treatments that patients are already taking, including topical minoxidil.
Again, like topical metformin, PRP is reasonably considered in patients who have failed standard therapies, according to Dr. Aguh. She cautioned that responses are not permanent. Patients who respond typically require retreatment a year or more later, but good responses have been seen after retreatment.
Appropriate hair care can help. Dr. Aguh recounted a case in which a patient with presumed CCCA was referred after failing intralesional triamcinolone injections. Ultimately, the patient was diagnosed with acquired trichorrhexis nodosa, but the large clinical improvements gained from better hair care practices, including avoidance of chemical relaxants and thermal styling, are relevant to CCCA, as well as other conditions resulting in hair loss.
In a book written by Dr. Aguh, titled “90 Days to Beautiful Hair,” strategies for better hair care practices include advice to reduce tension on hair follicles.
The role of increased traction is an issue in CCCA, agreed Amy McMichael, MD, chair of the department of dermatology, Wake Forest University, Winston-Salem, N.C. Although she provided data at the meeting suggesting that CCCA is a fibrosing disease linked to genetic susceptibility, she said there is also a “strong association” between the severity of CCCA and extensions, hair weaving, and other tension-associated hairstyles.
While there is an urgent need to develop therapies that address the underlying pathophysiology of CCCA, she concurred that patients with this or other conditions associated with hair loss, such as seborrheic dermatitis or frontal fibrosing alopecia, should not ignore appropriate hair care.
Dr. Aguh has financial relationships with LEO Pharma and UCB Pharma. Dr. McMichael’s disclosures included serving as an investigator and/or consultant for companies that included Allergan, Procter & Gamble, Nutrafol, Johnson & Johnson, and Aclaris.
FROM SOC 2020
How Kodak Gold contributed to bias in dermatology
A recent review looked at all articles describing skin manifestations associated with COVID-19 – 46 articles with a total of 130 clinical images – and found none that documented dermatologic conditions in people with dark skin. This was despite the disproportionate incidence of the disease in Black, Latino, and Native American/American Indian populations of color.
What’s going on? Temitayo Ogunleye, MD, an assistant professor of dermatology at the University of Pennsylvania, Philadelphia, spoke with lead investigator Jenna Lester, MD, a dermatologist and director of the Skin of Color Clinic at University of California, San Francisco, about the implications of her research.
Dr. Ogunleye: What prompted you to do this study in the first place?
Dr. Lester: It was actually driven by frustration. While we’re recognizing these COVID-related dermatologic manifestations, we’re still trying to figure out their clinical significance. We’ve learned what changes could be an early sign of infection and what might occur in people who are otherwise asymptomatic and should be tested. But in the process, we’re leaving out the group of people – dark-skinned populations – who are most heavily impacted by COVID. This is an injustice to the people who could benefit the most if found to have an early, visible sign of the disease on their skin. For example, pernio-like lesions and erythema, both of which have been seen in COVID patients, are harder to identify in darker skin.
As dermatologists, we know that the skin is the biggest organ and one that has the advantage of being visible. We partner with patients because they can see what we can see. We can explain what skin changes mean, and having examples to show them is really powerful. Because doctors typically respond best to numbers, I recognized that we needed data to prove that this lack of representation of persons of color in our COVID documentation was in fact true.
Can you tell us the key findings from your research?
We included any article that described the cutaneous manifestations of COVID – and also included a photograph – and was published over a period of 5 months. Then we categorized each image using the Fitzpatrick Skin Type Scale. We found that A handful, about 6%, depicted skin changes in patients with Fitzpatrick type IV skin.
Were you surprised by the findings?
No. I was not surprised at all, for a couple of reasons. First, many of the referrals that I had been getting to evaluate possible COVID manifestations were from primary care doctors. And as we both know, erythema, hyperpigmentation, and discoloration can be difficult for even a trained dermatologist to pick up on. So if these patients with skin changes potentially suggestive of COVID are presenting to their primary care doctor who could not determine what they were, perhaps because they had never seen them in someone with darker skin, it means those same clinicians are not likely to document these rashes. I suspect that a lot of these photos were sourced from primary care.
The other reason for my lack of surprise is that I have looked at this issue before. In a study I did in 2019 looking at images in dermatology textbooks, my coauthors and I found that there was a pretty dramatic underrepresentation of skin of color overall. Another analysis of images in core dermatology textbooks, published earlier this year by one of your colleagues at the University of Pennsylvania, Jules Lipoff, MD, showed that the percentage of images of dark skin ranged from as low as 4% to a high of about 18%.
So I wonder whether that makes us less likely to look for things in patients with darker skin, except for those conditions that we’re taught are more common in people with darker skin, like keloids, vitiligo, or certain types of hair loss. I wonder whether we just don’t think of other conditions because all the photos we ever see of psoriasis or rosacea, for example, are of people with lighter skin.
You bring up a good point about the cyclical nature of this process. If you don’t see skin conditions in darker skin, then you don’t know what to look for and so you never look for it.
Exactly. What if a Black patient says, for example: “This looks different on my skin; do you think this could be related to COVID?” And their doctor looks at their skin and says no. Not because it isn’t, but because they haven’t seen that before. Then they don’t take a picture of it and we’ll never know what that might have been.
The disturbing thing I have found is that there is an overrepresentation of dark skin in images of sexually transmitted infections. So based on what you are taught, you begin to create these powerful cognitive biases in your brain as a clinician and you start to put people in categories: “This person is more likely to get this because I’ve seen a lot of photos of it.”
Take the example of a 40ish Black woman with a cough who is presumed to have sarcoidosis, because we’ve all been taught that. But what we have not been taught, at least not as definitively, is that the highest prevalence of sarcoidosis is in Nordic countries, where there are not many Black people.
So these loops teach you things that don’t necessarily represent reality. We are taught to recognize patterns, but the patterns that we’ve created are not necessarily valid and carry the biases of the people who decided they were important for us to learn.
So the underrepresentation of persons of color in images depicting skin changes in COVID-19 is, in your perspective, a continuation of this pattern of bias?
I definitely think it is. It’s important to understand the history of photography and the development of color film in order to contextualize that question. Kodak Gold was one of the first color films made. To assist photographers, the company developed a Shirley card, which could be used for color balancing in developing this film. That card, which was distributed to film development labs across the country, depicted a fair-skinned White woman as the standard for how people should appear in the photograph. Film technology was built around this idea.
As a result, people with darker skin were never portrayed accurately and did not have a lot of detail to their features or their skin. A number of famous photographers boycotted by not using the film.
But it wasn’t until chocolate manufacturers and the furniture industries decided that Kodak Gold film was not showing their brown products in enough detail that Kodak was forced to change.
It took these big industries saying “we’re not going to use your film anymore” to spur the development of multicultural Shirley cards which included images of Asian, White, and Black women (a Latina was added later). That didn’t happen until 1995. By then, digital photography had already started to take off. Unfortunately, that advance built off of the original color film and still harbored some of the same issues.
So in addition to concerns about clinicians not recognizing a skin change in a darker-skinned person, if they do recognize it and do decide to photograph it, it just might not come out right. So then it’s possible that clinicians just decide to stop taking photos.
This is another example of structural racism – things that are just baked into the system about which people are unaware. I fear we’ll continue to perpetuate these unconscious biases with the development of augmented intelligence or various algorithms.
I think that this history – which I was unaware of – highlights what happens when White skin becomes the standard. It certainly explains the issue we’ve both seen of clinicians not recognizing erythema on dark skin.
That’s a big one. And I think it’s a big one because it’s a shared presenting sign of a lot of different rashes. It can also be a sign of a dermatologic emergency that requires rapid recognition and treatment. Erythema can be very subtle, especially in skin of color. It is one of the things that we use to grade severity of psoriasis, and as a result of it not being appreciated in people with darker skin, those patients have not been included in a lot of the clinical trials.
There has even been discussion of whether erythema is something we should deem to be an important finding in people with darker skin.
Maybe one of the problems is terminology. Erythema connotes pink or red coloration, and that does not really show up on dark skin as overtly.
Exactly. Emollient use is also different in people of color. So the “classic” scales of psoriasis often aren’t present in someone who uses a lot of lotion.
In addition to the different clinical appearance of many common skin conditions, cultural practices might be different in different groups, which may also alter your differential diagnoses and treatment recommendations – for instance, moisturizer use, shampooing frequency, or use of different hair styling products.
I totally agree. Hair is another big one. Identifying broken hairs, short hairs, texture changes, and variability in the size of the hair shaft is different in coiled, Black hair and is not really applicable to people with more textured hair patterns. People of different ethnicities and cultures do different things. Standards that we traditionally use, such as the hair-pull test, don’t work quite as well in different groups.
I think that speaks to the changes that we also need to make in educating both dermatologists and nondermatologists in diagnostic criteria and clinical findings.
Dermatology is the second least diverse specialty. And that means our experts – faculty, lecturers, mentors – are not likely to be people of color. You don’t know what you don’t know. You only have your own experiences. If you don’t have people who can explain why something may be different for a different group of people, you don’t have an opportunity to broaden your understanding. You and I noticed because we know what it’s like to have this type of hair. But it’s not something that other people who don’t share the same hair type would have the same perspective on.
It is even more reason to make sure that our dermatology workforce mirrors our population. About 3% of the dermatologists in the United States are Black; the numbers are equally bad for Latino and indigenous dermatologists. If you don’t have enough people in your immediate environment who can help broaden your perspective, that becomes a problem that can harm patients.
If we don’t have a diverse group of people in the field who are contributing to the literature, changing some of the ways that we think about practice, then everyone is just going to keep doing the wrong thing.
We need to build our evidence and pay more attention to the racial breakdown of patients included in studies. We are recognizing that we have blind spots but we don’t have people or data that can change that. If what we are publishing overrepresents a certain group, how will we ever learn to do things differently?
I recognize the fact that this is not a new idea. Others have worked on these issues for a long time. Your colleague, Susan Taylor, MD, a professor at University of Pennsylvania and a founder of the Skin of Color Society, used her energy and frustration about this issue and published a whole textbook on it: “Dermatology for Skin of Color.” When I tried to publish my first paper on this issue, I got a lot of pushback, but I’m happy that now it’s something that everyone is talking about. So just in the span of a couple of years, the acceptance of this idea has changed dramatically.
I hope that this is the start of sustainable, systemic changes that can have a real impact.
Let me ask a technical question. Is the excuse of not knowing how to photograph darker skin just that – an excuse? Or is that concern truly valid?
That’s a great question. There are certain techniques that one can employ. And yes, it can be more challenging if you are not used to taking photos of people with darker skin, but it certainly can be learned.
I think that an intelligent group of people who have faced things before that felt insurmountable could continue to push to figure out how to do it. But it is something that does require skills, and part of it is because there’s this bias built into the camera, so you have to make up for that.
I think every single dermatologist has that ability, and you just have to know that it’s worthwhile to do because your patient is that valuable.
A version of this article originally appeared on Medscape.com.
A recent review looked at all articles describing skin manifestations associated with COVID-19 – 46 articles with a total of 130 clinical images – and found none that documented dermatologic conditions in people with dark skin. This was despite the disproportionate incidence of the disease in Black, Latino, and Native American/American Indian populations of color.
What’s going on? Temitayo Ogunleye, MD, an assistant professor of dermatology at the University of Pennsylvania, Philadelphia, spoke with lead investigator Jenna Lester, MD, a dermatologist and director of the Skin of Color Clinic at University of California, San Francisco, about the implications of her research.
Dr. Ogunleye: What prompted you to do this study in the first place?
Dr. Lester: It was actually driven by frustration. While we’re recognizing these COVID-related dermatologic manifestations, we’re still trying to figure out their clinical significance. We’ve learned what changes could be an early sign of infection and what might occur in people who are otherwise asymptomatic and should be tested. But in the process, we’re leaving out the group of people – dark-skinned populations – who are most heavily impacted by COVID. This is an injustice to the people who could benefit the most if found to have an early, visible sign of the disease on their skin. For example, pernio-like lesions and erythema, both of which have been seen in COVID patients, are harder to identify in darker skin.
As dermatologists, we know that the skin is the biggest organ and one that has the advantage of being visible. We partner with patients because they can see what we can see. We can explain what skin changes mean, and having examples to show them is really powerful. Because doctors typically respond best to numbers, I recognized that we needed data to prove that this lack of representation of persons of color in our COVID documentation was in fact true.
Can you tell us the key findings from your research?
We included any article that described the cutaneous manifestations of COVID – and also included a photograph – and was published over a period of 5 months. Then we categorized each image using the Fitzpatrick Skin Type Scale. We found that A handful, about 6%, depicted skin changes in patients with Fitzpatrick type IV skin.
Were you surprised by the findings?
No. I was not surprised at all, for a couple of reasons. First, many of the referrals that I had been getting to evaluate possible COVID manifestations were from primary care doctors. And as we both know, erythema, hyperpigmentation, and discoloration can be difficult for even a trained dermatologist to pick up on. So if these patients with skin changes potentially suggestive of COVID are presenting to their primary care doctor who could not determine what they were, perhaps because they had never seen them in someone with darker skin, it means those same clinicians are not likely to document these rashes. I suspect that a lot of these photos were sourced from primary care.
The other reason for my lack of surprise is that I have looked at this issue before. In a study I did in 2019 looking at images in dermatology textbooks, my coauthors and I found that there was a pretty dramatic underrepresentation of skin of color overall. Another analysis of images in core dermatology textbooks, published earlier this year by one of your colleagues at the University of Pennsylvania, Jules Lipoff, MD, showed that the percentage of images of dark skin ranged from as low as 4% to a high of about 18%.
So I wonder whether that makes us less likely to look for things in patients with darker skin, except for those conditions that we’re taught are more common in people with darker skin, like keloids, vitiligo, or certain types of hair loss. I wonder whether we just don’t think of other conditions because all the photos we ever see of psoriasis or rosacea, for example, are of people with lighter skin.
You bring up a good point about the cyclical nature of this process. If you don’t see skin conditions in darker skin, then you don’t know what to look for and so you never look for it.
Exactly. What if a Black patient says, for example: “This looks different on my skin; do you think this could be related to COVID?” And their doctor looks at their skin and says no. Not because it isn’t, but because they haven’t seen that before. Then they don’t take a picture of it and we’ll never know what that might have been.
The disturbing thing I have found is that there is an overrepresentation of dark skin in images of sexually transmitted infections. So based on what you are taught, you begin to create these powerful cognitive biases in your brain as a clinician and you start to put people in categories: “This person is more likely to get this because I’ve seen a lot of photos of it.”
Take the example of a 40ish Black woman with a cough who is presumed to have sarcoidosis, because we’ve all been taught that. But what we have not been taught, at least not as definitively, is that the highest prevalence of sarcoidosis is in Nordic countries, where there are not many Black people.
So these loops teach you things that don’t necessarily represent reality. We are taught to recognize patterns, but the patterns that we’ve created are not necessarily valid and carry the biases of the people who decided they were important for us to learn.
So the underrepresentation of persons of color in images depicting skin changes in COVID-19 is, in your perspective, a continuation of this pattern of bias?
I definitely think it is. It’s important to understand the history of photography and the development of color film in order to contextualize that question. Kodak Gold was one of the first color films made. To assist photographers, the company developed a Shirley card, which could be used for color balancing in developing this film. That card, which was distributed to film development labs across the country, depicted a fair-skinned White woman as the standard for how people should appear in the photograph. Film technology was built around this idea.
As a result, people with darker skin were never portrayed accurately and did not have a lot of detail to their features or their skin. A number of famous photographers boycotted by not using the film.
But it wasn’t until chocolate manufacturers and the furniture industries decided that Kodak Gold film was not showing their brown products in enough detail that Kodak was forced to change.
It took these big industries saying “we’re not going to use your film anymore” to spur the development of multicultural Shirley cards which included images of Asian, White, and Black women (a Latina was added later). That didn’t happen until 1995. By then, digital photography had already started to take off. Unfortunately, that advance built off of the original color film and still harbored some of the same issues.
So in addition to concerns about clinicians not recognizing a skin change in a darker-skinned person, if they do recognize it and do decide to photograph it, it just might not come out right. So then it’s possible that clinicians just decide to stop taking photos.
This is another example of structural racism – things that are just baked into the system about which people are unaware. I fear we’ll continue to perpetuate these unconscious biases with the development of augmented intelligence or various algorithms.
I think that this history – which I was unaware of – highlights what happens when White skin becomes the standard. It certainly explains the issue we’ve both seen of clinicians not recognizing erythema on dark skin.
That’s a big one. And I think it’s a big one because it’s a shared presenting sign of a lot of different rashes. It can also be a sign of a dermatologic emergency that requires rapid recognition and treatment. Erythema can be very subtle, especially in skin of color. It is one of the things that we use to grade severity of psoriasis, and as a result of it not being appreciated in people with darker skin, those patients have not been included in a lot of the clinical trials.
There has even been discussion of whether erythema is something we should deem to be an important finding in people with darker skin.
Maybe one of the problems is terminology. Erythema connotes pink or red coloration, and that does not really show up on dark skin as overtly.
Exactly. Emollient use is also different in people of color. So the “classic” scales of psoriasis often aren’t present in someone who uses a lot of lotion.
In addition to the different clinical appearance of many common skin conditions, cultural practices might be different in different groups, which may also alter your differential diagnoses and treatment recommendations – for instance, moisturizer use, shampooing frequency, or use of different hair styling products.
I totally agree. Hair is another big one. Identifying broken hairs, short hairs, texture changes, and variability in the size of the hair shaft is different in coiled, Black hair and is not really applicable to people with more textured hair patterns. People of different ethnicities and cultures do different things. Standards that we traditionally use, such as the hair-pull test, don’t work quite as well in different groups.
I think that speaks to the changes that we also need to make in educating both dermatologists and nondermatologists in diagnostic criteria and clinical findings.
Dermatology is the second least diverse specialty. And that means our experts – faculty, lecturers, mentors – are not likely to be people of color. You don’t know what you don’t know. You only have your own experiences. If you don’t have people who can explain why something may be different for a different group of people, you don’t have an opportunity to broaden your understanding. You and I noticed because we know what it’s like to have this type of hair. But it’s not something that other people who don’t share the same hair type would have the same perspective on.
It is even more reason to make sure that our dermatology workforce mirrors our population. About 3% of the dermatologists in the United States are Black; the numbers are equally bad for Latino and indigenous dermatologists. If you don’t have enough people in your immediate environment who can help broaden your perspective, that becomes a problem that can harm patients.
If we don’t have a diverse group of people in the field who are contributing to the literature, changing some of the ways that we think about practice, then everyone is just going to keep doing the wrong thing.
We need to build our evidence and pay more attention to the racial breakdown of patients included in studies. We are recognizing that we have blind spots but we don’t have people or data that can change that. If what we are publishing overrepresents a certain group, how will we ever learn to do things differently?
I recognize the fact that this is not a new idea. Others have worked on these issues for a long time. Your colleague, Susan Taylor, MD, a professor at University of Pennsylvania and a founder of the Skin of Color Society, used her energy and frustration about this issue and published a whole textbook on it: “Dermatology for Skin of Color.” When I tried to publish my first paper on this issue, I got a lot of pushback, but I’m happy that now it’s something that everyone is talking about. So just in the span of a couple of years, the acceptance of this idea has changed dramatically.
I hope that this is the start of sustainable, systemic changes that can have a real impact.
Let me ask a technical question. Is the excuse of not knowing how to photograph darker skin just that – an excuse? Or is that concern truly valid?
That’s a great question. There are certain techniques that one can employ. And yes, it can be more challenging if you are not used to taking photos of people with darker skin, but it certainly can be learned.
I think that an intelligent group of people who have faced things before that felt insurmountable could continue to push to figure out how to do it. But it is something that does require skills, and part of it is because there’s this bias built into the camera, so you have to make up for that.
I think every single dermatologist has that ability, and you just have to know that it’s worthwhile to do because your patient is that valuable.
A version of this article originally appeared on Medscape.com.
A recent review looked at all articles describing skin manifestations associated with COVID-19 – 46 articles with a total of 130 clinical images – and found none that documented dermatologic conditions in people with dark skin. This was despite the disproportionate incidence of the disease in Black, Latino, and Native American/American Indian populations of color.
What’s going on? Temitayo Ogunleye, MD, an assistant professor of dermatology at the University of Pennsylvania, Philadelphia, spoke with lead investigator Jenna Lester, MD, a dermatologist and director of the Skin of Color Clinic at University of California, San Francisco, about the implications of her research.
Dr. Ogunleye: What prompted you to do this study in the first place?
Dr. Lester: It was actually driven by frustration. While we’re recognizing these COVID-related dermatologic manifestations, we’re still trying to figure out their clinical significance. We’ve learned what changes could be an early sign of infection and what might occur in people who are otherwise asymptomatic and should be tested. But in the process, we’re leaving out the group of people – dark-skinned populations – who are most heavily impacted by COVID. This is an injustice to the people who could benefit the most if found to have an early, visible sign of the disease on their skin. For example, pernio-like lesions and erythema, both of which have been seen in COVID patients, are harder to identify in darker skin.
As dermatologists, we know that the skin is the biggest organ and one that has the advantage of being visible. We partner with patients because they can see what we can see. We can explain what skin changes mean, and having examples to show them is really powerful. Because doctors typically respond best to numbers, I recognized that we needed data to prove that this lack of representation of persons of color in our COVID documentation was in fact true.
Can you tell us the key findings from your research?
We included any article that described the cutaneous manifestations of COVID – and also included a photograph – and was published over a period of 5 months. Then we categorized each image using the Fitzpatrick Skin Type Scale. We found that A handful, about 6%, depicted skin changes in patients with Fitzpatrick type IV skin.
Were you surprised by the findings?
No. I was not surprised at all, for a couple of reasons. First, many of the referrals that I had been getting to evaluate possible COVID manifestations were from primary care doctors. And as we both know, erythema, hyperpigmentation, and discoloration can be difficult for even a trained dermatologist to pick up on. So if these patients with skin changes potentially suggestive of COVID are presenting to their primary care doctor who could not determine what they were, perhaps because they had never seen them in someone with darker skin, it means those same clinicians are not likely to document these rashes. I suspect that a lot of these photos were sourced from primary care.
The other reason for my lack of surprise is that I have looked at this issue before. In a study I did in 2019 looking at images in dermatology textbooks, my coauthors and I found that there was a pretty dramatic underrepresentation of skin of color overall. Another analysis of images in core dermatology textbooks, published earlier this year by one of your colleagues at the University of Pennsylvania, Jules Lipoff, MD, showed that the percentage of images of dark skin ranged from as low as 4% to a high of about 18%.
So I wonder whether that makes us less likely to look for things in patients with darker skin, except for those conditions that we’re taught are more common in people with darker skin, like keloids, vitiligo, or certain types of hair loss. I wonder whether we just don’t think of other conditions because all the photos we ever see of psoriasis or rosacea, for example, are of people with lighter skin.
You bring up a good point about the cyclical nature of this process. If you don’t see skin conditions in darker skin, then you don’t know what to look for and so you never look for it.
Exactly. What if a Black patient says, for example: “This looks different on my skin; do you think this could be related to COVID?” And their doctor looks at their skin and says no. Not because it isn’t, but because they haven’t seen that before. Then they don’t take a picture of it and we’ll never know what that might have been.
The disturbing thing I have found is that there is an overrepresentation of dark skin in images of sexually transmitted infections. So based on what you are taught, you begin to create these powerful cognitive biases in your brain as a clinician and you start to put people in categories: “This person is more likely to get this because I’ve seen a lot of photos of it.”
Take the example of a 40ish Black woman with a cough who is presumed to have sarcoidosis, because we’ve all been taught that. But what we have not been taught, at least not as definitively, is that the highest prevalence of sarcoidosis is in Nordic countries, where there are not many Black people.
So these loops teach you things that don’t necessarily represent reality. We are taught to recognize patterns, but the patterns that we’ve created are not necessarily valid and carry the biases of the people who decided they were important for us to learn.
So the underrepresentation of persons of color in images depicting skin changes in COVID-19 is, in your perspective, a continuation of this pattern of bias?
I definitely think it is. It’s important to understand the history of photography and the development of color film in order to contextualize that question. Kodak Gold was one of the first color films made. To assist photographers, the company developed a Shirley card, which could be used for color balancing in developing this film. That card, which was distributed to film development labs across the country, depicted a fair-skinned White woman as the standard for how people should appear in the photograph. Film technology was built around this idea.
As a result, people with darker skin were never portrayed accurately and did not have a lot of detail to their features or their skin. A number of famous photographers boycotted by not using the film.
But it wasn’t until chocolate manufacturers and the furniture industries decided that Kodak Gold film was not showing their brown products in enough detail that Kodak was forced to change.
It took these big industries saying “we’re not going to use your film anymore” to spur the development of multicultural Shirley cards which included images of Asian, White, and Black women (a Latina was added later). That didn’t happen until 1995. By then, digital photography had already started to take off. Unfortunately, that advance built off of the original color film and still harbored some of the same issues.
So in addition to concerns about clinicians not recognizing a skin change in a darker-skinned person, if they do recognize it and do decide to photograph it, it just might not come out right. So then it’s possible that clinicians just decide to stop taking photos.
This is another example of structural racism – things that are just baked into the system about which people are unaware. I fear we’ll continue to perpetuate these unconscious biases with the development of augmented intelligence or various algorithms.
I think that this history – which I was unaware of – highlights what happens when White skin becomes the standard. It certainly explains the issue we’ve both seen of clinicians not recognizing erythema on dark skin.
That’s a big one. And I think it’s a big one because it’s a shared presenting sign of a lot of different rashes. It can also be a sign of a dermatologic emergency that requires rapid recognition and treatment. Erythema can be very subtle, especially in skin of color. It is one of the things that we use to grade severity of psoriasis, and as a result of it not being appreciated in people with darker skin, those patients have not been included in a lot of the clinical trials.
There has even been discussion of whether erythema is something we should deem to be an important finding in people with darker skin.
Maybe one of the problems is terminology. Erythema connotes pink or red coloration, and that does not really show up on dark skin as overtly.
Exactly. Emollient use is also different in people of color. So the “classic” scales of psoriasis often aren’t present in someone who uses a lot of lotion.
In addition to the different clinical appearance of many common skin conditions, cultural practices might be different in different groups, which may also alter your differential diagnoses and treatment recommendations – for instance, moisturizer use, shampooing frequency, or use of different hair styling products.
I totally agree. Hair is another big one. Identifying broken hairs, short hairs, texture changes, and variability in the size of the hair shaft is different in coiled, Black hair and is not really applicable to people with more textured hair patterns. People of different ethnicities and cultures do different things. Standards that we traditionally use, such as the hair-pull test, don’t work quite as well in different groups.
I think that speaks to the changes that we also need to make in educating both dermatologists and nondermatologists in diagnostic criteria and clinical findings.
Dermatology is the second least diverse specialty. And that means our experts – faculty, lecturers, mentors – are not likely to be people of color. You don’t know what you don’t know. You only have your own experiences. If you don’t have people who can explain why something may be different for a different group of people, you don’t have an opportunity to broaden your understanding. You and I noticed because we know what it’s like to have this type of hair. But it’s not something that other people who don’t share the same hair type would have the same perspective on.
It is even more reason to make sure that our dermatology workforce mirrors our population. About 3% of the dermatologists in the United States are Black; the numbers are equally bad for Latino and indigenous dermatologists. If you don’t have enough people in your immediate environment who can help broaden your perspective, that becomes a problem that can harm patients.
If we don’t have a diverse group of people in the field who are contributing to the literature, changing some of the ways that we think about practice, then everyone is just going to keep doing the wrong thing.
We need to build our evidence and pay more attention to the racial breakdown of patients included in studies. We are recognizing that we have blind spots but we don’t have people or data that can change that. If what we are publishing overrepresents a certain group, how will we ever learn to do things differently?
I recognize the fact that this is not a new idea. Others have worked on these issues for a long time. Your colleague, Susan Taylor, MD, a professor at University of Pennsylvania and a founder of the Skin of Color Society, used her energy and frustration about this issue and published a whole textbook on it: “Dermatology for Skin of Color.” When I tried to publish my first paper on this issue, I got a lot of pushback, but I’m happy that now it’s something that everyone is talking about. So just in the span of a couple of years, the acceptance of this idea has changed dramatically.
I hope that this is the start of sustainable, systemic changes that can have a real impact.
Let me ask a technical question. Is the excuse of not knowing how to photograph darker skin just that – an excuse? Or is that concern truly valid?
That’s a great question. There are certain techniques that one can employ. And yes, it can be more challenging if you are not used to taking photos of people with darker skin, but it certainly can be learned.
I think that an intelligent group of people who have faced things before that felt insurmountable could continue to push to figure out how to do it. But it is something that does require skills, and part of it is because there’s this bias built into the camera, so you have to make up for that.
I think every single dermatologist has that ability, and you just have to know that it’s worthwhile to do because your patient is that valuable.
A version of this article originally appeared on Medscape.com.