Prescription medications

Photo courtesy of the CDC

New research suggests that starting all patients with chronic myeloid leukemia (CML) on the generic form of Gleevec, imatinib, could result in substantial savings for patients and insurance companies in the US.

Researchers found that starting treatment with generic imatinib and then switching patients to the second-generation tyrosine kinase inhibitors (TKIs) dasatinib (Sprycel) and nilotinib (Tasigna) if necessary would be more cost-effective than the current standard of care, which allows physicians to start patients on any of the aforementioned TKIs.

In fact, the data suggest that starting all CML patients on generic imatinib could reduce the cost of treatment per patient over 5 years by nearly $90,000.

“If we start all patients on the generic form of Gleevec, and it works, then they are on a generic for the rest of their lives,” said study author William V. Padula, PhD, of Johns Hopkins University in Baltimore, Maryland.

“This amounts to a huge cost savings for them and their insurers.”

Dr Padula and his colleagues described these potential savings in the Journal of the National Cancer Institute.

The researchers compared the cost-effectiveness of the different TKIs by analyzing Truven Health Analytics MarketScan data from newly diagnosed CML patients between January 1, 2011, and December 31, 2012.

The team constructed Markov models to compare the 5-year cost-effectiveness of imatinib-first vs physician’s choice. The main outcome of the models was cost per quality-adjusted life-year (QALY).

The researchers interpreted outcomes based on a willingness-to-pay threshold of $100,000/QALY. They found that both imatinib-first and physician’s choice met that threshold.

However, imatinib-first cost less over 5 years and conferred only slightly fewer QALYs than physician’s choice—$277,401 and 3.87 QALYs for imatinib-first and $365,744 and 3.97 QALYs for physician’s choice.

So that’s a 0.10 decrement in QALYs and a savings of $88,343 over 5 years with imatinib-first. The imatinib-first incremental cost-effectiveness ratio was about $883,730/QALY.

“There is minimal risk to starting all patients on imatinib first,” Dr Padula said. “If the patient can’t tolerate the medication or it seems to be ineffective in that patient, then we can switch the patient to a more expensive drug.”

“Insurance companies have the ability to dictate which drugs physicians prescribe first, and they regularly do. Doing so here would mean very little risk to health and a lot of cost savings.”

Prescription medications

Photo courtesy of the CDC

New research suggests that starting all patients with chronic myeloid leukemia (CML) on the generic form of Gleevec, imatinib, could result in substantial savings for patients and insurance companies in the US.

Researchers found that starting treatment with generic imatinib and then switching patients to the second-generation tyrosine kinase inhibitors (TKIs) dasatinib (Sprycel) and nilotinib (Tasigna) if necessary would be more cost-effective than the current standard of care, which allows physicians to start patients on any of the aforementioned TKIs.

In fact, the data suggest that starting all CML patients on generic imatinib could reduce the cost of treatment per patient over 5 years by nearly $90,000.

“If we start all patients on the generic form of Gleevec, and it works, then they are on a generic for the rest of their lives,” said study author William V. Padula, PhD, of Johns Hopkins University in Baltimore, Maryland.

“This amounts to a huge cost savings for them and their insurers.”

Dr Padula and his colleagues described these potential savings in the Journal of the National Cancer Institute.

The researchers compared the cost-effectiveness of the different TKIs by analyzing Truven Health Analytics MarketScan data from newly diagnosed CML patients between January 1, 2011, and December 31, 2012.

The team constructed Markov models to compare the 5-year cost-effectiveness of imatinib-first vs physician’s choice. The main outcome of the models was cost per quality-adjusted life-year (QALY).

The researchers interpreted outcomes based on a willingness-to-pay threshold of $100,000/QALY. They found that both imatinib-first and physician’s choice met that threshold.

However, imatinib-first cost less over 5 years and conferred only slightly fewer QALYs than physician’s choice—$277,401 and 3.87 QALYs for imatinib-first and $365,744 and 3.97 QALYs for physician’s choice.

So that’s a 0.10 decrement in QALYs and a savings of $88,343 over 5 years with imatinib-first. The imatinib-first incremental cost-effectiveness ratio was about $883,730/QALY.

“There is minimal risk to starting all patients on imatinib first,” Dr Padula said. “If the patient can’t tolerate the medication or it seems to be ineffective in that patient, then we can switch the patient to a more expensive drug.”

“Insurance companies have the ability to dictate which drugs physicians prescribe first, and they regularly do. Doing so here would mean very little risk to health and a lot of cost savings.”

Prescription medications

Photo courtesy of the CDC

New research suggests that starting all patients with chronic myeloid leukemia (CML) on the generic form of Gleevec, imatinib, could result in substantial savings for patients and insurance companies in the US.

Researchers found that starting treatment with generic imatinib and then switching patients to the second-generation tyrosine kinase inhibitors (TKIs) dasatinib (Sprycel) and nilotinib (Tasigna) if necessary would be more cost-effective than the current standard of care, which allows physicians to start patients on any of the aforementioned TKIs.

In fact, the data suggest that starting all CML patients on generic imatinib could reduce the cost of treatment per patient over 5 years by nearly $90,000.

“If we start all patients on the generic form of Gleevec, and it works, then they are on a generic for the rest of their lives,” said study author William V. Padula, PhD, of Johns Hopkins University in Baltimore, Maryland.

“This amounts to a huge cost savings for them and their insurers.”

Dr Padula and his colleagues described these potential savings in the Journal of the National Cancer Institute.

The researchers compared the cost-effectiveness of the different TKIs by analyzing Truven Health Analytics MarketScan data from newly diagnosed CML patients between January 1, 2011, and December 31, 2012.

The team constructed Markov models to compare the 5-year cost-effectiveness of imatinib-first vs physician’s choice. The main outcome of the models was cost per quality-adjusted life-year (QALY).

The researchers interpreted outcomes based on a willingness-to-pay threshold of $100,000/QALY. They found that both imatinib-first and physician’s choice met that threshold.

However, imatinib-first cost less over 5 years and conferred only slightly fewer QALYs than physician’s choice—$277,401 and 3.87 QALYs for imatinib-first and $365,744 and 3.97 QALYs for physician’s choice.

So that’s a 0.10 decrement in QALYs and a savings of $88,343 over 5 years with imatinib-first. The imatinib-first incremental cost-effectiveness ratio was about $883,730/QALY.

“There is minimal risk to starting all patients on imatinib first,” Dr Padula said. “If the patient can’t tolerate the medication or it seems to be ineffective in that patient, then we can switch the patient to a more expensive drug.”

“Insurance companies have the ability to dictate which drugs physicians prescribe first, and they regularly do. Doing so here would mean very little risk to health and a lot of cost savings.”

Researchers in the lab

Photo by Rhoda Baer

A review of the biomedical literature indicates an increase in the use of P values in recent years, but researchers say this technique can provide misleading results.

“It’s usually a suboptimal technique, and then it’s used in a biased way, so it can become very misleading,” said John Ioannidis, MD, of Stanford University in California.

He and his colleagues reviewed the use of P values and recounted their findings in JAMA.

The team used automated text-mining analysis to extract data on P values reported in 12,821,790 MEDLINE abstracts and 843,884 abstracts and full-text articles in PubMed Central from 1990 to 2015.

The researchers also assessed the reporting of P values in 151 English-language core clinical journals and specific article types as classified by PubMed.

They manually evaluated a random sample of 1000 MEDLINE abstracts for reporting of P values and other types of statistical information. And of those abstracts reporting empirical data, 100 articles were assessed in their entirety.

The data showed that reporting of P values more than doubled from 1990 to 2014—increasing from 7.3% to 15.6%.

In abstracts from core medical journals, 33% reported P values in 2014. And in the subset of randomized, controlled clinical trials, nearly 55% reported P values in 2014.

Dr Ioannidis noted that some researchers mistakenly think a P value is an estimate of how likely it is that a result is true.

“The P value does not tell you whether something is true,” he explained. “If you get a P value of 0.01, it doesn’t mean you have a 1% chance of something not being true.”

“A P value of 0.01 could mean the result is 20% likely to be true, 80% likely to be true, or 0.1% likely to be true—all with the same P value. The P value alone doesn’t tell you how true your result is.”

For an actual estimate of how likely a result is to be true or false, Dr Ioannidis said, researchers should instead use false-discovery rates or Bayes factor calculations.

He and his colleagues assessed the use of false-discovery rates, Bayes factor calculations, effect sizes, and confidence intervals in the 796 papers in their review that contained empirical data.

They found that 111 of these papers reported effect sizes, and 18 reported confidence intervals. None of the papers reported Bayes factors or false-discovery rates.

Fewer than 2% of the abstracts the team reviewed reported both an effect size and a confidence interval.

In a manual review of 99 randomly selected full-text articles, the researchers found that 55 articles reported at least 1 P value. But only 4 articles reported confidence intervals for all effect sizes, none used Bayesian methods, and 1 used false-discovery rates.

In light of these findings, Dr Ioannidis advocates more stringent approaches to analyzing data.

“The way to move forward is that P values need to be used more selectively,” he said. “When used, they need to be complemented by effect sizes and uncertainty [confidence intervals]. And it would often be a good idea to use a Bayesian approach or a false-discovery rate to answer the question, ‘How likely is this result to be true?’”

Researchers in the lab

Photo by Rhoda Baer

A review of the biomedical literature indicates an increase in the use of P values in recent years, but researchers say this technique can provide misleading results.

“It’s usually a suboptimal technique, and then it’s used in a biased way, so it can become very misleading,” said John Ioannidis, MD, of Stanford University in California.

He and his colleagues reviewed the use of P values and recounted their findings in JAMA.

The team used automated text-mining analysis to extract data on P values reported in 12,821,790 MEDLINE abstracts and 843,884 abstracts and full-text articles in PubMed Central from 1990 to 2015.

The researchers also assessed the reporting of P values in 151 English-language core clinical journals and specific article types as classified by PubMed.

They manually evaluated a random sample of 1000 MEDLINE abstracts for reporting of P values and other types of statistical information. And of those abstracts reporting empirical data, 100 articles were assessed in their entirety.

The data showed that reporting of P values more than doubled from 1990 to 2014—increasing from 7.3% to 15.6%.

In abstracts from core medical journals, 33% reported P values in 2014. And in the subset of randomized, controlled clinical trials, nearly 55% reported P values in 2014.

Dr Ioannidis noted that some researchers mistakenly think a P value is an estimate of how likely it is that a result is true.

“The P value does not tell you whether something is true,” he explained. “If you get a P value of 0.01, it doesn’t mean you have a 1% chance of something not being true.”

“A P value of 0.01 could mean the result is 20% likely to be true, 80% likely to be true, or 0.1% likely to be true—all with the same P value. The P value alone doesn’t tell you how true your result is.”

For an actual estimate of how likely a result is to be true or false, Dr Ioannidis said, researchers should instead use false-discovery rates or Bayes factor calculations.

He and his colleagues assessed the use of false-discovery rates, Bayes factor calculations, effect sizes, and confidence intervals in the 796 papers in their review that contained empirical data.

They found that 111 of these papers reported effect sizes, and 18 reported confidence intervals. None of the papers reported Bayes factors or false-discovery rates.

Fewer than 2% of the abstracts the team reviewed reported both an effect size and a confidence interval.

In a manual review of 99 randomly selected full-text articles, the researchers found that 55 articles reported at least 1 P value. But only 4 articles reported confidence intervals for all effect sizes, none used Bayesian methods, and 1 used false-discovery rates.

In light of these findings, Dr Ioannidis advocates more stringent approaches to analyzing data.

“The way to move forward is that P values need to be used more selectively,” he said. “When used, they need to be complemented by effect sizes and uncertainty [confidence intervals]. And it would often be a good idea to use a Bayesian approach or a false-discovery rate to answer the question, ‘How likely is this result to be true?’”

Researchers in the lab

Photo by Rhoda Baer

A review of the biomedical literature indicates an increase in the use of P values in recent years, but researchers say this technique can provide misleading results.

“It’s usually a suboptimal technique, and then it’s used in a biased way, so it can become very misleading,” said John Ioannidis, MD, of Stanford University in California.

He and his colleagues reviewed the use of P values and recounted their findings in JAMA.

The team used automated text-mining analysis to extract data on P values reported in 12,821,790 MEDLINE abstracts and 843,884 abstracts and full-text articles in PubMed Central from 1990 to 2015.

The researchers also assessed the reporting of P values in 151 English-language core clinical journals and specific article types as classified by PubMed.

They manually evaluated a random sample of 1000 MEDLINE abstracts for reporting of P values and other types of statistical information. And of those abstracts reporting empirical data, 100 articles were assessed in their entirety.

The data showed that reporting of P values more than doubled from 1990 to 2014—increasing from 7.3% to 15.6%.

In abstracts from core medical journals, 33% reported P values in 2014. And in the subset of randomized, controlled clinical trials, nearly 55% reported P values in 2014.

Dr Ioannidis noted that some researchers mistakenly think a P value is an estimate of how likely it is that a result is true.

“The P value does not tell you whether something is true,” he explained. “If you get a P value of 0.01, it doesn’t mean you have a 1% chance of something not being true.”

“A P value of 0.01 could mean the result is 20% likely to be true, 80% likely to be true, or 0.1% likely to be true—all with the same P value. The P value alone doesn’t tell you how true your result is.”

For an actual estimate of how likely a result is to be true or false, Dr Ioannidis said, researchers should instead use false-discovery rates or Bayes factor calculations.

He and his colleagues assessed the use of false-discovery rates, Bayes factor calculations, effect sizes, and confidence intervals in the 796 papers in their review that contained empirical data.

They found that 111 of these papers reported effect sizes, and 18 reported confidence intervals. None of the papers reported Bayes factors or false-discovery rates.

Fewer than 2% of the abstracts the team reviewed reported both an effect size and a confidence interval.

In a manual review of 99 randomly selected full-text articles, the researchers found that 55 articles reported at least 1 P value. But only 4 articles reported confidence intervals for all effect sizes, none used Bayesian methods, and 1 used false-discovery rates.

In light of these findings, Dr Ioannidis advocates more stringent approaches to analyzing data.

“The way to move forward is that P values need to be used more selectively,” he said. “When used, they need to be complemented by effect sizes and uncertainty [confidence intervals]. And it would often be a good idea to use a Bayesian approach or a false-discovery rate to answer the question, ‘How likely is this result to be true?’”

The Food and Drug Administration has approved a new propylene glycol–free formulation of melphalan hydrochloride as a high-dose conditioning treatment for autologous stem cell transplantation, and as a palliative therapy for multiple myeloma.

Evomela (Spectrum Pharmaceuticals) is intended to be reconstituted with normal saline at the time of intravenous administration. The solution is stable for 4 hours using Captisol, a proprietary agent containing modified cyclodextrin. It is also stable for 1 hour after reconstitution.

Extended stability without the need for propylene glycol is its major advantage over the other formulations of melphalan, a chemotherapy agent originally approved in 1964, according to a statement by Spectrum.

Evomela was approved on the basis of a phase IIa pharmacokinetic trial comprising 24 patients undergoing autologous stem cell transplantation. Evomela was bioequivalent with Alkeran, with a 10% higher maximum plasma concentration and area under the plasma concentration-time curve (Bone Marrow Transplant. 2014 Aug;49[8]:1042-5).

According to that, and other studies, adverse reactions included decreased neutrophil count (100%), decreased white blood cell count (100%), decreased lymphocyte count (98%), decreased platelet count (98%), diarrhea (93%), nausea (90%), fatigue (77%), hypokalemia (74%), anemia (66%), and vomiting (64%). About 2% of patients have experienced hypersensitivity reactions.

For palliative treatment, the recommended does is 16 mg/m² infused over 15-20 minutes at 2-week intervals for four doses, and then, after adequate recovery from toxicity, at 4-week intervals.

For conditioning treatment, the recommended does is 100 mg/m² per day infused over 30 minutes for 2 consecutive days before stem cell transplant.

[email protected]

The Food and Drug Administration has approved a new propylene glycol–free formulation of melphalan hydrochloride as a high-dose conditioning treatment for autologous stem cell transplantation, and as a palliative therapy for multiple myeloma.

Evomela (Spectrum Pharmaceuticals) is intended to be reconstituted with normal saline at the time of intravenous administration. The solution is stable for 4 hours using Captisol, a proprietary agent containing modified cyclodextrin. It is also stable for 1 hour after reconstitution.

Extended stability without the need for propylene glycol is its major advantage over the other formulations of melphalan, a chemotherapy agent originally approved in 1964, according to a statement by Spectrum.

Evomela was approved on the basis of a phase IIa pharmacokinetic trial comprising 24 patients undergoing autologous stem cell transplantation. Evomela was bioequivalent with Alkeran, with a 10% higher maximum plasma concentration and area under the plasma concentration-time curve (Bone Marrow Transplant. 2014 Aug;49[8]:1042-5).

According to that, and other studies, adverse reactions included decreased neutrophil count (100%), decreased white blood cell count (100%), decreased lymphocyte count (98%), decreased platelet count (98%), diarrhea (93%), nausea (90%), fatigue (77%), hypokalemia (74%), anemia (66%), and vomiting (64%). About 2% of patients have experienced hypersensitivity reactions.

For palliative treatment, the recommended does is 16 mg/m² infused over 15-20 minutes at 2-week intervals for four doses, and then, after adequate recovery from toxicity, at 4-week intervals.

For conditioning treatment, the recommended does is 100 mg/m² per day infused over 30 minutes for 2 consecutive days before stem cell transplant.

[email protected]

The Food and Drug Administration has approved a new propylene glycol–free formulation of melphalan hydrochloride as a high-dose conditioning treatment for autologous stem cell transplantation, and as a palliative therapy for multiple myeloma.

Evomela (Spectrum Pharmaceuticals) is intended to be reconstituted with normal saline at the time of intravenous administration. The solution is stable for 4 hours using Captisol, a proprietary agent containing modified cyclodextrin. It is also stable for 1 hour after reconstitution.

Extended stability without the need for propylene glycol is its major advantage over the other formulations of melphalan, a chemotherapy agent originally approved in 1964, according to a statement by Spectrum.

Evomela was approved on the basis of a phase IIa pharmacokinetic trial comprising 24 patients undergoing autologous stem cell transplantation. Evomela was bioequivalent with Alkeran, with a 10% higher maximum plasma concentration and area under the plasma concentration-time curve (Bone Marrow Transplant. 2014 Aug;49[8]:1042-5).

According to that, and other studies, adverse reactions included decreased neutrophil count (100%), decreased white blood cell count (100%), decreased lymphocyte count (98%), decreased platelet count (98%), diarrhea (93%), nausea (90%), fatigue (77%), hypokalemia (74%), anemia (66%), and vomiting (64%). About 2% of patients have experienced hypersensitivity reactions.

For palliative treatment, the recommended does is 16 mg/m² infused over 15-20 minutes at 2-week intervals for four doses, and then, after adequate recovery from toxicity, at 4-week intervals.

For conditioning treatment, the recommended does is 100 mg/m² per day infused over 30 minutes for 2 consecutive days before stem cell transplant.

[email protected]

Nonopioid therapy is the preferred approach for managing chronic pain outside of active cancer, palliative, and end-of-life care, according to a new guideline released today by the Centers for Disease Control and Prevention.

The 12 recommendations included in the guideline center around this principle and two others: using the lowest possible effective dosage when opioids are used, and exercising caution and monitoring patients closely when prescribing opioids.

Specifically, the guideline states that “clinicians should consider opioid therapy only if expected benefits for both pain and function are anticipated to outweigh risks to the patient,” and that “treatment should be combined with nonpharmacologic and nonopioid therapy, as appropriate.”

The guideline also addresses steps to take before starting or continuing opioid therapy, and drug selection, dosage, duration, follow-up, and discontinuation. Recommendations for assessing risk and addressing harms of opioid use are also included.

The CDC developed the guideline as part of the U.S. government’s urgent response to the epidemic of overdose deaths, which has been fueled by a quadrupling of the prescribing and sales of opioids since 1999, according to a CDC press statement. The guideline’s purpose is to help prevent opioid misuse and overdose.

“The CDC Guideline for Prescribing Opioids for Chronic Pain, United States, 2016 will help primary care providers ensure the safest and most effective treatment for their patients,” according to the statement. The CDC’s director, Dr. Tom Frieden, noted that “overprescribing opioids – largely for chronic pain – is a key driver of America’s drug-overdose epidemic.”

In a CDC teleconference marking the release of the guideline, Dr. Frieden said it has become increasingly clear that opioids “carry substantial risks but only uncertain benefits, especially compared with other treatments for chronic pain.

“Beginning treatment with an opioid is a momentous decision, and it should only be done with full understanding by both the clinician and the patient of the substantial risks and uncertain benefits involved,” Dr. Frieden said. He added that he knows of no other medication “that’s routinely used for a nonfatal condition [and] that kills patients so frequently.

“With more than 250 million prescriptions written each year, it’s so important that doctors understand that any one of those prescriptions could potentially end a patient’s life,” he cautioned.

A 2015 study showed that 1 of every 550 patients treated with opioids for noncancer pain – and 1 of 32 who received the highest doses (more than 200 morphine milligram equivalents per day) – died within 2.5 years of the first prescription.

Dr. Frieden noted that opioids do have a place when the potential benefits outweigh the potential harms. “But for most patients – the vast majority of patients – the risks will outweigh the benefits,” he said.

The opioid epidemic is one of the most pressing public health issues in the United States today, said Sylvia M. Burwell, secretary of the Department of Health & Human Services. A year ago, she announced an HHS initiative to reduce prescription opioid and heroin-related drug overdose, death, and dependence.

“Last year, more Americans died from drug overdoses than car crashes,” Ms. Burwell said during the teleconference, noting that families across the nation and from all walks of life have been affected.

Combating the opioid epidemic is a national priority, she said, and the CDC guideline will help in that effort.

“We believe this guideline will help health care professionals provide safer and more effective care for patients dealing with chronic pain, and we also believe it will help these providers drive down the rates of opioid use disorder, overdose, and ... death,” she said.

The American Medical Association greeted the guideline with cautious support.

“While we are largely supportive of the guidelines, we remain concerned about the evidence base informing some of the recommendations,” noted Dr. Patrice A. Harris, chair-elect of the AMA board and chair of the AMA Task Force to Reduce Opioid Abuse, in a statement.

The AMA also cited potential conflicts between the guideline and product labeling and state laws, as well as obstacles such as insurance coverage limits on nonpharmacologic treatments.

“If these guidelines help reduce the deaths resulting from opioids, they will prove to be valuable,” Dr. Harris said in the statement. “If they produce unintended consequences, we will need to mitigate them.”

Of note, the guideline stresses the right of patients with chronic pain to receive safe and effective pain management, and focuses on giving primary care providers – who account for about half of all opioid prescriptions – a road map for providing such pain management by increasing the use of effective nonopioid and nonpharmacologic therapies.

It was developed through a “rigorous scientific process using the best available scientific evidence, consulting with experts, and listening to comments from the public and partner organizations,” according to the CDC statement. The organization “is dedicated to working with partners to improve the evidence base and will refine the recommendations as new research becomes available.

”In conjunction with the release of the guideline, the CDC has provided a checklist for prescribing opioids for chronic pain, and a website with additional tools for implementing the recommendations within the guideline.

The CDC's opioid recommendations

The Centers for Disease Control and Prevention’s new opioid prescription guideline includes 12 recommendations. Here they are, modified slightly for style:

1. Nonpharmacologic therapy and nonopioid pharmacologic therapy are preferred for chronic pain. Providers should only consider adding opioid therapy if expected benefits for both pain and function are anticipated to outweigh risks.

2. Before starting opioid therapy for chronic pain, providers should establish treatment goals with all patients, including realistic goals for pain and function. Providers should not initiate opioid therapy without consideration of how therapy will be discontinued if unsuccessful. Providers should continue opioid therapy only if there is clinically meaningful improvement in pain and function.

3. Before starting and periodically during opioid therapy, providers should discuss with patients known risks and realistic benefits of opioid therapy, and patient and provider responsibilities for managing therapy.

4. When starting opioid therapy for chronic pain, providers should prescribe immediate-release opioids instead of extended-release/long-acting opioids.

5. When opioids are started, providers should prescribe the lowest effective dosage. Providers should use caution when prescribing opioids at any dosage, should implement additional precautions when increasing dosage to 50 or more morphine milligram equivalents (MME) per day, and generally should avoid increasing dosage to 90 or more MME per day.

6. When opioids are used for acute pain, providers should prescribe the lowest effective dose of immediate-release opioids. Three or fewer days often will be sufficient.

7. Providers should evaluate the benefits and harms with patients within 1-4 weeks of starting opioid therapy for chronic pain or of dose escalation. They should reevaluate continued therapy’s benefits and harms every 3 months or more frequently. If continued therapy’s benefits do not outweigh harms, providers should work with patients to reduce dosages or discontinue opioids.

8. During therapy, providers should evaluate risk factors for opioid-related harm. Providers should incorporate into the management plan strategies to mitigate risk, including considering offering naloxone when factors that increase risk for opioid overdose – such as history of overdose, history of substance use disorder, or higher opioid dosage (50 MME or more) – are present.

9. Providers should review the patient’s history of controlled substance prescriptions using state prescription drug monitoring program (PDMP) data to determine whether the patient is receiving high opioid dosages or dangerous combinations that put him or her at high risk for overdose. Providers should review PDMP data when starting opioid therapy for chronic pain and periodically during opioid therapy for chronic pain, ranging from every prescription to every 3 months.

10. When prescribing opioids for chronic pain, providers should use urine drug testing before starting opioid therapy and consider urine drug testing at least annually to assess for prescribed medications, as well as other controlled prescription drugs and illicit drugs.

11. Providers should avoid concurrent prescriptions of opioid pain medication and benzodiazepines whenever possible.

12. Providers should offer or arrange evidence-based treatment (usually medication-assisted treatment with buprenorphine or methadone in combination with behavioral therapies) for patients with opioid use disorder.

M. Alexander Otto contributed to this article.

[email protected]

Nonopioid therapy is the preferred approach for managing chronic pain outside of active cancer, palliative, and end-of-life care, according to a new guideline released today by the Centers for Disease Control and Prevention.

The 12 recommendations included in the guideline center around this principle and two others: using the lowest possible effective dosage when opioids are used, and exercising caution and monitoring patients closely when prescribing opioids.

Specifically, the guideline states that “clinicians should consider opioid therapy only if expected benefits for both pain and function are anticipated to outweigh risks to the patient,” and that “treatment should be combined with nonpharmacologic and nonopioid therapy, as appropriate.”

The guideline also addresses steps to take before starting or continuing opioid therapy, and drug selection, dosage, duration, follow-up, and discontinuation. Recommendations for assessing risk and addressing harms of opioid use are also included.

The CDC developed the guideline as part of the U.S. government’s urgent response to the epidemic of overdose deaths, which has been fueled by a quadrupling of the prescribing and sales of opioids since 1999, according to a CDC press statement. The guideline’s purpose is to help prevent opioid misuse and overdose.

“The CDC Guideline for Prescribing Opioids for Chronic Pain, United States, 2016 will help primary care providers ensure the safest and most effective treatment for their patients,” according to the statement. The CDC’s director, Dr. Tom Frieden, noted that “overprescribing opioids – largely for chronic pain – is a key driver of America’s drug-overdose epidemic.”

In a CDC teleconference marking the release of the guideline, Dr. Frieden said it has become increasingly clear that opioids “carry substantial risks but only uncertain benefits, especially compared with other treatments for chronic pain.

“Beginning treatment with an opioid is a momentous decision, and it should only be done with full understanding by both the clinician and the patient of the substantial risks and uncertain benefits involved,” Dr. Frieden said. He added that he knows of no other medication “that’s routinely used for a nonfatal condition [and] that kills patients so frequently.

“With more than 250 million prescriptions written each year, it’s so important that doctors understand that any one of those prescriptions could potentially end a patient’s life,” he cautioned.

A 2015 study showed that 1 of every 550 patients treated with opioids for noncancer pain – and 1 of 32 who received the highest doses (more than 200 morphine milligram equivalents per day) – died within 2.5 years of the first prescription.

Dr. Frieden noted that opioids do have a place when the potential benefits outweigh the potential harms. “But for most patients – the vast majority of patients – the risks will outweigh the benefits,” he said.

The opioid epidemic is one of the most pressing public health issues in the United States today, said Sylvia M. Burwell, secretary of the Department of Health & Human Services. A year ago, she announced an HHS initiative to reduce prescription opioid and heroin-related drug overdose, death, and dependence.

“Last year, more Americans died from drug overdoses than car crashes,” Ms. Burwell said during the teleconference, noting that families across the nation and from all walks of life have been affected.

Combating the opioid epidemic is a national priority, she said, and the CDC guideline will help in that effort.

“We believe this guideline will help health care professionals provide safer and more effective care for patients dealing with chronic pain, and we also believe it will help these providers drive down the rates of opioid use disorder, overdose, and ... death,” she said.

The American Medical Association greeted the guideline with cautious support.

“While we are largely supportive of the guidelines, we remain concerned about the evidence base informing some of the recommendations,” noted Dr. Patrice A. Harris, chair-elect of the AMA board and chair of the AMA Task Force to Reduce Opioid Abuse, in a statement.

The AMA also cited potential conflicts between the guideline and product labeling and state laws, as well as obstacles such as insurance coverage limits on nonpharmacologic treatments.

“If these guidelines help reduce the deaths resulting from opioids, they will prove to be valuable,” Dr. Harris said in the statement. “If they produce unintended consequences, we will need to mitigate them.”

Of note, the guideline stresses the right of patients with chronic pain to receive safe and effective pain management, and focuses on giving primary care providers – who account for about half of all opioid prescriptions – a road map for providing such pain management by increasing the use of effective nonopioid and nonpharmacologic therapies.

It was developed through a “rigorous scientific process using the best available scientific evidence, consulting with experts, and listening to comments from the public and partner organizations,” according to the CDC statement. The organization “is dedicated to working with partners to improve the evidence base and will refine the recommendations as new research becomes available.

”In conjunction with the release of the guideline, the CDC has provided a checklist for prescribing opioids for chronic pain, and a website with additional tools for implementing the recommendations within the guideline.

The CDC's opioid recommendations

The Centers for Disease Control and Prevention’s new opioid prescription guideline includes 12 recommendations. Here they are, modified slightly for style:

1. Nonpharmacologic therapy and nonopioid pharmacologic therapy are preferred for chronic pain. Providers should only consider adding opioid therapy if expected benefits for both pain and function are anticipated to outweigh risks.

2. Before starting opioid therapy for chronic pain, providers should establish treatment goals with all patients, including realistic goals for pain and function. Providers should not initiate opioid therapy without consideration of how therapy will be discontinued if unsuccessful. Providers should continue opioid therapy only if there is clinically meaningful improvement in pain and function.

3. Before starting and periodically during opioid therapy, providers should discuss with patients known risks and realistic benefits of opioid therapy, and patient and provider responsibilities for managing therapy.

4. When starting opioid therapy for chronic pain, providers should prescribe immediate-release opioids instead of extended-release/long-acting opioids.

5. When opioids are started, providers should prescribe the lowest effective dosage. Providers should use caution when prescribing opioids at any dosage, should implement additional precautions when increasing dosage to 50 or more morphine milligram equivalents (MME) per day, and generally should avoid increasing dosage to 90 or more MME per day.

6. When opioids are used for acute pain, providers should prescribe the lowest effective dose of immediate-release opioids. Three or fewer days often will be sufficient.

7. Providers should evaluate the benefits and harms with patients within 1-4 weeks of starting opioid therapy for chronic pain or of dose escalation. They should reevaluate continued therapy’s benefits and harms every 3 months or more frequently. If continued therapy’s benefits do not outweigh harms, providers should work with patients to reduce dosages or discontinue opioids.

8. During therapy, providers should evaluate risk factors for opioid-related harm. Providers should incorporate into the management plan strategies to mitigate risk, including considering offering naloxone when factors that increase risk for opioid overdose – such as history of overdose, history of substance use disorder, or higher opioid dosage (50 MME or more) – are present.

9. Providers should review the patient’s history of controlled substance prescriptions using state prescription drug monitoring program (PDMP) data to determine whether the patient is receiving high opioid dosages or dangerous combinations that put him or her at high risk for overdose. Providers should review PDMP data when starting opioid therapy for chronic pain and periodically during opioid therapy for chronic pain, ranging from every prescription to every 3 months.

10. When prescribing opioids for chronic pain, providers should use urine drug testing before starting opioid therapy and consider urine drug testing at least annually to assess for prescribed medications, as well as other controlled prescription drugs and illicit drugs.

11. Providers should avoid concurrent prescriptions of opioid pain medication and benzodiazepines whenever possible.

12. Providers should offer or arrange evidence-based treatment (usually medication-assisted treatment with buprenorphine or methadone in combination with behavioral therapies) for patients with opioid use disorder.

M. Alexander Otto contributed to this article.

[email protected]

Nonopioid therapy is the preferred approach for managing chronic pain outside of active cancer, palliative, and end-of-life care, according to a new guideline released today by the Centers for Disease Control and Prevention.

The 12 recommendations included in the guideline center around this principle and two others: using the lowest possible effective dosage when opioids are used, and exercising caution and monitoring patients closely when prescribing opioids.

Specifically, the guideline states that “clinicians should consider opioid therapy only if expected benefits for both pain and function are anticipated to outweigh risks to the patient,” and that “treatment should be combined with nonpharmacologic and nonopioid therapy, as appropriate.”

The guideline also addresses steps to take before starting or continuing opioid therapy, and drug selection, dosage, duration, follow-up, and discontinuation. Recommendations for assessing risk and addressing harms of opioid use are also included.

The CDC developed the guideline as part of the U.S. government’s urgent response to the epidemic of overdose deaths, which has been fueled by a quadrupling of the prescribing and sales of opioids since 1999, according to a CDC press statement. The guideline’s purpose is to help prevent opioid misuse and overdose.

“The CDC Guideline for Prescribing Opioids for Chronic Pain, United States, 2016 will help primary care providers ensure the safest and most effective treatment for their patients,” according to the statement. The CDC’s director, Dr. Tom Frieden, noted that “overprescribing opioids – largely for chronic pain – is a key driver of America’s drug-overdose epidemic.”

In a CDC teleconference marking the release of the guideline, Dr. Frieden said it has become increasingly clear that opioids “carry substantial risks but only uncertain benefits, especially compared with other treatments for chronic pain.

“Beginning treatment with an opioid is a momentous decision, and it should only be done with full understanding by both the clinician and the patient of the substantial risks and uncertain benefits involved,” Dr. Frieden said. He added that he knows of no other medication “that’s routinely used for a nonfatal condition [and] that kills patients so frequently.

“With more than 250 million prescriptions written each year, it’s so important that doctors understand that any one of those prescriptions could potentially end a patient’s life,” he cautioned.

A 2015 study showed that 1 of every 550 patients treated with opioids for noncancer pain – and 1 of 32 who received the highest doses (more than 200 morphine milligram equivalents per day) – died within 2.5 years of the first prescription.

Dr. Frieden noted that opioids do have a place when the potential benefits outweigh the potential harms. “But for most patients – the vast majority of patients – the risks will outweigh the benefits,” he said.

The opioid epidemic is one of the most pressing public health issues in the United States today, said Sylvia M. Burwell, secretary of the Department of Health & Human Services. A year ago, she announced an HHS initiative to reduce prescription opioid and heroin-related drug overdose, death, and dependence.

“Last year, more Americans died from drug overdoses than car crashes,” Ms. Burwell said during the teleconference, noting that families across the nation and from all walks of life have been affected.

Combating the opioid epidemic is a national priority, she said, and the CDC guideline will help in that effort.

“We believe this guideline will help health care professionals provide safer and more effective care for patients dealing with chronic pain, and we also believe it will help these providers drive down the rates of opioid use disorder, overdose, and ... death,” she said.

The American Medical Association greeted the guideline with cautious support.

“While we are largely supportive of the guidelines, we remain concerned about the evidence base informing some of the recommendations,” noted Dr. Patrice A. Harris, chair-elect of the AMA board and chair of the AMA Task Force to Reduce Opioid Abuse, in a statement.

The AMA also cited potential conflicts between the guideline and product labeling and state laws, as well as obstacles such as insurance coverage limits on nonpharmacologic treatments.

“If these guidelines help reduce the deaths resulting from opioids, they will prove to be valuable,” Dr. Harris said in the statement. “If they produce unintended consequences, we will need to mitigate them.”

Of note, the guideline stresses the right of patients with chronic pain to receive safe and effective pain management, and focuses on giving primary care providers – who account for about half of all opioid prescriptions – a road map for providing such pain management by increasing the use of effective nonopioid and nonpharmacologic therapies.

It was developed through a “rigorous scientific process using the best available scientific evidence, consulting with experts, and listening to comments from the public and partner organizations,” according to the CDC statement. The organization “is dedicated to working with partners to improve the evidence base and will refine the recommendations as new research becomes available.

”In conjunction with the release of the guideline, the CDC has provided a checklist for prescribing opioids for chronic pain, and a website with additional tools for implementing the recommendations within the guideline.

The CDC's opioid recommendations

The Centers for Disease Control and Prevention’s new opioid prescription guideline includes 12 recommendations. Here they are, modified slightly for style:

1. Nonpharmacologic therapy and nonopioid pharmacologic therapy are preferred for chronic pain. Providers should only consider adding opioid therapy if expected benefits for both pain and function are anticipated to outweigh risks.

2. Before starting opioid therapy for chronic pain, providers should establish treatment goals with all patients, including realistic goals for pain and function. Providers should not initiate opioid therapy without consideration of how therapy will be discontinued if unsuccessful. Providers should continue opioid therapy only if there is clinically meaningful improvement in pain and function.

3. Before starting and periodically during opioid therapy, providers should discuss with patients known risks and realistic benefits of opioid therapy, and patient and provider responsibilities for managing therapy.

4. When starting opioid therapy for chronic pain, providers should prescribe immediate-release opioids instead of extended-release/long-acting opioids.

5. When opioids are started, providers should prescribe the lowest effective dosage. Providers should use caution when prescribing opioids at any dosage, should implement additional precautions when increasing dosage to 50 or more morphine milligram equivalents (MME) per day, and generally should avoid increasing dosage to 90 or more MME per day.

6. When opioids are used for acute pain, providers should prescribe the lowest effective dose of immediate-release opioids. Three or fewer days often will be sufficient.

7. Providers should evaluate the benefits and harms with patients within 1-4 weeks of starting opioid therapy for chronic pain or of dose escalation. They should reevaluate continued therapy’s benefits and harms every 3 months or more frequently. If continued therapy’s benefits do not outweigh harms, providers should work with patients to reduce dosages or discontinue opioids.

8. During therapy, providers should evaluate risk factors for opioid-related harm. Providers should incorporate into the management plan strategies to mitigate risk, including considering offering naloxone when factors that increase risk for opioid overdose – such as history of overdose, history of substance use disorder, or higher opioid dosage (50 MME or more) – are present.

9. Providers should review the patient’s history of controlled substance prescriptions using state prescription drug monitoring program (PDMP) data to determine whether the patient is receiving high opioid dosages or dangerous combinations that put him or her at high risk for overdose. Providers should review PDMP data when starting opioid therapy for chronic pain and periodically during opioid therapy for chronic pain, ranging from every prescription to every 3 months.

10. When prescribing opioids for chronic pain, providers should use urine drug testing before starting opioid therapy and consider urine drug testing at least annually to assess for prescribed medications, as well as other controlled prescription drugs and illicit drugs.

11. Providers should avoid concurrent prescriptions of opioid pain medication and benzodiazepines whenever possible.

12. Providers should offer or arrange evidence-based treatment (usually medication-assisted treatment with buprenorphine or methadone in combination with behavioral therapies) for patients with opioid use disorder.

M. Alexander Otto contributed to this article.

[email protected]

I hear it at least 6 times a month: “How can I get involved? How do I get on an AAD committee?” The quick answer is to pick a committee where you have some expertise, and get others (including other organizations where you have done committee work) to write supporting letters to the American Academy of Dermatology president-elect (this year Henry Lim). In October, the president-elect fills the empty committee spots, and whoever has the most expertise and support usually gets the spot. The support of the existing committee chair is most helpful as well.

The focus of the question above, however, is too limited. AAD committee work is important, but there are many other venues in which you can develop your skills and make an impact. The best spot to start is probably your local and state dermatology or county and state medical societies. They are always looking for new enthusiastic members. You will learn about parliamentary order and how to write and defend a resolution, and you may advance quickly – perhaps right up to a state leadership position or the state American Medical Association delegation. In the state and local societies, you will also learn about challenges practitioners face outside of dermatology. The skills you will develop are useful in any physician organization, including the AAD. The state medical societies are always interested in members who will travel to testify at the state legislature. This can be a valuable experience as well.

There are many state dermatology societies that need you for advocacy, service, and leadership. These are superb places to learn leadership skills and state advocacy.

The AAD “sister” societies – including the American Society for Dermatologic Surgery (ASDS), the American College of Mohs Surgery (ACMS), the American Society for Mohs Surgery ASMS, and the Women’s Dermatologic Society (WDS) – also have multiple committees, boards, and officer positions, which do advocacy and develop policy, and are arenas in which you can learn and contribute.

You should attend a meeting of the advisory board to the AAD. This is full-throttle democracy. State and local dermatology organizations are allowed to send delegates and alternate delegates to the advisory board, and these spots often go empty. The advisory board’s resolutions go directly to the AAD board of directors to be acted on. In addition, the advisory board also appoints one of the directors to the AAD board of directors. This opportunity is underappreciated.

Involvement in SkinPAC would be most welcome (and earns you an asterisk by your name on the committee nomination roster!). The importance of legislative efforts cannot be overemphasized. Attending the legislative conference should be high on your list of things to do when you ask how to get involved.

You should also consider community involvement, regardless of your other activities. This will help your larger community in ways you could never imagine. I have served on the local health department for many years and find it rewarding and interesting. They are always keen to have more medical doctors on the board.

You can get appointed by writing the local officials (the county judge executive or mayor of the city) and expressing an interest, or to the medical director of the health department.

State medical boards are a large time commitment and a lot of work, but can be most important. We need more dermatologists on state medical boards since we are a unique specialty, and other physicians have no idea what you do in your office. Medical boards often make policy, and can have a huge impact. These positions are competitive in larger states and may require some political support from the governor in order for you to be appointed.

Charitable work is also important. Most of us volunteer to do skin cancer screenings, but there are also opportunities to provide dermatology services overseas. Dermatologists are rare in most of the world, and you will find the service most gratifying. There are opportunities closer to home in the free clinics almost anywhere.

Engagement and service by as many as possible is crucial for a specialty as small as ours, and your efforts will be noted and appreciated. There are thousands of ways to get involved, and I encourage you to get in there and do it.

Dr. Coldiron is a past president of the American Academy of Dermatology. He is currently in private practice, but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics.

I hear it at least 6 times a month: “How can I get involved? How do I get on an AAD committee?” The quick answer is to pick a committee where you have some expertise, and get others (including other organizations where you have done committee work) to write supporting letters to the American Academy of Dermatology president-elect (this year Henry Lim). In October, the president-elect fills the empty committee spots, and whoever has the most expertise and support usually gets the spot. The support of the existing committee chair is most helpful as well.

The focus of the question above, however, is too limited. AAD committee work is important, but there are many other venues in which you can develop your skills and make an impact. The best spot to start is probably your local and state dermatology or county and state medical societies. They are always looking for new enthusiastic members. You will learn about parliamentary order and how to write and defend a resolution, and you may advance quickly – perhaps right up to a state leadership position or the state American Medical Association delegation. In the state and local societies, you will also learn about challenges practitioners face outside of dermatology. The skills you will develop are useful in any physician organization, including the AAD. The state medical societies are always interested in members who will travel to testify at the state legislature. This can be a valuable experience as well.

There are many state dermatology societies that need you for advocacy, service, and leadership. These are superb places to learn leadership skills and state advocacy.

The AAD “sister” societies – including the American Society for Dermatologic Surgery (ASDS), the American College of Mohs Surgery (ACMS), the American Society for Mohs Surgery ASMS, and the Women’s Dermatologic Society (WDS) – also have multiple committees, boards, and officer positions, which do advocacy and develop policy, and are arenas in which you can learn and contribute.

You should attend a meeting of the advisory board to the AAD. This is full-throttle democracy. State and local dermatology organizations are allowed to send delegates and alternate delegates to the advisory board, and these spots often go empty. The advisory board’s resolutions go directly to the AAD board of directors to be acted on. In addition, the advisory board also appoints one of the directors to the AAD board of directors. This opportunity is underappreciated.

Involvement in SkinPAC would be most welcome (and earns you an asterisk by your name on the committee nomination roster!). The importance of legislative efforts cannot be overemphasized. Attending the legislative conference should be high on your list of things to do when you ask how to get involved.

You should also consider community involvement, regardless of your other activities. This will help your larger community in ways you could never imagine. I have served on the local health department for many years and find it rewarding and interesting. They are always keen to have more medical doctors on the board.

You can get appointed by writing the local officials (the county judge executive or mayor of the city) and expressing an interest, or to the medical director of the health department.

State medical boards are a large time commitment and a lot of work, but can be most important. We need more dermatologists on state medical boards since we are a unique specialty, and other physicians have no idea what you do in your office. Medical boards often make policy, and can have a huge impact. These positions are competitive in larger states and may require some political support from the governor in order for you to be appointed.

Charitable work is also important. Most of us volunteer to do skin cancer screenings, but there are also opportunities to provide dermatology services overseas. Dermatologists are rare in most of the world, and you will find the service most gratifying. There are opportunities closer to home in the free clinics almost anywhere.

Engagement and service by as many as possible is crucial for a specialty as small as ours, and your efforts will be noted and appreciated. There are thousands of ways to get involved, and I encourage you to get in there and do it.

Dr. Coldiron is a past president of the American Academy of Dermatology. He is currently in private practice, but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics.

I hear it at least 6 times a month: “How can I get involved? How do I get on an AAD committee?” The quick answer is to pick a committee where you have some expertise, and get others (including other organizations where you have done committee work) to write supporting letters to the American Academy of Dermatology president-elect (this year Henry Lim). In October, the president-elect fills the empty committee spots, and whoever has the most expertise and support usually gets the spot. The support of the existing committee chair is most helpful as well.

The focus of the question above, however, is too limited. AAD committee work is important, but there are many other venues in which you can develop your skills and make an impact. The best spot to start is probably your local and state dermatology or county and state medical societies. They are always looking for new enthusiastic members. You will learn about parliamentary order and how to write and defend a resolution, and you may advance quickly – perhaps right up to a state leadership position or the state American Medical Association delegation. In the state and local societies, you will also learn about challenges practitioners face outside of dermatology. The skills you will develop are useful in any physician organization, including the AAD. The state medical societies are always interested in members who will travel to testify at the state legislature. This can be a valuable experience as well.

There are many state dermatology societies that need you for advocacy, service, and leadership. These are superb places to learn leadership skills and state advocacy.

The AAD “sister” societies – including the American Society for Dermatologic Surgery (ASDS), the American College of Mohs Surgery (ACMS), the American Society for Mohs Surgery ASMS, and the Women’s Dermatologic Society (WDS) – also have multiple committees, boards, and officer positions, which do advocacy and develop policy, and are arenas in which you can learn and contribute.

You should attend a meeting of the advisory board to the AAD. This is full-throttle democracy. State and local dermatology organizations are allowed to send delegates and alternate delegates to the advisory board, and these spots often go empty. The advisory board’s resolutions go directly to the AAD board of directors to be acted on. In addition, the advisory board also appoints one of the directors to the AAD board of directors. This opportunity is underappreciated.

Involvement in SkinPAC would be most welcome (and earns you an asterisk by your name on the committee nomination roster!). The importance of legislative efforts cannot be overemphasized. Attending the legislative conference should be high on your list of things to do when you ask how to get involved.

You should also consider community involvement, regardless of your other activities. This will help your larger community in ways you could never imagine. I have served on the local health department for many years and find it rewarding and interesting. They are always keen to have more medical doctors on the board.

You can get appointed by writing the local officials (the county judge executive or mayor of the city) and expressing an interest, or to the medical director of the health department.

State medical boards are a large time commitment and a lot of work, but can be most important. We need more dermatologists on state medical boards since we are a unique specialty, and other physicians have no idea what you do in your office. Medical boards often make policy, and can have a huge impact. These positions are competitive in larger states and may require some political support from the governor in order for you to be appointed.

Charitable work is also important. Most of us volunteer to do skin cancer screenings, but there are also opportunities to provide dermatology services overseas. Dermatologists are rare in most of the world, and you will find the service most gratifying. There are opportunities closer to home in the free clinics almost anywhere.

Engagement and service by as many as possible is crucial for a specialty as small as ours, and your efforts will be noted and appreciated. There are thousands of ways to get involved, and I encourage you to get in there and do it.

Dr. Coldiron is a past president of the American Academy of Dermatology. He is currently in private practice, but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics.

An increased rate of adverse events, including deaths, have been reported in clinical trials with idelalisib (Zydelig) in combination with other cancer medicines, the U.S. Food and Drug Administration announced.

Gilead Sciences, Inc. has confirmed that they are stopping six clinical trials in patients with chronic lymphocytic leukemia, small lymphocytic lymphoma and indolent non-Hodgkin lymphomas. The FDA is reviewing the findings of the clinical trials and will communicate new information as necessary, according to the FDA press release.

Idelalisib is not approved for previously untreated chronic lymphocytic leukemia. It is approved by the FDA for the treatment of:

• Relapsed chronic lymphocytic leukemia, in combination with rituximab, in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities.

• Relapsed follicular B-cell non-Hodgkin lymphoma in patients who have received at least two prior systemic therapies.

• Relapsed small lymphocytic lymphoma in patients who have received at least two prior systemic therapies.

Adverse events involving idelalisib should be reported to the FDA MedWatch program, the release advised.

[email protected]

On Twitter @maryjodales

An increased rate of adverse events, including deaths, have been reported in clinical trials with idelalisib (Zydelig) in combination with other cancer medicines, the U.S. Food and Drug Administration announced.

Gilead Sciences, Inc. has confirmed that they are stopping six clinical trials in patients with chronic lymphocytic leukemia, small lymphocytic lymphoma and indolent non-Hodgkin lymphomas. The FDA is reviewing the findings of the clinical trials and will communicate new information as necessary, according to the FDA press release.

Idelalisib is not approved for previously untreated chronic lymphocytic leukemia. It is approved by the FDA for the treatment of:

• Relapsed chronic lymphocytic leukemia, in combination with rituximab, in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities.

• Relapsed follicular B-cell non-Hodgkin lymphoma in patients who have received at least two prior systemic therapies.

• Relapsed small lymphocytic lymphoma in patients who have received at least two prior systemic therapies.

Adverse events involving idelalisib should be reported to the FDA MedWatch program, the release advised.

[email protected]

On Twitter @maryjodales

An increased rate of adverse events, including deaths, have been reported in clinical trials with idelalisib (Zydelig) in combination with other cancer medicines, the U.S. Food and Drug Administration announced.

Gilead Sciences, Inc. has confirmed that they are stopping six clinical trials in patients with chronic lymphocytic leukemia, small lymphocytic lymphoma and indolent non-Hodgkin lymphomas. The FDA is reviewing the findings of the clinical trials and will communicate new information as necessary, according to the FDA press release.

Idelalisib is not approved for previously untreated chronic lymphocytic leukemia. It is approved by the FDA for the treatment of:

• Relapsed chronic lymphocytic leukemia, in combination with rituximab, in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities.

• Relapsed follicular B-cell non-Hodgkin lymphoma in patients who have received at least two prior systemic therapies.

• Relapsed small lymphocytic lymphoma in patients who have received at least two prior systemic therapies.

Adverse events involving idelalisib should be reported to the FDA MedWatch program, the release advised.

[email protected]

On Twitter @maryjodales

I’m happier doing patient messages these days. That’s because of a little feature that we turned on in EPIC, our electronic medical record. The change doesn’t make me any faster or smarter. It doesn’t make me any more money. It merely adds a sprinkle of meaning to the work I do, and that has made all the difference.

In contrast to the usually glamorous portrayal of physicians’ work, most of our days are mundane. On a typical clinic day I’ll get up to a dozen requests from patients asking for something. Usually it’s just a refill, but several are from patients asking for a earlier appointment, when there are none. Or asking for a stronger treatment, when there aren’t any. Most of these requests are from patients who do not have interesting diagnoses or require sophisticated treatments. They are the itchy, and they remain itchy despite my advice. After a long day of seeing patients, the long list of messages that requires action feels endless, burdensome. Optimizing extenders has made me more efficient, but the work that remains isn’t fulfilling. A subtle change in our EMR has helped, though.

What is different? Our EPIC now includes a photo of each patient. That’s it. Ostensibly, having a photo is a security feature: it allows us to positively identify a patient, thereby reducing the risk that we treat an imposter posing as that patient (a small but real problem with drug seekers).

Why might this matter for physician satisfaction? Because seeing a patient photo brings an actual person to the top of mind. This changes our emotional connection to the work: how we interpret work is all that matters when it comes to job satisfaction. This is why volunteer work is so rewarding, despite having no monetary incentive, and why highly compensated professions, like those of many Wall Street traders, can ultimately fail to be fulfilling.

Tonight, long after the sun has set, I’m still working through messages. The next one, however, is not from any patient with nummular eczema. I see it’s from Mrs. Morales (not her real name), a sweet older woman with a warm smile and rich accent. She teaches water aerobics and she spent 5 minutes describing a typical Puerto Rican dinner (lots of stews) during her last appointment with me. Seeing her smiling face in the top left corner of the chart reminds me that the work I’m doing is for someone I know, someone I care for.

Radiologists have actually studied this phenomenon. Like much of medicine, radiology can be tedious. Researchers devised a simple test to see if making radiology work more human could improve not only the experience for, but also the effectiveness of, doctors. With patients’ consent, they took photos of 300 participants before their films were sent for reading. Radiologists who saw a patient’s photo along with their radiographic studies reported feeling more empathy for their patients. They also reported reading cases with photos more meticulously than those cases without photos. But that’s not all. When the radiologists were later shown the same films but without the patient photos, the doctors were less likely to notice incidental findings in the radiographs. The authors concluded that seeing patient photos made radiologists both more effective and more empathic (ScienceDaily 2008 Dec 14).

So consider adding photos of your patients to your EMR. Then remember to take a second or two to look at them before engaging in the task to be done. You, and your patients, will be better off because of it.

Dr. Benabio is a partner physician in the department of dermatology of the Southern California Permanente Group in San Diego, and a volunteer clinical assistant professor at the University of California, San Diego. He is @dermdoc on Twitter. He has no conflicts related to the topic of this column.

I’m happier doing patient messages these days. That’s because of a little feature that we turned on in EPIC, our electronic medical record. The change doesn’t make me any faster or smarter. It doesn’t make me any more money. It merely adds a sprinkle of meaning to the work I do, and that has made all the difference.

In contrast to the usually glamorous portrayal of physicians’ work, most of our days are mundane. On a typical clinic day I’ll get up to a dozen requests from patients asking for something. Usually it’s just a refill, but several are from patients asking for a earlier appointment, when there are none. Or asking for a stronger treatment, when there aren’t any. Most of these requests are from patients who do not have interesting diagnoses or require sophisticated treatments. They are the itchy, and they remain itchy despite my advice. After a long day of seeing patients, the long list of messages that requires action feels endless, burdensome. Optimizing extenders has made me more efficient, but the work that remains isn’t fulfilling. A subtle change in our EMR has helped, though.

What is different? Our EPIC now includes a photo of each patient. That’s it. Ostensibly, having a photo is a security feature: it allows us to positively identify a patient, thereby reducing the risk that we treat an imposter posing as that patient (a small but real problem with drug seekers).

Why might this matter for physician satisfaction? Because seeing a patient photo brings an actual person to the top of mind. This changes our emotional connection to the work: how we interpret work is all that matters when it comes to job satisfaction. This is why volunteer work is so rewarding, despite having no monetary incentive, and why highly compensated professions, like those of many Wall Street traders, can ultimately fail to be fulfilling.

Tonight, long after the sun has set, I’m still working through messages. The next one, however, is not from any patient with nummular eczema. I see it’s from Mrs. Morales (not her real name), a sweet older woman with a warm smile and rich accent. She teaches water aerobics and she spent 5 minutes describing a typical Puerto Rican dinner (lots of stews) during her last appointment with me. Seeing her smiling face in the top left corner of the chart reminds me that the work I’m doing is for someone I know, someone I care for.

Radiologists have actually studied this phenomenon. Like much of medicine, radiology can be tedious. Researchers devised a simple test to see if making radiology work more human could improve not only the experience for, but also the effectiveness of, doctors. With patients’ consent, they took photos of 300 participants before their films were sent for reading. Radiologists who saw a patient’s photo along with their radiographic studies reported feeling more empathy for their patients. They also reported reading cases with photos more meticulously than those cases without photos. But that’s not all. When the radiologists were later shown the same films but without the patient photos, the doctors were less likely to notice incidental findings in the radiographs. The authors concluded that seeing patient photos made radiologists both more effective and more empathic (ScienceDaily 2008 Dec 14).

So consider adding photos of your patients to your EMR. Then remember to take a second or two to look at them before engaging in the task to be done. You, and your patients, will be better off because of it.

Dr. Benabio is a partner physician in the department of dermatology of the Southern California Permanente Group in San Diego, and a volunteer clinical assistant professor at the University of California, San Diego. He is @dermdoc on Twitter. He has no conflicts related to the topic of this column.

I’m happier doing patient messages these days. That’s because of a little feature that we turned on in EPIC, our electronic medical record. The change doesn’t make me any faster or smarter. It doesn’t make me any more money. It merely adds a sprinkle of meaning to the work I do, and that has made all the difference.

In contrast to the usually glamorous portrayal of physicians’ work, most of our days are mundane. On a typical clinic day I’ll get up to a dozen requests from patients asking for something. Usually it’s just a refill, but several are from patients asking for a earlier appointment, when there are none. Or asking for a stronger treatment, when there aren’t any. Most of these requests are from patients who do not have interesting diagnoses or require sophisticated treatments. They are the itchy, and they remain itchy despite my advice. After a long day of seeing patients, the long list of messages that requires action feels endless, burdensome. Optimizing extenders has made me more efficient, but the work that remains isn’t fulfilling. A subtle change in our EMR has helped, though.

What is different? Our EPIC now includes a photo of each patient. That’s it. Ostensibly, having a photo is a security feature: it allows us to positively identify a patient, thereby reducing the risk that we treat an imposter posing as that patient (a small but real problem with drug seekers).

Why might this matter for physician satisfaction? Because seeing a patient photo brings an actual person to the top of mind. This changes our emotional connection to the work: how we interpret work is all that matters when it comes to job satisfaction. This is why volunteer work is so rewarding, despite having no monetary incentive, and why highly compensated professions, like those of many Wall Street traders, can ultimately fail to be fulfilling.

Tonight, long after the sun has set, I’m still working through messages. The next one, however, is not from any patient with nummular eczema. I see it’s from Mrs. Morales (not her real name), a sweet older woman with a warm smile and rich accent. She teaches water aerobics and she spent 5 minutes describing a typical Puerto Rican dinner (lots of stews) during her last appointment with me. Seeing her smiling face in the top left corner of the chart reminds me that the work I’m doing is for someone I know, someone I care for.

Radiologists have actually studied this phenomenon. Like much of medicine, radiology can be tedious. Researchers devised a simple test to see if making radiology work more human could improve not only the experience for, but also the effectiveness of, doctors. With patients’ consent, they took photos of 300 participants before their films were sent for reading. Radiologists who saw a patient’s photo along with their radiographic studies reported feeling more empathy for their patients. They also reported reading cases with photos more meticulously than those cases without photos. But that’s not all. When the radiologists were later shown the same films but without the patient photos, the doctors were less likely to notice incidental findings in the radiographs. The authors concluded that seeing patient photos made radiologists both more effective and more empathic (ScienceDaily 2008 Dec 14).

So consider adding photos of your patients to your EMR. Then remember to take a second or two to look at them before engaging in the task to be done. You, and your patients, will be better off because of it.

Dr. Benabio is a partner physician in the department of dermatology of the Southern California Permanente Group in San Diego, and a volunteer clinical assistant professor at the University of California, San Diego. He is @dermdoc on Twitter. He has no conflicts related to the topic of this column.

Micrograph showing B-ALL

An RNA binding protein promotes the development of MLL-rearranged B-cell acute lymphoblastic leukemia (B-ALL), according to research published in The Journal of Clinical Investigation.

Researchers found an overabundance of the protein, IGF2BP3, in MLL-rearranged B-ALL.

They also identified genes that are directly regulated by IFG2BP3, and many of them turned out to be oncogenes that have already been implicated in cancers.

The overall effect of IFG2BP3 in MLL-rearranged B-ALL is to promote the proliferation of B cells by shifting the expression of a large number of genes, explained study author Jeremy Sanford, PhD, of the University of California Santa Cruz.

“This protein, IFG2BP3, has been correlated with many types of malignancies and with the worst prognoses,” he noted. “What is exciting about this study is that it goes beyond correlation and shows causation, because we demonstrated, for the first time, that aberrant expression of this protein is sufficient to induce pathology.”

This research began in the lab of Dinesh Rao, PhD, an assistant professor at the University of California Los Angeles who was studying MLL-rearranged B-ALL.

After researchers in Dr Rao’s lab identified IGF2BP3 as one of the top dysregulated genes in this malignancy, they began working with Dr Sanford’s lab to figure out which genes were being directly regulated by IGF2BP3.

Dr Sanford’s lab was among the few using individual nucleotide resolution crosslinking immunoprecipitation (iCLIP), a technique that can capture RNA molecules bound to a particular protein.

iCLIP enabled the researchers to identify IGF2BP3 binding sites in several hundred RNA transcripts in 2 B-ALL cell lines.

The work also revealed that IGF2BP3 enhanced the expression of MYC and other oncogenes in hematopoietic stem cells.

In experiments with mice, the researchers found that overexpression of IGF2BP3 in the bone marrow leads to proliferation of hematopoietic stem cells and B-cell progenitors, reproducing some features of MLL-rearranged B-ALL.

“Understanding its mechanism of action is important for thinking about therapeutics that might interfere with the action of this protein in disease,” Dr Sanford said.

“One possibility is an RNA-based therapeutic that could sequester the protein and keep it from binding to RNA transcripts. That would be a way to influence the expression of many genes involved in the proliferation of cancer cells.”

Micrograph showing B-ALL

An RNA binding protein promotes the development of MLL-rearranged B-cell acute lymphoblastic leukemia (B-ALL), according to research published in The Journal of Clinical Investigation.

Researchers found an overabundance of the protein, IGF2BP3, in MLL-rearranged B-ALL.

They also identified genes that are directly regulated by IFG2BP3, and many of them turned out to be oncogenes that have already been implicated in cancers.

The overall effect of IFG2BP3 in MLL-rearranged B-ALL is to promote the proliferation of B cells by shifting the expression of a large number of genes, explained study author Jeremy Sanford, PhD, of the University of California Santa Cruz.

“This protein, IFG2BP3, has been correlated with many types of malignancies and with the worst prognoses,” he noted. “What is exciting about this study is that it goes beyond correlation and shows causation, because we demonstrated, for the first time, that aberrant expression of this protein is sufficient to induce pathology.”

This research began in the lab of Dinesh Rao, PhD, an assistant professor at the University of California Los Angeles who was studying MLL-rearranged B-ALL.

After researchers in Dr Rao’s lab identified IGF2BP3 as one of the top dysregulated genes in this malignancy, they began working with Dr Sanford’s lab to figure out which genes were being directly regulated by IGF2BP3.

Dr Sanford’s lab was among the few using individual nucleotide resolution crosslinking immunoprecipitation (iCLIP), a technique that can capture RNA molecules bound to a particular protein.

iCLIP enabled the researchers to identify IGF2BP3 binding sites in several hundred RNA transcripts in 2 B-ALL cell lines.

The work also revealed that IGF2BP3 enhanced the expression of MYC and other oncogenes in hematopoietic stem cells.

In experiments with mice, the researchers found that overexpression of IGF2BP3 in the bone marrow leads to proliferation of hematopoietic stem cells and B-cell progenitors, reproducing some features of MLL-rearranged B-ALL.

“Understanding its mechanism of action is important for thinking about therapeutics that might interfere with the action of this protein in disease,” Dr Sanford said.

“One possibility is an RNA-based therapeutic that could sequester the protein and keep it from binding to RNA transcripts. That would be a way to influence the expression of many genes involved in the proliferation of cancer cells.”

Micrograph showing B-ALL

An RNA binding protein promotes the development of MLL-rearranged B-cell acute lymphoblastic leukemia (B-ALL), according to research published in The Journal of Clinical Investigation.

Researchers found an overabundance of the protein, IGF2BP3, in MLL-rearranged B-ALL.

They also identified genes that are directly regulated by IFG2BP3, and many of them turned out to be oncogenes that have already been implicated in cancers.

The overall effect of IFG2BP3 in MLL-rearranged B-ALL is to promote the proliferation of B cells by shifting the expression of a large number of genes, explained study author Jeremy Sanford, PhD, of the University of California Santa Cruz.

“This protein, IFG2BP3, has been correlated with many types of malignancies and with the worst prognoses,” he noted. “What is exciting about this study is that it goes beyond correlation and shows causation, because we demonstrated, for the first time, that aberrant expression of this protein is sufficient to induce pathology.”

This research began in the lab of Dinesh Rao, PhD, an assistant professor at the University of California Los Angeles who was studying MLL-rearranged B-ALL.

After researchers in Dr Rao’s lab identified IGF2BP3 as one of the top dysregulated genes in this malignancy, they began working with Dr Sanford’s lab to figure out which genes were being directly regulated by IGF2BP3.

Dr Sanford’s lab was among the few using individual nucleotide resolution crosslinking immunoprecipitation (iCLIP), a technique that can capture RNA molecules bound to a particular protein.

iCLIP enabled the researchers to identify IGF2BP3 binding sites in several hundred RNA transcripts in 2 B-ALL cell lines.

The work also revealed that IGF2BP3 enhanced the expression of MYC and other oncogenes in hematopoietic stem cells.

In experiments with mice, the researchers found that overexpression of IGF2BP3 in the bone marrow leads to proliferation of hematopoietic stem cells and B-cell progenitors, reproducing some features of MLL-rearranged B-ALL.

“Understanding its mechanism of action is important for thinking about therapeutics that might interfere with the action of this protein in disease,” Dr Sanford said.

“One possibility is an RNA-based therapeutic that could sequester the protein and keep it from binding to RNA transcripts. That would be a way to influence the expression of many genes involved in the proliferation of cancer cells.”

SHM recently developed the only maintenance of certification (MOC) exam by hospitalists for hospitalists. SHM SPARK is a fantastic complement to MOC tools already on the market and will help hospitalists succeed in the upcoming exam; it delivers access to relevant hospital medicine review content to enhance patient care while at the same time giving you the flexibility to fill your knowledge gaps and study needs at your own pace.

Featuring a unique online platform, SHM SPARK offers 175 vignette-style multiple-choice questions that bridge the primary knowledge gaps found within existing MOC exam-preparation products today. Other preparation tools are targeted toward the ABIM Internal Medicine exam and cover only roughly 60% of the Focused Practice in Hospital Medicine exam.

SHM SPARK is designed to serve as a supplemental study guide providing targeted study in the remaining roughly 40% of the Focused Practice in Hospital Medicine exam blueprint.

SHM SPARK provides in-depth review on the following systems-based content:

• Palliative care, ethics, and decision making
• Patient safety
• Perioperative care and consultative co-management
• Quality, cost, and clinical reasoning

The tool’s self-study provides detailed learning objectives and discussion points and allows users to define individual areas of strengths and weaknesses. Users will have the option to claim applicable ABIM MOC Part II Medical Knowledge points as they complete each module with a minimum passing score of 80%. After successful completion of all four modules, participants may claim up to 10.5 AMA PRA Category 1 Credits.

Order SPARK today at www.hospitalmedicine.org/SPARK.

SHM recently developed the only maintenance of certification (MOC) exam by hospitalists for hospitalists. SHM SPARK is a fantastic complement to MOC tools already on the market and will help hospitalists succeed in the upcoming exam; it delivers access to relevant hospital medicine review content to enhance patient care while at the same time giving you the flexibility to fill your knowledge gaps and study needs at your own pace.

Featuring a unique online platform, SHM SPARK offers 175 vignette-style multiple-choice questions that bridge the primary knowledge gaps found within existing MOC exam-preparation products today. Other preparation tools are targeted toward the ABIM Internal Medicine exam and cover only roughly 60% of the Focused Practice in Hospital Medicine exam.

SHM SPARK is designed to serve as a supplemental study guide providing targeted study in the remaining roughly 40% of the Focused Practice in Hospital Medicine exam blueprint.

SHM SPARK provides in-depth review on the following systems-based content:

• Palliative care, ethics, and decision making
• Patient safety
• Perioperative care and consultative co-management
• Quality, cost, and clinical reasoning

The tool’s self-study provides detailed learning objectives and discussion points and allows users to define individual areas of strengths and weaknesses. Users will have the option to claim applicable ABIM MOC Part II Medical Knowledge points as they complete each module with a minimum passing score of 80%. After successful completion of all four modules, participants may claim up to 10.5 AMA PRA Category 1 Credits.

Order SPARK today at www.hospitalmedicine.org/SPARK.

SHM recently developed the only maintenance of certification (MOC) exam by hospitalists for hospitalists. SHM SPARK is a fantastic complement to MOC tools already on the market and will help hospitalists succeed in the upcoming exam; it delivers access to relevant hospital medicine review content to enhance patient care while at the same time giving you the flexibility to fill your knowledge gaps and study needs at your own pace.

Featuring a unique online platform, SHM SPARK offers 175 vignette-style multiple-choice questions that bridge the primary knowledge gaps found within existing MOC exam-preparation products today. Other preparation tools are targeted toward the ABIM Internal Medicine exam and cover only roughly 60% of the Focused Practice in Hospital Medicine exam.

SHM SPARK is designed to serve as a supplemental study guide providing targeted study in the remaining roughly 40% of the Focused Practice in Hospital Medicine exam blueprint.

SHM SPARK provides in-depth review on the following systems-based content:

• Palliative care, ethics, and decision making
• Patient safety
• Perioperative care and consultative co-management
• Quality, cost, and clinical reasoning

The tool’s self-study provides detailed learning objectives and discussion points and allows users to define individual areas of strengths and weaknesses. Users will have the option to claim applicable ABIM MOC Part II Medical Knowledge points as they complete each module with a minimum passing score of 80%. After successful completion of all four modules, participants may claim up to 10.5 AMA PRA Category 1 Credits.

Order SPARK today at www.hospitalmedicine.org/SPARK.

Idelalisib (Zydelig)

Photo courtesy of

Gilead Sciences

The US Food and Drug Administration (FDA) has reported that Gilead Sciences, Inc., is stopping 6 clinical trials of idelalisib (Zydelig) due to adverse events (AEs) observed in patients receiving idelalisib in combination with other drugs.

The AEs, which include deaths, were mostly related to infections.

The trials include patients with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma, and indolent non-Hodgkin lymphomas.

The FDA said it is reviewing the findings of these trials and will communicate new information as necessary.

A few days ago, the European Medicines Agency (EMA) announced its decision to review the safety of idelalisib due to the aforementioned AEs. The EMA said it is reviewing data from 3 idelalisib trials.

While this review is underway, the EMA advised that patients starting or already on treatment with idelalisib be carefully monitored for signs of infection. If the drug is well tolerated, treatment should not be stopped.

The FDA has not made any recommendations about treatment with idelalisib.

About idelalisib

Idelalisib is currently approved by the FDA for use in combination with rituximab to treat patients with relapsed CLL who cannot receive rituximab alone.

Idelalisib also has accelerated approval from the FDA to treat patients with relapsed follicular lymphoma who have received at least 2 prior systemic therapies and patients with relapsed small lymphocytic lymphoma who have received at least 2 prior systemic therapies.

In the European Union, idelalisib is approved for use in combination with rituximab to treat adults with CLL who have received at least 1 prior therapy or as first-line treatment in the presence of 17p deletion or TP53 mutation in CLL patients deemed unsuitable for chemo-immunotherapy.

Idelalisib is also approved in the European Union as monotherapy for adults with follicular lymphoma that is refractory to 2 prior lines of treatment.

Idelalisib (Zydelig)

Photo courtesy of

Gilead Sciences

The US Food and Drug Administration (FDA) has reported that Gilead Sciences, Inc., is stopping 6 clinical trials of idelalisib (Zydelig) due to adverse events (AEs) observed in patients receiving idelalisib in combination with other drugs.

The AEs, which include deaths, were mostly related to infections.

The trials include patients with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma, and indolent non-Hodgkin lymphomas.

The FDA said it is reviewing the findings of these trials and will communicate new information as necessary.

A few days ago, the European Medicines Agency (EMA) announced its decision to review the safety of idelalisib due to the aforementioned AEs. The EMA said it is reviewing data from 3 idelalisib trials.

While this review is underway, the EMA advised that patients starting or already on treatment with idelalisib be carefully monitored for signs of infection. If the drug is well tolerated, treatment should not be stopped.

The FDA has not made any recommendations about treatment with idelalisib.

About idelalisib

Idelalisib is currently approved by the FDA for use in combination with rituximab to treat patients with relapsed CLL who cannot receive rituximab alone.

Idelalisib also has accelerated approval from the FDA to treat patients with relapsed follicular lymphoma who have received at least 2 prior systemic therapies and patients with relapsed small lymphocytic lymphoma who have received at least 2 prior systemic therapies.

In the European Union, idelalisib is approved for use in combination with rituximab to treat adults with CLL who have received at least 1 prior therapy or as first-line treatment in the presence of 17p deletion or TP53 mutation in CLL patients deemed unsuitable for chemo-immunotherapy.

Idelalisib is also approved in the European Union as monotherapy for adults with follicular lymphoma that is refractory to 2 prior lines of treatment.

Idelalisib (Zydelig)

Photo courtesy of

Gilead Sciences

The US Food and Drug Administration (FDA) has reported that Gilead Sciences, Inc., is stopping 6 clinical trials of idelalisib (Zydelig) due to adverse events (AEs) observed in patients receiving idelalisib in combination with other drugs.

The AEs, which include deaths, were mostly related to infections.

The trials include patients with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma, and indolent non-Hodgkin lymphomas.

The FDA said it is reviewing the findings of these trials and will communicate new information as necessary.

A few days ago, the European Medicines Agency (EMA) announced its decision to review the safety of idelalisib due to the aforementioned AEs. The EMA said it is reviewing data from 3 idelalisib trials.

While this review is underway, the EMA advised that patients starting or already on treatment with idelalisib be carefully monitored for signs of infection. If the drug is well tolerated, treatment should not be stopped.

The FDA has not made any recommendations about treatment with idelalisib.

About idelalisib

Idelalisib is currently approved by the FDA for use in combination with rituximab to treat patients with relapsed CLL who cannot receive rituximab alone.

Idelalisib also has accelerated approval from the FDA to treat patients with relapsed follicular lymphoma who have received at least 2 prior systemic therapies and patients with relapsed small lymphocytic lymphoma who have received at least 2 prior systemic therapies.

In the European Union, idelalisib is approved for use in combination with rituximab to treat adults with CLL who have received at least 1 prior therapy or as first-line treatment in the presence of 17p deletion or TP53 mutation in CLL patients deemed unsuitable for chemo-immunotherapy.

Idelalisib is also approved in the European Union as monotherapy for adults with follicular lymphoma that is refractory to 2 prior lines of treatment.