The Food and Drug Administration has rejected Intercept Pharmaceutical’s second bid for approval of obeticholic acid (OCA) for treatment of nonalcoholic steatohepatitis (NASH) with stage 2 or 3 fibrosis.

In response, the company has decided to discontinue all NASH-related investment.

Intercept first sought FDA approval for OCA in treatment of NASH in 2019 and received a complete response letter. The company refiled for a new drug application in December 2022. A second resubmission would require a completion of the long-term outcomes phase of an ongoing clinical trial, according to an Intercept press release.

The FDA decision follows the recommendation from May’s FDA Gastrointestinal Drugs Advisory Committee meeting. During the meeting, members voted 15 to 1 to advise deferring approval until clinical outcome data became available. Intercept’s clinical trial data demonstrated that OCA showed moderate benefit over placebo in improving fibrosis in NASH patients, but “there is uncertainty how the magnitude of changes in these surrogate endpoints may translate to meaningful changes in clinical outcomes,” an FDA meeting briefing document stated. There were also notable safety concerns including an increased risk for drug-induced liver injury.

An estimated 16.8 million Americans have NASH, and there are no FDA-approved medications for the condition.

Intercept plans to promptly begin closing out their NASH clinical trial and restructuring to focus on rare and serious liver diseases.

“While this is clearly not the outcome that we have worked toward, I’m proud of the impact that Intercept has made to move the science of NASH forward and bring the field closer to a treatment option,” said Jerry Durso, the president and CEO of Intercept, in a statement. “Intercept thanks the scientists, clinicians, and patients whose contributions to the clinical development of OCA in NASH have significantly advanced the understanding of this deadly disease.”

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

The Food and Drug Administration has rejected Intercept Pharmaceutical’s second bid for approval of obeticholic acid (OCA) for treatment of nonalcoholic steatohepatitis (NASH) with stage 2 or 3 fibrosis.

In response, the company has decided to discontinue all NASH-related investment.

Intercept first sought FDA approval for OCA in treatment of NASH in 2019 and received a complete response letter. The company refiled for a new drug application in December 2022. A second resubmission would require a completion of the long-term outcomes phase of an ongoing clinical trial, according to an Intercept press release.

The FDA decision follows the recommendation from May’s FDA Gastrointestinal Drugs Advisory Committee meeting. During the meeting, members voted 15 to 1 to advise deferring approval until clinical outcome data became available. Intercept’s clinical trial data demonstrated that OCA showed moderate benefit over placebo in improving fibrosis in NASH patients, but “there is uncertainty how the magnitude of changes in these surrogate endpoints may translate to meaningful changes in clinical outcomes,” an FDA meeting briefing document stated. There were also notable safety concerns including an increased risk for drug-induced liver injury.

An estimated 16.8 million Americans have NASH, and there are no FDA-approved medications for the condition.

Intercept plans to promptly begin closing out their NASH clinical trial and restructuring to focus on rare and serious liver diseases.

“While this is clearly not the outcome that we have worked toward, I’m proud of the impact that Intercept has made to move the science of NASH forward and bring the field closer to a treatment option,” said Jerry Durso, the president and CEO of Intercept, in a statement. “Intercept thanks the scientists, clinicians, and patients whose contributions to the clinical development of OCA in NASH have significantly advanced the understanding of this deadly disease.”

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

The Food and Drug Administration has rejected Intercept Pharmaceutical’s second bid for approval of obeticholic acid (OCA) for treatment of nonalcoholic steatohepatitis (NASH) with stage 2 or 3 fibrosis.

In response, the company has decided to discontinue all NASH-related investment.

Intercept first sought FDA approval for OCA in treatment of NASH in 2019 and received a complete response letter. The company refiled for a new drug application in December 2022. A second resubmission would require a completion of the long-term outcomes phase of an ongoing clinical trial, according to an Intercept press release.

The FDA decision follows the recommendation from May’s FDA Gastrointestinal Drugs Advisory Committee meeting. During the meeting, members voted 15 to 1 to advise deferring approval until clinical outcome data became available. Intercept’s clinical trial data demonstrated that OCA showed moderate benefit over placebo in improving fibrosis in NASH patients, but “there is uncertainty how the magnitude of changes in these surrogate endpoints may translate to meaningful changes in clinical outcomes,” an FDA meeting briefing document stated. There were also notable safety concerns including an increased risk for drug-induced liver injury.

An estimated 16.8 million Americans have NASH, and there are no FDA-approved medications for the condition.

Intercept plans to promptly begin closing out their NASH clinical trial and restructuring to focus on rare and serious liver diseases.

“While this is clearly not the outcome that we have worked toward, I’m proud of the impact that Intercept has made to move the science of NASH forward and bring the field closer to a treatment option,” said Jerry Durso, the president and CEO of Intercept, in a statement. “Intercept thanks the scientists, clinicians, and patients whose contributions to the clinical development of OCA in NASH have significantly advanced the understanding of this deadly disease.”

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

The European Society for Medical Oncology (ESMO), in collaboration with the European Hematology Association, has released a tool to help hematologists evaluate the magnitude of clinical benefit expected from new blood cancer treatments.

It consists of 11 2- to 3-page forms with checklists to grade treatment trials on the extent to which they meet efficacy and safety thresholds. Each of the 11 forms covers a specific trial scenario, such as a randomized controlled trial with curative intent or a trial of a therapy that is not likely to be curative with a primary endpoint of overall survival.

Treatments with curative intent are graded A, B, or C, while treatments in the noncurative setting are graded on a descending scale from 5 to 1. Scores of A and B in the curative setting and 5 and 4 in the noncurative setting represent substantial benefit.

On the form for RCTs with curative intent, for instance, a survival improvement of 5% or more garners an A but an improvement of less than 3% gets a C. Scores are also annotated for serious acute and/or persistent toxicity if present.

The tool, dubbed the ESMO-MCBS:H (European Society for Medical Oncology Magnitude of Clinical Benefit Scale: Hematology), is explained in an article published in Annals of Oncology. The evaluation forms are available online.

The idea behind the work is to help health care professionals and others to more “accurately assess the value of and prioritise therapies for patients with blood cancers. For clinicians, ESMO-MCBS:H will aid in their clinical decision-making and in the development of evidence-based practice and guidelines,” ESMO said in a press release.

To develop ESMO-MCBS:H, the group tailored its tool for evaluating solid tumor therapies, the ESMO-MCBS, to account for the sometimes different endpoints used in hematologic malignancy trials and the very indolent nature of some blood cancers, such as follicular lymphoma, which hampers development of mature data.

Specific changes include adding a new evaluation form to grade single-arm trials with curative intent, such as those used for CAR-T-cell therapies; incorporating molecular surrogate endpoints used in CML trials; and adding a way to grade outcomes for indolent cancers, among others.

The development process included applying the solid tumor tool to 80 blood cancer studies to identify shortcomings and improve its applicability. The final tool was field tested with 51 international experts from EHA and ESMO who largely agreed on the reasonableness of the trial scores.

ESMO said it expects ESMO-MCBS:H will be useful. The solid tumor tool, first published in 2015, is used by the World Health Organization to screen medications for its essential medicines list as well as by ESMO to generate guidelines and oncology centers across Europe to help with resource allocation decisions.

The European Society for Medical Oncology (ESMO), in collaboration with the European Hematology Association, has released a tool to help hematologists evaluate the magnitude of clinical benefit expected from new blood cancer treatments.

It consists of 11 2- to 3-page forms with checklists to grade treatment trials on the extent to which they meet efficacy and safety thresholds. Each of the 11 forms covers a specific trial scenario, such as a randomized controlled trial with curative intent or a trial of a therapy that is not likely to be curative with a primary endpoint of overall survival.

Treatments with curative intent are graded A, B, or C, while treatments in the noncurative setting are graded on a descending scale from 5 to 1. Scores of A and B in the curative setting and 5 and 4 in the noncurative setting represent substantial benefit.

On the form for RCTs with curative intent, for instance, a survival improvement of 5% or more garners an A but an improvement of less than 3% gets a C. Scores are also annotated for serious acute and/or persistent toxicity if present.

The tool, dubbed the ESMO-MCBS:H (European Society for Medical Oncology Magnitude of Clinical Benefit Scale: Hematology), is explained in an article published in Annals of Oncology. The evaluation forms are available online.

The idea behind the work is to help health care professionals and others to more “accurately assess the value of and prioritise therapies for patients with blood cancers. For clinicians, ESMO-MCBS:H will aid in their clinical decision-making and in the development of evidence-based practice and guidelines,” ESMO said in a press release.

To develop ESMO-MCBS:H, the group tailored its tool for evaluating solid tumor therapies, the ESMO-MCBS, to account for the sometimes different endpoints used in hematologic malignancy trials and the very indolent nature of some blood cancers, such as follicular lymphoma, which hampers development of mature data.

Specific changes include adding a new evaluation form to grade single-arm trials with curative intent, such as those used for CAR-T-cell therapies; incorporating molecular surrogate endpoints used in CML trials; and adding a way to grade outcomes for indolent cancers, among others.

The development process included applying the solid tumor tool to 80 blood cancer studies to identify shortcomings and improve its applicability. The final tool was field tested with 51 international experts from EHA and ESMO who largely agreed on the reasonableness of the trial scores.

ESMO said it expects ESMO-MCBS:H will be useful. The solid tumor tool, first published in 2015, is used by the World Health Organization to screen medications for its essential medicines list as well as by ESMO to generate guidelines and oncology centers across Europe to help with resource allocation decisions.

The European Society for Medical Oncology (ESMO), in collaboration with the European Hematology Association, has released a tool to help hematologists evaluate the magnitude of clinical benefit expected from new blood cancer treatments.

It consists of 11 2- to 3-page forms with checklists to grade treatment trials on the extent to which they meet efficacy and safety thresholds. Each of the 11 forms covers a specific trial scenario, such as a randomized controlled trial with curative intent or a trial of a therapy that is not likely to be curative with a primary endpoint of overall survival.

Treatments with curative intent are graded A, B, or C, while treatments in the noncurative setting are graded on a descending scale from 5 to 1. Scores of A and B in the curative setting and 5 and 4 in the noncurative setting represent substantial benefit.

On the form for RCTs with curative intent, for instance, a survival improvement of 5% or more garners an A but an improvement of less than 3% gets a C. Scores are also annotated for serious acute and/or persistent toxicity if present.

The tool, dubbed the ESMO-MCBS:H (European Society for Medical Oncology Magnitude of Clinical Benefit Scale: Hematology), is explained in an article published in Annals of Oncology. The evaluation forms are available online.

The idea behind the work is to help health care professionals and others to more “accurately assess the value of and prioritise therapies for patients with blood cancers. For clinicians, ESMO-MCBS:H will aid in their clinical decision-making and in the development of evidence-based practice and guidelines,” ESMO said in a press release.

To develop ESMO-MCBS:H, the group tailored its tool for evaluating solid tumor therapies, the ESMO-MCBS, to account for the sometimes different endpoints used in hematologic malignancy trials and the very indolent nature of some blood cancers, such as follicular lymphoma, which hampers development of mature data.

Specific changes include adding a new evaluation form to grade single-arm trials with curative intent, such as those used for CAR-T-cell therapies; incorporating molecular surrogate endpoints used in CML trials; and adding a way to grade outcomes for indolent cancers, among others.

The development process included applying the solid tumor tool to 80 blood cancer studies to identify shortcomings and improve its applicability. The final tool was field tested with 51 international experts from EHA and ESMO who largely agreed on the reasonableness of the trial scores.

ESMO said it expects ESMO-MCBS:H will be useful. The solid tumor tool, first published in 2015, is used by the World Health Organization to screen medications for its essential medicines list as well as by ESMO to generate guidelines and oncology centers across Europe to help with resource allocation decisions.

The US Preventive Services Task Force (USPSTF) recently issued draft recommendations on breast cancer screening that lower the starting age for routine mammography screening for those at average risk.¹ The proposed recommendations are an update to USPSTF’s 2016 guidance on this topic.

What’s different. There are 2 major differences in the new recommendations:

• Recommendation for routine mammography starting at age 40 for women at average risk for breast cancer (eg, no personal or family history or genetic risk factors). This is a “B” recommendation (offer or provide the service). Previously, the recommended age to start routine mammography was 50 years, with a “C” recommendation (individual decision-making) for those ages 40 to 49 years.
• No mention of digital tomosynthesis. Previously, this screening modality was rated as an “I” (insufficient evidence to assess). While the new draft recommendation does not mention tomosynthesis, the related evidence report concludes that there is still insufficient evidence to assess it.²

What’s the same. Several important recommendations have not changed. The USPSTF continues to state that the evidence is insufficient to assess the value of (1) supplemental screening with breast ultrasonography and magnetic resonance imaging in women with dense breasts and negative mammograms and (2) mammography in women ages 75 years and older.

And, most importantly, the USPSTF continues to recommend biennial, rather than annual, mammography screening. This recommendation is based on studies that show very little difference in outcomes between these strategies but higher rates of false-positive tests and subsequent biopsies with annual testing.²

What others say. USPSTF’s draft recommendations continue to differ from those of the American Cancer Society, which for average-risk women recommend individual decision-making from ages 40 to 45 years; routine annual mammography for those ages 45 to 54 years; annual or biennial mammography for those ages 55 years and older; and continued screening for women older than 75 years who are in good health and have a life expectancy ≥ 10 years.³

The USPSTF’s rationale for lowering the age at which to start routine mammography is a little puzzling. Several conclusions in the draft evidence report seem to contradict this recommendation:

In the summary of screening effectiveness, the report states “For women ages 39 to 49 years, the combined [relative risk] for breast cancer mortality was 0.92 (95% CI, 0.75 to 1.02; 9 trials); absolute breast cancer mortality reduction was 2.9 (95% CI, –0.6 to 8.9) deaths prevented per 10,000 women over 10 years. None of the trials indicated statistically significantly reduced breast cancer mortality with screening….”²

And in a summary of screening harms, it states that for “every case of invasive breast cancer detected by mammography screening in women age[s] 40 to 49 years, 464 women had screening mammography, 58 were recommended for additional diagnostic imaging, and 10 were recommended for biopsies.”²

The USPSTF apparently based its decision on a modeling study conducted by the Cancer Intervention and Surveillance Modeling Network (CISNET) at USPSTF’s request. This analysis found that screening biennially from ages 50 to 74 years resulted in about 7 breast cancer deaths averted over the lifetimes of 1000 females and that 1 additional death was averted if the starting age for screening was 40 years.⁴

Financial implications. The USPSTF’s change from a “C” to a “B” recommendation for women ages 40 to 49 years has financial implications. The Affordable Care Act mandates that all “A” and “B” recommendations by the USPSTF have to be provided by commercial health plans with no out-of-pocket costs. (This is currently being challenged in the courts.) However, any follow-up testing for abnormal results is not subject to this provision—so false-positive work-ups and biopsies may result in out-of-pocket costs.

What to discuss with your patients. For women ages 40 to 50 years, discuss the differences in mammography recommendations and the potential risks and benefits of the procedure, as well as financial implications; respect the patient’s decision.

For those ages 50 to 74 years, recommend biennial mammography.

For those older than 74 years, assess life expectancy and other health problems. Discuss the potential risks and benefits of the procedure and respect the patient’s decision.

For all patients, document all discussions and decisions.

The US Preventive Services Task Force (USPSTF) recently issued draft recommendations on breast cancer screening that lower the starting age for routine mammography screening for those at average risk.¹ The proposed recommendations are an update to USPSTF’s 2016 guidance on this topic.

What’s different. There are 2 major differences in the new recommendations:

• Recommendation for routine mammography starting at age 40 for women at average risk for breast cancer (eg, no personal or family history or genetic risk factors). This is a “B” recommendation (offer or provide the service). Previously, the recommended age to start routine mammography was 50 years, with a “C” recommendation (individual decision-making) for those ages 40 to 49 years.
• No mention of digital tomosynthesis. Previously, this screening modality was rated as an “I” (insufficient evidence to assess). While the new draft recommendation does not mention tomosynthesis, the related evidence report concludes that there is still insufficient evidence to assess it.²

What’s the same. Several important recommendations have not changed. The USPSTF continues to state that the evidence is insufficient to assess the value of (1) supplemental screening with breast ultrasonography and magnetic resonance imaging in women with dense breasts and negative mammograms and (2) mammography in women ages 75 years and older.

And, most importantly, the USPSTF continues to recommend biennial, rather than annual, mammography screening. This recommendation is based on studies that show very little difference in outcomes between these strategies but higher rates of false-positive tests and subsequent biopsies with annual testing.²

What others say. USPSTF’s draft recommendations continue to differ from those of the American Cancer Society, which for average-risk women recommend individual decision-making from ages 40 to 45 years; routine annual mammography for those ages 45 to 54 years; annual or biennial mammography for those ages 55 years and older; and continued screening for women older than 75 years who are in good health and have a life expectancy ≥ 10 years.³

The USPSTF’s rationale for lowering the age at which to start routine mammography is a little puzzling. Several conclusions in the draft evidence report seem to contradict this recommendation:

In the summary of screening effectiveness, the report states “For women ages 39 to 49 years, the combined [relative risk] for breast cancer mortality was 0.92 (95% CI, 0.75 to 1.02; 9 trials); absolute breast cancer mortality reduction was 2.9 (95% CI, –0.6 to 8.9) deaths prevented per 10,000 women over 10 years. None of the trials indicated statistically significantly reduced breast cancer mortality with screening….”²

And in a summary of screening harms, it states that for “every case of invasive breast cancer detected by mammography screening in women age[s] 40 to 49 years, 464 women had screening mammography, 58 were recommended for additional diagnostic imaging, and 10 were recommended for biopsies.”²

The USPSTF apparently based its decision on a modeling study conducted by the Cancer Intervention and Surveillance Modeling Network (CISNET) at USPSTF’s request. This analysis found that screening biennially from ages 50 to 74 years resulted in about 7 breast cancer deaths averted over the lifetimes of 1000 females and that 1 additional death was averted if the starting age for screening was 40 years.⁴

Financial implications. The USPSTF’s change from a “C” to a “B” recommendation for women ages 40 to 49 years has financial implications. The Affordable Care Act mandates that all “A” and “B” recommendations by the USPSTF have to be provided by commercial health plans with no out-of-pocket costs. (This is currently being challenged in the courts.) However, any follow-up testing for abnormal results is not subject to this provision—so false-positive work-ups and biopsies may result in out-of-pocket costs.

What to discuss with your patients. For women ages 40 to 50 years, discuss the differences in mammography recommendations and the potential risks and benefits of the procedure, as well as financial implications; respect the patient’s decision.

For those ages 50 to 74 years, recommend biennial mammography.

For those older than 74 years, assess life expectancy and other health problems. Discuss the potential risks and benefits of the procedure and respect the patient’s decision.

For all patients, document all discussions and decisions.

The US Preventive Services Task Force (USPSTF) recently issued draft recommendations on breast cancer screening that lower the starting age for routine mammography screening for those at average risk.¹ The proposed recommendations are an update to USPSTF’s 2016 guidance on this topic.

What’s different. There are 2 major differences in the new recommendations:

• Recommendation for routine mammography starting at age 40 for women at average risk for breast cancer (eg, no personal or family history or genetic risk factors). This is a “B” recommendation (offer or provide the service). Previously, the recommended age to start routine mammography was 50 years, with a “C” recommendation (individual decision-making) for those ages 40 to 49 years.
• No mention of digital tomosynthesis. Previously, this screening modality was rated as an “I” (insufficient evidence to assess). While the new draft recommendation does not mention tomosynthesis, the related evidence report concludes that there is still insufficient evidence to assess it.²

What’s the same. Several important recommendations have not changed. The USPSTF continues to state that the evidence is insufficient to assess the value of (1) supplemental screening with breast ultrasonography and magnetic resonance imaging in women with dense breasts and negative mammograms and (2) mammography in women ages 75 years and older.

And, most importantly, the USPSTF continues to recommend biennial, rather than annual, mammography screening. This recommendation is based on studies that show very little difference in outcomes between these strategies but higher rates of false-positive tests and subsequent biopsies with annual testing.²

What others say. USPSTF’s draft recommendations continue to differ from those of the American Cancer Society, which for average-risk women recommend individual decision-making from ages 40 to 45 years; routine annual mammography for those ages 45 to 54 years; annual or biennial mammography for those ages 55 years and older; and continued screening for women older than 75 years who are in good health and have a life expectancy ≥ 10 years.³

The USPSTF’s rationale for lowering the age at which to start routine mammography is a little puzzling. Several conclusions in the draft evidence report seem to contradict this recommendation:

In the summary of screening effectiveness, the report states “For women ages 39 to 49 years, the combined [relative risk] for breast cancer mortality was 0.92 (95% CI, 0.75 to 1.02; 9 trials); absolute breast cancer mortality reduction was 2.9 (95% CI, –0.6 to 8.9) deaths prevented per 10,000 women over 10 years. None of the trials indicated statistically significantly reduced breast cancer mortality with screening….”²

And in a summary of screening harms, it states that for “every case of invasive breast cancer detected by mammography screening in women age[s] 40 to 49 years, 464 women had screening mammography, 58 were recommended for additional diagnostic imaging, and 10 were recommended for biopsies.”²

The USPSTF apparently based its decision on a modeling study conducted by the Cancer Intervention and Surveillance Modeling Network (CISNET) at USPSTF’s request. This analysis found that screening biennially from ages 50 to 74 years resulted in about 7 breast cancer deaths averted over the lifetimes of 1000 females and that 1 additional death was averted if the starting age for screening was 40 years.⁴

Financial implications. The USPSTF’s change from a “C” to a “B” recommendation for women ages 40 to 49 years has financial implications. The Affordable Care Act mandates that all “A” and “B” recommendations by the USPSTF have to be provided by commercial health plans with no out-of-pocket costs. (This is currently being challenged in the courts.) However, any follow-up testing for abnormal results is not subject to this provision—so false-positive work-ups and biopsies may result in out-of-pocket costs.

What to discuss with your patients. For women ages 40 to 50 years, discuss the differences in mammography recommendations and the potential risks and benefits of the procedure, as well as financial implications; respect the patient’s decision.

For those ages 50 to 74 years, recommend biennial mammography.

For those older than 74 years, assess life expectancy and other health problems. Discuss the potential risks and benefits of the procedure and respect the patient’s decision.

For all patients, document all discussions and decisions.

An expert panel of pain management clinicians has released what they say are the first international guidelines for general practitioners on opioid analgesic deprescribing in adults.

The recommendations describe best practices for stopping opioid therapy and emphasize slow tapering and individualized deprescribing plans tailored to each patient.

Developed by general practitioners, pain specialists, addiction specialists, pharmacists, registered nurses, consumers, and physiotherapists, the guidelines note that deprescribing may not be appropriate for every patient and that stopping abruptly can be associated with an increased risk of overdose.

“Internationally, we were seeing significant harms from opioids but also significant harms from unsolicited and abrupt opioid cessation,” said lead author Aili Langford, PhD, who conducted the study as a doctoral student at the University of Sydney. “It was clear that recommendations to support safe and person-centered opioid deprescribing were required.”

The findings were published online  in the Medical Journal of Australia.
 

Deprescribing plan

The consensus guidelines include 11 recommendations for deprescribing in adult patients who take at least one opioid for any type of pain.

Recommendations include implementing a deprescribing plan when opioids are first prescribed and gradual and individualized deprescribing, with regular monitoring and review.

Clinicians should consider opioid deprescribing in patients who experience no clinically meaningful improvement in function, quality of life, or pain at high risk with opioid therapy, they note. Patients who are at high risk for opioid-related harm are also good candidates for deprescribing.

Stopping opioid therapy is not recommended for patients with severe opioid use disorder (OUD). In those patients, medication-assisted OUD treatment and other evidence-based interventions are recommended.

“Opioids can be effective in pain management,” co-author Carl Schneider, PhD, an associate professor of pharmacy at the University of Sydney, said in a press release. “However, over the longer term, the risk of harms may outweigh the benefits.”
 

A ‘global problem’

Commenting on the guidelines, Orman Trent Hall, DO, assistant professor of addiction medicine, department of psychiatry and behavioral health at the Ohio State University Wexner Medical Center, Columbus, said they are similar to recommendations published by the U.S. Centers for Disease Control and Prevention in 2016 and 2022 but offer additional information that could be helpful.

“This new guideline provides more explicit advice about tapering and withdrawal management, which may be useful to practitioners. The opioid crisis is a global problem, and while individual countries may require local solutions, the new international guideline may offer a framework for approaching this issue,” he said.

The guideline’s emphasis on the potential risks of deprescribing in some patients is also key, Dr. Hall added. Patients who are tapering off opioid therapy may have worsening pain and loss of function that can affect their quality of life.

“Patients may also experience psychological harm and increased risk of opioid use disorder and death by suicide following opioid deprescribing,” Dr. Hall said. “Therefore, it is important for providers to carefully weigh the risks of prescribing and deprescribing and engage patients with person-centered communication and shared decision-making.”

The work was funded by grants from the University of Sydney and the National Health and Medical Research Council. Full disclosures are available in the original article. Dr. Hall has provided expert opinion to the health care consultancy firm Lumanity and Emergent BioSolutions regarding the overdose crisis.

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

An expert panel of pain management clinicians has released what they say are the first international guidelines for general practitioners on opioid analgesic deprescribing in adults.

The recommendations describe best practices for stopping opioid therapy and emphasize slow tapering and individualized deprescribing plans tailored to each patient.

Developed by general practitioners, pain specialists, addiction specialists, pharmacists, registered nurses, consumers, and physiotherapists, the guidelines note that deprescribing may not be appropriate for every patient and that stopping abruptly can be associated with an increased risk of overdose.

“Internationally, we were seeing significant harms from opioids but also significant harms from unsolicited and abrupt opioid cessation,” said lead author Aili Langford, PhD, who conducted the study as a doctoral student at the University of Sydney. “It was clear that recommendations to support safe and person-centered opioid deprescribing were required.”

The findings were published online  in the Medical Journal of Australia.
 

Deprescribing plan

The consensus guidelines include 11 recommendations for deprescribing in adult patients who take at least one opioid for any type of pain.

Recommendations include implementing a deprescribing plan when opioids are first prescribed and gradual and individualized deprescribing, with regular monitoring and review.

Clinicians should consider opioid deprescribing in patients who experience no clinically meaningful improvement in function, quality of life, or pain at high risk with opioid therapy, they note. Patients who are at high risk for opioid-related harm are also good candidates for deprescribing.

Stopping opioid therapy is not recommended for patients with severe opioid use disorder (OUD). In those patients, medication-assisted OUD treatment and other evidence-based interventions are recommended.

“Opioids can be effective in pain management,” co-author Carl Schneider, PhD, an associate professor of pharmacy at the University of Sydney, said in a press release. “However, over the longer term, the risk of harms may outweigh the benefits.”
 

A ‘global problem’

Commenting on the guidelines, Orman Trent Hall, DO, assistant professor of addiction medicine, department of psychiatry and behavioral health at the Ohio State University Wexner Medical Center, Columbus, said they are similar to recommendations published by the U.S. Centers for Disease Control and Prevention in 2016 and 2022 but offer additional information that could be helpful.

“This new guideline provides more explicit advice about tapering and withdrawal management, which may be useful to practitioners. The opioid crisis is a global problem, and while individual countries may require local solutions, the new international guideline may offer a framework for approaching this issue,” he said.

The guideline’s emphasis on the potential risks of deprescribing in some patients is also key, Dr. Hall added. Patients who are tapering off opioid therapy may have worsening pain and loss of function that can affect their quality of life.

“Patients may also experience psychological harm and increased risk of opioid use disorder and death by suicide following opioid deprescribing,” Dr. Hall said. “Therefore, it is important for providers to carefully weigh the risks of prescribing and deprescribing and engage patients with person-centered communication and shared decision-making.”

The work was funded by grants from the University of Sydney and the National Health and Medical Research Council. Full disclosures are available in the original article. Dr. Hall has provided expert opinion to the health care consultancy firm Lumanity and Emergent BioSolutions regarding the overdose crisis.

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

An expert panel of pain management clinicians has released what they say are the first international guidelines for general practitioners on opioid analgesic deprescribing in adults.

The recommendations describe best practices for stopping opioid therapy and emphasize slow tapering and individualized deprescribing plans tailored to each patient.

Developed by general practitioners, pain specialists, addiction specialists, pharmacists, registered nurses, consumers, and physiotherapists, the guidelines note that deprescribing may not be appropriate for every patient and that stopping abruptly can be associated with an increased risk of overdose.

“Internationally, we were seeing significant harms from opioids but also significant harms from unsolicited and abrupt opioid cessation,” said lead author Aili Langford, PhD, who conducted the study as a doctoral student at the University of Sydney. “It was clear that recommendations to support safe and person-centered opioid deprescribing were required.”

The findings were published online  in the Medical Journal of Australia.
 

Deprescribing plan

The consensus guidelines include 11 recommendations for deprescribing in adult patients who take at least one opioid for any type of pain.

Recommendations include implementing a deprescribing plan when opioids are first prescribed and gradual and individualized deprescribing, with regular monitoring and review.

Clinicians should consider opioid deprescribing in patients who experience no clinically meaningful improvement in function, quality of life, or pain at high risk with opioid therapy, they note. Patients who are at high risk for opioid-related harm are also good candidates for deprescribing.

Stopping opioid therapy is not recommended for patients with severe opioid use disorder (OUD). In those patients, medication-assisted OUD treatment and other evidence-based interventions are recommended.

“Opioids can be effective in pain management,” co-author Carl Schneider, PhD, an associate professor of pharmacy at the University of Sydney, said in a press release. “However, over the longer term, the risk of harms may outweigh the benefits.”
 

A ‘global problem’

Commenting on the guidelines, Orman Trent Hall, DO, assistant professor of addiction medicine, department of psychiatry and behavioral health at the Ohio State University Wexner Medical Center, Columbus, said they are similar to recommendations published by the U.S. Centers for Disease Control and Prevention in 2016 and 2022 but offer additional information that could be helpful.

“This new guideline provides more explicit advice about tapering and withdrawal management, which may be useful to practitioners. The opioid crisis is a global problem, and while individual countries may require local solutions, the new international guideline may offer a framework for approaching this issue,” he said.

The guideline’s emphasis on the potential risks of deprescribing in some patients is also key, Dr. Hall added. Patients who are tapering off opioid therapy may have worsening pain and loss of function that can affect their quality of life.

“Patients may also experience psychological harm and increased risk of opioid use disorder and death by suicide following opioid deprescribing,” Dr. Hall said. “Therefore, it is important for providers to carefully weigh the risks of prescribing and deprescribing and engage patients with person-centered communication and shared decision-making.”

The work was funded by grants from the University of Sydney and the National Health and Medical Research Council. Full disclosures are available in the original article. Dr. Hall has provided expert opinion to the health care consultancy firm Lumanity and Emergent BioSolutions regarding the overdose crisis.

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

Despite using methotrexate (MTX) in the management of psoriasis and PsA for more than 50 years, there is paucity of data on its effectiveness in PsA. It is also largely assumed that MTX is more effective for rheumatoid arthritis (RA) than for PsA. To evaluate MTX effectiveness vis-à-vis RA, Lindström and colleagues conducted an observational study with disease-modifying antirheumatic drug (DMARD)–naive patients with newly diagnosed PsA (n = 3642) who initiated MTX and matched comparator patients with RA (n = 3642) from national Swedish registers. At 6 months, although both groups of patients had improvement in pain, global health, and remission, the rates were higher in RA compared with PsA. Overall, 71% of patients with PsA and 76% of patients with RA were still taking MTX 2 years after initiating MTX. The time to starting another DMARD was shorter in RA compared with PsA. Thus, in early PsA, MTX treatment seems to provide significant benefits. However, the improvements are less impressive than they are for RA.

Biologic agents are generally safe and effective in the treatment of PsA. However, there are limited data on the safety and effectiveness in older and younger populations with PsA. Gossec and colleagues conducted a post hoc analysis of the PsABio trial that included patients with PsA who received ustekinumab, an interleukin 12/23 inhibitor, and were subgrouped into those < 60 years (n = 336) and ≥ 60 years (n = 103). At 6 months, a numerically higher proportion of patients < 60 years achieved clinical Disease Activity Index for Psoriatic Arthritis low disease activity compared with those ≥ 60 years. The proportions of patients reporting at least one (32.7% vs 40.9%) or serious (5.3% vs 9.6%) adverse events were numerically higher in the older population. However, treatment persistence was numerically higher in the older subgroup. These differences were not clinically meaningful; thus, ustekinumab may be safely used in older populations.

There are also limited data on the effectiveness of biologics in patients with juvenile PsA (jPsA). To address this, Correll and colleagues evaluated the safety and effectiveness of etanercept, an anti–tumor necrosis factor agent, in patients with jPsA using data from the Childhood Arthritis and Rheumatology Research Alliance Registry. In 226 patients, the overall incidence of adverse events of special interest and serious adverse events were low and included three cases of uveitis (incidence rate [IR]/100 person-years 0.55; 95% CI 0.18-1.69), one of neuropathy (IR/100 person-years 0.18; 95% CI 0.03-1.29), and one of cancer (IR/100 person-years 0.13; 95% CI 0.02-0.90). The ACR provisional criteria for inactive disease were achieved by 51.9% and 43.8% of patients at 6 and 12 months. Thus, etanercept is safe and effective in jPsA.

Despite using methotrexate (MTX) in the management of psoriasis and PsA for more than 50 years, there is paucity of data on its effectiveness in PsA. It is also largely assumed that MTX is more effective for rheumatoid arthritis (RA) than for PsA. To evaluate MTX effectiveness vis-à-vis RA, Lindström and colleagues conducted an observational study with disease-modifying antirheumatic drug (DMARD)–naive patients with newly diagnosed PsA (n = 3642) who initiated MTX and matched comparator patients with RA (n = 3642) from national Swedish registers. At 6 months, although both groups of patients had improvement in pain, global health, and remission, the rates were higher in RA compared with PsA. Overall, 71% of patients with PsA and 76% of patients with RA were still taking MTX 2 years after initiating MTX. The time to starting another DMARD was shorter in RA compared with PsA. Thus, in early PsA, MTX treatment seems to provide significant benefits. However, the improvements are less impressive than they are for RA.

Biologic agents are generally safe and effective in the treatment of PsA. However, there are limited data on the safety and effectiveness in older and younger populations with PsA. Gossec and colleagues conducted a post hoc analysis of the PsABio trial that included patients with PsA who received ustekinumab, an interleukin 12/23 inhibitor, and were subgrouped into those < 60 years (n = 336) and ≥ 60 years (n = 103). At 6 months, a numerically higher proportion of patients < 60 years achieved clinical Disease Activity Index for Psoriatic Arthritis low disease activity compared with those ≥ 60 years. The proportions of patients reporting at least one (32.7% vs 40.9%) or serious (5.3% vs 9.6%) adverse events were numerically higher in the older population. However, treatment persistence was numerically higher in the older subgroup. These differences were not clinically meaningful; thus, ustekinumab may be safely used in older populations.

There are also limited data on the effectiveness of biologics in patients with juvenile PsA (jPsA). To address this, Correll and colleagues evaluated the safety and effectiveness of etanercept, an anti–tumor necrosis factor agent, in patients with jPsA using data from the Childhood Arthritis and Rheumatology Research Alliance Registry. In 226 patients, the overall incidence of adverse events of special interest and serious adverse events were low and included three cases of uveitis (incidence rate [IR]/100 person-years 0.55; 95% CI 0.18-1.69), one of neuropathy (IR/100 person-years 0.18; 95% CI 0.03-1.29), and one of cancer (IR/100 person-years 0.13; 95% CI 0.02-0.90). The ACR provisional criteria for inactive disease were achieved by 51.9% and 43.8% of patients at 6 and 12 months. Thus, etanercept is safe and effective in jPsA.

Despite using methotrexate (MTX) in the management of psoriasis and PsA for more than 50 years, there is paucity of data on its effectiveness in PsA. It is also largely assumed that MTX is more effective for rheumatoid arthritis (RA) than for PsA. To evaluate MTX effectiveness vis-à-vis RA, Lindström and colleagues conducted an observational study with disease-modifying antirheumatic drug (DMARD)–naive patients with newly diagnosed PsA (n = 3642) who initiated MTX and matched comparator patients with RA (n = 3642) from national Swedish registers. At 6 months, although both groups of patients had improvement in pain, global health, and remission, the rates were higher in RA compared with PsA. Overall, 71% of patients with PsA and 76% of patients with RA were still taking MTX 2 years after initiating MTX. The time to starting another DMARD was shorter in RA compared with PsA. Thus, in early PsA, MTX treatment seems to provide significant benefits. However, the improvements are less impressive than they are for RA.

Biologic agents are generally safe and effective in the treatment of PsA. However, there are limited data on the safety and effectiveness in older and younger populations with PsA. Gossec and colleagues conducted a post hoc analysis of the PsABio trial that included patients with PsA who received ustekinumab, an interleukin 12/23 inhibitor, and were subgrouped into those < 60 years (n = 336) and ≥ 60 years (n = 103). At 6 months, a numerically higher proportion of patients < 60 years achieved clinical Disease Activity Index for Psoriatic Arthritis low disease activity compared with those ≥ 60 years. The proportions of patients reporting at least one (32.7% vs 40.9%) or serious (5.3% vs 9.6%) adverse events were numerically higher in the older population. However, treatment persistence was numerically higher in the older subgroup. These differences were not clinically meaningful; thus, ustekinumab may be safely used in older populations.

There are also limited data on the effectiveness of biologics in patients with juvenile PsA (jPsA). To address this, Correll and colleagues evaluated the safety and effectiveness of etanercept, an anti–tumor necrosis factor agent, in patients with jPsA using data from the Childhood Arthritis and Rheumatology Research Alliance Registry. In 226 patients, the overall incidence of adverse events of special interest and serious adverse events were low and included three cases of uveitis (incidence rate [IR]/100 person-years 0.55; 95% CI 0.18-1.69), one of neuropathy (IR/100 person-years 0.18; 95% CI 0.03-1.29), and one of cancer (IR/100 person-years 0.13; 95% CI 0.02-0.90). The ACR provisional criteria for inactive disease were achieved by 51.9% and 43.8% of patients at 6 and 12 months. Thus, etanercept is safe and effective in jPsA.

To the Editor:

Peer-reviewed publications are important determinants for promotions, academic leadership, and grants in dermatology.¹ The impact of the COVID-19 pandemic on dermatology research productivity remains an area of investigation. We sought to determine authorship trends for males and females during the pandemic.

A cross-sectional retrospective study of the top 20 dermatology journals—determined by impact factor and Google Scholar H5-index—was conducted to identify manuscripts with submission date specified prepandemic (May 1, 2019–October 31, 2019) and during the pandemic (May 1, 2020–October 31, 2020). Submission date, first/last author name, sex, and affiliated country were extracted. Single authors were designated as first authors. Gender API (https://gender-api.com/en/) classified gender. A χ² test (P<.05) compared differences in proportions of female first/last authors from 2019 to 2020.

Overall, 811 and 1061 articles submitted in 2019 and 2020, respectively, were included. There were 1517 articles submitted to clinical journals and 355 articles submitted to basic science journals (Table). For the 7 clinical journals included, there was a 7.7% decrease in the proportion of female last authors in 2020 vs 2019 (P=.002), with the largest decrease between August and September 2020. Although other comparisons did not yield statistically significant differences (P>.05 all)(Table), several trends were observed. For clinical journals, there was a 1.8% decrease in the proportion of female first authors. For the 4 basic science journals included, there was a 4.9% increase and a 0.3% decrease in percentages of female first and last authors, respectively, for 2020 vs 2019.

Our findings indicate that the COVID-19 pandemic may have impacted female authors’ productivity in clinical dermatology publications. In a survey-based study for 2010 to 2011, female physician-researchers (n=437) spent 8.5 more hours per week on domestic activities and childcare and were more likely to take time off for childcare if their partner worked full time compared with males (n=612)(42.6% vs 12.4%, respectively).² Our observation that female last authors had a significant decrease in publications may suggest that this population had a disproportionate burden of domestic labor and childcare during the pandemic. It is possible that last authors, who generally are more senior researchers, may be more likely to have childcare, eldercare, and other types of domestic responsibilities. Similarly, in a study of surgery submissions (n=1068), there were 6%, 7%, and 4% decreases in percentages of female last, corresponding, and first authors, respectively, from 2019 to 2020.³Our study had limitations. Only 11 journals were analyzed because others did not have specified submission dates. Some journals only provided submission information for a subset of articles (eg, those published in the In Press section), which may have accounted for the large discrepancy in submission numbers for 2019 to 2020. Gender could not be determined for 1% of authors and was limited to female and male. Although our study submission time frame (May–October 2020) aimed at identifying research conducted during the height of the COVID-19 pandemic, some of these studies may have been conducted months or years before the pandemic. Future studies should focus on longer and more comprehensive time frames. Finally, estimated dates of stay-at-home orders fail to consider differences within countries.

The proportion of female US-affiliated first and last authors publishing in dermatology journals increased from 12% to 48% in 1976 and from 6% to 31% in 2006,⁴ which is encouraging. However, a gender gap persists, with one-third of National Institutes of Health grants in dermatology and one-fourth of research project grants in dermatology awarded to women.⁵ Consequences of the pandemic on academic productivity may include fewer women represented in higher academic ranks, lower compensation, and lower career satisfaction compared with men.¹ We urge academic institutions and funding agencies to recognize and take action to mitigate long-term sequelae. Extended grant end dates and submission periods, funding opportunities dedicated to women, and prioritization of female-authored submissions are some strategies that can safeguard equitable career progression in dermatology research.

To the Editor:

Peer-reviewed publications are important determinants for promotions, academic leadership, and grants in dermatology.¹ The impact of the COVID-19 pandemic on dermatology research productivity remains an area of investigation. We sought to determine authorship trends for males and females during the pandemic.

A cross-sectional retrospective study of the top 20 dermatology journals—determined by impact factor and Google Scholar H5-index—was conducted to identify manuscripts with submission date specified prepandemic (May 1, 2019–October 31, 2019) and during the pandemic (May 1, 2020–October 31, 2020). Submission date, first/last author name, sex, and affiliated country were extracted. Single authors were designated as first authors. Gender API (https://gender-api.com/en/) classified gender. A χ² test (P<.05) compared differences in proportions of female first/last authors from 2019 to 2020.

Overall, 811 and 1061 articles submitted in 2019 and 2020, respectively, were included. There were 1517 articles submitted to clinical journals and 355 articles submitted to basic science journals (Table). For the 7 clinical journals included, there was a 7.7% decrease in the proportion of female last authors in 2020 vs 2019 (P=.002), with the largest decrease between August and September 2020. Although other comparisons did not yield statistically significant differences (P>.05 all)(Table), several trends were observed. For clinical journals, there was a 1.8% decrease in the proportion of female first authors. For the 4 basic science journals included, there was a 4.9% increase and a 0.3% decrease in percentages of female first and last authors, respectively, for 2020 vs 2019.

Our findings indicate that the COVID-19 pandemic may have impacted female authors’ productivity in clinical dermatology publications. In a survey-based study for 2010 to 2011, female physician-researchers (n=437) spent 8.5 more hours per week on domestic activities and childcare and were more likely to take time off for childcare if their partner worked full time compared with males (n=612)(42.6% vs 12.4%, respectively).² Our observation that female last authors had a significant decrease in publications may suggest that this population had a disproportionate burden of domestic labor and childcare during the pandemic. It is possible that last authors, who generally are more senior researchers, may be more likely to have childcare, eldercare, and other types of domestic responsibilities. Similarly, in a study of surgery submissions (n=1068), there were 6%, 7%, and 4% decreases in percentages of female last, corresponding, and first authors, respectively, from 2019 to 2020.³Our study had limitations. Only 11 journals were analyzed because others did not have specified submission dates. Some journals only provided submission information for a subset of articles (eg, those published in the In Press section), which may have accounted for the large discrepancy in submission numbers for 2019 to 2020. Gender could not be determined for 1% of authors and was limited to female and male. Although our study submission time frame (May–October 2020) aimed at identifying research conducted during the height of the COVID-19 pandemic, some of these studies may have been conducted months or years before the pandemic. Future studies should focus on longer and more comprehensive time frames. Finally, estimated dates of stay-at-home orders fail to consider differences within countries.

The proportion of female US-affiliated first and last authors publishing in dermatology journals increased from 12% to 48% in 1976 and from 6% to 31% in 2006,⁴ which is encouraging. However, a gender gap persists, with one-third of National Institutes of Health grants in dermatology and one-fourth of research project grants in dermatology awarded to women.⁵ Consequences of the pandemic on academic productivity may include fewer women represented in higher academic ranks, lower compensation, and lower career satisfaction compared with men.¹ We urge academic institutions and funding agencies to recognize and take action to mitigate long-term sequelae. Extended grant end dates and submission periods, funding opportunities dedicated to women, and prioritization of female-authored submissions are some strategies that can safeguard equitable career progression in dermatology research.

To the Editor:

Peer-reviewed publications are important determinants for promotions, academic leadership, and grants in dermatology.¹ The impact of the COVID-19 pandemic on dermatology research productivity remains an area of investigation. We sought to determine authorship trends for males and females during the pandemic.

A cross-sectional retrospective study of the top 20 dermatology journals—determined by impact factor and Google Scholar H5-index—was conducted to identify manuscripts with submission date specified prepandemic (May 1, 2019–October 31, 2019) and during the pandemic (May 1, 2020–October 31, 2020). Submission date, first/last author name, sex, and affiliated country were extracted. Single authors were designated as first authors. Gender API (https://gender-api.com/en/) classified gender. A χ² test (P<.05) compared differences in proportions of female first/last authors from 2019 to 2020.

Overall, 811 and 1061 articles submitted in 2019 and 2020, respectively, were included. There were 1517 articles submitted to clinical journals and 355 articles submitted to basic science journals (Table). For the 7 clinical journals included, there was a 7.7% decrease in the proportion of female last authors in 2020 vs 2019 (P=.002), with the largest decrease between August and September 2020. Although other comparisons did not yield statistically significant differences (P>.05 all)(Table), several trends were observed. For clinical journals, there was a 1.8% decrease in the proportion of female first authors. For the 4 basic science journals included, there was a 4.9% increase and a 0.3% decrease in percentages of female first and last authors, respectively, for 2020 vs 2019.

Our findings indicate that the COVID-19 pandemic may have impacted female authors’ productivity in clinical dermatology publications. In a survey-based study for 2010 to 2011, female physician-researchers (n=437) spent 8.5 more hours per week on domestic activities and childcare and were more likely to take time off for childcare if their partner worked full time compared with males (n=612)(42.6% vs 12.4%, respectively).² Our observation that female last authors had a significant decrease in publications may suggest that this population had a disproportionate burden of domestic labor and childcare during the pandemic. It is possible that last authors, who generally are more senior researchers, may be more likely to have childcare, eldercare, and other types of domestic responsibilities. Similarly, in a study of surgery submissions (n=1068), there were 6%, 7%, and 4% decreases in percentages of female last, corresponding, and first authors, respectively, from 2019 to 2020.³Our study had limitations. Only 11 journals were analyzed because others did not have specified submission dates. Some journals only provided submission information for a subset of articles (eg, those published in the In Press section), which may have accounted for the large discrepancy in submission numbers for 2019 to 2020. Gender could not be determined for 1% of authors and was limited to female and male. Although our study submission time frame (May–October 2020) aimed at identifying research conducted during the height of the COVID-19 pandemic, some of these studies may have been conducted months or years before the pandemic. Future studies should focus on longer and more comprehensive time frames. Finally, estimated dates of stay-at-home orders fail to consider differences within countries.

The proportion of female US-affiliated first and last authors publishing in dermatology journals increased from 12% to 48% in 1976 and from 6% to 31% in 2006,⁴ which is encouraging. However, a gender gap persists, with one-third of National Institutes of Health grants in dermatology and one-fourth of research project grants in dermatology awarded to women.⁵ Consequences of the pandemic on academic productivity may include fewer women represented in higher academic ranks, lower compensation, and lower career satisfaction compared with men.¹ We urge academic institutions and funding agencies to recognize and take action to mitigate long-term sequelae. Extended grant end dates and submission periods, funding opportunities dedicated to women, and prioritization of female-authored submissions are some strategies that can safeguard equitable career progression in dermatology research.

Sweet syndrome (SS), also known as acute febrile neutrophilic dermatosis, was first described in 1964. ¹ Since then, several subtypes of SS have been recognized, including classic or idiopathic, which typically follows an acute viral illness; cancer related, typically in the form of a paraneoplastic syndrome; and drug induced. ² Drug-induced SS is defined by the following: (1) an abrupt onset of painful erythematous plaques or nodules; (2) histopathologic evidence of a dense neutrophilic infiltrate without evidence of leukocytoclastic vasculitis; (3) pyrexia above 38 ° C; (4) temporal relationship between drug and clinical presentation or temporally related recurrence after rechallenge; and (5) temporally related resolution of lesions after drug withdrawal or treatment with systemic corticosteroids. ³ All 5 criteria must be met to make a diagnosis of drug-induced SS. Since these criteria were established by Walker and Cohen, ³ various drugs have been identified as causative agents, including antibiotics, antiepileptics, antiretrovirals, antineoplastic agents, antipsychotics, oral contraceptives, nonsteroidal anti-inflammatory agents, and retinoids. ⁴ W e present a rare case of SS caused by dupilumab, a monoclonal antibody therapy, used in the treatment of severe eosinophilic asthma and atopic dermatitis.

Case Report

A 53-year-old woman presented with painful skin lesions, arthralgia, fever, and leukocytosis following initiation of dupilumab. She had a history of adult-onset, severe, persistent eosinophilic asthma, as well as chronic rhinosinusitis with nasal polyps, plaque psoriasis, and hypertrophic cardiomyopathy. She started mepolizumab 3 years prior to the current presentation for persistently uncontrolled asthma with a baseline peripheral eosinophil count of 860 cells/µL. After 3 years of minimal response to mepolizumab, she was started on dupilumab. Within 2 weeks of the first dose of dupilumab, she started experiencing bilateral knee pain. She subsequently developed daily fevers (temperature, 38.3 °C to 39.4 °C), fatigue, and pain in the back of the neck and head. After the second dose of dupilumab, she started experiencing painful skin lesions on the bilateral knuckles, elbows, and abdomen (Figure 1). She had difficulty using her hands and walking secondary to intense arthralgia involving the bilateral finger joints, elbows, and knees. Her primary care physician obtained a laboratory evaluation, which revealed an elevated total white blood cell count of 20×10³/mm³ (reference range, 4–11×10³/mm³) with 27.5% neutrophils and severely elevated eosinophils above her baseline to 57.3% with an absolute eosinophil count of 11,700 cells/µL (reference range, <400 cells/µL). Further assessment revealed an elevated erythrocyte sedimentation rate of 64 mm/h (reference range, 0–30 mm/h) and C-reactive protein level of 34 mg/dL (reference range, ≤0.80 mg/dL), with negative antinuclear antibody, rheumatoid factor, antineutrophilic cytoplasmic antibody, and Lyme antibody. IgG, IgA, and IgM levels were within reference range, and the IgE level was not elevated above her baseline. She had normal serum tryptase, and a peripheral D816V c-KIT mutation was not detected. She was subsequently hospitalized for further evaluation, at which time there was no fever or localizing infectious signs or symptoms. An infectious evaluation including urinalysis; respiratory swab for adenovirus, coronaviruses, human metapneumovirus, rhinovirus/enterovirus, influenza A and B, parainfluenza viruses, respiratory syncytial virus, Chlamydophila pneumoniae, and Mycoplasma pneumoniae; Lyme serology; and a computed tomography (CT) scan of the chest, abdomen, and pelvis revealed no evidence of infection. A parasite evaluation was ordered but was not performed. There was no evidence of malignancy on CT of the chest, abdomen, and pelvis or CT of the head without contrast. A lumbar puncture was considered but was ultimately deferred.

At the current presentation, the patient was following up in the dermatology clinic shortly after discharge. The lesions on the fingers and arms were described by the dermatologist as deep, erythematous, 0.5-cm bullous papules. The differential diagnosis at this time included a cutaneous or systemic infection, vasculitis, drug eruption, or cutaneous manifestation of an autoimmune condition. A shave biopsy of a skin lesion on the right hand demonstrated epidermal necrosis with a dense dermal neutrophilic infiltrate consistent with a neutrophilic dermatosis (Figure 2). There was no evidence of leukocytoclastic vasculitis. The histologic differential diagnosis included cutaneous infection, neutrophilic dermatosis of the hand, and SS. Special stains for infectious organisms including Gram, Grocott methenamine-silver, and auramine-rhodamine stains were negative for bacterial, fungal, and mycobacterial organisms, ruling out cutaneous infection. A diagnosis of drug-induced SS was made based on the histologic findings, diffuse distribution of the lesions, negative infectious evaluation, lack of underlying malignancy or autoimmune conditions, and onset following initiation of dupilumab.

Dupilumab was discontinued, and the patient was started on prednisone with rapid improvement in the symptoms. She underwent a slow taper of the prednisone over approximately 2 months with a slow downtrend of eosinophils. She was transitioned to a different biologic agent, benralizumab, with no further recurrence of the rash or arthralgia.

Comment

Dupilumab is a human monoclonal IgG4 antibody that inhibits IL-4 and IL-13 signaling by binding to the IL-4Rα subunit. By blocking IL-4Rα, dupilumab inhibits IL-4 and IL-13 cytokine-induced inflammatory responses, including the release of proinflammatory cytokines, chemokines, nitric oxide, and IgE. Currently, dupilumab is approved to treat refractory forms of moderate to severe asthma characterized by an eosinophilic phenotype or with corticosteroid-dependent asthma, moderate to severe atopic dermatitis, chronic rhinosinusitis with nasal polyposis, and eosinophilic esophagitis. The most common adverse events (incidence ≥1%) are injection-site reactions, oropharyngeal pain, and eosinophilia.⁵ Interestingly, our patient did exhibit a high degree of eosinophilia; however, she met all criteria for drug-induced SS, and the skin biopsy was not consistent with an eosinophilic process. Notably, the peripheral neutrophils were not elevated. Neutrophilia often is seen in classic SS but is not required for a diagnosis of drug-induced SS. Rare cases of dupilumab-associated arthritis and serum sickness–like reaction have been described,^6-8 but our patient’s presentation was distinct, given other described signs, symptoms, and skin biopsy results. Histopathology results were not consistent with leukocytoclastic vasculitis, a potential mimicker of SS. Although the infectious and paraneoplastic evaluation was not exhaustive, the negative imaging from head to pelvis, the lack of recurrence of skin lesions, and the laboratory abnormalities after dupilumab discontinuation supported the conclusion that the culprit was not an infection or underlying malignancy. She had not started any other medications during this time frame, leaving dupilumab as the most likely offending agent. The mechanism for this reaction is not clear. It is possible that inhibition of IL-4 and IL-13 in the T helper 2 (T_H2) cell pathway may have led to upregulated IL-17–mediated inflammation⁹ as well as a neutrophilic process in the skin, but this would not explain the concurrent peripheral eosinophilia that was noted. Further studies are needed to investigate the pathophysiology of SS.

Conclusion

We report a rare case of dupilumab-induced SS. Corticosteroids accompanied by cessation of the medication proved to be an effective treatment. Prescribers must be aware of SS as a potential adverse reaction, as prompt recognition and treatment are needed.

Sweet syndrome (SS), also known as acute febrile neutrophilic dermatosis, was first described in 1964. ¹ Since then, several subtypes of SS have been recognized, including classic or idiopathic, which typically follows an acute viral illness; cancer related, typically in the form of a paraneoplastic syndrome; and drug induced. ² Drug-induced SS is defined by the following: (1) an abrupt onset of painful erythematous plaques or nodules; (2) histopathologic evidence of a dense neutrophilic infiltrate without evidence of leukocytoclastic vasculitis; (3) pyrexia above 38 ° C; (4) temporal relationship between drug and clinical presentation or temporally related recurrence after rechallenge; and (5) temporally related resolution of lesions after drug withdrawal or treatment with systemic corticosteroids. ³ All 5 criteria must be met to make a diagnosis of drug-induced SS. Since these criteria were established by Walker and Cohen, ³ various drugs have been identified as causative agents, including antibiotics, antiepileptics, antiretrovirals, antineoplastic agents, antipsychotics, oral contraceptives, nonsteroidal anti-inflammatory agents, and retinoids. ⁴ W e present a rare case of SS caused by dupilumab, a monoclonal antibody therapy, used in the treatment of severe eosinophilic asthma and atopic dermatitis.

Case Report

A 53-year-old woman presented with painful skin lesions, arthralgia, fever, and leukocytosis following initiation of dupilumab. She had a history of adult-onset, severe, persistent eosinophilic asthma, as well as chronic rhinosinusitis with nasal polyps, plaque psoriasis, and hypertrophic cardiomyopathy. She started mepolizumab 3 years prior to the current presentation for persistently uncontrolled asthma with a baseline peripheral eosinophil count of 860 cells/µL. After 3 years of minimal response to mepolizumab, she was started on dupilumab. Within 2 weeks of the first dose of dupilumab, she started experiencing bilateral knee pain. She subsequently developed daily fevers (temperature, 38.3 °C to 39.4 °C), fatigue, and pain in the back of the neck and head. After the second dose of dupilumab, she started experiencing painful skin lesions on the bilateral knuckles, elbows, and abdomen (Figure 1). She had difficulty using her hands and walking secondary to intense arthralgia involving the bilateral finger joints, elbows, and knees. Her primary care physician obtained a laboratory evaluation, which revealed an elevated total white blood cell count of 20×10³/mm³ (reference range, 4–11×10³/mm³) with 27.5% neutrophils and severely elevated eosinophils above her baseline to 57.3% with an absolute eosinophil count of 11,700 cells/µL (reference range, <400 cells/µL). Further assessment revealed an elevated erythrocyte sedimentation rate of 64 mm/h (reference range, 0–30 mm/h) and C-reactive protein level of 34 mg/dL (reference range, ≤0.80 mg/dL), with negative antinuclear antibody, rheumatoid factor, antineutrophilic cytoplasmic antibody, and Lyme antibody. IgG, IgA, and IgM levels were within reference range, and the IgE level was not elevated above her baseline. She had normal serum tryptase, and a peripheral D816V c-KIT mutation was not detected. She was subsequently hospitalized for further evaluation, at which time there was no fever or localizing infectious signs or symptoms. An infectious evaluation including urinalysis; respiratory swab for adenovirus, coronaviruses, human metapneumovirus, rhinovirus/enterovirus, influenza A and B, parainfluenza viruses, respiratory syncytial virus, Chlamydophila pneumoniae, and Mycoplasma pneumoniae; Lyme serology; and a computed tomography (CT) scan of the chest, abdomen, and pelvis revealed no evidence of infection. A parasite evaluation was ordered but was not performed. There was no evidence of malignancy on CT of the chest, abdomen, and pelvis or CT of the head without contrast. A lumbar puncture was considered but was ultimately deferred.

At the current presentation, the patient was following up in the dermatology clinic shortly after discharge. The lesions on the fingers and arms were described by the dermatologist as deep, erythematous, 0.5-cm bullous papules. The differential diagnosis at this time included a cutaneous or systemic infection, vasculitis, drug eruption, or cutaneous manifestation of an autoimmune condition. A shave biopsy of a skin lesion on the right hand demonstrated epidermal necrosis with a dense dermal neutrophilic infiltrate consistent with a neutrophilic dermatosis (Figure 2). There was no evidence of leukocytoclastic vasculitis. The histologic differential diagnosis included cutaneous infection, neutrophilic dermatosis of the hand, and SS. Special stains for infectious organisms including Gram, Grocott methenamine-silver, and auramine-rhodamine stains were negative for bacterial, fungal, and mycobacterial organisms, ruling out cutaneous infection. A diagnosis of drug-induced SS was made based on the histologic findings, diffuse distribution of the lesions, negative infectious evaluation, lack of underlying malignancy or autoimmune conditions, and onset following initiation of dupilumab.

Dupilumab was discontinued, and the patient was started on prednisone with rapid improvement in the symptoms. She underwent a slow taper of the prednisone over approximately 2 months with a slow downtrend of eosinophils. She was transitioned to a different biologic agent, benralizumab, with no further recurrence of the rash or arthralgia.

Comment

Dupilumab is a human monoclonal IgG4 antibody that inhibits IL-4 and IL-13 signaling by binding to the IL-4Rα subunit. By blocking IL-4Rα, dupilumab inhibits IL-4 and IL-13 cytokine-induced inflammatory responses, including the release of proinflammatory cytokines, chemokines, nitric oxide, and IgE. Currently, dupilumab is approved to treat refractory forms of moderate to severe asthma characterized by an eosinophilic phenotype or with corticosteroid-dependent asthma, moderate to severe atopic dermatitis, chronic rhinosinusitis with nasal polyposis, and eosinophilic esophagitis. The most common adverse events (incidence ≥1%) are injection-site reactions, oropharyngeal pain, and eosinophilia.⁵ Interestingly, our patient did exhibit a high degree of eosinophilia; however, she met all criteria for drug-induced SS, and the skin biopsy was not consistent with an eosinophilic process. Notably, the peripheral neutrophils were not elevated. Neutrophilia often is seen in classic SS but is not required for a diagnosis of drug-induced SS. Rare cases of dupilumab-associated arthritis and serum sickness–like reaction have been described,^6-8 but our patient’s presentation was distinct, given other described signs, symptoms, and skin biopsy results. Histopathology results were not consistent with leukocytoclastic vasculitis, a potential mimicker of SS. Although the infectious and paraneoplastic evaluation was not exhaustive, the negative imaging from head to pelvis, the lack of recurrence of skin lesions, and the laboratory abnormalities after dupilumab discontinuation supported the conclusion that the culprit was not an infection or underlying malignancy. She had not started any other medications during this time frame, leaving dupilumab as the most likely offending agent. The mechanism for this reaction is not clear. It is possible that inhibition of IL-4 and IL-13 in the T helper 2 (T_H2) cell pathway may have led to upregulated IL-17–mediated inflammation⁹ as well as a neutrophilic process in the skin, but this would not explain the concurrent peripheral eosinophilia that was noted. Further studies are needed to investigate the pathophysiology of SS.

Conclusion

We report a rare case of dupilumab-induced SS. Corticosteroids accompanied by cessation of the medication proved to be an effective treatment. Prescribers must be aware of SS as a potential adverse reaction, as prompt recognition and treatment are needed.

Sweet syndrome (SS), also known as acute febrile neutrophilic dermatosis, was first described in 1964. ¹ Since then, several subtypes of SS have been recognized, including classic or idiopathic, which typically follows an acute viral illness; cancer related, typically in the form of a paraneoplastic syndrome; and drug induced. ² Drug-induced SS is defined by the following: (1) an abrupt onset of painful erythematous plaques or nodules; (2) histopathologic evidence of a dense neutrophilic infiltrate without evidence of leukocytoclastic vasculitis; (3) pyrexia above 38 ° C; (4) temporal relationship between drug and clinical presentation or temporally related recurrence after rechallenge; and (5) temporally related resolution of lesions after drug withdrawal or treatment with systemic corticosteroids. ³ All 5 criteria must be met to make a diagnosis of drug-induced SS. Since these criteria were established by Walker and Cohen, ³ various drugs have been identified as causative agents, including antibiotics, antiepileptics, antiretrovirals, antineoplastic agents, antipsychotics, oral contraceptives, nonsteroidal anti-inflammatory agents, and retinoids. ⁴ W e present a rare case of SS caused by dupilumab, a monoclonal antibody therapy, used in the treatment of severe eosinophilic asthma and atopic dermatitis.

Case Report

A 53-year-old woman presented with painful skin lesions, arthralgia, fever, and leukocytosis following initiation of dupilumab. She had a history of adult-onset, severe, persistent eosinophilic asthma, as well as chronic rhinosinusitis with nasal polyps, plaque psoriasis, and hypertrophic cardiomyopathy. She started mepolizumab 3 years prior to the current presentation for persistently uncontrolled asthma with a baseline peripheral eosinophil count of 860 cells/µL. After 3 years of minimal response to mepolizumab, she was started on dupilumab. Within 2 weeks of the first dose of dupilumab, she started experiencing bilateral knee pain. She subsequently developed daily fevers (temperature, 38.3 °C to 39.4 °C), fatigue, and pain in the back of the neck and head. After the second dose of dupilumab, she started experiencing painful skin lesions on the bilateral knuckles, elbows, and abdomen (Figure 1). She had difficulty using her hands and walking secondary to intense arthralgia involving the bilateral finger joints, elbows, and knees. Her primary care physician obtained a laboratory evaluation, which revealed an elevated total white blood cell count of 20×10³/mm³ (reference range, 4–11×10³/mm³) with 27.5% neutrophils and severely elevated eosinophils above her baseline to 57.3% with an absolute eosinophil count of 11,700 cells/µL (reference range, <400 cells/µL). Further assessment revealed an elevated erythrocyte sedimentation rate of 64 mm/h (reference range, 0–30 mm/h) and C-reactive protein level of 34 mg/dL (reference range, ≤0.80 mg/dL), with negative antinuclear antibody, rheumatoid factor, antineutrophilic cytoplasmic antibody, and Lyme antibody. IgG, IgA, and IgM levels were within reference range, and the IgE level was not elevated above her baseline. She had normal serum tryptase, and a peripheral D816V c-KIT mutation was not detected. She was subsequently hospitalized for further evaluation, at which time there was no fever or localizing infectious signs or symptoms. An infectious evaluation including urinalysis; respiratory swab for adenovirus, coronaviruses, human metapneumovirus, rhinovirus/enterovirus, influenza A and B, parainfluenza viruses, respiratory syncytial virus, Chlamydophila pneumoniae, and Mycoplasma pneumoniae; Lyme serology; and a computed tomography (CT) scan of the chest, abdomen, and pelvis revealed no evidence of infection. A parasite evaluation was ordered but was not performed. There was no evidence of malignancy on CT of the chest, abdomen, and pelvis or CT of the head without contrast. A lumbar puncture was considered but was ultimately deferred.

At the current presentation, the patient was following up in the dermatology clinic shortly after discharge. The lesions on the fingers and arms were described by the dermatologist as deep, erythematous, 0.5-cm bullous papules. The differential diagnosis at this time included a cutaneous or systemic infection, vasculitis, drug eruption, or cutaneous manifestation of an autoimmune condition. A shave biopsy of a skin lesion on the right hand demonstrated epidermal necrosis with a dense dermal neutrophilic infiltrate consistent with a neutrophilic dermatosis (Figure 2). There was no evidence of leukocytoclastic vasculitis. The histologic differential diagnosis included cutaneous infection, neutrophilic dermatosis of the hand, and SS. Special stains for infectious organisms including Gram, Grocott methenamine-silver, and auramine-rhodamine stains were negative for bacterial, fungal, and mycobacterial organisms, ruling out cutaneous infection. A diagnosis of drug-induced SS was made based on the histologic findings, diffuse distribution of the lesions, negative infectious evaluation, lack of underlying malignancy or autoimmune conditions, and onset following initiation of dupilumab.

Dupilumab was discontinued, and the patient was started on prednisone with rapid improvement in the symptoms. She underwent a slow taper of the prednisone over approximately 2 months with a slow downtrend of eosinophils. She was transitioned to a different biologic agent, benralizumab, with no further recurrence of the rash or arthralgia.

Comment

Dupilumab is a human monoclonal IgG4 antibody that inhibits IL-4 and IL-13 signaling by binding to the IL-4Rα subunit. By blocking IL-4Rα, dupilumab inhibits IL-4 and IL-13 cytokine-induced inflammatory responses, including the release of proinflammatory cytokines, chemokines, nitric oxide, and IgE. Currently, dupilumab is approved to treat refractory forms of moderate to severe asthma characterized by an eosinophilic phenotype or with corticosteroid-dependent asthma, moderate to severe atopic dermatitis, chronic rhinosinusitis with nasal polyposis, and eosinophilic esophagitis. The most common adverse events (incidence ≥1%) are injection-site reactions, oropharyngeal pain, and eosinophilia.⁵ Interestingly, our patient did exhibit a high degree of eosinophilia; however, she met all criteria for drug-induced SS, and the skin biopsy was not consistent with an eosinophilic process. Notably, the peripheral neutrophils were not elevated. Neutrophilia often is seen in classic SS but is not required for a diagnosis of drug-induced SS. Rare cases of dupilumab-associated arthritis and serum sickness–like reaction have been described,^6-8 but our patient’s presentation was distinct, given other described signs, symptoms, and skin biopsy results. Histopathology results were not consistent with leukocytoclastic vasculitis, a potential mimicker of SS. Although the infectious and paraneoplastic evaluation was not exhaustive, the negative imaging from head to pelvis, the lack of recurrence of skin lesions, and the laboratory abnormalities after dupilumab discontinuation supported the conclusion that the culprit was not an infection or underlying malignancy. She had not started any other medications during this time frame, leaving dupilumab as the most likely offending agent. The mechanism for this reaction is not clear. It is possible that inhibition of IL-4 and IL-13 in the T helper 2 (T_H2) cell pathway may have led to upregulated IL-17–mediated inflammation⁹ as well as a neutrophilic process in the skin, but this would not explain the concurrent peripheral eosinophilia that was noted. Further studies are needed to investigate the pathophysiology of SS.

Conclusion

We report a rare case of dupilumab-induced SS. Corticosteroids accompanied by cessation of the medication proved to be an effective treatment. Prescribers must be aware of SS as a potential adverse reaction, as prompt recognition and treatment are needed.

Younger colorectal cancer patients with metastatic disease had distinct patterns of adverse events and worse survival than older patients with the same type of cancer, results of a new study indicate.

The incidence of metastatic colorectal cancer (mCRC) among adults younger than 50 years has been increasing, and although younger patients are treated with aggressive regimens similarly to older patients, outcomes data, including incidence of toxic effects, across age groups are limited, wrote Lingbin Meng, MD, of H. Lee Moffitt Cancer Center & Research Institute, Tampa, Fla., and colleagues, in their paper on the new research.

“Studies on the age-related disparity ... provided mixed findings,” said corresponding author Hao Xie, MD, of the Mayo Clinic in Rochester, Minn., in an interview.

According to the paper, published in JAMA Network Open, the researchers sought to evaluate the association between age and mCRC treatment-related adverse events and survival.

The study population included 1,223 mCRC patients who underwent first-line treatment with fluorouracil and oxaliplatin therapy in three clinical trials. An additional 736 patients with mCRC from the Moffitt Cancer Center were used to assess genomic alterations and serve as an external validation cohort.
 

Methods and results

Patients were divided into three age groups: younger than 50 years, 50-65 years, and 65 years and older. Early onset was defined as younger than 50 years. Approximately 58% of the study population was male.

The primary outcomes were treatment-related adverse events and survival rates. Overall survival (OS) and progression-free survival (PFS) were was significantly shorter in the early-onset group, compared with the 50-65 years group (hazard ratios, 1.48 and 1.46, respectively, P < .001 for both) in a multivariate analysis. The shorter OS in the early-onset group was confirmed in the validation cohort.

The early-onset patients had significantly higher incidence of nausea and vomiting, severe abdominal pain, severe anemia, and severe rash, compared with patients in both the 50- to 65-year-old group and the older than 65 years group. In addition, abdominal pain and severe liver toxicity effects were associated with shorter survival in the early-onset patients.

Genomic data from the Moffitt cohort showed a higher prevalence of CTNNB1 mutation among patients younger than 50 years, compared with the 50- to 65-year-old group and the older than 65 years group (6.6%, 3.1%, and 2.3%, respectively; P = .047), as well as ERBB2 amplification (5.1%, 0.6%, and 2.3%, respectively; P = .005), and CREBBP mutation (3.1%, 0.9%, and 0.5%; P = .05), although the prevalence of BRAF mutation was significantly lower in the younger patients, compared with patients in the older groups (7.7%, 8.5%, and 16.7%, respectively; P = .002).

These data suggest that distinct genomic profiles may play a role in the worse outcomes for patients with early-onset mCRC, the researchers said.

The findings were limited by several factors, including the timing of the trials prior to the use of biologics as standard first-line therapy, the researchers noted. Other limitations include a lack of data on treatment adherence and intensity and the location and number of metastases, and potential limited generalizability to other populations given that the majority of the participants were white, they said.
 

Data support individualized treatment

“We were surprised to find that patients with early-onset metastatic colorectal cancer had worse survival outcome, compared to older patients with metastatic colorectal cancer,” Dr. Xie said, in an interview. “On the other hand, we were not surprised to find unique adverse-event patterns in patients with early-onset metastatic colorectal cancer.”

For clinicians, “The take home message is that we should adopt individualized management approaches [regarding] cancer-direct treatments and treatment-related side effects in patients with early-onset metastatic colorectal cancer,” said Dr. Xie. However, more research is needed in the form of prospective and interventional studies to address treatment-related side effects and to develop novel and personalized therapeutics for patients with early-onset metastatic colorectal cancer, Dr. Xie added.
 

Early-onset cancer concerns persist

“The increasing shift in early colon cancers demands better understanding, in particular as we attempt a more patient-focused approach to treatments,” said David A. Johnson, MD, chief of gastroenterology at Eastern Virginia Medical School, Norfolk, in an interview. “Clearly, genetic amplifications and oncogene mutations play an essential role in tumorigenesis and tumor progression, but data on specifics are needed.”

With regard to the current study, “it makes sense that the pathways to CRC development and progression at least in part play a role in age-related cancers,” said Dr. Johnson, who was not involved in the study.

The clinical implications from the study are that early-onset CRC “can be aggressive and progressive,” Dr. Johnson said. “Younger patients need to recognize the earlier ages for beginning CRC screening, age 45 years for those at average risk, and certainly report any new sign or symptom to their care provider, in particular blood in the stool.”

As for additional research, “The oncogenetic markers will be helpful in guiding treatment approaches to be more individual specific, rather than just disease focused,” Dr. Johnson said. “The role of the gut microbiome will need evaluation as it relates to these oncogenetic factors,” he noted. Considerations include not only the potential influence of the gut microbiome on the expression of these factors, but also the impact of the gut microbiome on the chemotherapeutic response, as has been evident with checkpoint inhibitors, he added.

The study was supported by a Moffitt Support Grant to Dr. Xie and the University of South Florida Continuing Medical Education Funding. The researchers had no financial conflicts to disclose. Dr. Johnson had no relevant financial conflicts to disclose.

Younger colorectal cancer patients with metastatic disease had distinct patterns of adverse events and worse survival than older patients with the same type of cancer, results of a new study indicate.

The incidence of metastatic colorectal cancer (mCRC) among adults younger than 50 years has been increasing, and although younger patients are treated with aggressive regimens similarly to older patients, outcomes data, including incidence of toxic effects, across age groups are limited, wrote Lingbin Meng, MD, of H. Lee Moffitt Cancer Center & Research Institute, Tampa, Fla., and colleagues, in their paper on the new research.

“Studies on the age-related disparity ... provided mixed findings,” said corresponding author Hao Xie, MD, of the Mayo Clinic in Rochester, Minn., in an interview.

According to the paper, published in JAMA Network Open, the researchers sought to evaluate the association between age and mCRC treatment-related adverse events and survival.

The study population included 1,223 mCRC patients who underwent first-line treatment with fluorouracil and oxaliplatin therapy in three clinical trials. An additional 736 patients with mCRC from the Moffitt Cancer Center were used to assess genomic alterations and serve as an external validation cohort.
 

Methods and results

Patients were divided into three age groups: younger than 50 years, 50-65 years, and 65 years and older. Early onset was defined as younger than 50 years. Approximately 58% of the study population was male.

The primary outcomes were treatment-related adverse events and survival rates. Overall survival (OS) and progression-free survival (PFS) were was significantly shorter in the early-onset group, compared with the 50-65 years group (hazard ratios, 1.48 and 1.46, respectively, P < .001 for both) in a multivariate analysis. The shorter OS in the early-onset group was confirmed in the validation cohort.

The early-onset patients had significantly higher incidence of nausea and vomiting, severe abdominal pain, severe anemia, and severe rash, compared with patients in both the 50- to 65-year-old group and the older than 65 years group. In addition, abdominal pain and severe liver toxicity effects were associated with shorter survival in the early-onset patients.

Genomic data from the Moffitt cohort showed a higher prevalence of CTNNB1 mutation among patients younger than 50 years, compared with the 50- to 65-year-old group and the older than 65 years group (6.6%, 3.1%, and 2.3%, respectively; P = .047), as well as ERBB2 amplification (5.1%, 0.6%, and 2.3%, respectively; P = .005), and CREBBP mutation (3.1%, 0.9%, and 0.5%; P = .05), although the prevalence of BRAF mutation was significantly lower in the younger patients, compared with patients in the older groups (7.7%, 8.5%, and 16.7%, respectively; P = .002).

These data suggest that distinct genomic profiles may play a role in the worse outcomes for patients with early-onset mCRC, the researchers said.

The findings were limited by several factors, including the timing of the trials prior to the use of biologics as standard first-line therapy, the researchers noted. Other limitations include a lack of data on treatment adherence and intensity and the location and number of metastases, and potential limited generalizability to other populations given that the majority of the participants were white, they said.
 

Data support individualized treatment

“We were surprised to find that patients with early-onset metastatic colorectal cancer had worse survival outcome, compared to older patients with metastatic colorectal cancer,” Dr. Xie said, in an interview. “On the other hand, we were not surprised to find unique adverse-event patterns in patients with early-onset metastatic colorectal cancer.”

For clinicians, “The take home message is that we should adopt individualized management approaches [regarding] cancer-direct treatments and treatment-related side effects in patients with early-onset metastatic colorectal cancer,” said Dr. Xie. However, more research is needed in the form of prospective and interventional studies to address treatment-related side effects and to develop novel and personalized therapeutics for patients with early-onset metastatic colorectal cancer, Dr. Xie added.
 

Early-onset cancer concerns persist

“The increasing shift in early colon cancers demands better understanding, in particular as we attempt a more patient-focused approach to treatments,” said David A. Johnson, MD, chief of gastroenterology at Eastern Virginia Medical School, Norfolk, in an interview. “Clearly, genetic amplifications and oncogene mutations play an essential role in tumorigenesis and tumor progression, but data on specifics are needed.”

With regard to the current study, “it makes sense that the pathways to CRC development and progression at least in part play a role in age-related cancers,” said Dr. Johnson, who was not involved in the study.

The clinical implications from the study are that early-onset CRC “can be aggressive and progressive,” Dr. Johnson said. “Younger patients need to recognize the earlier ages for beginning CRC screening, age 45 years for those at average risk, and certainly report any new sign or symptom to their care provider, in particular blood in the stool.”

As for additional research, “The oncogenetic markers will be helpful in guiding treatment approaches to be more individual specific, rather than just disease focused,” Dr. Johnson said. “The role of the gut microbiome will need evaluation as it relates to these oncogenetic factors,” he noted. Considerations include not only the potential influence of the gut microbiome on the expression of these factors, but also the impact of the gut microbiome on the chemotherapeutic response, as has been evident with checkpoint inhibitors, he added.

The study was supported by a Moffitt Support Grant to Dr. Xie and the University of South Florida Continuing Medical Education Funding. The researchers had no financial conflicts to disclose. Dr. Johnson had no relevant financial conflicts to disclose.

Younger colorectal cancer patients with metastatic disease had distinct patterns of adverse events and worse survival than older patients with the same type of cancer, results of a new study indicate.

The incidence of metastatic colorectal cancer (mCRC) among adults younger than 50 years has been increasing, and although younger patients are treated with aggressive regimens similarly to older patients, outcomes data, including incidence of toxic effects, across age groups are limited, wrote Lingbin Meng, MD, of H. Lee Moffitt Cancer Center & Research Institute, Tampa, Fla., and colleagues, in their paper on the new research.

“Studies on the age-related disparity ... provided mixed findings,” said corresponding author Hao Xie, MD, of the Mayo Clinic in Rochester, Minn., in an interview.

According to the paper, published in JAMA Network Open, the researchers sought to evaluate the association between age and mCRC treatment-related adverse events and survival.

The study population included 1,223 mCRC patients who underwent first-line treatment with fluorouracil and oxaliplatin therapy in three clinical trials. An additional 736 patients with mCRC from the Moffitt Cancer Center were used to assess genomic alterations and serve as an external validation cohort.
 

Methods and results

Patients were divided into three age groups: younger than 50 years, 50-65 years, and 65 years and older. Early onset was defined as younger than 50 years. Approximately 58% of the study population was male.

The primary outcomes were treatment-related adverse events and survival rates. Overall survival (OS) and progression-free survival (PFS) were was significantly shorter in the early-onset group, compared with the 50-65 years group (hazard ratios, 1.48 and 1.46, respectively, P < .001 for both) in a multivariate analysis. The shorter OS in the early-onset group was confirmed in the validation cohort.

The early-onset patients had significantly higher incidence of nausea and vomiting, severe abdominal pain, severe anemia, and severe rash, compared with patients in both the 50- to 65-year-old group and the older than 65 years group. In addition, abdominal pain and severe liver toxicity effects were associated with shorter survival in the early-onset patients.

Genomic data from the Moffitt cohort showed a higher prevalence of CTNNB1 mutation among patients younger than 50 years, compared with the 50- to 65-year-old group and the older than 65 years group (6.6%, 3.1%, and 2.3%, respectively; P = .047), as well as ERBB2 amplification (5.1%, 0.6%, and 2.3%, respectively; P = .005), and CREBBP mutation (3.1%, 0.9%, and 0.5%; P = .05), although the prevalence of BRAF mutation was significantly lower in the younger patients, compared with patients in the older groups (7.7%, 8.5%, and 16.7%, respectively; P = .002).

These data suggest that distinct genomic profiles may play a role in the worse outcomes for patients with early-onset mCRC, the researchers said.

The findings were limited by several factors, including the timing of the trials prior to the use of biologics as standard first-line therapy, the researchers noted. Other limitations include a lack of data on treatment adherence and intensity and the location and number of metastases, and potential limited generalizability to other populations given that the majority of the participants were white, they said.
 

Data support individualized treatment

“We were surprised to find that patients with early-onset metastatic colorectal cancer had worse survival outcome, compared to older patients with metastatic colorectal cancer,” Dr. Xie said, in an interview. “On the other hand, we were not surprised to find unique adverse-event patterns in patients with early-onset metastatic colorectal cancer.”

For clinicians, “The take home message is that we should adopt individualized management approaches [regarding] cancer-direct treatments and treatment-related side effects in patients with early-onset metastatic colorectal cancer,” said Dr. Xie. However, more research is needed in the form of prospective and interventional studies to address treatment-related side effects and to develop novel and personalized therapeutics for patients with early-onset metastatic colorectal cancer, Dr. Xie added.
 

Early-onset cancer concerns persist

“The increasing shift in early colon cancers demands better understanding, in particular as we attempt a more patient-focused approach to treatments,” said David A. Johnson, MD, chief of gastroenterology at Eastern Virginia Medical School, Norfolk, in an interview. “Clearly, genetic amplifications and oncogene mutations play an essential role in tumorigenesis and tumor progression, but data on specifics are needed.”

With regard to the current study, “it makes sense that the pathways to CRC development and progression at least in part play a role in age-related cancers,” said Dr. Johnson, who was not involved in the study.

The clinical implications from the study are that early-onset CRC “can be aggressive and progressive,” Dr. Johnson said. “Younger patients need to recognize the earlier ages for beginning CRC screening, age 45 years for those at average risk, and certainly report any new sign or symptom to their care provider, in particular blood in the stool.”

As for additional research, “The oncogenetic markers will be helpful in guiding treatment approaches to be more individual specific, rather than just disease focused,” Dr. Johnson said. “The role of the gut microbiome will need evaluation as it relates to these oncogenetic factors,” he noted. Considerations include not only the potential influence of the gut microbiome on the expression of these factors, but also the impact of the gut microbiome on the chemotherapeutic response, as has been evident with checkpoint inhibitors, he added.

The study was supported by a Moffitt Support Grant to Dr. Xie and the University of South Florida Continuing Medical Education Funding. The researchers had no financial conflicts to disclose. Dr. Johnson had no relevant financial conflicts to disclose.

AUSTIN, TEX. – Treatment with the anticalcitonin gene-related peptide (anti-CGRP) fremanezumab (Ajovy, Teva Pharmaceuticals) reduces depressive symptoms in patients with migraine and comorbid major depressive disorder, new research shows.

Patients with both conditions who were randomly assigned to receive fremanezumab showed a statistically significant reduction in both the 17-item Hamilton Depression Rating Scale (HAMD-17) and the nine-criteria Patient Health Questionnaire (PHQ-9) scores, compared with matched controls who received placebo.

The results from the UNITE trial were presented at the annual meeting of the American Headache Society.
 

Long-standing questions

“It’s been well known for a long time that migraine is comorbid with a number of illnesses, and one of the most common is depression,” said study investigator Richard B. Lipton, a professor of neurology at Albert Einstein College of Medicine and the director of the Montefiore Headache Center, New York.

“Do you treat the depression? Do you treat the migraine? Do you independently treat both? Those have been long-standing questions for clinicians,” Dr. Lipton said.

Investigators randomly assigned 330 adults with migraine who were diagnosed with moderate-to-severe MDD (defined as a PHQ-9 score of 10 or greater) to receive 225 mg subcutaneous monthly fremanezumab (n = 164) or placebo (n = 166) for 12 weeks.

The trial continued as an open-label trial for another 12 weeks.

During the double-blind phase of the study, the mean change from baseline in the HAMD-17 score with placebo was –4.6 at week 8 and –5.4 at week 12, compared with –6.0 with fremanezumab at week 8 (P = .0205) and –6.7 at week 12 (P = .0228).

The change from baseline in PHQ-9 total score at week 8 was –5.8 for placebo and –7.1 for fremanezumab (P = .0283). At week 12, the change was –6.3 for placebo versus –7.8 for fremanezumab (P = .0108). These reductions were maintained throughout the open-label period of the trial.

The beneficial effect on depression and migraine demonstrated in the study is interesting on several levels, Dr. Lipton said.

“One, it tells us that if the patient has migraine and depression and you treat with fremanezumab, both disorders get better to a statistically significant degree. That’s critically important,” he said.

“The other thing, and this is actually what I find most interesting about this study, is that fremanezumab doesn’t get into the brain. There are many antimigraine therapies that do, so you can treat a patient with migraine and depression with a tricyclic antidepressant.”

“It may make the migraine better and the depression better, but you don’t know if the benefit in depression comes from the improvement in migraine, because of course the antidepressant works for both conditions. Maybe there are people who would disagree with this, but my interpretation [of the trial results] is that the depression got better because the migraine got better,” he added.

The link between migraine and depression is well established, Dr. Lipton added. Longitudinal studies have shown that people with depression but without migraine develop migraine at increased rates, compared with people with no depression. Conversely, people with migraine but no depression develop depression at increased rates.

“Both disorders may have a common substrate, but I also think many forms of chronic pain lead to depression, and that’s the part we’re making better,” he said.

If fremanezumab has this dual effect on migraine and depression, it is possible that other anti-CGRP drugs will have a similar effect, Dr. Lipton said.

“Honestly, my hope is that other companies that make effective drugs will do similar studies to see if other monoclonal antibodies that target CGRP have the same effect. My guess is that all of them work but until the studies are done, I’m going to use fremanezumab, the one that has been studied, in my patients.”

He added that depression is an important comorbidity of migraine and represents a huge challenge for clinicians. “A lot of headache patients want to know what to do about comorbid anxiety or comorbid depression. I run a headache center in a specialty practice, and when people come in with migraine, they almost always come in with migraine and depression or anxiety or another pain disorder, or something else, and one of the great challenges in the practice is managing these comorbidities,” he said.
 

A bidirectional relationship

The overlap between migraine and depression and anxiety has been known for quite a while, agreed Elizabeth W. Loder, MD, MPH, vice chair of academic affairs, department of neurology, Brigham and Women’s Hospital, and professor of neurology at Harvard Medical School, both in Boston.

“I think the relationship is generally viewed as bidirectional and causality is uncertain. I still do not think I would assume that any drug that reduces migraine would reduce depression,” said Dr. Loder.

However, she added, the fremanezumab study data are interesting. “The effects of any drug on depression could be due to improvement of migraine or it could be due to some other effect of the treatment on depression. That is what makes these results so intriguing. If the findings are borne out by other studies, it could mean that these treatments would be preferred to those older ones in patients with depression,” Dr. Loder said.

Also commenting on the findings, Huma Sheikh, MD, CEO of NY Neurology Medicine PC, said the study is important because it confirms the strong association between migraine and depression. “Both conditions have similar underlying neurobiological pathophysiologies, and if you are impacting one area in the brain with the CGRP inhibitors, you might also be targeting some of the receptors or pathways that are involved in depression,” Dr. Sheikh said.

The study was funded by Teva Pharmaceuticals. Dr. Lipton reported financial relationships with Teva and multiple other pharmaceutical companies. Dr. Loder and Dr. Sheikh have disclosed no relevant financial relationships.

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

AUSTIN, TEX. – Treatment with the anticalcitonin gene-related peptide (anti-CGRP) fremanezumab (Ajovy, Teva Pharmaceuticals) reduces depressive symptoms in patients with migraine and comorbid major depressive disorder, new research shows.

Patients with both conditions who were randomly assigned to receive fremanezumab showed a statistically significant reduction in both the 17-item Hamilton Depression Rating Scale (HAMD-17) and the nine-criteria Patient Health Questionnaire (PHQ-9) scores, compared with matched controls who received placebo.

The results from the UNITE trial were presented at the annual meeting of the American Headache Society.
 

Long-standing questions

“It’s been well known for a long time that migraine is comorbid with a number of illnesses, and one of the most common is depression,” said study investigator Richard B. Lipton, a professor of neurology at Albert Einstein College of Medicine and the director of the Montefiore Headache Center, New York.

“Do you treat the depression? Do you treat the migraine? Do you independently treat both? Those have been long-standing questions for clinicians,” Dr. Lipton said.

Investigators randomly assigned 330 adults with migraine who were diagnosed with moderate-to-severe MDD (defined as a PHQ-9 score of 10 or greater) to receive 225 mg subcutaneous monthly fremanezumab (n = 164) or placebo (n = 166) for 12 weeks.

The trial continued as an open-label trial for another 12 weeks.

During the double-blind phase of the study, the mean change from baseline in the HAMD-17 score with placebo was –4.6 at week 8 and –5.4 at week 12, compared with –6.0 with fremanezumab at week 8 (P = .0205) and –6.7 at week 12 (P = .0228).

The change from baseline in PHQ-9 total score at week 8 was –5.8 for placebo and –7.1 for fremanezumab (P = .0283). At week 12, the change was –6.3 for placebo versus –7.8 for fremanezumab (P = .0108). These reductions were maintained throughout the open-label period of the trial.

The beneficial effect on depression and migraine demonstrated in the study is interesting on several levels, Dr. Lipton said.

“One, it tells us that if the patient has migraine and depression and you treat with fremanezumab, both disorders get better to a statistically significant degree. That’s critically important,” he said.

“The other thing, and this is actually what I find most interesting about this study, is that fremanezumab doesn’t get into the brain. There are many antimigraine therapies that do, so you can treat a patient with migraine and depression with a tricyclic antidepressant.”

“It may make the migraine better and the depression better, but you don’t know if the benefit in depression comes from the improvement in migraine, because of course the antidepressant works for both conditions. Maybe there are people who would disagree with this, but my interpretation [of the trial results] is that the depression got better because the migraine got better,” he added.

The link between migraine and depression is well established, Dr. Lipton added. Longitudinal studies have shown that people with depression but without migraine develop migraine at increased rates, compared with people with no depression. Conversely, people with migraine but no depression develop depression at increased rates.

“Both disorders may have a common substrate, but I also think many forms of chronic pain lead to depression, and that’s the part we’re making better,” he said.

If fremanezumab has this dual effect on migraine and depression, it is possible that other anti-CGRP drugs will have a similar effect, Dr. Lipton said.

“Honestly, my hope is that other companies that make effective drugs will do similar studies to see if other monoclonal antibodies that target CGRP have the same effect. My guess is that all of them work but until the studies are done, I’m going to use fremanezumab, the one that has been studied, in my patients.”

He added that depression is an important comorbidity of migraine and represents a huge challenge for clinicians. “A lot of headache patients want to know what to do about comorbid anxiety or comorbid depression. I run a headache center in a specialty practice, and when people come in with migraine, they almost always come in with migraine and depression or anxiety or another pain disorder, or something else, and one of the great challenges in the practice is managing these comorbidities,” he said.
 

A bidirectional relationship

The overlap between migraine and depression and anxiety has been known for quite a while, agreed Elizabeth W. Loder, MD, MPH, vice chair of academic affairs, department of neurology, Brigham and Women’s Hospital, and professor of neurology at Harvard Medical School, both in Boston.

“I think the relationship is generally viewed as bidirectional and causality is uncertain. I still do not think I would assume that any drug that reduces migraine would reduce depression,” said Dr. Loder.

However, she added, the fremanezumab study data are interesting. “The effects of any drug on depression could be due to improvement of migraine or it could be due to some other effect of the treatment on depression. That is what makes these results so intriguing. If the findings are borne out by other studies, it could mean that these treatments would be preferred to those older ones in patients with depression,” Dr. Loder said.

Also commenting on the findings, Huma Sheikh, MD, CEO of NY Neurology Medicine PC, said the study is important because it confirms the strong association between migraine and depression. “Both conditions have similar underlying neurobiological pathophysiologies, and if you are impacting one area in the brain with the CGRP inhibitors, you might also be targeting some of the receptors or pathways that are involved in depression,” Dr. Sheikh said.

The study was funded by Teva Pharmaceuticals. Dr. Lipton reported financial relationships with Teva and multiple other pharmaceutical companies. Dr. Loder and Dr. Sheikh have disclosed no relevant financial relationships.

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

AUSTIN, TEX. – Treatment with the anticalcitonin gene-related peptide (anti-CGRP) fremanezumab (Ajovy, Teva Pharmaceuticals) reduces depressive symptoms in patients with migraine and comorbid major depressive disorder, new research shows.

Patients with both conditions who were randomly assigned to receive fremanezumab showed a statistically significant reduction in both the 17-item Hamilton Depression Rating Scale (HAMD-17) and the nine-criteria Patient Health Questionnaire (PHQ-9) scores, compared with matched controls who received placebo.

The results from the UNITE trial were presented at the annual meeting of the American Headache Society.
 

Long-standing questions

“It’s been well known for a long time that migraine is comorbid with a number of illnesses, and one of the most common is depression,” said study investigator Richard B. Lipton, a professor of neurology at Albert Einstein College of Medicine and the director of the Montefiore Headache Center, New York.

“Do you treat the depression? Do you treat the migraine? Do you independently treat both? Those have been long-standing questions for clinicians,” Dr. Lipton said.

Investigators randomly assigned 330 adults with migraine who were diagnosed with moderate-to-severe MDD (defined as a PHQ-9 score of 10 or greater) to receive 225 mg subcutaneous monthly fremanezumab (n = 164) or placebo (n = 166) for 12 weeks.

The trial continued as an open-label trial for another 12 weeks.

During the double-blind phase of the study, the mean change from baseline in the HAMD-17 score with placebo was –4.6 at week 8 and –5.4 at week 12, compared with –6.0 with fremanezumab at week 8 (P = .0205) and –6.7 at week 12 (P = .0228).

The change from baseline in PHQ-9 total score at week 8 was –5.8 for placebo and –7.1 for fremanezumab (P = .0283). At week 12, the change was –6.3 for placebo versus –7.8 for fremanezumab (P = .0108). These reductions were maintained throughout the open-label period of the trial.

The beneficial effect on depression and migraine demonstrated in the study is interesting on several levels, Dr. Lipton said.

“One, it tells us that if the patient has migraine and depression and you treat with fremanezumab, both disorders get better to a statistically significant degree. That’s critically important,” he said.

“The other thing, and this is actually what I find most interesting about this study, is that fremanezumab doesn’t get into the brain. There are many antimigraine therapies that do, so you can treat a patient with migraine and depression with a tricyclic antidepressant.”

“It may make the migraine better and the depression better, but you don’t know if the benefit in depression comes from the improvement in migraine, because of course the antidepressant works for both conditions. Maybe there are people who would disagree with this, but my interpretation [of the trial results] is that the depression got better because the migraine got better,” he added.

The link between migraine and depression is well established, Dr. Lipton added. Longitudinal studies have shown that people with depression but without migraine develop migraine at increased rates, compared with people with no depression. Conversely, people with migraine but no depression develop depression at increased rates.

“Both disorders may have a common substrate, but I also think many forms of chronic pain lead to depression, and that’s the part we’re making better,” he said.

If fremanezumab has this dual effect on migraine and depression, it is possible that other anti-CGRP drugs will have a similar effect, Dr. Lipton said.

“Honestly, my hope is that other companies that make effective drugs will do similar studies to see if other monoclonal antibodies that target CGRP have the same effect. My guess is that all of them work but until the studies are done, I’m going to use fremanezumab, the one that has been studied, in my patients.”

He added that depression is an important comorbidity of migraine and represents a huge challenge for clinicians. “A lot of headache patients want to know what to do about comorbid anxiety or comorbid depression. I run a headache center in a specialty practice, and when people come in with migraine, they almost always come in with migraine and depression or anxiety or another pain disorder, or something else, and one of the great challenges in the practice is managing these comorbidities,” he said.
 

A bidirectional relationship

The overlap between migraine and depression and anxiety has been known for quite a while, agreed Elizabeth W. Loder, MD, MPH, vice chair of academic affairs, department of neurology, Brigham and Women’s Hospital, and professor of neurology at Harvard Medical School, both in Boston.

“I think the relationship is generally viewed as bidirectional and causality is uncertain. I still do not think I would assume that any drug that reduces migraine would reduce depression,” said Dr. Loder.

However, she added, the fremanezumab study data are interesting. “The effects of any drug on depression could be due to improvement of migraine or it could be due to some other effect of the treatment on depression. That is what makes these results so intriguing. If the findings are borne out by other studies, it could mean that these treatments would be preferred to those older ones in patients with depression,” Dr. Loder said.

Also commenting on the findings, Huma Sheikh, MD, CEO of NY Neurology Medicine PC, said the study is important because it confirms the strong association between migraine and depression. “Both conditions have similar underlying neurobiological pathophysiologies, and if you are impacting one area in the brain with the CGRP inhibitors, you might also be targeting some of the receptors or pathways that are involved in depression,” Dr. Sheikh said.

The study was funded by Teva Pharmaceuticals. Dr. Lipton reported financial relationships with Teva and multiple other pharmaceutical companies. Dr. Loder and Dr. Sheikh have disclosed no relevant financial relationships.

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

Despite using methotrexate (MTX) in the management of psoriasis and PsA for more than 50 years, there is paucity of data on its effectiveness in PsA. It is also largely assumed that MTX is more effective for rheumatoid arthritis (RA) than for PsA. To evaluate MTX effectiveness vis-à-vis RA, Lindström and colleagues conducted an observational study with disease-modifying antirheumatic drug (DMARD)–naive patients with newly diagnosed PsA (n = 3642) who initiated MTX and matched comparator patients with RA (n = 3642) from national Swedish registers. At 6 months, although both groups of patients had improvement in pain, global health, and remission, the rates were higher in RA compared with PsA. Overall, 71% of patients with PsA and 76% of patients with RA were still taking MTX 2 years after initiating MTX. The time to starting another DMARD was shorter in RA compared with PsA. Thus, in early PsA, MTX treatment seems to provide significant benefits. However, the improvements are less impressive than they are for RA.

Biologic agents are generally safe and effective in the treatment of PsA. However, there are limited data on the safety and effectiveness in older and younger populations with PsA. Gossec and colleagues conducted a post hoc analysis of the PsABio trial that included patients with PsA who received ustekinumab, an interleukin 12/23 inhibitor, and were subgrouped into those < 60 years (n = 336) and ≥ 60 years (n = 103). At 6 months, a numerically higher proportion of patients < 60 years achieved clinical Disease Activity Index for Psoriatic Arthritis low disease activity compared with those ≥ 60 years. The proportions of patients reporting at least one (32.7% vs 40.9%) or serious (5.3% vs 9.6%) adverse events were numerically higher in the older population. However, treatment persistence was numerically higher in the older subgroup. These differences were not clinically meaningful; thus, ustekinumab may be safely used in older populations.

There are also limited data on the effectiveness of biologics in patients with juvenile PsA (jPsA). To address this, Correll and colleagues evaluated the safety and effectiveness of etanercept, an anti–tumor necrosis factor agent, in patients with jPsA using data from the Childhood Arthritis and Rheumatology Research Alliance Registry. In 226 patients, the overall incidence of adverse events of special interest and serious adverse events were low and included three cases of uveitis (incidence rate [IR]/100 person-years 0.55; 95% CI 0.18-1.69), one of neuropathy (IR/100 person-years 0.18; 95% CI 0.03-1.29), and one of cancer (IR/100 person-years 0.13; 95% CI 0.02-0.90). The ACR provisional criteria for inactive disease were achieved by 51.9% and 43.8% of patients at 6 and 12 months. Thus, etanercept is safe and effective in jPsA.

Despite using methotrexate (MTX) in the management of psoriasis and PsA for more than 50 years, there is paucity of data on its effectiveness in PsA. It is also largely assumed that MTX is more effective for rheumatoid arthritis (RA) than for PsA. To evaluate MTX effectiveness vis-à-vis RA, Lindström and colleagues conducted an observational study with disease-modifying antirheumatic drug (DMARD)–naive patients with newly diagnosed PsA (n = 3642) who initiated MTX and matched comparator patients with RA (n = 3642) from national Swedish registers. At 6 months, although both groups of patients had improvement in pain, global health, and remission, the rates were higher in RA compared with PsA. Overall, 71% of patients with PsA and 76% of patients with RA were still taking MTX 2 years after initiating MTX. The time to starting another DMARD was shorter in RA compared with PsA. Thus, in early PsA, MTX treatment seems to provide significant benefits. However, the improvements are less impressive than they are for RA.

Biologic agents are generally safe and effective in the treatment of PsA. However, there are limited data on the safety and effectiveness in older and younger populations with PsA. Gossec and colleagues conducted a post hoc analysis of the PsABio trial that included patients with PsA who received ustekinumab, an interleukin 12/23 inhibitor, and were subgrouped into those < 60 years (n = 336) and ≥ 60 years (n = 103). At 6 months, a numerically higher proportion of patients < 60 years achieved clinical Disease Activity Index for Psoriatic Arthritis low disease activity compared with those ≥ 60 years. The proportions of patients reporting at least one (32.7% vs 40.9%) or serious (5.3% vs 9.6%) adverse events were numerically higher in the older population. However, treatment persistence was numerically higher in the older subgroup. These differences were not clinically meaningful; thus, ustekinumab may be safely used in older populations.

There are also limited data on the effectiveness of biologics in patients with juvenile PsA (jPsA). To address this, Correll and colleagues evaluated the safety and effectiveness of etanercept, an anti–tumor necrosis factor agent, in patients with jPsA using data from the Childhood Arthritis and Rheumatology Research Alliance Registry. In 226 patients, the overall incidence of adverse events of special interest and serious adverse events were low and included three cases of uveitis (incidence rate [IR]/100 person-years 0.55; 95% CI 0.18-1.69), one of neuropathy (IR/100 person-years 0.18; 95% CI 0.03-1.29), and one of cancer (IR/100 person-years 0.13; 95% CI 0.02-0.90). The ACR provisional criteria for inactive disease were achieved by 51.9% and 43.8% of patients at 6 and 12 months. Thus, etanercept is safe and effective in jPsA.

Despite using methotrexate (MTX) in the management of psoriasis and PsA for more than 50 years, there is paucity of data on its effectiveness in PsA. It is also largely assumed that MTX is more effective for rheumatoid arthritis (RA) than for PsA. To evaluate MTX effectiveness vis-à-vis RA, Lindström and colleagues conducted an observational study with disease-modifying antirheumatic drug (DMARD)–naive patients with newly diagnosed PsA (n = 3642) who initiated MTX and matched comparator patients with RA (n = 3642) from national Swedish registers. At 6 months, although both groups of patients had improvement in pain, global health, and remission, the rates were higher in RA compared with PsA. Overall, 71% of patients with PsA and 76% of patients with RA were still taking MTX 2 years after initiating MTX. The time to starting another DMARD was shorter in RA compared with PsA. Thus, in early PsA, MTX treatment seems to provide significant benefits. However, the improvements are less impressive than they are for RA.

Biologic agents are generally safe and effective in the treatment of PsA. However, there are limited data on the safety and effectiveness in older and younger populations with PsA. Gossec and colleagues conducted a post hoc analysis of the PsABio trial that included patients with PsA who received ustekinumab, an interleukin 12/23 inhibitor, and were subgrouped into those < 60 years (n = 336) and ≥ 60 years (n = 103). At 6 months, a numerically higher proportion of patients < 60 years achieved clinical Disease Activity Index for Psoriatic Arthritis low disease activity compared with those ≥ 60 years. The proportions of patients reporting at least one (32.7% vs 40.9%) or serious (5.3% vs 9.6%) adverse events were numerically higher in the older population. However, treatment persistence was numerically higher in the older subgroup. These differences were not clinically meaningful; thus, ustekinumab may be safely used in older populations.

There are also limited data on the effectiveness of biologics in patients with juvenile PsA (jPsA). To address this, Correll and colleagues evaluated the safety and effectiveness of etanercept, an anti–tumor necrosis factor agent, in patients with jPsA using data from the Childhood Arthritis and Rheumatology Research Alliance Registry. In 226 patients, the overall incidence of adverse events of special interest and serious adverse events were low and included three cases of uveitis (incidence rate [IR]/100 person-years 0.55; 95% CI 0.18-1.69), one of neuropathy (IR/100 person-years 0.18; 95% CI 0.03-1.29), and one of cancer (IR/100 person-years 0.13; 95% CI 0.02-0.90). The ACR provisional criteria for inactive disease were achieved by 51.9% and 43.8% of patients at 6 and 12 months. Thus, etanercept is safe and effective in jPsA.