Drug Therapy

The American Society of Addiction Medicine has released an updated practice guideline for patients with opioid use disorder.

The guideline, called a focused update, advances ASAM’s 2015 National Practice Guidelines for the Treament of Opioid Use Disorder. “During the ongoing COVID-19 pandemic and the associated need for social distancing, it is especially important that clinicians and health care providers across the country take steps to ensure that individuals with OUD can continue to receive evidence-based care,” said Paul H. Earley, MD, president of ASAM, in a press release announcing the new guideline.

The guideline specifies that home-based buprenorphine induction is safe and effective for treatment of opioid use disorder and that no individual entering the criminal justice system should be subjected to opioid withdrawal.

“The research is clear, providing methadone or buprenorphine, even without psychosocial treatment, reduces the patient’s risk of death,” said Kyle Kampman, MD, chair of the group’s Guideline Writing Committee, in the release. “Ultimately, keeping patients with the disease of addiction alive and engaged to become ready for recovery is absolutely critical in the context of the deadly overdose epidemic that has struck communities across our country.”

The society released this focused update to reflect new medications and formulations, published evidence, and clinical guidance related to treatment of OUD. This update includes the addition of 13 new recommendations and major revisions to 35 existing recommendations. One concern the society has is how to help patients being treated for OUD who are limited in their ability to leave their homes. Because of these same concerns, the Substance Abuse and Mental Health Services Administration relaxed regulations on March 16 regarding patient eligibility for take-home medications, such as buprenorphine and methadone, which dovetails with the society’s guidance regarding home-based induction.

The update includes guidance for treating pregnant women as early as possible, continuing on to pharmacologic treatment even if the patient declines recommended psychosocial treatment, keeping naloxone kits available in correctional facilities, and more. Additional information about this update can be found on ASAM’s website.

[email protected]

The American Society of Addiction Medicine has released an updated practice guideline for patients with opioid use disorder.

The guideline, called a focused update, advances ASAM’s 2015 National Practice Guidelines for the Treament of Opioid Use Disorder. “During the ongoing COVID-19 pandemic and the associated need for social distancing, it is especially important that clinicians and health care providers across the country take steps to ensure that individuals with OUD can continue to receive evidence-based care,” said Paul H. Earley, MD, president of ASAM, in a press release announcing the new guideline.

The guideline specifies that home-based buprenorphine induction is safe and effective for treatment of opioid use disorder and that no individual entering the criminal justice system should be subjected to opioid withdrawal.

“The research is clear, providing methadone or buprenorphine, even without psychosocial treatment, reduces the patient’s risk of death,” said Kyle Kampman, MD, chair of the group’s Guideline Writing Committee, in the release. “Ultimately, keeping patients with the disease of addiction alive and engaged to become ready for recovery is absolutely critical in the context of the deadly overdose epidemic that has struck communities across our country.”

The society released this focused update to reflect new medications and formulations, published evidence, and clinical guidance related to treatment of OUD. This update includes the addition of 13 new recommendations and major revisions to 35 existing recommendations. One concern the society has is how to help patients being treated for OUD who are limited in their ability to leave their homes. Because of these same concerns, the Substance Abuse and Mental Health Services Administration relaxed regulations on March 16 regarding patient eligibility for take-home medications, such as buprenorphine and methadone, which dovetails with the society’s guidance regarding home-based induction.

The update includes guidance for treating pregnant women as early as possible, continuing on to pharmacologic treatment even if the patient declines recommended psychosocial treatment, keeping naloxone kits available in correctional facilities, and more. Additional information about this update can be found on ASAM’s website.

[email protected]

The American Society of Addiction Medicine has released an updated practice guideline for patients with opioid use disorder.

The guideline, called a focused update, advances ASAM’s 2015 National Practice Guidelines for the Treament of Opioid Use Disorder. “During the ongoing COVID-19 pandemic and the associated need for social distancing, it is especially important that clinicians and health care providers across the country take steps to ensure that individuals with OUD can continue to receive evidence-based care,” said Paul H. Earley, MD, president of ASAM, in a press release announcing the new guideline.

The guideline specifies that home-based buprenorphine induction is safe and effective for treatment of opioid use disorder and that no individual entering the criminal justice system should be subjected to opioid withdrawal.

“The research is clear, providing methadone or buprenorphine, even without psychosocial treatment, reduces the patient’s risk of death,” said Kyle Kampman, MD, chair of the group’s Guideline Writing Committee, in the release. “Ultimately, keeping patients with the disease of addiction alive and engaged to become ready for recovery is absolutely critical in the context of the deadly overdose epidemic that has struck communities across our country.”

The society released this focused update to reflect new medications and formulations, published evidence, and clinical guidance related to treatment of OUD. This update includes the addition of 13 new recommendations and major revisions to 35 existing recommendations. One concern the society has is how to help patients being treated for OUD who are limited in their ability to leave their homes. Because of these same concerns, the Substance Abuse and Mental Health Services Administration relaxed regulations on March 16 regarding patient eligibility for take-home medications, such as buprenorphine and methadone, which dovetails with the society’s guidance regarding home-based induction.

The update includes guidance for treating pregnant women as early as possible, continuing on to pharmacologic treatment even if the patient declines recommended psychosocial treatment, keeping naloxone kits available in correctional facilities, and more. Additional information about this update can be found on ASAM’s website.

[email protected]

MAUI, HAWAII – Arguably the most important development in the field of rheumatology during the past year was the emergence of persuasive clinical trials data predictive of a bright future for the oral Janus kinase inhibitors as major new drugs for treating ankylosing spondylitis, two experts agreed at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

“These drugs are the first oral DMARDs [disease-modifying antirheumatic drugs], if you will, in AS [ankylosing spondylitis] ... I think obviously they are going to move forward to regulatory approval,” commented Arthur F. Kavanaugh, MD, professor of medicine at the University of California, San Diego, and the RWCS program director.

“I think they’re going to hit the ground running,” predicted Eric M. Ruderman, MD, professor of medicine and associate chief for clinical affairs in the division of rheumatology at Northwestern University, Chicago.

Upon approval, the Janus kinase (JAK) inhibitors will quickly change the treatment paradigm in AS, the rheumatologists forecast.

“I think this is a way forward to go with strictly oral therapy without necessarily going first with parenteral therapy in these patients. It gives you an alternative, and my guess is, by the time these drugs are approved in this space, there’ll be more and more of their preferential use over biologics in rheumatoid arthritis and potentially in psoriatic arthritis, so people will be more familiar with them. A lot of patients are much happier taking a pill once a day with none of the tolerability issues that we have with shots,” Dr. Ruderman said.

“And they act fast,” noted Dr. Kavanaugh. “You can make a case for trying a JAK inhibitor for a month or 2, and then if you’re not better, then we go to the other option.”

Dr. Ruderman cautioned that the increased need for laboratory monitoring with the oral JAK inhibitors as compared with the annual monitoring with tumor necrosis factor inhibitors could be an issue, especially since AS patients tend to be on the younger side and often dislike coming in regularly for office visits and laboratory tests.

“There may be more of a headache in having to tell patients, ‘You’re not getting your JAK inhibitor refilled until you get your labs done,’ ” he said.

In December 2019, rheumatologists received a holiday present in the form of publication of the results of SELECT-AXIS 1, a multicenter, double-blind, randomized, placebo-controlled phase 2/3 trial in which 187 patients with active AS were randomized to placebo or to the JAK inhibitor upadacitinib (Rinvoq) at the same 15-mg dose approved by the FDA earlier in the year for rheumatoid arthritis. In SELECT-AXIS 1, upadacitinib not only demonstrated clinical efficacy, with a week-14 Assessment of SpondyloArthritis International Society-40 (ASAS 40) response rate of 52% – twice that for placebo – but the active treatment arm also experienced significantly reduced inflammatory disease activity as measured by Spondyloarthritis Research Consortium of Canada (SPARCC) MRI scores of the spine and sacroiliac joint. In contrast, MRI scores remained unchanged from baseline in the placebo arm.

“This suggests a biologic effect, a hook beyond clinical disease. And the time of onset was pretty impressive, much like with our experience with JAK inhibitors in RA. Within 2 weeks, there was significant separation from placebo on the ASDAS [Ankylosing Spondylitis Disease Activity Score],” Dr. Ruderman noted.

Positive clinical trials in AS have also been reported for the oral JAK inhibitors filgotinib and tofacitinib (Xeljanz).

Dr. Ruderman and Dr. Kavanaugh also touched on other major developments in AS within the past year, including the landmark FDA approval of certolizumab pegol (Cimzia) as the first-ever drug for treatment of nonradiographic axial spondyloarthritis (nr-axSpA). Also, Dr. Kavanaugh and Dr. Ruderman gave two thumbs down to the 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis.

 

More biologics coming for nr-AxSpA

In order to gain an indication for treatment of nr-axSpA, the FDA requires completion of a 52-week, randomized, placebo-controlled clinical trial. That’s what UCB did with the company’s TNF inhibitor, certolizumab. Similarly, Eli Lilly sprang for the mandated 52-week trial in 303 nr-axSpA patients for its interleukin-17 inhibitor ixekizumab (Taltz), with positive findings (Lancet. 2020 Jan 4;395[10217]:53-64). And Novartis has done so with its IL-17 inhibitor secukinumab (Cosentyx) in the 555-patient PREVENT trial, again with positive outcomes. So the two IL-17 inhibitors, which are already approved for AS, are seemingly a lock for approval in nr-axSpA as well.

Will the makers of other TNF inhibitors already approved for AS fork over the considerable money entailed in a 52-week randomized trial, or will they ride on certolizumab’s coattails? Dr. Ruderman said he doesn’t know the answer, but it’s certain that, if they don’t complete the trial, they can’t market their biologic for nr-axSpA in the United States, even though there might well be a drug class effect at work.

 

ACR/SAA/SPARTAN guidelines critiqued

The two panelists had plenty to say about the 2019 update of the guidelines, none of it favorable. Among their criticisms: The guidelines are already out of date several months after their release, they are based heavily on opinion rather than on evidence, they appear to take medication cost into consideration when they’re not supposed to, they are complicated, and they are just not practical or useful.

“I don’t know when these guidelines would potentially be used,” Dr. Kavanaugh commented in response to an audience question.

Specifically, the guidelines strongly recommend a TNF inhibitor over the IL-17 inhibitors secukinumab or ixekizumab as the first-line biologic in AS patients with active disease while on NSAIDs, guidance that is already out of date.

“You’d almost think it would have been better just to wait a few months to see the published literature, which I think is going to have a tremendous impact on practice,” Dr. Kavanaugh said.

He also said he was troubled by the strong recommendation against switching to a TNF inhibitor–biosimilar after receiving treatment with an originator TNF inhibitor. That’s something rheumatologists all across Europe are routinely doing now for economic reasons without known harm, with the caveat that patients must be switched to a biosimilar of a different TNF inhibitor than the originator.

“There’s absolutely no data to support a recommendation against switching. I think they’re going out on a limb a little bit,” he added.

Dr. Ruderman said he struggles with the guideline development methodology, which involves posing a series of key questions at the outset, with a strict charge to provide answers.

“They always have to have an answer to the question. And in the event that there’s no data to support an answer, then it becomes a matter of the expert opinion of the people on the committee. I think many rheumatologists would say, ‘Why are they any more expert than a clinical rheumatologist who’s been seeing AS patients for 20 years?’ And the answer is they’re probably not. The fact that most of these are conditional recommendations, meaning they’re not supported by strong evidence, makes them less useful,” according to Dr. Ruderman.

Both he and Dr. Kavanaugh reported receiving research funding from and/or serving as a consultant to numerous pharmaceutical companies.

[email protected]

MAUI, HAWAII – Arguably the most important development in the field of rheumatology during the past year was the emergence of persuasive clinical trials data predictive of a bright future for the oral Janus kinase inhibitors as major new drugs for treating ankylosing spondylitis, two experts agreed at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

“These drugs are the first oral DMARDs [disease-modifying antirheumatic drugs], if you will, in AS [ankylosing spondylitis] ... I think obviously they are going to move forward to regulatory approval,” commented Arthur F. Kavanaugh, MD, professor of medicine at the University of California, San Diego, and the RWCS program director.

“I think they’re going to hit the ground running,” predicted Eric M. Ruderman, MD, professor of medicine and associate chief for clinical affairs in the division of rheumatology at Northwestern University, Chicago.

Upon approval, the Janus kinase (JAK) inhibitors will quickly change the treatment paradigm in AS, the rheumatologists forecast.

“I think this is a way forward to go with strictly oral therapy without necessarily going first with parenteral therapy in these patients. It gives you an alternative, and my guess is, by the time these drugs are approved in this space, there’ll be more and more of their preferential use over biologics in rheumatoid arthritis and potentially in psoriatic arthritis, so people will be more familiar with them. A lot of patients are much happier taking a pill once a day with none of the tolerability issues that we have with shots,” Dr. Ruderman said.

“And they act fast,” noted Dr. Kavanaugh. “You can make a case for trying a JAK inhibitor for a month or 2, and then if you’re not better, then we go to the other option.”

Dr. Ruderman cautioned that the increased need for laboratory monitoring with the oral JAK inhibitors as compared with the annual monitoring with tumor necrosis factor inhibitors could be an issue, especially since AS patients tend to be on the younger side and often dislike coming in regularly for office visits and laboratory tests.

“There may be more of a headache in having to tell patients, ‘You’re not getting your JAK inhibitor refilled until you get your labs done,’ ” he said.

In December 2019, rheumatologists received a holiday present in the form of publication of the results of SELECT-AXIS 1, a multicenter, double-blind, randomized, placebo-controlled phase 2/3 trial in which 187 patients with active AS were randomized to placebo or to the JAK inhibitor upadacitinib (Rinvoq) at the same 15-mg dose approved by the FDA earlier in the year for rheumatoid arthritis. In SELECT-AXIS 1, upadacitinib not only demonstrated clinical efficacy, with a week-14 Assessment of SpondyloArthritis International Society-40 (ASAS 40) response rate of 52% – twice that for placebo – but the active treatment arm also experienced significantly reduced inflammatory disease activity as measured by Spondyloarthritis Research Consortium of Canada (SPARCC) MRI scores of the spine and sacroiliac joint. In contrast, MRI scores remained unchanged from baseline in the placebo arm.

“This suggests a biologic effect, a hook beyond clinical disease. And the time of onset was pretty impressive, much like with our experience with JAK inhibitors in RA. Within 2 weeks, there was significant separation from placebo on the ASDAS [Ankylosing Spondylitis Disease Activity Score],” Dr. Ruderman noted.

Positive clinical trials in AS have also been reported for the oral JAK inhibitors filgotinib and tofacitinib (Xeljanz).

Dr. Ruderman and Dr. Kavanaugh also touched on other major developments in AS within the past year, including the landmark FDA approval of certolizumab pegol (Cimzia) as the first-ever drug for treatment of nonradiographic axial spondyloarthritis (nr-axSpA). Also, Dr. Kavanaugh and Dr. Ruderman gave two thumbs down to the 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis.

 

More biologics coming for nr-AxSpA

In order to gain an indication for treatment of nr-axSpA, the FDA requires completion of a 52-week, randomized, placebo-controlled clinical trial. That’s what UCB did with the company’s TNF inhibitor, certolizumab. Similarly, Eli Lilly sprang for the mandated 52-week trial in 303 nr-axSpA patients for its interleukin-17 inhibitor ixekizumab (Taltz), with positive findings (Lancet. 2020 Jan 4;395[10217]:53-64). And Novartis has done so with its IL-17 inhibitor secukinumab (Cosentyx) in the 555-patient PREVENT trial, again with positive outcomes. So the two IL-17 inhibitors, which are already approved for AS, are seemingly a lock for approval in nr-axSpA as well.

Will the makers of other TNF inhibitors already approved for AS fork over the considerable money entailed in a 52-week randomized trial, or will they ride on certolizumab’s coattails? Dr. Ruderman said he doesn’t know the answer, but it’s certain that, if they don’t complete the trial, they can’t market their biologic for nr-axSpA in the United States, even though there might well be a drug class effect at work.

 

ACR/SAA/SPARTAN guidelines critiqued

The two panelists had plenty to say about the 2019 update of the guidelines, none of it favorable. Among their criticisms: The guidelines are already out of date several months after their release, they are based heavily on opinion rather than on evidence, they appear to take medication cost into consideration when they’re not supposed to, they are complicated, and they are just not practical or useful.

“I don’t know when these guidelines would potentially be used,” Dr. Kavanaugh commented in response to an audience question.

Specifically, the guidelines strongly recommend a TNF inhibitor over the IL-17 inhibitors secukinumab or ixekizumab as the first-line biologic in AS patients with active disease while on NSAIDs, guidance that is already out of date.

“You’d almost think it would have been better just to wait a few months to see the published literature, which I think is going to have a tremendous impact on practice,” Dr. Kavanaugh said.

He also said he was troubled by the strong recommendation against switching to a TNF inhibitor–biosimilar after receiving treatment with an originator TNF inhibitor. That’s something rheumatologists all across Europe are routinely doing now for economic reasons without known harm, with the caveat that patients must be switched to a biosimilar of a different TNF inhibitor than the originator.

“There’s absolutely no data to support a recommendation against switching. I think they’re going out on a limb a little bit,” he added.

Dr. Ruderman said he struggles with the guideline development methodology, which involves posing a series of key questions at the outset, with a strict charge to provide answers.

“They always have to have an answer to the question. And in the event that there’s no data to support an answer, then it becomes a matter of the expert opinion of the people on the committee. I think many rheumatologists would say, ‘Why are they any more expert than a clinical rheumatologist who’s been seeing AS patients for 20 years?’ And the answer is they’re probably not. The fact that most of these are conditional recommendations, meaning they’re not supported by strong evidence, makes them less useful,” according to Dr. Ruderman.

Both he and Dr. Kavanaugh reported receiving research funding from and/or serving as a consultant to numerous pharmaceutical companies.

[email protected]

MAUI, HAWAII – Arguably the most important development in the field of rheumatology during the past year was the emergence of persuasive clinical trials data predictive of a bright future for the oral Janus kinase inhibitors as major new drugs for treating ankylosing spondylitis, two experts agreed at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

“These drugs are the first oral DMARDs [disease-modifying antirheumatic drugs], if you will, in AS [ankylosing spondylitis] ... I think obviously they are going to move forward to regulatory approval,” commented Arthur F. Kavanaugh, MD, professor of medicine at the University of California, San Diego, and the RWCS program director.

“I think they’re going to hit the ground running,” predicted Eric M. Ruderman, MD, professor of medicine and associate chief for clinical affairs in the division of rheumatology at Northwestern University, Chicago.

Upon approval, the Janus kinase (JAK) inhibitors will quickly change the treatment paradigm in AS, the rheumatologists forecast.

“I think this is a way forward to go with strictly oral therapy without necessarily going first with parenteral therapy in these patients. It gives you an alternative, and my guess is, by the time these drugs are approved in this space, there’ll be more and more of their preferential use over biologics in rheumatoid arthritis and potentially in psoriatic arthritis, so people will be more familiar with them. A lot of patients are much happier taking a pill once a day with none of the tolerability issues that we have with shots,” Dr. Ruderman said.

“And they act fast,” noted Dr. Kavanaugh. “You can make a case for trying a JAK inhibitor for a month or 2, and then if you’re not better, then we go to the other option.”

Dr. Ruderman cautioned that the increased need for laboratory monitoring with the oral JAK inhibitors as compared with the annual monitoring with tumor necrosis factor inhibitors could be an issue, especially since AS patients tend to be on the younger side and often dislike coming in regularly for office visits and laboratory tests.

“There may be more of a headache in having to tell patients, ‘You’re not getting your JAK inhibitor refilled until you get your labs done,’ ” he said.

In December 2019, rheumatologists received a holiday present in the form of publication of the results of SELECT-AXIS 1, a multicenter, double-blind, randomized, placebo-controlled phase 2/3 trial in which 187 patients with active AS were randomized to placebo or to the JAK inhibitor upadacitinib (Rinvoq) at the same 15-mg dose approved by the FDA earlier in the year for rheumatoid arthritis. In SELECT-AXIS 1, upadacitinib not only demonstrated clinical efficacy, with a week-14 Assessment of SpondyloArthritis International Society-40 (ASAS 40) response rate of 52% – twice that for placebo – but the active treatment arm also experienced significantly reduced inflammatory disease activity as measured by Spondyloarthritis Research Consortium of Canada (SPARCC) MRI scores of the spine and sacroiliac joint. In contrast, MRI scores remained unchanged from baseline in the placebo arm.

“This suggests a biologic effect, a hook beyond clinical disease. And the time of onset was pretty impressive, much like with our experience with JAK inhibitors in RA. Within 2 weeks, there was significant separation from placebo on the ASDAS [Ankylosing Spondylitis Disease Activity Score],” Dr. Ruderman noted.

Positive clinical trials in AS have also been reported for the oral JAK inhibitors filgotinib and tofacitinib (Xeljanz).

Dr. Ruderman and Dr. Kavanaugh also touched on other major developments in AS within the past year, including the landmark FDA approval of certolizumab pegol (Cimzia) as the first-ever drug for treatment of nonradiographic axial spondyloarthritis (nr-axSpA). Also, Dr. Kavanaugh and Dr. Ruderman gave two thumbs down to the 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis.

 

More biologics coming for nr-AxSpA

In order to gain an indication for treatment of nr-axSpA, the FDA requires completion of a 52-week, randomized, placebo-controlled clinical trial. That’s what UCB did with the company’s TNF inhibitor, certolizumab. Similarly, Eli Lilly sprang for the mandated 52-week trial in 303 nr-axSpA patients for its interleukin-17 inhibitor ixekizumab (Taltz), with positive findings (Lancet. 2020 Jan 4;395[10217]:53-64). And Novartis has done so with its IL-17 inhibitor secukinumab (Cosentyx) in the 555-patient PREVENT trial, again with positive outcomes. So the two IL-17 inhibitors, which are already approved for AS, are seemingly a lock for approval in nr-axSpA as well.

Will the makers of other TNF inhibitors already approved for AS fork over the considerable money entailed in a 52-week randomized trial, or will they ride on certolizumab’s coattails? Dr. Ruderman said he doesn’t know the answer, but it’s certain that, if they don’t complete the trial, they can’t market their biologic for nr-axSpA in the United States, even though there might well be a drug class effect at work.

 

ACR/SAA/SPARTAN guidelines critiqued

The two panelists had plenty to say about the 2019 update of the guidelines, none of it favorable. Among their criticisms: The guidelines are already out of date several months after their release, they are based heavily on opinion rather than on evidence, they appear to take medication cost into consideration when they’re not supposed to, they are complicated, and they are just not practical or useful.

“I don’t know when these guidelines would potentially be used,” Dr. Kavanaugh commented in response to an audience question.

Specifically, the guidelines strongly recommend a TNF inhibitor over the IL-17 inhibitors secukinumab or ixekizumab as the first-line biologic in AS patients with active disease while on NSAIDs, guidance that is already out of date.

“You’d almost think it would have been better just to wait a few months to see the published literature, which I think is going to have a tremendous impact on practice,” Dr. Kavanaugh said.

He also said he was troubled by the strong recommendation against switching to a TNF inhibitor–biosimilar after receiving treatment with an originator TNF inhibitor. That’s something rheumatologists all across Europe are routinely doing now for economic reasons without known harm, with the caveat that patients must be switched to a biosimilar of a different TNF inhibitor than the originator.

“There’s absolutely no data to support a recommendation against switching. I think they’re going out on a limb a little bit,” he added.

Dr. Ruderman said he struggles with the guideline development methodology, which involves posing a series of key questions at the outset, with a strict charge to provide answers.

“They always have to have an answer to the question. And in the event that there’s no data to support an answer, then it becomes a matter of the expert opinion of the people on the committee. I think many rheumatologists would say, ‘Why are they any more expert than a clinical rheumatologist who’s been seeing AS patients for 20 years?’ And the answer is they’re probably not. The fact that most of these are conditional recommendations, meaning they’re not supported by strong evidence, makes them less useful,” according to Dr. Ruderman.

Both he and Dr. Kavanaugh reported receiving research funding from and/or serving as a consultant to numerous pharmaceutical companies.

[email protected]

More than a third (35%) of patients with relapsed non–small cell lung cancer (NSCLC) treated with pembrolizumab (Keytruda, Merck) were still alive at 3 years, according to long-term results from a pivotal clinical trial.

The results also showed that, among the 10% of patients who completed all 35 cycles of pembrolizumab, the 3-year overall survival was approximately 99%, with progression-free survival (PFS) at around 70%.

“It is too soon to say that pembrolizumab is a potential cure...and we know that it doesn’t work for all patients, but the agent remains very, very promising,” said lead investigator Roy Herbst, MD, PhD, Department of Medical Oncology, Yale Comprehensive Cancer Center, New Haven, Connecticut.

These new results come from the KEYNOTE-010 trial, conducted in more than 1000 patients with NSCLC who had progressed on chemotherapy, randomized to receive immunotherapy with pembrolizumab or chemotherapy with docetaxel.

The results were published online on February 20 in the Journal of Clinical Oncology and were previously presented at the 2018 annual meeting of the European Society of Medical Oncology.

Overall survival at 3 years was 35% in patients with PD-L1 expression ≥ 50% in the tumor, and 23% in those with PD-L1 ≥ 1%.

This compares with 3-year overall survival of 11-13% with docetaxel.

These results are “really extraordinary,” Herbst commented to Medscape Medical News.

The 3-year overall survival rate of 35% in patients with PD-L1 ≥ 50% “is huge,” he said. “It really shows the durability of the response.”

Herbst commented that the “almost 100%” survival at 3 years among patients who completed 35 cycles of pembrolizumab shows that this treatment period (of about 2 years) is “probably about the right time to treat.”

“Currently, the agent is being used in all potential settings, before any other treatment, after other treatment, and with other treatments,” he said.

“Our hope is to find the very best way to use pembrolizumab to treat individual lung cancer patients, assessing how much PD-L1 a tumor expresses, what stage the patient is in, as well as other variables and biomarkers we are working on. This is the story of tailored therapy,” Herbst said.

Approached for comment, Solange Peters, MD, PhD, Oncology Department, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, said that the results are “very good” and “confirm the paradigms we have been seeing in melanoma,” with good long-term control, which is “very reassuring.”

However, she told Medscape Medical News that the trial raises an important question: «How long do you need to expose your patient with lung cancer to immunotherapy in order to get this long-term control?»

She said the “good news” is that, for the 10% of patients who completed 2 years of treatment per protocol, almost all of them are still alive at 3 years, “which is not observed with chemotherapy.”

The question for Peters is “more about the definition of long-term control,” as it was seen that almost one in three patients nevertheless had some form of progression.

This suggests that you have a group of people “who are nicely controlled, you stop the drug, and 1 year later a third of them have progressed.”

Peters said: “So how long do you need to treat these patients? I would say I still don’t know.”

“If I were one of these patients probably I would still want to continue [on the drug]. Of course, some might have progressed even while remaining on the drug, but the proportion who would have progressed is probably smaller than this one.”
 

Responses on Re-introduction of Therapy

The study also allowed patients who had completed 35 cycles of pembrolizumab to be restarted on the drug if they experienced progression.

The team found that, among 14 patients, 43% had a partial response and 36% had stable disease.

Herbst highlighted this finding and told Medscape Medical News that this «could be very important to physicians because they might want to think about using the drug again» in patients who have progressed on it.

He believes that the progression was not because of any resistance per se but rather a slowing down of the adaptive immune response.

“It’s just that it needs a boost,” he said, while noting that tissue specimens will nevertheless be required to demonstrate the theory.

Peters agreed that these results are “very promising,” but questioned their overall significance, as it is “a very small number of patients” from a subset whose disease was controlled while on treatment and then progressed after stopping.

She also pointed out that, in another study in patients with lung cancer (CheckMate-153), some patients were rechallenged with immunotherapy after having stopped treatment at 1 year “with very poor results.”

Peters said studies in melanoma have shown “rechallenge can be useful in a significant proportion of patients, but still you have not demonstrated that stopping and rechallenging is the same as not stopping.”

Study Details

KEYNOTE-010 involved patients with NSCLC from 202 centers in 24 countries with stage IIIB/IV disease expressing PD-L1 who had experienced disease progression after at least two cycles of platinum-based chemotherapy.

They were randomized 1:1:1 to open-label pembrolizumab 2 mg/kg, pembrolizumab 10 mg/kg, or docetaxel 75 mg/m² every 3 weeks.

Pembrolizumab was continued for 35 treatment cycles over 2 years and docetaxel was continued for the maximum duration allowed by local regulators.

Patients who stopped pembrolizumab after a complete response or completing all 35 cycles, and who subsequently experienced disease progression, could receive up to 17 additional cycles over 1 year if they had not received another anticancer therapy in the meantime.

Among the 1,034 patients originally recruited between August 2013 and February 2015, 691 were assigned to pembrolizumab at 3 mg/kg or 10 mg/kg and 343 to docetaxel.

For the intention-to-treat analysis in 1033 patients, the mean duration of follow-up was 42.6 months, with a median treatment duration of 3.5 months in the pembrolizumab group and 2.0 months in the docetaxel group.

Compared with docetaxel, pembrolizumab was associated with a significant reduction in the risk of death, at a hazard ratio of 0.53 in patients with PD-L1 ≥ 50% and 0.69 in those with PD-L1 ≥ 1% (both P < .0001).

In patients with PD-L1 ≥ 50%, median overall survival was 16.9 months in those given pembrolizumab and 8.2 months with docetaxel. Among those with PD-L1 ≥ 1%, median overall survival was 11.8 months with pembrolizumab versus 8.4 months with docetaxel.

Overall survival on Kaplan-Meier analysis was 34.5% with pembrolizumab and 12.7% with docetaxel in the PD-L1 ≥ 50% group, and 22.9% versus 11.0% in the PD-L1 ≥ 1% group.

PFS significantly improved with pembrolizumab versus docetaxel, at a hazard ratio of 0.57 (P < .00001) among patients with PD-L1 ≥ 50% and 0.83 (P < .005) in those with PD-L1 ≥ 1%.

In terms of safety, 17.7% of patients who completed 2 years of pembrolizumab had grade 3-5 treatment-related adverse events, compared with 16.6% among all pembrolizumab-treated patients and 36.6% of those given docetaxel.

The team reports that 79 patients completed 35 cycles of pembrolizumab, with a median follow-up of 43.4 months.

Compared with the overall patient group, these patients were less likely to be aged ≥ 65 years and to have received two or more prior treatment lines, although they were more likely to be current or former smokers and to have squamous tumor histology.

Patients who completed 35 cycles had an objective response rate of 94.9%, and 91.0% were still alive at the data cutoff. Overall survival rates were 98.7% at 12 months and 86.3% at 24 months.

Of 71 patients eligible for analysis, 23 experienced progression after completing pembrolizumab, at PFS rates at 12 and 24 months of 72.5% and 57.7%, respectively.

A total of 14 patients were given a second course of pembrolizumab, of whom six had a partial response and five had stable disease. At the data cutoff, five patients had completed 17 additional cycles and 11 were alive.

Pembro Approved at Fixed Dose

One notable aspect of the study is that patients in the pembrolizumab arm were given two different doses of the drug based on body weight, whereas the drug is approved in the United States at a fixed dose of 200 mg.

Herbst told Medscape Medical News he considers the 200-mg dose to be appropriate.

“I didn’t think that the 3-mg versus 10-mg dose per kg that we used in our study made much difference in an average-sized person,” he said, adding that the 200-mg dose “is something a little bit more than 3 mg/kg.”

“So I think that this is clearly the right dos, and I don’t think more would make any difference,” he said.

The study was funded by Merck, the manufacturer of pembrolizumab. Herbst has reported having a consulting or advisory role for many pharmaceutical companies. Other coauthors have also reported relationships with industry, and some of the authors are Merck employees. Peters has reported receiving education grants, providing consultation, attending advisory boards, and/or providing lectures for many pharmaceutical companies.
 

This article first appeared on Medscape.com.

More than a third (35%) of patients with relapsed non–small cell lung cancer (NSCLC) treated with pembrolizumab (Keytruda, Merck) were still alive at 3 years, according to long-term results from a pivotal clinical trial.

The results also showed that, among the 10% of patients who completed all 35 cycles of pembrolizumab, the 3-year overall survival was approximately 99%, with progression-free survival (PFS) at around 70%.

“It is too soon to say that pembrolizumab is a potential cure...and we know that it doesn’t work for all patients, but the agent remains very, very promising,” said lead investigator Roy Herbst, MD, PhD, Department of Medical Oncology, Yale Comprehensive Cancer Center, New Haven, Connecticut.

These new results come from the KEYNOTE-010 trial, conducted in more than 1000 patients with NSCLC who had progressed on chemotherapy, randomized to receive immunotherapy with pembrolizumab or chemotherapy with docetaxel.

The results were published online on February 20 in the Journal of Clinical Oncology and were previously presented at the 2018 annual meeting of the European Society of Medical Oncology.

Overall survival at 3 years was 35% in patients with PD-L1 expression ≥ 50% in the tumor, and 23% in those with PD-L1 ≥ 1%.

This compares with 3-year overall survival of 11-13% with docetaxel.

These results are “really extraordinary,” Herbst commented to Medscape Medical News.

The 3-year overall survival rate of 35% in patients with PD-L1 ≥ 50% “is huge,” he said. “It really shows the durability of the response.”

Herbst commented that the “almost 100%” survival at 3 years among patients who completed 35 cycles of pembrolizumab shows that this treatment period (of about 2 years) is “probably about the right time to treat.”

“Currently, the agent is being used in all potential settings, before any other treatment, after other treatment, and with other treatments,” he said.

“Our hope is to find the very best way to use pembrolizumab to treat individual lung cancer patients, assessing how much PD-L1 a tumor expresses, what stage the patient is in, as well as other variables and biomarkers we are working on. This is the story of tailored therapy,” Herbst said.

Approached for comment, Solange Peters, MD, PhD, Oncology Department, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, said that the results are “very good” and “confirm the paradigms we have been seeing in melanoma,” with good long-term control, which is “very reassuring.”

However, she told Medscape Medical News that the trial raises an important question: «How long do you need to expose your patient with lung cancer to immunotherapy in order to get this long-term control?»

She said the “good news” is that, for the 10% of patients who completed 2 years of treatment per protocol, almost all of them are still alive at 3 years, “which is not observed with chemotherapy.”

The question for Peters is “more about the definition of long-term control,” as it was seen that almost one in three patients nevertheless had some form of progression.

This suggests that you have a group of people “who are nicely controlled, you stop the drug, and 1 year later a third of them have progressed.”

Peters said: “So how long do you need to treat these patients? I would say I still don’t know.”

“If I were one of these patients probably I would still want to continue [on the drug]. Of course, some might have progressed even while remaining on the drug, but the proportion who would have progressed is probably smaller than this one.”
 

Responses on Re-introduction of Therapy

The study also allowed patients who had completed 35 cycles of pembrolizumab to be restarted on the drug if they experienced progression.

The team found that, among 14 patients, 43% had a partial response and 36% had stable disease.

Herbst highlighted this finding and told Medscape Medical News that this «could be very important to physicians because they might want to think about using the drug again» in patients who have progressed on it.

He believes that the progression was not because of any resistance per se but rather a slowing down of the adaptive immune response.

“It’s just that it needs a boost,” he said, while noting that tissue specimens will nevertheless be required to demonstrate the theory.

Peters agreed that these results are “very promising,” but questioned their overall significance, as it is “a very small number of patients” from a subset whose disease was controlled while on treatment and then progressed after stopping.

She also pointed out that, in another study in patients with lung cancer (CheckMate-153), some patients were rechallenged with immunotherapy after having stopped treatment at 1 year “with very poor results.”

Peters said studies in melanoma have shown “rechallenge can be useful in a significant proportion of patients, but still you have not demonstrated that stopping and rechallenging is the same as not stopping.”

Study Details

KEYNOTE-010 involved patients with NSCLC from 202 centers in 24 countries with stage IIIB/IV disease expressing PD-L1 who had experienced disease progression after at least two cycles of platinum-based chemotherapy.

They were randomized 1:1:1 to open-label pembrolizumab 2 mg/kg, pembrolizumab 10 mg/kg, or docetaxel 75 mg/m² every 3 weeks.

Pembrolizumab was continued for 35 treatment cycles over 2 years and docetaxel was continued for the maximum duration allowed by local regulators.

Patients who stopped pembrolizumab after a complete response or completing all 35 cycles, and who subsequently experienced disease progression, could receive up to 17 additional cycles over 1 year if they had not received another anticancer therapy in the meantime.

Among the 1,034 patients originally recruited between August 2013 and February 2015, 691 were assigned to pembrolizumab at 3 mg/kg or 10 mg/kg and 343 to docetaxel.

For the intention-to-treat analysis in 1033 patients, the mean duration of follow-up was 42.6 months, with a median treatment duration of 3.5 months in the pembrolizumab group and 2.0 months in the docetaxel group.

Compared with docetaxel, pembrolizumab was associated with a significant reduction in the risk of death, at a hazard ratio of 0.53 in patients with PD-L1 ≥ 50% and 0.69 in those with PD-L1 ≥ 1% (both P < .0001).

In patients with PD-L1 ≥ 50%, median overall survival was 16.9 months in those given pembrolizumab and 8.2 months with docetaxel. Among those with PD-L1 ≥ 1%, median overall survival was 11.8 months with pembrolizumab versus 8.4 months with docetaxel.

Overall survival on Kaplan-Meier analysis was 34.5% with pembrolizumab and 12.7% with docetaxel in the PD-L1 ≥ 50% group, and 22.9% versus 11.0% in the PD-L1 ≥ 1% group.

PFS significantly improved with pembrolizumab versus docetaxel, at a hazard ratio of 0.57 (P < .00001) among patients with PD-L1 ≥ 50% and 0.83 (P < .005) in those with PD-L1 ≥ 1%.

In terms of safety, 17.7% of patients who completed 2 years of pembrolizumab had grade 3-5 treatment-related adverse events, compared with 16.6% among all pembrolizumab-treated patients and 36.6% of those given docetaxel.

The team reports that 79 patients completed 35 cycles of pembrolizumab, with a median follow-up of 43.4 months.

Compared with the overall patient group, these patients were less likely to be aged ≥ 65 years and to have received two or more prior treatment lines, although they were more likely to be current or former smokers and to have squamous tumor histology.

Patients who completed 35 cycles had an objective response rate of 94.9%, and 91.0% were still alive at the data cutoff. Overall survival rates were 98.7% at 12 months and 86.3% at 24 months.

Of 71 patients eligible for analysis, 23 experienced progression after completing pembrolizumab, at PFS rates at 12 and 24 months of 72.5% and 57.7%, respectively.

A total of 14 patients were given a second course of pembrolizumab, of whom six had a partial response and five had stable disease. At the data cutoff, five patients had completed 17 additional cycles and 11 were alive.

Pembro Approved at Fixed Dose

One notable aspect of the study is that patients in the pembrolizumab arm were given two different doses of the drug based on body weight, whereas the drug is approved in the United States at a fixed dose of 200 mg.

Herbst told Medscape Medical News he considers the 200-mg dose to be appropriate.

“I didn’t think that the 3-mg versus 10-mg dose per kg that we used in our study made much difference in an average-sized person,” he said, adding that the 200-mg dose “is something a little bit more than 3 mg/kg.”

“So I think that this is clearly the right dos, and I don’t think more would make any difference,” he said.

The study was funded by Merck, the manufacturer of pembrolizumab. Herbst has reported having a consulting or advisory role for many pharmaceutical companies. Other coauthors have also reported relationships with industry, and some of the authors are Merck employees. Peters has reported receiving education grants, providing consultation, attending advisory boards, and/or providing lectures for many pharmaceutical companies.
 

This article first appeared on Medscape.com.

More than a third (35%) of patients with relapsed non–small cell lung cancer (NSCLC) treated with pembrolizumab (Keytruda, Merck) were still alive at 3 years, according to long-term results from a pivotal clinical trial.

The results also showed that, among the 10% of patients who completed all 35 cycles of pembrolizumab, the 3-year overall survival was approximately 99%, with progression-free survival (PFS) at around 70%.

“It is too soon to say that pembrolizumab is a potential cure...and we know that it doesn’t work for all patients, but the agent remains very, very promising,” said lead investigator Roy Herbst, MD, PhD, Department of Medical Oncology, Yale Comprehensive Cancer Center, New Haven, Connecticut.

These new results come from the KEYNOTE-010 trial, conducted in more than 1000 patients with NSCLC who had progressed on chemotherapy, randomized to receive immunotherapy with pembrolizumab or chemotherapy with docetaxel.

The results were published online on February 20 in the Journal of Clinical Oncology and were previously presented at the 2018 annual meeting of the European Society of Medical Oncology.

Overall survival at 3 years was 35% in patients with PD-L1 expression ≥ 50% in the tumor, and 23% in those with PD-L1 ≥ 1%.

This compares with 3-year overall survival of 11-13% with docetaxel.

These results are “really extraordinary,” Herbst commented to Medscape Medical News.

The 3-year overall survival rate of 35% in patients with PD-L1 ≥ 50% “is huge,” he said. “It really shows the durability of the response.”

Herbst commented that the “almost 100%” survival at 3 years among patients who completed 35 cycles of pembrolizumab shows that this treatment period (of about 2 years) is “probably about the right time to treat.”

“Currently, the agent is being used in all potential settings, before any other treatment, after other treatment, and with other treatments,” he said.

“Our hope is to find the very best way to use pembrolizumab to treat individual lung cancer patients, assessing how much PD-L1 a tumor expresses, what stage the patient is in, as well as other variables and biomarkers we are working on. This is the story of tailored therapy,” Herbst said.

Approached for comment, Solange Peters, MD, PhD, Oncology Department, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, said that the results are “very good” and “confirm the paradigms we have been seeing in melanoma,” with good long-term control, which is “very reassuring.”

However, she told Medscape Medical News that the trial raises an important question: «How long do you need to expose your patient with lung cancer to immunotherapy in order to get this long-term control?»

She said the “good news” is that, for the 10% of patients who completed 2 years of treatment per protocol, almost all of them are still alive at 3 years, “which is not observed with chemotherapy.”

The question for Peters is “more about the definition of long-term control,” as it was seen that almost one in three patients nevertheless had some form of progression.

This suggests that you have a group of people “who are nicely controlled, you stop the drug, and 1 year later a third of them have progressed.”

Peters said: “So how long do you need to treat these patients? I would say I still don’t know.”

“If I were one of these patients probably I would still want to continue [on the drug]. Of course, some might have progressed even while remaining on the drug, but the proportion who would have progressed is probably smaller than this one.”
 

Responses on Re-introduction of Therapy

The study also allowed patients who had completed 35 cycles of pembrolizumab to be restarted on the drug if they experienced progression.

The team found that, among 14 patients, 43% had a partial response and 36% had stable disease.

Herbst highlighted this finding and told Medscape Medical News that this «could be very important to physicians because they might want to think about using the drug again» in patients who have progressed on it.

He believes that the progression was not because of any resistance per se but rather a slowing down of the adaptive immune response.

“It’s just that it needs a boost,” he said, while noting that tissue specimens will nevertheless be required to demonstrate the theory.

Peters agreed that these results are “very promising,” but questioned their overall significance, as it is “a very small number of patients” from a subset whose disease was controlled while on treatment and then progressed after stopping.

She also pointed out that, in another study in patients with lung cancer (CheckMate-153), some patients were rechallenged with immunotherapy after having stopped treatment at 1 year “with very poor results.”

Peters said studies in melanoma have shown “rechallenge can be useful in a significant proportion of patients, but still you have not demonstrated that stopping and rechallenging is the same as not stopping.”

Study Details

KEYNOTE-010 involved patients with NSCLC from 202 centers in 24 countries with stage IIIB/IV disease expressing PD-L1 who had experienced disease progression after at least two cycles of platinum-based chemotherapy.

They were randomized 1:1:1 to open-label pembrolizumab 2 mg/kg, pembrolizumab 10 mg/kg, or docetaxel 75 mg/m² every 3 weeks.

Pembrolizumab was continued for 35 treatment cycles over 2 years and docetaxel was continued for the maximum duration allowed by local regulators.

Patients who stopped pembrolizumab after a complete response or completing all 35 cycles, and who subsequently experienced disease progression, could receive up to 17 additional cycles over 1 year if they had not received another anticancer therapy in the meantime.

Among the 1,034 patients originally recruited between August 2013 and February 2015, 691 were assigned to pembrolizumab at 3 mg/kg or 10 mg/kg and 343 to docetaxel.

For the intention-to-treat analysis in 1033 patients, the mean duration of follow-up was 42.6 months, with a median treatment duration of 3.5 months in the pembrolizumab group and 2.0 months in the docetaxel group.

Compared with docetaxel, pembrolizumab was associated with a significant reduction in the risk of death, at a hazard ratio of 0.53 in patients with PD-L1 ≥ 50% and 0.69 in those with PD-L1 ≥ 1% (both P < .0001).

In patients with PD-L1 ≥ 50%, median overall survival was 16.9 months in those given pembrolizumab and 8.2 months with docetaxel. Among those with PD-L1 ≥ 1%, median overall survival was 11.8 months with pembrolizumab versus 8.4 months with docetaxel.

Overall survival on Kaplan-Meier analysis was 34.5% with pembrolizumab and 12.7% with docetaxel in the PD-L1 ≥ 50% group, and 22.9% versus 11.0% in the PD-L1 ≥ 1% group.

PFS significantly improved with pembrolizumab versus docetaxel, at a hazard ratio of 0.57 (P < .00001) among patients with PD-L1 ≥ 50% and 0.83 (P < .005) in those with PD-L1 ≥ 1%.

In terms of safety, 17.7% of patients who completed 2 years of pembrolizumab had grade 3-5 treatment-related adverse events, compared with 16.6% among all pembrolizumab-treated patients and 36.6% of those given docetaxel.

The team reports that 79 patients completed 35 cycles of pembrolizumab, with a median follow-up of 43.4 months.

Compared with the overall patient group, these patients were less likely to be aged ≥ 65 years and to have received two or more prior treatment lines, although they were more likely to be current or former smokers and to have squamous tumor histology.

Patients who completed 35 cycles had an objective response rate of 94.9%, and 91.0% were still alive at the data cutoff. Overall survival rates were 98.7% at 12 months and 86.3% at 24 months.

Of 71 patients eligible for analysis, 23 experienced progression after completing pembrolizumab, at PFS rates at 12 and 24 months of 72.5% and 57.7%, respectively.

A total of 14 patients were given a second course of pembrolizumab, of whom six had a partial response and five had stable disease. At the data cutoff, five patients had completed 17 additional cycles and 11 were alive.

Pembro Approved at Fixed Dose

One notable aspect of the study is that patients in the pembrolizumab arm were given two different doses of the drug based on body weight, whereas the drug is approved in the United States at a fixed dose of 200 mg.

Herbst told Medscape Medical News he considers the 200-mg dose to be appropriate.

“I didn’t think that the 3-mg versus 10-mg dose per kg that we used in our study made much difference in an average-sized person,” he said, adding that the 200-mg dose “is something a little bit more than 3 mg/kg.”

“So I think that this is clearly the right dos, and I don’t think more would make any difference,” he said.

The study was funded by Merck, the manufacturer of pembrolizumab. Herbst has reported having a consulting or advisory role for many pharmaceutical companies. Other coauthors have also reported relationships with industry, and some of the authors are Merck employees. Peters has reported receiving education grants, providing consultation, attending advisory boards, and/or providing lectures for many pharmaceutical companies.
 

This article first appeared on Medscape.com.

The U.S. Food and Drug Administration today approved isatuximab (Sarclisa, Sanofi) in combination with pomalidomide (Revlimid, Celgene) and dexamethasone for the treatment of adult patients with multiple myeloma who have received two or more prior therapies including lenalidomide and a proteasome inhibitor.

Isatuximab is an anti-CD38 monoclonal antibody administered by intravenous infusion that works by helping the immune system attack multiple myeloma cancer cells.

“While there is no cure for multiple myeloma, Sarclisa is now another CD38-directed treatment option added to the list of FDA-approved treatments of patients with multiple myeloma who have progressive disease after previous therapies,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research.

“In the clinical trial, there was a 40% reduction in the risk of disease progression or death with this therapy,” he added.

The new approval is based on results from ICARIA-MM, an open-label, randomized phase 3 clinical trial of isatuximab among 307 patients in this setting.

In the trial, at a median follow-up of 11.6 months, median progression-free survival was 11.5 months in the isatuximab-pomalidomide-dexamethasone group versus 6.5 months in the pomalidomide-dexamethasone group (hazard ratio, 0.60; P = .001), as reported last year. Overall response rates were 60.4% for the triplet-treated group versus 35.3% for the doublet-treated group.

The most common side effects for isatuximab included neutropenia, infusion-related reactions, pneumonia, upper respiratory tract infection, diarrhea, anemia, lymphopenia, and thrombocytopenia.

Deaths because of treatment-related adverse events were reported for one patient (less than 1%) in the isatuximab-pomalidomide-dexamethasone group (sepsis) and two patients (1%) in the pomalidomide-dexamethasone group (pneumonia and urinary tract infection).

The drug can also cause serious side effects, including IV infusion-related reactions. In the case of a grade 3 or higher reaction, the drug should be permanently discontinued and health care professionals should institute appropriate medical management.

The FDA notes there have been higher incidences of second primary malignancies observed in a controlled clinical trial of patients with multiple myeloma receiving the drug.

The FDA also highlighted that laboratory test interference may be caused by isatuximab and that blood banks should be informed that patients are receiving the drug. Isatuximab may interfere with, for example, antibody screening for patients who need a blood transfusion. Isatuximab may also interfere with the assays used to monitor M-protein, which may impact the determination of complete response.

This article originally appeared on Medscape.com.

The U.S. Food and Drug Administration today approved isatuximab (Sarclisa, Sanofi) in combination with pomalidomide (Revlimid, Celgene) and dexamethasone for the treatment of adult patients with multiple myeloma who have received two or more prior therapies including lenalidomide and a proteasome inhibitor.

Isatuximab is an anti-CD38 monoclonal antibody administered by intravenous infusion that works by helping the immune system attack multiple myeloma cancer cells.

“While there is no cure for multiple myeloma, Sarclisa is now another CD38-directed treatment option added to the list of FDA-approved treatments of patients with multiple myeloma who have progressive disease after previous therapies,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research.

“In the clinical trial, there was a 40% reduction in the risk of disease progression or death with this therapy,” he added.

The new approval is based on results from ICARIA-MM, an open-label, randomized phase 3 clinical trial of isatuximab among 307 patients in this setting.

In the trial, at a median follow-up of 11.6 months, median progression-free survival was 11.5 months in the isatuximab-pomalidomide-dexamethasone group versus 6.5 months in the pomalidomide-dexamethasone group (hazard ratio, 0.60; P = .001), as reported last year. Overall response rates were 60.4% for the triplet-treated group versus 35.3% for the doublet-treated group.

The most common side effects for isatuximab included neutropenia, infusion-related reactions, pneumonia, upper respiratory tract infection, diarrhea, anemia, lymphopenia, and thrombocytopenia.

Deaths because of treatment-related adverse events were reported for one patient (less than 1%) in the isatuximab-pomalidomide-dexamethasone group (sepsis) and two patients (1%) in the pomalidomide-dexamethasone group (pneumonia and urinary tract infection).

The drug can also cause serious side effects, including IV infusion-related reactions. In the case of a grade 3 or higher reaction, the drug should be permanently discontinued and health care professionals should institute appropriate medical management.

The FDA notes there have been higher incidences of second primary malignancies observed in a controlled clinical trial of patients with multiple myeloma receiving the drug.

The FDA also highlighted that laboratory test interference may be caused by isatuximab and that blood banks should be informed that patients are receiving the drug. Isatuximab may interfere with, for example, antibody screening for patients who need a blood transfusion. Isatuximab may also interfere with the assays used to monitor M-protein, which may impact the determination of complete response.

This article originally appeared on Medscape.com.

The U.S. Food and Drug Administration today approved isatuximab (Sarclisa, Sanofi) in combination with pomalidomide (Revlimid, Celgene) and dexamethasone for the treatment of adult patients with multiple myeloma who have received two or more prior therapies including lenalidomide and a proteasome inhibitor.

Isatuximab is an anti-CD38 monoclonal antibody administered by intravenous infusion that works by helping the immune system attack multiple myeloma cancer cells.

“While there is no cure for multiple myeloma, Sarclisa is now another CD38-directed treatment option added to the list of FDA-approved treatments of patients with multiple myeloma who have progressive disease after previous therapies,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research.

“In the clinical trial, there was a 40% reduction in the risk of disease progression or death with this therapy,” he added.

The new approval is based on results from ICARIA-MM, an open-label, randomized phase 3 clinical trial of isatuximab among 307 patients in this setting.

In the trial, at a median follow-up of 11.6 months, median progression-free survival was 11.5 months in the isatuximab-pomalidomide-dexamethasone group versus 6.5 months in the pomalidomide-dexamethasone group (hazard ratio, 0.60; P = .001), as reported last year. Overall response rates were 60.4% for the triplet-treated group versus 35.3% for the doublet-treated group.

The most common side effects for isatuximab included neutropenia, infusion-related reactions, pneumonia, upper respiratory tract infection, diarrhea, anemia, lymphopenia, and thrombocytopenia.

Deaths because of treatment-related adverse events were reported for one patient (less than 1%) in the isatuximab-pomalidomide-dexamethasone group (sepsis) and two patients (1%) in the pomalidomide-dexamethasone group (pneumonia and urinary tract infection).

The drug can also cause serious side effects, including IV infusion-related reactions. In the case of a grade 3 or higher reaction, the drug should be permanently discontinued and health care professionals should institute appropriate medical management.

The FDA notes there have been higher incidences of second primary malignancies observed in a controlled clinical trial of patients with multiple myeloma receiving the drug.

The FDA also highlighted that laboratory test interference may be caused by isatuximab and that blood banks should be informed that patients are receiving the drug. Isatuximab may interfere with, for example, antibody screening for patients who need a blood transfusion. Isatuximab may also interfere with the assays used to monitor M-protein, which may impact the determination of complete response.

This article originally appeared on Medscape.com.

A new guideline from the American College of Rheumatology offers the organization’s first clinical recommendations on how to manage reproductive health issues in patients with rheumatic and musculoskeletal diseases (RMDs).

Bruce Jancin/MDedge News

“With the development of this guideline, the ACR recognizes the key role of clinical rheumatologists not only in managing disease activity but also in understanding the interactions of RMDs and their therapies in the context of reproductive health,” wrote Lisa R. Sammaritano, MD, of Weill Cornell Medicine and the Hospital for Special Surgery in New York, and coauthors. The guideline was published in Arthritis & Rheumatology.

To develop an evidence-based guideline on reproductive health in RMD patients, the researchers embarked on a systematic review of studies in areas like contraception, pregnancy and lactation, assisted reproductive technology (ART), fertility preservation, and hormone therapy. The guideline contains 12 ungraded good practice statements and 131 graded recommendations, all developed through the Grading of Recommendations Assessment, Development, and Evaluation methodology.

In counseling patients about these areas of care, the guideline says that rheumatologists and other clinicians “must collaborate with specialists in the fields of obstetrics-gynecology, maternal-fetal medicine, and reproductive endocrinology and infertility.”

Mitchel L. Zoler/Frontline Medical News

“One thing this guideline does well is highlight the importance of involving maternal-fetal medicine colleagues,” Alison Cahill, MD, a professor in the department of women’s health at the University of Texas at Austin and a maternal-fetal medicine specialist within UT Health Austin’s Women’s Health Institute, said when asked for comment on the guideline. “We’re always very happy to see patients ahead of time who are planning pregnancy to be able to discuss what the care plan would look like. And specifically, to address medications, if required, for their rheumatologic care.

“As we learn more and more,” she added, “we’ve come to understand that most treatments and medications are actually safe or relatively safe to take in pregnancy. Certainly, the benefit of taking them outweighs any small or theoretic risks. On the flip side, the guideline does a nice job of highlighting the importance of good disease control, both at the time of conception and during pregnancy.”
 

Contraception

In regard to contraception, the guideline strongly recommends the use of effective contraceptives – with a conditional recommendation of IUDs or a subdermal progestin implant – in fertile women with a RMD who have neither systemic lupus erythematosus (SLE) nor positive antiphospholipid antibody (aPL). They also strongly recommend discussing the use of emergency contraception with all RMD patients.

For SLE patients, the guideline strongly recommends the use of effective contraceptives in those with stable or low disease activity who are not positive for aPL. They also strongly recommend progestin‐only or IUD contraceptives over combined estrogen‐progestin contraception. For aPL-positive patients, the guideline strongly recommends against combined estrogen‐progestin contraceptives and for levonorgestrel or copper IUDs or the progestin‐only pill.
 

Assisted reproductive technology

In regard to ART, the guideline strongly recommends proceeding as needed in aPL-negative women with uncomplicated, stable RMD who are on pregnancy‐compatible medications. They also strongly recommend deferring ART in any RMD patients with moderately or severely active disease.

For aPL-positive patients undergoing ART procedures, they strongly recommend prophylactic anticoagulation with heparin or low-molecular-weight heparin (LMWH) in women with obstetric antiphospholipid syndrome (APS) and therapeutic anticoagulation in women with thrombotic APS. In patients undergoing embryo and oocyte cryopreservation, they strongly recommend continuing immunosuppressive and biologic therapies – the exception being cyclophosphamide (CYC) – for anyone in stable condition.
 

Fertility preservation

In regard to fertility preservation in patients taking CYC, the guideline strongly suggests sperm cryopreservation as good practice prior to treatment. They also conditionally recommend monthly gonadotropin‐releasing hormone agonist cotherapy in premenopausal women with RMD.

Hormone therapy

In regard to menopause and hormone therapy, the guideline strongly suggests hormone therapy as good practice in postmenopausal women with RMD, without SLE or positive aPL, and who have severe vasomotor symptoms. Hormone therapy is conditionally recommended in patients with SLE, without positive aPL, and with no contraindications. For aPL-positive patients, they strongly recommend against hormone therapy in women with obstetric and/or thrombotic APS.

Pregnancy assessment and management

Among the many recommendations regarding pregnancy assessment and management, the guideline strongly suggests counseling women with RMD who are considering pregnancy to take into account the improved outcomes for pregnant women with low disease activity. They strongly recommend that women considering pregnancy should switch to pregnancy‐compatible medication and pause to assess its efficacy and tolerability before moving forward, along with strongly recommending that pregnant women with active disease initiate or continue a pregnancy‐compatible steroid‐sparing medication. They also recommend testing for anti‐Ro/SS-A and anti‐La/SS-B in women with SLE, Sjögren’s syndrome, systemic sclerosis, or rheumatoid arthritis, but only once and only before or early in the pregnancy.

For women with systemic sclerosis who develop scleroderma renal crisis during pregnancy, the authors strongly advise using ACE inhibitors or angiotensin receptor blockers “because the risk of maternal or fetal death with untreated disease is higher than the risk associated with use of these medications during pregnancy.”

Among women with SLE, the recommendations strongly call for testing either before or early in pregnancy for anticardiolipin antibody, anti–beta2-glycoprotein I, or positive lupus anticoagulant, as well as initiating or continuing hydroxychloroquine (HCQ) if possible. Starting in the first trimester, the authors also conditionally recommend that SLE patients take low-dose aspirin daily

For pregnant women who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the guideline conditionally recommends prophylactic treatment with low-dose aspirin daily to protect against preeclampsia. When obstetric APS criteria are met, the guideline strongly advises combined treatment with daily low-dose aspirin and prophylactic-dose heparin (or LMWH), as well as prophylactic-dose anticoagulation for 6-12 weeks post partum. When patients have thrombotic APS, this combination treatment should contain heparin dose at a therapeutic level throughout pregnancy and postpartum. However, the authors conditionally recommend against giving low-dose aspirin plus prophylactic-dose heparin to women without obstetric APS. For refractory obstetric APS, the guideline also contains recommendations that are conditionally against treatment with intravenous immunoglobulin or an increased LMWH dose and strongly against adding prednisone to prophylactic-dose heparin or LMWH and low-dose aspirin. In pregnant patients with primary APS, the authors conditionally advise adding HCQ to prophylactic-dose heparin or LMWH and low-dose aspirin therapy. However, women with aPL who do not meet APS criteria or have another indication for HCQ are conditionally advised against prophylactic treatment with the antimalarial.

For women with Anti-Ro/SS-A and/or anti-La/SS-B antibodies in pregnancy, there is conditional advice to use HCQ. When there is no history of an infant with complete heart block or neonatal lupus erythematosus among women with these antibodies, the guideline conditionally advises serial fetal echocardiography (less often than weekly) starting between 16 and 18 weeks and continuing through 26 weeks, but this should be weekly when there is a prior history. Treatment with oral dexamethasone 4 mg daily is conditionally advised when there is echocardiographic evidence of fetal first- or second-degree heart block, but dexamethasone is not recommended when complete heart block is present.

Finally, in regard to medication use, the authors strongly recommend that men who are planning to be fathers continue on HCQ, azathioprine, 6‐mercaptopurine, colchicine, or tumor necrosis factor inhibitors. Conditional treatment recommendations for men planning for pregnancy include methotrexate, mycophenolate mofetil/mycophenolic acid (MMF), leflunomide, sulfasalazine, calcineurin inhibitors, and NSAIDs. They also strongly recommend that this group of men discontinue CYC and thalidomide.

Pregnant women are strongly recommended to discontinue methotrexate, leflunomide (with cholestyramine washout if there are detectable serum levels of its metabolite prior to pregnancy or as soon as it is confirmed), MMF, CYC, and thalidomide within 3 months prior to conception, and they strongly recommend HCQ (in women with SLE), azathioprine/6‐mercaptopurine, colchicine, or sulfasalazine for use throughout pregnancy. They strongly recommend a combination of low‐dose aspirin and prophylactic‐dose heparin for pregnant women with obstetric APS, along with low‐dose aspirin and therapeutic‐dose heparin for women with thrombotic APS throughout pregnancy and postpartum. However, for women with SLE and those who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the authors conditionally recommend low-dose aspirin starting in the first trimester.

The guideline suggests that women with RMD should be encouraged to breastfeed if they are willing and able; they also suggest that disease control be maintained through lactation‐compatible medications and that the risks and benefits be reviewed on a patient-by-patient basis. Treatment with HCQ, colchicine, sulfasalazine, rituximab, and all tumor necrosis factor inhibitors are strongly recommended as being compatible with breastfeeding, and they strongly recommend against using CYC, leflunomide, MMF, and thalidomide while breastfeeding.

The authors acknowledged the limitations of their guideline, including the literature review being conducted on studies involving adults and an “inability to include recommendations for uncommon but important clinical situations,” including those involving transgender patients and hormonal therapies.

The authors reported numerous potential conflicts of interest, including receiving research support, consulting fees, speaking fees, and honoraria from various pharmaceutical companies.

SOURCE: Sammaritano LR et al. Arthritis Rheumatol. 2020 Feb 23. doi: 10.1002/art.41191.

A new guideline from the American College of Rheumatology offers the organization’s first clinical recommendations on how to manage reproductive health issues in patients with rheumatic and musculoskeletal diseases (RMDs).

Bruce Jancin/MDedge News

“With the development of this guideline, the ACR recognizes the key role of clinical rheumatologists not only in managing disease activity but also in understanding the interactions of RMDs and their therapies in the context of reproductive health,” wrote Lisa R. Sammaritano, MD, of Weill Cornell Medicine and the Hospital for Special Surgery in New York, and coauthors. The guideline was published in Arthritis & Rheumatology.

To develop an evidence-based guideline on reproductive health in RMD patients, the researchers embarked on a systematic review of studies in areas like contraception, pregnancy and lactation, assisted reproductive technology (ART), fertility preservation, and hormone therapy. The guideline contains 12 ungraded good practice statements and 131 graded recommendations, all developed through the Grading of Recommendations Assessment, Development, and Evaluation methodology.

In counseling patients about these areas of care, the guideline says that rheumatologists and other clinicians “must collaborate with specialists in the fields of obstetrics-gynecology, maternal-fetal medicine, and reproductive endocrinology and infertility.”

Mitchel L. Zoler/Frontline Medical News

“One thing this guideline does well is highlight the importance of involving maternal-fetal medicine colleagues,” Alison Cahill, MD, a professor in the department of women’s health at the University of Texas at Austin and a maternal-fetal medicine specialist within UT Health Austin’s Women’s Health Institute, said when asked for comment on the guideline. “We’re always very happy to see patients ahead of time who are planning pregnancy to be able to discuss what the care plan would look like. And specifically, to address medications, if required, for their rheumatologic care.

“As we learn more and more,” she added, “we’ve come to understand that most treatments and medications are actually safe or relatively safe to take in pregnancy. Certainly, the benefit of taking them outweighs any small or theoretic risks. On the flip side, the guideline does a nice job of highlighting the importance of good disease control, both at the time of conception and during pregnancy.”
 

Contraception

In regard to contraception, the guideline strongly recommends the use of effective contraceptives – with a conditional recommendation of IUDs or a subdermal progestin implant – in fertile women with a RMD who have neither systemic lupus erythematosus (SLE) nor positive antiphospholipid antibody (aPL). They also strongly recommend discussing the use of emergency contraception with all RMD patients.

For SLE patients, the guideline strongly recommends the use of effective contraceptives in those with stable or low disease activity who are not positive for aPL. They also strongly recommend progestin‐only or IUD contraceptives over combined estrogen‐progestin contraception. For aPL-positive patients, the guideline strongly recommends against combined estrogen‐progestin contraceptives and for levonorgestrel or copper IUDs or the progestin‐only pill.
 

Assisted reproductive technology

In regard to ART, the guideline strongly recommends proceeding as needed in aPL-negative women with uncomplicated, stable RMD who are on pregnancy‐compatible medications. They also strongly recommend deferring ART in any RMD patients with moderately or severely active disease.

For aPL-positive patients undergoing ART procedures, they strongly recommend prophylactic anticoagulation with heparin or low-molecular-weight heparin (LMWH) in women with obstetric antiphospholipid syndrome (APS) and therapeutic anticoagulation in women with thrombotic APS. In patients undergoing embryo and oocyte cryopreservation, they strongly recommend continuing immunosuppressive and biologic therapies – the exception being cyclophosphamide (CYC) – for anyone in stable condition.
 

Fertility preservation

In regard to fertility preservation in patients taking CYC, the guideline strongly suggests sperm cryopreservation as good practice prior to treatment. They also conditionally recommend monthly gonadotropin‐releasing hormone agonist cotherapy in premenopausal women with RMD.

Hormone therapy

In regard to menopause and hormone therapy, the guideline strongly suggests hormone therapy as good practice in postmenopausal women with RMD, without SLE or positive aPL, and who have severe vasomotor symptoms. Hormone therapy is conditionally recommended in patients with SLE, without positive aPL, and with no contraindications. For aPL-positive patients, they strongly recommend against hormone therapy in women with obstetric and/or thrombotic APS.

Pregnancy assessment and management

Among the many recommendations regarding pregnancy assessment and management, the guideline strongly suggests counseling women with RMD who are considering pregnancy to take into account the improved outcomes for pregnant women with low disease activity. They strongly recommend that women considering pregnancy should switch to pregnancy‐compatible medication and pause to assess its efficacy and tolerability before moving forward, along with strongly recommending that pregnant women with active disease initiate or continue a pregnancy‐compatible steroid‐sparing medication. They also recommend testing for anti‐Ro/SS-A and anti‐La/SS-B in women with SLE, Sjögren’s syndrome, systemic sclerosis, or rheumatoid arthritis, but only once and only before or early in the pregnancy.

For women with systemic sclerosis who develop scleroderma renal crisis during pregnancy, the authors strongly advise using ACE inhibitors or angiotensin receptor blockers “because the risk of maternal or fetal death with untreated disease is higher than the risk associated with use of these medications during pregnancy.”

Among women with SLE, the recommendations strongly call for testing either before or early in pregnancy for anticardiolipin antibody, anti–beta2-glycoprotein I, or positive lupus anticoagulant, as well as initiating or continuing hydroxychloroquine (HCQ) if possible. Starting in the first trimester, the authors also conditionally recommend that SLE patients take low-dose aspirin daily

For pregnant women who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the guideline conditionally recommends prophylactic treatment with low-dose aspirin daily to protect against preeclampsia. When obstetric APS criteria are met, the guideline strongly advises combined treatment with daily low-dose aspirin and prophylactic-dose heparin (or LMWH), as well as prophylactic-dose anticoagulation for 6-12 weeks post partum. When patients have thrombotic APS, this combination treatment should contain heparin dose at a therapeutic level throughout pregnancy and postpartum. However, the authors conditionally recommend against giving low-dose aspirin plus prophylactic-dose heparin to women without obstetric APS. For refractory obstetric APS, the guideline also contains recommendations that are conditionally against treatment with intravenous immunoglobulin or an increased LMWH dose and strongly against adding prednisone to prophylactic-dose heparin or LMWH and low-dose aspirin. In pregnant patients with primary APS, the authors conditionally advise adding HCQ to prophylactic-dose heparin or LMWH and low-dose aspirin therapy. However, women with aPL who do not meet APS criteria or have another indication for HCQ are conditionally advised against prophylactic treatment with the antimalarial.

For women with Anti-Ro/SS-A and/or anti-La/SS-B antibodies in pregnancy, there is conditional advice to use HCQ. When there is no history of an infant with complete heart block or neonatal lupus erythematosus among women with these antibodies, the guideline conditionally advises serial fetal echocardiography (less often than weekly) starting between 16 and 18 weeks and continuing through 26 weeks, but this should be weekly when there is a prior history. Treatment with oral dexamethasone 4 mg daily is conditionally advised when there is echocardiographic evidence of fetal first- or second-degree heart block, but dexamethasone is not recommended when complete heart block is present.

Finally, in regard to medication use, the authors strongly recommend that men who are planning to be fathers continue on HCQ, azathioprine, 6‐mercaptopurine, colchicine, or tumor necrosis factor inhibitors. Conditional treatment recommendations for men planning for pregnancy include methotrexate, mycophenolate mofetil/mycophenolic acid (MMF), leflunomide, sulfasalazine, calcineurin inhibitors, and NSAIDs. They also strongly recommend that this group of men discontinue CYC and thalidomide.

Pregnant women are strongly recommended to discontinue methotrexate, leflunomide (with cholestyramine washout if there are detectable serum levels of its metabolite prior to pregnancy or as soon as it is confirmed), MMF, CYC, and thalidomide within 3 months prior to conception, and they strongly recommend HCQ (in women with SLE), azathioprine/6‐mercaptopurine, colchicine, or sulfasalazine for use throughout pregnancy. They strongly recommend a combination of low‐dose aspirin and prophylactic‐dose heparin for pregnant women with obstetric APS, along with low‐dose aspirin and therapeutic‐dose heparin for women with thrombotic APS throughout pregnancy and postpartum. However, for women with SLE and those who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the authors conditionally recommend low-dose aspirin starting in the first trimester.

The guideline suggests that women with RMD should be encouraged to breastfeed if they are willing and able; they also suggest that disease control be maintained through lactation‐compatible medications and that the risks and benefits be reviewed on a patient-by-patient basis. Treatment with HCQ, colchicine, sulfasalazine, rituximab, and all tumor necrosis factor inhibitors are strongly recommended as being compatible with breastfeeding, and they strongly recommend against using CYC, leflunomide, MMF, and thalidomide while breastfeeding.

The authors acknowledged the limitations of their guideline, including the literature review being conducted on studies involving adults and an “inability to include recommendations for uncommon but important clinical situations,” including those involving transgender patients and hormonal therapies.

The authors reported numerous potential conflicts of interest, including receiving research support, consulting fees, speaking fees, and honoraria from various pharmaceutical companies.

SOURCE: Sammaritano LR et al. Arthritis Rheumatol. 2020 Feb 23. doi: 10.1002/art.41191.

A new guideline from the American College of Rheumatology offers the organization’s first clinical recommendations on how to manage reproductive health issues in patients with rheumatic and musculoskeletal diseases (RMDs).

Bruce Jancin/MDedge News

“With the development of this guideline, the ACR recognizes the key role of clinical rheumatologists not only in managing disease activity but also in understanding the interactions of RMDs and their therapies in the context of reproductive health,” wrote Lisa R. Sammaritano, MD, of Weill Cornell Medicine and the Hospital for Special Surgery in New York, and coauthors. The guideline was published in Arthritis & Rheumatology.

To develop an evidence-based guideline on reproductive health in RMD patients, the researchers embarked on a systematic review of studies in areas like contraception, pregnancy and lactation, assisted reproductive technology (ART), fertility preservation, and hormone therapy. The guideline contains 12 ungraded good practice statements and 131 graded recommendations, all developed through the Grading of Recommendations Assessment, Development, and Evaluation methodology.

In counseling patients about these areas of care, the guideline says that rheumatologists and other clinicians “must collaborate with specialists in the fields of obstetrics-gynecology, maternal-fetal medicine, and reproductive endocrinology and infertility.”

Mitchel L. Zoler/Frontline Medical News

“One thing this guideline does well is highlight the importance of involving maternal-fetal medicine colleagues,” Alison Cahill, MD, a professor in the department of women’s health at the University of Texas at Austin and a maternal-fetal medicine specialist within UT Health Austin’s Women’s Health Institute, said when asked for comment on the guideline. “We’re always very happy to see patients ahead of time who are planning pregnancy to be able to discuss what the care plan would look like. And specifically, to address medications, if required, for their rheumatologic care.

“As we learn more and more,” she added, “we’ve come to understand that most treatments and medications are actually safe or relatively safe to take in pregnancy. Certainly, the benefit of taking them outweighs any small or theoretic risks. On the flip side, the guideline does a nice job of highlighting the importance of good disease control, both at the time of conception and during pregnancy.”
 

Contraception

In regard to contraception, the guideline strongly recommends the use of effective contraceptives – with a conditional recommendation of IUDs or a subdermal progestin implant – in fertile women with a RMD who have neither systemic lupus erythematosus (SLE) nor positive antiphospholipid antibody (aPL). They also strongly recommend discussing the use of emergency contraception with all RMD patients.

For SLE patients, the guideline strongly recommends the use of effective contraceptives in those with stable or low disease activity who are not positive for aPL. They also strongly recommend progestin‐only or IUD contraceptives over combined estrogen‐progestin contraception. For aPL-positive patients, the guideline strongly recommends against combined estrogen‐progestin contraceptives and for levonorgestrel or copper IUDs or the progestin‐only pill.
 

Assisted reproductive technology

In regard to ART, the guideline strongly recommends proceeding as needed in aPL-negative women with uncomplicated, stable RMD who are on pregnancy‐compatible medications. They also strongly recommend deferring ART in any RMD patients with moderately or severely active disease.

For aPL-positive patients undergoing ART procedures, they strongly recommend prophylactic anticoagulation with heparin or low-molecular-weight heparin (LMWH) in women with obstetric antiphospholipid syndrome (APS) and therapeutic anticoagulation in women with thrombotic APS. In patients undergoing embryo and oocyte cryopreservation, they strongly recommend continuing immunosuppressive and biologic therapies – the exception being cyclophosphamide (CYC) – for anyone in stable condition.
 

Fertility preservation

In regard to fertility preservation in patients taking CYC, the guideline strongly suggests sperm cryopreservation as good practice prior to treatment. They also conditionally recommend monthly gonadotropin‐releasing hormone agonist cotherapy in premenopausal women with RMD.

Hormone therapy

In regard to menopause and hormone therapy, the guideline strongly suggests hormone therapy as good practice in postmenopausal women with RMD, without SLE or positive aPL, and who have severe vasomotor symptoms. Hormone therapy is conditionally recommended in patients with SLE, without positive aPL, and with no contraindications. For aPL-positive patients, they strongly recommend against hormone therapy in women with obstetric and/or thrombotic APS.

Pregnancy assessment and management

Among the many recommendations regarding pregnancy assessment and management, the guideline strongly suggests counseling women with RMD who are considering pregnancy to take into account the improved outcomes for pregnant women with low disease activity. They strongly recommend that women considering pregnancy should switch to pregnancy‐compatible medication and pause to assess its efficacy and tolerability before moving forward, along with strongly recommending that pregnant women with active disease initiate or continue a pregnancy‐compatible steroid‐sparing medication. They also recommend testing for anti‐Ro/SS-A and anti‐La/SS-B in women with SLE, Sjögren’s syndrome, systemic sclerosis, or rheumatoid arthritis, but only once and only before or early in the pregnancy.

For women with systemic sclerosis who develop scleroderma renal crisis during pregnancy, the authors strongly advise using ACE inhibitors or angiotensin receptor blockers “because the risk of maternal or fetal death with untreated disease is higher than the risk associated with use of these medications during pregnancy.”

Among women with SLE, the recommendations strongly call for testing either before or early in pregnancy for anticardiolipin antibody, anti–beta2-glycoprotein I, or positive lupus anticoagulant, as well as initiating or continuing hydroxychloroquine (HCQ) if possible. Starting in the first trimester, the authors also conditionally recommend that SLE patients take low-dose aspirin daily

For pregnant women who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the guideline conditionally recommends prophylactic treatment with low-dose aspirin daily to protect against preeclampsia. When obstetric APS criteria are met, the guideline strongly advises combined treatment with daily low-dose aspirin and prophylactic-dose heparin (or LMWH), as well as prophylactic-dose anticoagulation for 6-12 weeks post partum. When patients have thrombotic APS, this combination treatment should contain heparin dose at a therapeutic level throughout pregnancy and postpartum. However, the authors conditionally recommend against giving low-dose aspirin plus prophylactic-dose heparin to women without obstetric APS. For refractory obstetric APS, the guideline also contains recommendations that are conditionally against treatment with intravenous immunoglobulin or an increased LMWH dose and strongly against adding prednisone to prophylactic-dose heparin or LMWH and low-dose aspirin. In pregnant patients with primary APS, the authors conditionally advise adding HCQ to prophylactic-dose heparin or LMWH and low-dose aspirin therapy. However, women with aPL who do not meet APS criteria or have another indication for HCQ are conditionally advised against prophylactic treatment with the antimalarial.

For women with Anti-Ro/SS-A and/or anti-La/SS-B antibodies in pregnancy, there is conditional advice to use HCQ. When there is no history of an infant with complete heart block or neonatal lupus erythematosus among women with these antibodies, the guideline conditionally advises serial fetal echocardiography (less often than weekly) starting between 16 and 18 weeks and continuing through 26 weeks, but this should be weekly when there is a prior history. Treatment with oral dexamethasone 4 mg daily is conditionally advised when there is echocardiographic evidence of fetal first- or second-degree heart block, but dexamethasone is not recommended when complete heart block is present.

Finally, in regard to medication use, the authors strongly recommend that men who are planning to be fathers continue on HCQ, azathioprine, 6‐mercaptopurine, colchicine, or tumor necrosis factor inhibitors. Conditional treatment recommendations for men planning for pregnancy include methotrexate, mycophenolate mofetil/mycophenolic acid (MMF), leflunomide, sulfasalazine, calcineurin inhibitors, and NSAIDs. They also strongly recommend that this group of men discontinue CYC and thalidomide.

Pregnant women are strongly recommended to discontinue methotrexate, leflunomide (with cholestyramine washout if there are detectable serum levels of its metabolite prior to pregnancy or as soon as it is confirmed), MMF, CYC, and thalidomide within 3 months prior to conception, and they strongly recommend HCQ (in women with SLE), azathioprine/6‐mercaptopurine, colchicine, or sulfasalazine for use throughout pregnancy. They strongly recommend a combination of low‐dose aspirin and prophylactic‐dose heparin for pregnant women with obstetric APS, along with low‐dose aspirin and therapeutic‐dose heparin for women with thrombotic APS throughout pregnancy and postpartum. However, for women with SLE and those who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the authors conditionally recommend low-dose aspirin starting in the first trimester.

The guideline suggests that women with RMD should be encouraged to breastfeed if they are willing and able; they also suggest that disease control be maintained through lactation‐compatible medications and that the risks and benefits be reviewed on a patient-by-patient basis. Treatment with HCQ, colchicine, sulfasalazine, rituximab, and all tumor necrosis factor inhibitors are strongly recommended as being compatible with breastfeeding, and they strongly recommend against using CYC, leflunomide, MMF, and thalidomide while breastfeeding.

The authors acknowledged the limitations of their guideline, including the literature review being conducted on studies involving adults and an “inability to include recommendations for uncommon but important clinical situations,” including those involving transgender patients and hormonal therapies.

The authors reported numerous potential conflicts of interest, including receiving research support, consulting fees, speaking fees, and honoraria from various pharmaceutical companies.

SOURCE: Sammaritano LR et al. Arthritis Rheumatol. 2020 Feb 23. doi: 10.1002/art.41191.

WEST PALM BEACH, FLA. – Cancer incidence among patients with multiple sclerosis (MS) treated after the advent of immune therapies showed an increase, compared with prior generations, according to a large study of Norwegian MS patients.

“We detected a similar cancer risk among MS patients, compared to the general Norwegian population before 1996, [however] MS patients had increased risk of cancer compared to the general population after 1996,” first author Nina Grytten, PhD, of the department of neurology at the Norwegian Multiple Sclerosis Centre, Bergen, Norway, said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

“This finding suggests that clinicians should be aware of this increased risk of cancer when caring for MS patients.”

With the widespread use of disease-modifying therapies (DMTs) in patients with MS, such findings are always of interest to clinicians and patients alike, commented ACTRIMS president, Jeffrey A. Cohen, MD.

“Something that’s already on the mind of most people with MS is what are the long-term safety characteristics of these medicines because we’re talking about a life-long therapy for most people,” Dr. Cohen, who is the director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research at the Cleveland Clinic, said in an interview.

“With such a large sample size and such a long study, this is on one hand reassuring and tells us the cancer risk is likely low, but it also suggests that it’s something we should pay attention to,” he said.

In previous research, Dr. Grytten and her team identified an increased risk of cancer among patients with MS in Norway, but conflicting results have been reported in other studies looking at cancer risk and MS.

The authors therefore sought to dig deeper into the risk in the Norwegian population, looking into the specifics of cancer incidence according to sex and the period of diagnosis.

For the study, they identified a total of 6,638 patients with MS from previous prevalence studies in Norway, as well as in the Norwegian MS Registry and Biobank.

The data from the cohort was matched with 36,957 Norwegian citizens without MS in a 5:1 ratio, with the participants matched according to age, gender, and county. The cohort was further linked to data from the Norwegian Cancer Registry for additional information on the year and type of cancer diagnosis, as well as cause and year of death data. The participants were born between 1930 and 1979.

Over the course of the full 65-year observation period, the cancer diagnosis rates were similar between participants with MS (774; 11.2%) and those without MS (4,017; 10.6%).

And in looking at cancer incidence rate ratios of those with MS, compared with controls between the years 1953 and 1995, the rate was similar (IRR, 1.05; 95% confidence interval, 0.97-1.14). However, after 1995, the rate increased, with a higher cancer incidence among MS patients, compared with those without MS (IRR, 1.40; 95% CI, 1.30-1.51).

Cancer rates were additionally higher among those with MS in cancers of various organs, including the brain (IRR, 1.75; 95% CI, 1.28-2.40), meninges (IRR, 2.28; 95% CI, 1.47-3.53), urinary organs (IRR, 2.06; 95% CI, 1.52-2.79), digestive system (IRR, 1.47; 95% CI, 1.20-1.80), endocrine glands (IRR, 1.64; 95% CI, 1.06-2.54), and respiratory organs (IRR, 2.05; 95% CI, 1.55-2.07).

Dr. Grytten noted, however, that the study cannot rule out various other possible causes for the differences. For instance, “cancer in urinary system and respiratory organs showed increased risk in MS both before and after introduction of disease-modifying therapies,” she noted. “Those are possibly caused by smoking, which is a habit more common among MS patients in Norway.”

Furthermore, “increased cancer in the central nervous system in MS could possibly be explained by frequent use of magnetic resonance imaging and the ability to detect CNS cancer at early stages.”

“There is increasing evidence that patients with MS are also more susceptible to other diseases, and increased cancer risk seems to be one of these comorbidities.”

However, the finding that increased cancers were observed after 1996 in other organs in MS patients as well does raise the issue of a possible role of DMTs.

Of note, mitoxantrone has been associated with an increased risk of leukemia and colorectal cancer.

And “other immunosuppressant drugs, including the MS drug fingolimod, are believed to possibly be linked to an increased cancer risk, although evidence has not yet been established,” Dr. Grytten said.

“The increased risk of cancer associated with MS was detected in the era of disease-modifying treatment of MS, and this association suggests that DMTs might possibly increase cancer risk.”

In general, “clinicians should be aware of comorbidity in MS,” Dr. Grytten said. “More data is needed on the long-time effects of immunomodulatory treatment.”

Dr. Cohen added that, in addition to mitoxantrone, azathioprine and cyclophosphamide have shown risk, but “clinical trials and follow-up studies of individual MS DMTs have not shown clear cut increased risk of cancer, which is reassuring.”

“Nevertheless, this study suggests that, in aggregate, there may be a mild increased risk. There are many other potential explanations, so the research needs to be followed up,” he said.

Dr. Cohen reported receiving personal compensation for consulting for Adamas, Convelo, MedDay, Mylan, and Population Council; and serving as an Editor of Multiple Sclerosis Journal.

SOURCE: Torkildsen NG et al. ACTRIMS Forum 2020, Abstract P126.

WEST PALM BEACH, FLA. – Cancer incidence among patients with multiple sclerosis (MS) treated after the advent of immune therapies showed an increase, compared with prior generations, according to a large study of Norwegian MS patients.

“We detected a similar cancer risk among MS patients, compared to the general Norwegian population before 1996, [however] MS patients had increased risk of cancer compared to the general population after 1996,” first author Nina Grytten, PhD, of the department of neurology at the Norwegian Multiple Sclerosis Centre, Bergen, Norway, said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

“This finding suggests that clinicians should be aware of this increased risk of cancer when caring for MS patients.”

With the widespread use of disease-modifying therapies (DMTs) in patients with MS, such findings are always of interest to clinicians and patients alike, commented ACTRIMS president, Jeffrey A. Cohen, MD.

“Something that’s already on the mind of most people with MS is what are the long-term safety characteristics of these medicines because we’re talking about a life-long therapy for most people,” Dr. Cohen, who is the director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research at the Cleveland Clinic, said in an interview.

“With such a large sample size and such a long study, this is on one hand reassuring and tells us the cancer risk is likely low, but it also suggests that it’s something we should pay attention to,” he said.

In previous research, Dr. Grytten and her team identified an increased risk of cancer among patients with MS in Norway, but conflicting results have been reported in other studies looking at cancer risk and MS.

The authors therefore sought to dig deeper into the risk in the Norwegian population, looking into the specifics of cancer incidence according to sex and the period of diagnosis.

For the study, they identified a total of 6,638 patients with MS from previous prevalence studies in Norway, as well as in the Norwegian MS Registry and Biobank.

The data from the cohort was matched with 36,957 Norwegian citizens without MS in a 5:1 ratio, with the participants matched according to age, gender, and county. The cohort was further linked to data from the Norwegian Cancer Registry for additional information on the year and type of cancer diagnosis, as well as cause and year of death data. The participants were born between 1930 and 1979.

Over the course of the full 65-year observation period, the cancer diagnosis rates were similar between participants with MS (774; 11.2%) and those without MS (4,017; 10.6%).

And in looking at cancer incidence rate ratios of those with MS, compared with controls between the years 1953 and 1995, the rate was similar (IRR, 1.05; 95% confidence interval, 0.97-1.14). However, after 1995, the rate increased, with a higher cancer incidence among MS patients, compared with those without MS (IRR, 1.40; 95% CI, 1.30-1.51).

Cancer rates were additionally higher among those with MS in cancers of various organs, including the brain (IRR, 1.75; 95% CI, 1.28-2.40), meninges (IRR, 2.28; 95% CI, 1.47-3.53), urinary organs (IRR, 2.06; 95% CI, 1.52-2.79), digestive system (IRR, 1.47; 95% CI, 1.20-1.80), endocrine glands (IRR, 1.64; 95% CI, 1.06-2.54), and respiratory organs (IRR, 2.05; 95% CI, 1.55-2.07).

Dr. Grytten noted, however, that the study cannot rule out various other possible causes for the differences. For instance, “cancer in urinary system and respiratory organs showed increased risk in MS both before and after introduction of disease-modifying therapies,” she noted. “Those are possibly caused by smoking, which is a habit more common among MS patients in Norway.”

Furthermore, “increased cancer in the central nervous system in MS could possibly be explained by frequent use of magnetic resonance imaging and the ability to detect CNS cancer at early stages.”

“There is increasing evidence that patients with MS are also more susceptible to other diseases, and increased cancer risk seems to be one of these comorbidities.”

However, the finding that increased cancers were observed after 1996 in other organs in MS patients as well does raise the issue of a possible role of DMTs.

Of note, mitoxantrone has been associated with an increased risk of leukemia and colorectal cancer.

And “other immunosuppressant drugs, including the MS drug fingolimod, are believed to possibly be linked to an increased cancer risk, although evidence has not yet been established,” Dr. Grytten said.

“The increased risk of cancer associated with MS was detected in the era of disease-modifying treatment of MS, and this association suggests that DMTs might possibly increase cancer risk.”

In general, “clinicians should be aware of comorbidity in MS,” Dr. Grytten said. “More data is needed on the long-time effects of immunomodulatory treatment.”

Dr. Cohen added that, in addition to mitoxantrone, azathioprine and cyclophosphamide have shown risk, but “clinical trials and follow-up studies of individual MS DMTs have not shown clear cut increased risk of cancer, which is reassuring.”

“Nevertheless, this study suggests that, in aggregate, there may be a mild increased risk. There are many other potential explanations, so the research needs to be followed up,” he said.

Dr. Cohen reported receiving personal compensation for consulting for Adamas, Convelo, MedDay, Mylan, and Population Council; and serving as an Editor of Multiple Sclerosis Journal.

SOURCE: Torkildsen NG et al. ACTRIMS Forum 2020, Abstract P126.

WEST PALM BEACH, FLA. – Cancer incidence among patients with multiple sclerosis (MS) treated after the advent of immune therapies showed an increase, compared with prior generations, according to a large study of Norwegian MS patients.

“We detected a similar cancer risk among MS patients, compared to the general Norwegian population before 1996, [however] MS patients had increased risk of cancer compared to the general population after 1996,” first author Nina Grytten, PhD, of the department of neurology at the Norwegian Multiple Sclerosis Centre, Bergen, Norway, said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

“This finding suggests that clinicians should be aware of this increased risk of cancer when caring for MS patients.”

With the widespread use of disease-modifying therapies (DMTs) in patients with MS, such findings are always of interest to clinicians and patients alike, commented ACTRIMS president, Jeffrey A. Cohen, MD.

“Something that’s already on the mind of most people with MS is what are the long-term safety characteristics of these medicines because we’re talking about a life-long therapy for most people,” Dr. Cohen, who is the director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research at the Cleveland Clinic, said in an interview.

“With such a large sample size and such a long study, this is on one hand reassuring and tells us the cancer risk is likely low, but it also suggests that it’s something we should pay attention to,” he said.

In previous research, Dr. Grytten and her team identified an increased risk of cancer among patients with MS in Norway, but conflicting results have been reported in other studies looking at cancer risk and MS.

The authors therefore sought to dig deeper into the risk in the Norwegian population, looking into the specifics of cancer incidence according to sex and the period of diagnosis.

For the study, they identified a total of 6,638 patients with MS from previous prevalence studies in Norway, as well as in the Norwegian MS Registry and Biobank.

The data from the cohort was matched with 36,957 Norwegian citizens without MS in a 5:1 ratio, with the participants matched according to age, gender, and county. The cohort was further linked to data from the Norwegian Cancer Registry for additional information on the year and type of cancer diagnosis, as well as cause and year of death data. The participants were born between 1930 and 1979.

Over the course of the full 65-year observation period, the cancer diagnosis rates were similar between participants with MS (774; 11.2%) and those without MS (4,017; 10.6%).

And in looking at cancer incidence rate ratios of those with MS, compared with controls between the years 1953 and 1995, the rate was similar (IRR, 1.05; 95% confidence interval, 0.97-1.14). However, after 1995, the rate increased, with a higher cancer incidence among MS patients, compared with those without MS (IRR, 1.40; 95% CI, 1.30-1.51).

Cancer rates were additionally higher among those with MS in cancers of various organs, including the brain (IRR, 1.75; 95% CI, 1.28-2.40), meninges (IRR, 2.28; 95% CI, 1.47-3.53), urinary organs (IRR, 2.06; 95% CI, 1.52-2.79), digestive system (IRR, 1.47; 95% CI, 1.20-1.80), endocrine glands (IRR, 1.64; 95% CI, 1.06-2.54), and respiratory organs (IRR, 2.05; 95% CI, 1.55-2.07).

Dr. Grytten noted, however, that the study cannot rule out various other possible causes for the differences. For instance, “cancer in urinary system and respiratory organs showed increased risk in MS both before and after introduction of disease-modifying therapies,” she noted. “Those are possibly caused by smoking, which is a habit more common among MS patients in Norway.”

Furthermore, “increased cancer in the central nervous system in MS could possibly be explained by frequent use of magnetic resonance imaging and the ability to detect CNS cancer at early stages.”

“There is increasing evidence that patients with MS are also more susceptible to other diseases, and increased cancer risk seems to be one of these comorbidities.”

However, the finding that increased cancers were observed after 1996 in other organs in MS patients as well does raise the issue of a possible role of DMTs.

Of note, mitoxantrone has been associated with an increased risk of leukemia and colorectal cancer.

And “other immunosuppressant drugs, including the MS drug fingolimod, are believed to possibly be linked to an increased cancer risk, although evidence has not yet been established,” Dr. Grytten said.

“The increased risk of cancer associated with MS was detected in the era of disease-modifying treatment of MS, and this association suggests that DMTs might possibly increase cancer risk.”

In general, “clinicians should be aware of comorbidity in MS,” Dr. Grytten said. “More data is needed on the long-time effects of immunomodulatory treatment.”

Dr. Cohen added that, in addition to mitoxantrone, azathioprine and cyclophosphamide have shown risk, but “clinical trials and follow-up studies of individual MS DMTs have not shown clear cut increased risk of cancer, which is reassuring.”

“Nevertheless, this study suggests that, in aggregate, there may be a mild increased risk. There are many other potential explanations, so the research needs to be followed up,” he said.

Dr. Cohen reported receiving personal compensation for consulting for Adamas, Convelo, MedDay, Mylan, and Population Council; and serving as an Editor of Multiple Sclerosis Journal.

SOURCE: Torkildsen NG et al. ACTRIMS Forum 2020, Abstract P126.

The US Food and Drug Administration (FDA) has approved rimegepant (Nurtec ODT, Biohaven), the first calcitonin gene-related peptide (CGRP) receptor antagonist available in a fast-acting orally disintegrating tablet for the acute treatment of migraine in adults.

This story first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved rimegepant (Nurtec ODT, Biohaven), the first calcitonin gene-related peptide (CGRP) receptor antagonist available in a fast-acting orally disintegrating tablet for the acute treatment of migraine in adults.

This story first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved rimegepant (Nurtec ODT, Biohaven), the first calcitonin gene-related peptide (CGRP) receptor antagonist available in a fast-acting orally disintegrating tablet for the acute treatment of migraine in adults.

This story first appeared on Medscape.com.

Latest guidelines on the treatment of osteoporosis have been released that include new recommendations for the use of romosozumab (Evenity) in postmenopausal women with severe osteoporosis, but they contain caveats as to which women should – and should not – receive the drug.

The updated clinical practice guideline from the Endocrine Society is in response to the approval of romosozumab by the Food and Drug Administration (FDA) in April 2019, and more recently, by the European Medicines Agency.

It was published online February 18 in the Journal of Clinical Endocrinology & Metabolism.

In the new guidelines, committee members recommend the use of romosozumab for postmenopausal women with osteoporosis at very high risk of fracture. Candidates would include women with severe osteoporosis (T-score of less than –2.5 and a prior fracture) or women with a history of multiple vertebral fractures.

Women should be treated with romosozumab for up to 1 year, followed by an antiresorptive agent to maintain bone mineral density gains and further reduce fracture risk.

“The recommended dosage is 210 mg monthly by subcutaneous injection for 12 months,” the authors wrote.

However, and very importantly, romosozumab should not be considered for women at high risk of cardiovascular disease (CVD) or cerebrovascular disease. A high risk of CVD includes women who have had a previous myocardial infarction (MI) or stroke.

Experts questioned by Medscape Medical News stressed that romosozumab should not be a first-line, or even generally a second-line, option for osteoporosis, but it can be a considered for select patients with severe osteoporosis, taking into account CV risk.

Boxed warning

In the Active-Controlled Fracture Study in Postmenopausal Women With Osteoporosis at High Risk (ARCH), there were more major adverse cardiovascular events (MACE) in the first year of the trial with romosozumab, and patients had a 31% higher risk of MACE with romosozumab, compared with the bisphosphonate alendronate.

As a result, the drug was initially rejected by a number of regulatory agencies.

In the United States and Canada, it was eventually approved with a boxed warning, which cautions against the use of the drug in patients at risk for myocardial infarction, stroke, and CVD-related death.

“Romosozumab offers promising results for postmenopausal women with severe osteoporosis or who have a history of fractures,” Clifford Rosen, MD, Maine Medical Center Research Institute in Scarborough and chair of the writing committee, said in an Endocrine Society statement. “It does, however, come with a risk of heart disease, so clinicians need to be careful when selecting patients for this therapy.”

Exact risk unknown

Asked by Medscape Medical News to comment, Kenneth Saag, MD, professor of medicine, University of Alabama at Birmingham and principle investigator of the ARCH study, said that physicians needed more data from real-world studies to resolve the issue around whether romosozumab heightens the risk of CV events in women with osteoporosis or whether that particular finding from ARCH was an artifact.

“Women who have had a recent cardiovascular event should not receive the drug,” he said, agreeing with the new guidelines.

But it remains unclear, for example, whether women who are at slightly higher risk of having a CV event by virtue of their age alone, are also at risk, he noted.

In the meantime, results from the ARCH study clearly showed that not only was romosozumab more effective than alendronate, “but it is more effective than other bone-building drugs as well,” Dr. Saag observed, and it leads to a significantly greater reduction in vertebral, nonvertebral, and hip fractures, compared with the alendronate, the current standard of care in osteoporosis.

“In patients who have very severe osteoporosis and who have had a recent fracture or who are at risk for imminent future fracture, physicians need to balance the benefit versus the risk in favor of using romosozumab,” Dr. Saag suggested.

“And while I would say most women prefer not to inject themselves, the women I have put on this medicine have all had recent fractures and they are very aware of the pain and the disability of having a broken bone, so it is something they are willing to do,” he added.
 

Not for all women

Giving his opinion, Bart Clarke, MD, of the Mayo Clinic in Rochester, Minnesota, underscored the fact that the Fracture Study in Postmenopausal Women With Osteoporosis (FRAME), again conducted in postmenopausal women, showed no increase in CV events in patients treated with romosozumab compared with placebo.

“So there are questions about what this means, because if these events really were a drug effect, then that effect would be even more evident compared with placebo and they did not see any signal of CV events [in FRAME],” said Dr. Clarke, past president of the American Society of Bone and Mineral Research.

Like everything else in medicine, “there is always some risk,” Dr. Clarke observed.

However, what physicians should do is talk to women, ensure they have not had either an MI or stroke in the last year, and if patients have severe osteoporosis and a high risk of fracture, “then we can say, here’s another option,” he suggested.

“Then, if a woman develops chest pain or shortness of breath while on the drug, [she needs] to let us know ,and then we’ll stop the drug and reassess the situation,” he added.

Dr. Clarke also pointed out that if the FDA had received further reports of CV events linked to romosozumab, physicians would know about it by now, but to his knowledge, there has been no change to the drug’s current warning label.

Furthermore, neither he nor any of his colleagues who treat metabolic bone disease at the Mayo Clinic has seen a single CV event in patients prescribed the agent.

“This is not a drug we would use as first-line for most patients, and we don’t even use it as second-line for most patients, but in people who have not responded to other drugs or who have had terrible things happen to them already, hip fracture especially, then we are saying, you can consider this, he concluded.

The guidelines were supported by the Endocrine Society. Dr. Rosen and Dr. Clarke reported no relevant financial relationships. Dr. Saag reported receiving grants and personal fees from Amgen, personal fees from Radius, and is a consultant for Amgen, Radius, Roche, and Daiichi Sankyo.

This article first appeared on Medscape.com.

Latest guidelines on the treatment of osteoporosis have been released that include new recommendations for the use of romosozumab (Evenity) in postmenopausal women with severe osteoporosis, but they contain caveats as to which women should – and should not – receive the drug.

The updated clinical practice guideline from the Endocrine Society is in response to the approval of romosozumab by the Food and Drug Administration (FDA) in April 2019, and more recently, by the European Medicines Agency.

It was published online February 18 in the Journal of Clinical Endocrinology & Metabolism.

In the new guidelines, committee members recommend the use of romosozumab for postmenopausal women with osteoporosis at very high risk of fracture. Candidates would include women with severe osteoporosis (T-score of less than –2.5 and a prior fracture) or women with a history of multiple vertebral fractures.

Women should be treated with romosozumab for up to 1 year, followed by an antiresorptive agent to maintain bone mineral density gains and further reduce fracture risk.

“The recommended dosage is 210 mg monthly by subcutaneous injection for 12 months,” the authors wrote.

However, and very importantly, romosozumab should not be considered for women at high risk of cardiovascular disease (CVD) or cerebrovascular disease. A high risk of CVD includes women who have had a previous myocardial infarction (MI) or stroke.

Experts questioned by Medscape Medical News stressed that romosozumab should not be a first-line, or even generally a second-line, option for osteoporosis, but it can be a considered for select patients with severe osteoporosis, taking into account CV risk.

Boxed warning

In the Active-Controlled Fracture Study in Postmenopausal Women With Osteoporosis at High Risk (ARCH), there were more major adverse cardiovascular events (MACE) in the first year of the trial with romosozumab, and patients had a 31% higher risk of MACE with romosozumab, compared with the bisphosphonate alendronate.

As a result, the drug was initially rejected by a number of regulatory agencies.

In the United States and Canada, it was eventually approved with a boxed warning, which cautions against the use of the drug in patients at risk for myocardial infarction, stroke, and CVD-related death.

“Romosozumab offers promising results for postmenopausal women with severe osteoporosis or who have a history of fractures,” Clifford Rosen, MD, Maine Medical Center Research Institute in Scarborough and chair of the writing committee, said in an Endocrine Society statement. “It does, however, come with a risk of heart disease, so clinicians need to be careful when selecting patients for this therapy.”

Exact risk unknown

Asked by Medscape Medical News to comment, Kenneth Saag, MD, professor of medicine, University of Alabama at Birmingham and principle investigator of the ARCH study, said that physicians needed more data from real-world studies to resolve the issue around whether romosozumab heightens the risk of CV events in women with osteoporosis or whether that particular finding from ARCH was an artifact.

“Women who have had a recent cardiovascular event should not receive the drug,” he said, agreeing with the new guidelines.

But it remains unclear, for example, whether women who are at slightly higher risk of having a CV event by virtue of their age alone, are also at risk, he noted.

In the meantime, results from the ARCH study clearly showed that not only was romosozumab more effective than alendronate, “but it is more effective than other bone-building drugs as well,” Dr. Saag observed, and it leads to a significantly greater reduction in vertebral, nonvertebral, and hip fractures, compared with the alendronate, the current standard of care in osteoporosis.

“In patients who have very severe osteoporosis and who have had a recent fracture or who are at risk for imminent future fracture, physicians need to balance the benefit versus the risk in favor of using romosozumab,” Dr. Saag suggested.

“And while I would say most women prefer not to inject themselves, the women I have put on this medicine have all had recent fractures and they are very aware of the pain and the disability of having a broken bone, so it is something they are willing to do,” he added.
 

Not for all women

Giving his opinion, Bart Clarke, MD, of the Mayo Clinic in Rochester, Minnesota, underscored the fact that the Fracture Study in Postmenopausal Women With Osteoporosis (FRAME), again conducted in postmenopausal women, showed no increase in CV events in patients treated with romosozumab compared with placebo.

“So there are questions about what this means, because if these events really were a drug effect, then that effect would be even more evident compared with placebo and they did not see any signal of CV events [in FRAME],” said Dr. Clarke, past president of the American Society of Bone and Mineral Research.

Like everything else in medicine, “there is always some risk,” Dr. Clarke observed.

However, what physicians should do is talk to women, ensure they have not had either an MI or stroke in the last year, and if patients have severe osteoporosis and a high risk of fracture, “then we can say, here’s another option,” he suggested.

“Then, if a woman develops chest pain or shortness of breath while on the drug, [she needs] to let us know ,and then we’ll stop the drug and reassess the situation,” he added.

Dr. Clarke also pointed out that if the FDA had received further reports of CV events linked to romosozumab, physicians would know about it by now, but to his knowledge, there has been no change to the drug’s current warning label.

Furthermore, neither he nor any of his colleagues who treat metabolic bone disease at the Mayo Clinic has seen a single CV event in patients prescribed the agent.

“This is not a drug we would use as first-line for most patients, and we don’t even use it as second-line for most patients, but in people who have not responded to other drugs or who have had terrible things happen to them already, hip fracture especially, then we are saying, you can consider this, he concluded.

The guidelines were supported by the Endocrine Society. Dr. Rosen and Dr. Clarke reported no relevant financial relationships. Dr. Saag reported receiving grants and personal fees from Amgen, personal fees from Radius, and is a consultant for Amgen, Radius, Roche, and Daiichi Sankyo.

This article first appeared on Medscape.com.

Latest guidelines on the treatment of osteoporosis have been released that include new recommendations for the use of romosozumab (Evenity) in postmenopausal women with severe osteoporosis, but they contain caveats as to which women should – and should not – receive the drug.

The updated clinical practice guideline from the Endocrine Society is in response to the approval of romosozumab by the Food and Drug Administration (FDA) in April 2019, and more recently, by the European Medicines Agency.

It was published online February 18 in the Journal of Clinical Endocrinology & Metabolism.

In the new guidelines, committee members recommend the use of romosozumab for postmenopausal women with osteoporosis at very high risk of fracture. Candidates would include women with severe osteoporosis (T-score of less than –2.5 and a prior fracture) or women with a history of multiple vertebral fractures.

Women should be treated with romosozumab for up to 1 year, followed by an antiresorptive agent to maintain bone mineral density gains and further reduce fracture risk.

“The recommended dosage is 210 mg monthly by subcutaneous injection for 12 months,” the authors wrote.

However, and very importantly, romosozumab should not be considered for women at high risk of cardiovascular disease (CVD) or cerebrovascular disease. A high risk of CVD includes women who have had a previous myocardial infarction (MI) or stroke.

Experts questioned by Medscape Medical News stressed that romosozumab should not be a first-line, or even generally a second-line, option for osteoporosis, but it can be a considered for select patients with severe osteoporosis, taking into account CV risk.

Boxed warning

In the Active-Controlled Fracture Study in Postmenopausal Women With Osteoporosis at High Risk (ARCH), there were more major adverse cardiovascular events (MACE) in the first year of the trial with romosozumab, and patients had a 31% higher risk of MACE with romosozumab, compared with the bisphosphonate alendronate.

As a result, the drug was initially rejected by a number of regulatory agencies.

In the United States and Canada, it was eventually approved with a boxed warning, which cautions against the use of the drug in patients at risk for myocardial infarction, stroke, and CVD-related death.

“Romosozumab offers promising results for postmenopausal women with severe osteoporosis or who have a history of fractures,” Clifford Rosen, MD, Maine Medical Center Research Institute in Scarborough and chair of the writing committee, said in an Endocrine Society statement. “It does, however, come with a risk of heart disease, so clinicians need to be careful when selecting patients for this therapy.”

Exact risk unknown

Asked by Medscape Medical News to comment, Kenneth Saag, MD, professor of medicine, University of Alabama at Birmingham and principle investigator of the ARCH study, said that physicians needed more data from real-world studies to resolve the issue around whether romosozumab heightens the risk of CV events in women with osteoporosis or whether that particular finding from ARCH was an artifact.

“Women who have had a recent cardiovascular event should not receive the drug,” he said, agreeing with the new guidelines.

But it remains unclear, for example, whether women who are at slightly higher risk of having a CV event by virtue of their age alone, are also at risk, he noted.

In the meantime, results from the ARCH study clearly showed that not only was romosozumab more effective than alendronate, “but it is more effective than other bone-building drugs as well,” Dr. Saag observed, and it leads to a significantly greater reduction in vertebral, nonvertebral, and hip fractures, compared with the alendronate, the current standard of care in osteoporosis.

“In patients who have very severe osteoporosis and who have had a recent fracture or who are at risk for imminent future fracture, physicians need to balance the benefit versus the risk in favor of using romosozumab,” Dr. Saag suggested.

“And while I would say most women prefer not to inject themselves, the women I have put on this medicine have all had recent fractures and they are very aware of the pain and the disability of having a broken bone, so it is something they are willing to do,” he added.
 

Not for all women

Giving his opinion, Bart Clarke, MD, of the Mayo Clinic in Rochester, Minnesota, underscored the fact that the Fracture Study in Postmenopausal Women With Osteoporosis (FRAME), again conducted in postmenopausal women, showed no increase in CV events in patients treated with romosozumab compared with placebo.

“So there are questions about what this means, because if these events really were a drug effect, then that effect would be even more evident compared with placebo and they did not see any signal of CV events [in FRAME],” said Dr. Clarke, past president of the American Society of Bone and Mineral Research.

Like everything else in medicine, “there is always some risk,” Dr. Clarke observed.

However, what physicians should do is talk to women, ensure they have not had either an MI or stroke in the last year, and if patients have severe osteoporosis and a high risk of fracture, “then we can say, here’s another option,” he suggested.

“Then, if a woman develops chest pain or shortness of breath while on the drug, [she needs] to let us know ,and then we’ll stop the drug and reassess the situation,” he added.

Dr. Clarke also pointed out that if the FDA had received further reports of CV events linked to romosozumab, physicians would know about it by now, but to his knowledge, there has been no change to the drug’s current warning label.

Furthermore, neither he nor any of his colleagues who treat metabolic bone disease at the Mayo Clinic has seen a single CV event in patients prescribed the agent.

“This is not a drug we would use as first-line for most patients, and we don’t even use it as second-line for most patients, but in people who have not responded to other drugs or who have had terrible things happen to them already, hip fracture especially, then we are saying, you can consider this, he concluded.

The guidelines were supported by the Endocrine Society. Dr. Rosen and Dr. Clarke reported no relevant financial relationships. Dr. Saag reported receiving grants and personal fees from Amgen, personal fees from Radius, and is a consultant for Amgen, Radius, Roche, and Daiichi Sankyo.

This article first appeared on Medscape.com.

The Food and Drug Administration is collaborating with the Federal Trade Commission (FTC) to expand the biosimilars market.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The two agencies signed a joint statement on Feb. 3, 2020, outlining four sets of goals aimed at creating meaningful competition from biosimilars against their reference biologic products.

“Competition is key for helping American patients have access to affordable medicines,” FDA Commissioner Stephen Hahn, MD, said in a statement. “Strengthening efforts to curtail and discourage anticompetitive behavior is key for facilitating robust competition for patients in the biologics marketplace, including through biosimilars, bringing down the costs of these crucial products for patients.”

“We appreciate and applaud the FDA and FTC in recognizing that biosimilar development and approval has not been as robust as many stakeholders had hoped,” said Colin Edgerton, MD, chair of the American College of Rheumatology’s Committee on Rheumatologic Care. “We continue to see anticompetitive activities that prevent manufacturers from developing biosimilar products. We hope that a greater focus on these practices will pave the way for more biosimilars to be developed.”

The statement highlighted four goals. First is that the agencies will coordinate to promote greater competition in the biologic market, including the development of materials to educate the market about biosimilars. The FDA and FTC also will be sponsoring a public workshop on March 9 to discuss competition for biologics.

“This workshop is the first step,” Dr. Edgerton said. “ACR will continue to work with other organizations and patient groups to help educate providers and patients on the scientific rigor that is required in developing and approving biosimilars. Additionally, we look forward to working with the FDA and FTC to continue this conversation on ways to encourage more development of biosimilar products and greater education for the providers and patients.”

The second goal has the FDA and FTC working together “to deter behavior that impedes access to samples needed for the development of biologics, including biosimilars,” the joint statement notes.

Third, the agencies will crack down on “false or misleading communications about biologics, including biosimilars, within their respective authorities,” according to the joint statement.

“FDA and FTC, as authorized by their respective statutes, will work together to address false or misleading communications about biologics, including biosimilars,” the statement continues. “In particular, if a communication makes a false or misleading comparison between a reference product and a biosimilar in a manner that misrepresents the safety or efficacy of biosimilars, deceives consumers, or deters competition, FDA and FTC intend to take appropriate action within their respective authorities. FDA intends to take appropriate action to address such communications where those communications have the potential to impact public health.”

Finally, the FTC committed to review patent settlement agreements involving biologics, including biosimilars, for antitrust violations.

Dr. Edgerton highlighted why this agreement between the two agencies is so important.

“Biologics are life-changing treatments for many of our patients,” he said. “Due to the high cost of discovery and development, the cost of biologics has resulted in delayed access and financial hardships for so many. It has always been our hope that biosimilars would offer the same life-changing treatment for patients at a lower price point. A robust biosimilars market is imperative to allow greater access to these treatments that can help patients to have a better quality of life.”

Separately, the FDA issued a draft guidance document for comment on manufacturers seeking licensure of biosimilar products that do not cover all the approved uses of the reference product, as well as how to add uses over time that were not part of the initial license of the biosimilar product. The draft guidance covers licensure of products, labeling of biosimilars with fewer indications than the reference product, supplemental applications for indications not on the initial biosimilar application but covered by the reference product, and the timing of applications.

The FDA notes in the draft guidance that this is needed to cover situations such as when some indications on the reference product are covered by exclusivity, although it does encourage a biosimilar manufacturer to seek licensure for all indications that the reference product does have.

[email protected]

The Food and Drug Administration is collaborating with the Federal Trade Commission (FTC) to expand the biosimilars market.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The two agencies signed a joint statement on Feb. 3, 2020, outlining four sets of goals aimed at creating meaningful competition from biosimilars against their reference biologic products.

“Competition is key for helping American patients have access to affordable medicines,” FDA Commissioner Stephen Hahn, MD, said in a statement. “Strengthening efforts to curtail and discourage anticompetitive behavior is key for facilitating robust competition for patients in the biologics marketplace, including through biosimilars, bringing down the costs of these crucial products for patients.”

“We appreciate and applaud the FDA and FTC in recognizing that biosimilar development and approval has not been as robust as many stakeholders had hoped,” said Colin Edgerton, MD, chair of the American College of Rheumatology’s Committee on Rheumatologic Care. “We continue to see anticompetitive activities that prevent manufacturers from developing biosimilar products. We hope that a greater focus on these practices will pave the way for more biosimilars to be developed.”

The statement highlighted four goals. First is that the agencies will coordinate to promote greater competition in the biologic market, including the development of materials to educate the market about biosimilars. The FDA and FTC also will be sponsoring a public workshop on March 9 to discuss competition for biologics.

“This workshop is the first step,” Dr. Edgerton said. “ACR will continue to work with other organizations and patient groups to help educate providers and patients on the scientific rigor that is required in developing and approving biosimilars. Additionally, we look forward to working with the FDA and FTC to continue this conversation on ways to encourage more development of biosimilar products and greater education for the providers and patients.”

The second goal has the FDA and FTC working together “to deter behavior that impedes access to samples needed for the development of biologics, including biosimilars,” the joint statement notes.

Third, the agencies will crack down on “false or misleading communications about biologics, including biosimilars, within their respective authorities,” according to the joint statement.

“FDA and FTC, as authorized by their respective statutes, will work together to address false or misleading communications about biologics, including biosimilars,” the statement continues. “In particular, if a communication makes a false or misleading comparison between a reference product and a biosimilar in a manner that misrepresents the safety or efficacy of biosimilars, deceives consumers, or deters competition, FDA and FTC intend to take appropriate action within their respective authorities. FDA intends to take appropriate action to address such communications where those communications have the potential to impact public health.”

Finally, the FTC committed to review patent settlement agreements involving biologics, including biosimilars, for antitrust violations.

Dr. Edgerton highlighted why this agreement between the two agencies is so important.

“Biologics are life-changing treatments for many of our patients,” he said. “Due to the high cost of discovery and development, the cost of biologics has resulted in delayed access and financial hardships for so many. It has always been our hope that biosimilars would offer the same life-changing treatment for patients at a lower price point. A robust biosimilars market is imperative to allow greater access to these treatments that can help patients to have a better quality of life.”

Separately, the FDA issued a draft guidance document for comment on manufacturers seeking licensure of biosimilar products that do not cover all the approved uses of the reference product, as well as how to add uses over time that were not part of the initial license of the biosimilar product. The draft guidance covers licensure of products, labeling of biosimilars with fewer indications than the reference product, supplemental applications for indications not on the initial biosimilar application but covered by the reference product, and the timing of applications.

The FDA notes in the draft guidance that this is needed to cover situations such as when some indications on the reference product are covered by exclusivity, although it does encourage a biosimilar manufacturer to seek licensure for all indications that the reference product does have.

[email protected]

The Food and Drug Administration is collaborating with the Federal Trade Commission (FTC) to expand the biosimilars market.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The two agencies signed a joint statement on Feb. 3, 2020, outlining four sets of goals aimed at creating meaningful competition from biosimilars against their reference biologic products.

“Competition is key for helping American patients have access to affordable medicines,” FDA Commissioner Stephen Hahn, MD, said in a statement. “Strengthening efforts to curtail and discourage anticompetitive behavior is key for facilitating robust competition for patients in the biologics marketplace, including through biosimilars, bringing down the costs of these crucial products for patients.”

“We appreciate and applaud the FDA and FTC in recognizing that biosimilar development and approval has not been as robust as many stakeholders had hoped,” said Colin Edgerton, MD, chair of the American College of Rheumatology’s Committee on Rheumatologic Care. “We continue to see anticompetitive activities that prevent manufacturers from developing biosimilar products. We hope that a greater focus on these practices will pave the way for more biosimilars to be developed.”

The statement highlighted four goals. First is that the agencies will coordinate to promote greater competition in the biologic market, including the development of materials to educate the market about biosimilars. The FDA and FTC also will be sponsoring a public workshop on March 9 to discuss competition for biologics.

“This workshop is the first step,” Dr. Edgerton said. “ACR will continue to work with other organizations and patient groups to help educate providers and patients on the scientific rigor that is required in developing and approving biosimilars. Additionally, we look forward to working with the FDA and FTC to continue this conversation on ways to encourage more development of biosimilar products and greater education for the providers and patients.”

The second goal has the FDA and FTC working together “to deter behavior that impedes access to samples needed for the development of biologics, including biosimilars,” the joint statement notes.

Third, the agencies will crack down on “false or misleading communications about biologics, including biosimilars, within their respective authorities,” according to the joint statement.

“FDA and FTC, as authorized by their respective statutes, will work together to address false or misleading communications about biologics, including biosimilars,” the statement continues. “In particular, if a communication makes a false or misleading comparison between a reference product and a biosimilar in a manner that misrepresents the safety or efficacy of biosimilars, deceives consumers, or deters competition, FDA and FTC intend to take appropriate action within their respective authorities. FDA intends to take appropriate action to address such communications where those communications have the potential to impact public health.”

Finally, the FTC committed to review patent settlement agreements involving biologics, including biosimilars, for antitrust violations.

Dr. Edgerton highlighted why this agreement between the two agencies is so important.

“Biologics are life-changing treatments for many of our patients,” he said. “Due to the high cost of discovery and development, the cost of biologics has resulted in delayed access and financial hardships for so many. It has always been our hope that biosimilars would offer the same life-changing treatment for patients at a lower price point. A robust biosimilars market is imperative to allow greater access to these treatments that can help patients to have a better quality of life.”

Separately, the FDA issued a draft guidance document for comment on manufacturers seeking licensure of biosimilar products that do not cover all the approved uses of the reference product, as well as how to add uses over time that were not part of the initial license of the biosimilar product. The draft guidance covers licensure of products, labeling of biosimilars with fewer indications than the reference product, supplemental applications for indications not on the initial biosimilar application but covered by the reference product, and the timing of applications.

The FDA notes in the draft guidance that this is needed to cover situations such as when some indications on the reference product are covered by exclusivity, although it does encourage a biosimilar manufacturer to seek licensure for all indications that the reference product does have.

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The US Food and Drug Administration has approved eptinezumab-jjmr (Vyepti, Lundbeck), the first intravenous (IV) migraine prevention medication, the company has announced.

As previously reported by Medscape Medical News, the drug’s approval is based on results from two clinical studies – PROMISE-1 in episodic migraine and PROMISE-2 in chronic migraine.

The recommended dose is 100 mg every 3 months although some patients may benefit from a dose of 300 mg, the company notes. Lundbeck reports that the drug will likely be available in early April.

Roger Cady, MD, vice-president of neurology at Lundbeck, told Medscape Medical News the drug has almost immediate efficacy.

“Because it’s an IV [medication], it has very rapid benefit. In fact, we were able to demonstrate benefit on Day 1. Truly, it is going to impact on the unmet need for patients because of its profile, the way it’s delivered, and its uniqueness,” Cady said.

“Having preventive activity the day following an infusion is really important. We have in our data, if you take that time between the first day and the 28th day, whether they have episodic migraine or chronic migraine, that about 30% of the population had a 75% or more reduction in migraine days through that first month,” he added.

The clinical trial program demonstrated a treatment benefit over placebo that was observed for both doses of Vyepti as early as day 1 post-infusion, and the percentage of patients experiencing a migraine was lower for Vyepti than with placebo for most of the first 7 days, the company reports.

The safety of Vyepti was evaluated in 2076 patients with migraine who received at least one dose of the drug. The most common adverse reactions were nasopharyngitis and hypersensitivity. In PROMISE-1 and PROMISE-2, 1.9% of patients treated with Vyepti discontinued treatment as a result of adverse reactions.

“The PROMISE-2 data showed that many patients can achieve reduction in migraine days of at least 75% and experience a sustained migraine improvement through 6 months, which is clinically meaningful to both physicians and patients,” said Peter Goadsby, MD, professor of neurology at King’s College, London, UK, and the University of California, San Francisco, in a press release. “Vyepti is a valuable addition for the treatment of migraine, which can help reduce the burden of this serious disease.”
 

This article first appeared on Medscape.com.

The US Food and Drug Administration has approved eptinezumab-jjmr (Vyepti, Lundbeck), the first intravenous (IV) migraine prevention medication, the company has announced.

As previously reported by Medscape Medical News, the drug’s approval is based on results from two clinical studies – PROMISE-1 in episodic migraine and PROMISE-2 in chronic migraine.

The recommended dose is 100 mg every 3 months although some patients may benefit from a dose of 300 mg, the company notes. Lundbeck reports that the drug will likely be available in early April.

Roger Cady, MD, vice-president of neurology at Lundbeck, told Medscape Medical News the drug has almost immediate efficacy.

“Because it’s an IV [medication], it has very rapid benefit. In fact, we were able to demonstrate benefit on Day 1. Truly, it is going to impact on the unmet need for patients because of its profile, the way it’s delivered, and its uniqueness,” Cady said.

“Having preventive activity the day following an infusion is really important. We have in our data, if you take that time between the first day and the 28th day, whether they have episodic migraine or chronic migraine, that about 30% of the population had a 75% or more reduction in migraine days through that first month,” he added.

The clinical trial program demonstrated a treatment benefit over placebo that was observed for both doses of Vyepti as early as day 1 post-infusion, and the percentage of patients experiencing a migraine was lower for Vyepti than with placebo for most of the first 7 days, the company reports.

The safety of Vyepti was evaluated in 2076 patients with migraine who received at least one dose of the drug. The most common adverse reactions were nasopharyngitis and hypersensitivity. In PROMISE-1 and PROMISE-2, 1.9% of patients treated with Vyepti discontinued treatment as a result of adverse reactions.

“The PROMISE-2 data showed that many patients can achieve reduction in migraine days of at least 75% and experience a sustained migraine improvement through 6 months, which is clinically meaningful to both physicians and patients,” said Peter Goadsby, MD, professor of neurology at King’s College, London, UK, and the University of California, San Francisco, in a press release. “Vyepti is a valuable addition for the treatment of migraine, which can help reduce the burden of this serious disease.”
 

This article first appeared on Medscape.com.

The US Food and Drug Administration has approved eptinezumab-jjmr (Vyepti, Lundbeck), the first intravenous (IV) migraine prevention medication, the company has announced.

As previously reported by Medscape Medical News, the drug’s approval is based on results from two clinical studies – PROMISE-1 in episodic migraine and PROMISE-2 in chronic migraine.

The recommended dose is 100 mg every 3 months although some patients may benefit from a dose of 300 mg, the company notes. Lundbeck reports that the drug will likely be available in early April.

Roger Cady, MD, vice-president of neurology at Lundbeck, told Medscape Medical News the drug has almost immediate efficacy.

“Because it’s an IV [medication], it has very rapid benefit. In fact, we were able to demonstrate benefit on Day 1. Truly, it is going to impact on the unmet need for patients because of its profile, the way it’s delivered, and its uniqueness,” Cady said.

“Having preventive activity the day following an infusion is really important. We have in our data, if you take that time between the first day and the 28th day, whether they have episodic migraine or chronic migraine, that about 30% of the population had a 75% or more reduction in migraine days through that first month,” he added.

The clinical trial program demonstrated a treatment benefit over placebo that was observed for both doses of Vyepti as early as day 1 post-infusion, and the percentage of patients experiencing a migraine was lower for Vyepti than with placebo for most of the first 7 days, the company reports.

The safety of Vyepti was evaluated in 2076 patients with migraine who received at least one dose of the drug. The most common adverse reactions were nasopharyngitis and hypersensitivity. In PROMISE-1 and PROMISE-2, 1.9% of patients treated with Vyepti discontinued treatment as a result of adverse reactions.

“The PROMISE-2 data showed that many patients can achieve reduction in migraine days of at least 75% and experience a sustained migraine improvement through 6 months, which is clinically meaningful to both physicians and patients,” said Peter Goadsby, MD, professor of neurology at King’s College, London, UK, and the University of California, San Francisco, in a press release. “Vyepti is a valuable addition for the treatment of migraine, which can help reduce the burden of this serious disease.”
 

This article first appeared on Medscape.com.