Ankylosing spondylitis

Las Vegas – A fibromyalgia survey may provide important information about the degree to which patients with rheumatic disease experience centralized pain. This information may guide treatment decisions, said Daniel J. Clauw, MD, professor of anesthesiology, rheumatology, and psychiatry and director of the Chronic Pain and Fatigue Research Center at the University of Michigan in Ann Arbor.

Jake Remaly/MDedge News

The questionnaire that Dr. Clauw uses is a patient self-report survey for the assessment of fibromyalgia based on criteria in the 2011 modification of the American College of Rheumatology preliminary diagnostic criteria for fibromyalgia. In it, he asks patients to report where they experience pain throughout the body and symptoms such as fatigue, sleep problems, and memory problems. The survey predicts outcomes of surgery for osteoarthritis better than x-rays, MRI scans, or psychological factors do, he said.

Physicians should ask every patient with chronic pain, including patients with OA, rheumatoid arthritis, or lupus, to complete the survey, Dr. Clauw said at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education. “This score will tell you the degree to which their central nervous system is augmenting or amplifying what is going on in their body,” he said. “And the higher their score is, the more you should treat them like you would someone with fibromyalgia, even if their underlying disease might be an autoimmune disease.”

Physicians should not use a cutoff of 13 points on the fibromyalgia measure to define whether a patient has the disease, as has been done in the past, he said. The threshold is arbitrary, he said. “We should not think about fibromyalgia as ‘yes’ or ‘no.’ We should think of the degree of fibromyalgia that people have.”
 

A poor relationship between pain and imaging

Some patients who have severe knee OA on imaging walk without pain. Other patients have normal x-rays, but severe pain. “There is a terrible relationship between what you see on a knee x-ray or an MRI and whether someone has pain,” Dr. Clauw said. Furthermore, the poor relationship between imaging and pain is common across chronic pain conditions, he said.

This phenomenon may occur because pain manifests in different ways, similar to there being multiple ways to adjust the volume of an electric guitar, he said. How hard the strings are strummed affects the volume. But so does the amplifier setting. “In these centralized pain conditions, the problem is an amplifier problem, not a guitar problem,” he said. “The amplifier, i.e., the central nervous system, is set too high.”

Researchers have found that people who have severe OA of the knee on x-ray but do not experience pain “have a very low amplifier setting,” he said. That is, they are nontender and less sensitive to pain. Most of these patients are men. “On average, men have a much lower amplifier setting than women,” he said. “This is also why ... women have 1.5 to 2 times the rate of any type of chronic pain than men, because on average women have a higher amplifier setting. ... In OA, at any given age, men and women have the exact same percentage of radiographic OA. But if you look at the clinical condition of OA, it is always two-thirds women, one-third men.”
 

Opioid responsiveness

To examine whether fibromyalgia survey results correlate with outcomes after knee and hip arthroplasty, Dr. Clauw and colleagues conducted a prospective, observational cohort study that included approximately 500 people. Patients completed the questionnaire on the day of surgery.

Patients with higher levels of fibromyalgia were less responsive to opioids. “For each 1-point increase in the fibromyalgia score, people needed about one more hydrocodone tablet in the first 24-48 hours to control their pain,” he said (Anesthesiology. 2013 Dec;119[6]:1434-43). In addition, each 1-point increase in the fibromyalgia score made people about 25% less likely to have a 50% improvement in knee pain level after 6 months (Arthritis Rheumatol. 2015 May;67[5]:1386-94). The correlations were independent of psychological factors. In addition, the associations were linear. “There was nothing magical about a fibromyalgia score of 13,” Dr. Clauw said.

Dr. Clauw is a coauthor of a study to be presented at the 2019 American College of Rheumatology/Association of Rheumatology Professionals annual meeting that found pain centralization in patients with RA is associated with poor response to disease-modifying antirheumatic drugs (DMARDs).

Prior studies in patients with RA have found that the degree of fibromyalgia is a better predictor of pain and disability than erythrocyte sedimentation rate or the number of swollen joints.
 

Diagnosed cases are the “tip of the iceberg”

Researchers at Dr. Clauw’s institution have identified dozens of patients undergoing knee surgery who met criteria for fibromyalgia but had not received the diagnosis. “This is at the University of Michigan, which is the epicenter for fibromyalgia research. If we are not seeing fibromyalgia superimposed on OA in our patients, no one is seeing it,” he said.

Patients with diagnosed fibromyalgia are “the tip of the iceberg,” he said. “There are far greater numbers of individuals whose primary diagnosis is OA, RA, lupus, ankylosing spondylitis, cancer pain, or sickle cell disease that have the same fundamental problem as fibromyalgia patients. But you do not see it because you label them as having an autoimmune disease or osteoarthritis. And that is at your peril and at their peril. Because treating that individual as if all of their pain and other symptoms are due to a problem out on the periphery will not make that person better.”

Patients with high levels of centralized pain may be less responsive to peripherally directed therapies such as surgery or injections, Dr. Clauw said. Pharmacologic options for patients with centralized pain include gabapentinoids (e.g., pregabalin and gabapentin), serotonin-norepinephrine reuptake inhibitors (e.g., duloxetine and milnacipran), and tricyclic compounds (e.g., amitriptyline and cyclobenzaprine), he said. “Opioids are going to be quite unlikely to help these individuals,” he said. “In fact, it is likely that opioids will make this kind of pain worse.”

Dr. Clauw is a consultant for Aptinyx, Daiichi Sankyo, Eli Lilly, Intec Pharma, Pfizer, Samumed, Theravance, Tonix, and Zynerba Pharma. He has received grant or research support from Aptinyx and Pfizer and is an expert witness.

Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

Las Vegas – A fibromyalgia survey may provide important information about the degree to which patients with rheumatic disease experience centralized pain. This information may guide treatment decisions, said Daniel J. Clauw, MD, professor of anesthesiology, rheumatology, and psychiatry and director of the Chronic Pain and Fatigue Research Center at the University of Michigan in Ann Arbor.

Jake Remaly/MDedge News

The questionnaire that Dr. Clauw uses is a patient self-report survey for the assessment of fibromyalgia based on criteria in the 2011 modification of the American College of Rheumatology preliminary diagnostic criteria for fibromyalgia. In it, he asks patients to report where they experience pain throughout the body and symptoms such as fatigue, sleep problems, and memory problems. The survey predicts outcomes of surgery for osteoarthritis better than x-rays, MRI scans, or psychological factors do, he said.

Physicians should ask every patient with chronic pain, including patients with OA, rheumatoid arthritis, or lupus, to complete the survey, Dr. Clauw said at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education. “This score will tell you the degree to which their central nervous system is augmenting or amplifying what is going on in their body,” he said. “And the higher their score is, the more you should treat them like you would someone with fibromyalgia, even if their underlying disease might be an autoimmune disease.”

Physicians should not use a cutoff of 13 points on the fibromyalgia measure to define whether a patient has the disease, as has been done in the past, he said. The threshold is arbitrary, he said. “We should not think about fibromyalgia as ‘yes’ or ‘no.’ We should think of the degree of fibromyalgia that people have.”
 

A poor relationship between pain and imaging

Some patients who have severe knee OA on imaging walk without pain. Other patients have normal x-rays, but severe pain. “There is a terrible relationship between what you see on a knee x-ray or an MRI and whether someone has pain,” Dr. Clauw said. Furthermore, the poor relationship between imaging and pain is common across chronic pain conditions, he said.

This phenomenon may occur because pain manifests in different ways, similar to there being multiple ways to adjust the volume of an electric guitar, he said. How hard the strings are strummed affects the volume. But so does the amplifier setting. “In these centralized pain conditions, the problem is an amplifier problem, not a guitar problem,” he said. “The amplifier, i.e., the central nervous system, is set too high.”

Researchers have found that people who have severe OA of the knee on x-ray but do not experience pain “have a very low amplifier setting,” he said. That is, they are nontender and less sensitive to pain. Most of these patients are men. “On average, men have a much lower amplifier setting than women,” he said. “This is also why ... women have 1.5 to 2 times the rate of any type of chronic pain than men, because on average women have a higher amplifier setting. ... In OA, at any given age, men and women have the exact same percentage of radiographic OA. But if you look at the clinical condition of OA, it is always two-thirds women, one-third men.”
 

Opioid responsiveness

To examine whether fibromyalgia survey results correlate with outcomes after knee and hip arthroplasty, Dr. Clauw and colleagues conducted a prospective, observational cohort study that included approximately 500 people. Patients completed the questionnaire on the day of surgery.

Patients with higher levels of fibromyalgia were less responsive to opioids. “For each 1-point increase in the fibromyalgia score, people needed about one more hydrocodone tablet in the first 24-48 hours to control their pain,” he said (Anesthesiology. 2013 Dec;119[6]:1434-43). In addition, each 1-point increase in the fibromyalgia score made people about 25% less likely to have a 50% improvement in knee pain level after 6 months (Arthritis Rheumatol. 2015 May;67[5]:1386-94). The correlations were independent of psychological factors. In addition, the associations were linear. “There was nothing magical about a fibromyalgia score of 13,” Dr. Clauw said.

Dr. Clauw is a coauthor of a study to be presented at the 2019 American College of Rheumatology/Association of Rheumatology Professionals annual meeting that found pain centralization in patients with RA is associated with poor response to disease-modifying antirheumatic drugs (DMARDs).

Prior studies in patients with RA have found that the degree of fibromyalgia is a better predictor of pain and disability than erythrocyte sedimentation rate or the number of swollen joints.
 

Diagnosed cases are the “tip of the iceberg”

Researchers at Dr. Clauw’s institution have identified dozens of patients undergoing knee surgery who met criteria for fibromyalgia but had not received the diagnosis. “This is at the University of Michigan, which is the epicenter for fibromyalgia research. If we are not seeing fibromyalgia superimposed on OA in our patients, no one is seeing it,” he said.

Patients with diagnosed fibromyalgia are “the tip of the iceberg,” he said. “There are far greater numbers of individuals whose primary diagnosis is OA, RA, lupus, ankylosing spondylitis, cancer pain, or sickle cell disease that have the same fundamental problem as fibromyalgia patients. But you do not see it because you label them as having an autoimmune disease or osteoarthritis. And that is at your peril and at their peril. Because treating that individual as if all of their pain and other symptoms are due to a problem out on the periphery will not make that person better.”

Patients with high levels of centralized pain may be less responsive to peripherally directed therapies such as surgery or injections, Dr. Clauw said. Pharmacologic options for patients with centralized pain include gabapentinoids (e.g., pregabalin and gabapentin), serotonin-norepinephrine reuptake inhibitors (e.g., duloxetine and milnacipran), and tricyclic compounds (e.g., amitriptyline and cyclobenzaprine), he said. “Opioids are going to be quite unlikely to help these individuals,” he said. “In fact, it is likely that opioids will make this kind of pain worse.”

Dr. Clauw is a consultant for Aptinyx, Daiichi Sankyo, Eli Lilly, Intec Pharma, Pfizer, Samumed, Theravance, Tonix, and Zynerba Pharma. He has received grant or research support from Aptinyx and Pfizer and is an expert witness.

Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

Las Vegas – A fibromyalgia survey may provide important information about the degree to which patients with rheumatic disease experience centralized pain. This information may guide treatment decisions, said Daniel J. Clauw, MD, professor of anesthesiology, rheumatology, and psychiatry and director of the Chronic Pain and Fatigue Research Center at the University of Michigan in Ann Arbor.

Jake Remaly/MDedge News

The questionnaire that Dr. Clauw uses is a patient self-report survey for the assessment of fibromyalgia based on criteria in the 2011 modification of the American College of Rheumatology preliminary diagnostic criteria for fibromyalgia. In it, he asks patients to report where they experience pain throughout the body and symptoms such as fatigue, sleep problems, and memory problems. The survey predicts outcomes of surgery for osteoarthritis better than x-rays, MRI scans, or psychological factors do, he said.

Physicians should ask every patient with chronic pain, including patients with OA, rheumatoid arthritis, or lupus, to complete the survey, Dr. Clauw said at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education. “This score will tell you the degree to which their central nervous system is augmenting or amplifying what is going on in their body,” he said. “And the higher their score is, the more you should treat them like you would someone with fibromyalgia, even if their underlying disease might be an autoimmune disease.”

Physicians should not use a cutoff of 13 points on the fibromyalgia measure to define whether a patient has the disease, as has been done in the past, he said. The threshold is arbitrary, he said. “We should not think about fibromyalgia as ‘yes’ or ‘no.’ We should think of the degree of fibromyalgia that people have.”
 

A poor relationship between pain and imaging

Some patients who have severe knee OA on imaging walk without pain. Other patients have normal x-rays, but severe pain. “There is a terrible relationship between what you see on a knee x-ray or an MRI and whether someone has pain,” Dr. Clauw said. Furthermore, the poor relationship between imaging and pain is common across chronic pain conditions, he said.

This phenomenon may occur because pain manifests in different ways, similar to there being multiple ways to adjust the volume of an electric guitar, he said. How hard the strings are strummed affects the volume. But so does the amplifier setting. “In these centralized pain conditions, the problem is an amplifier problem, not a guitar problem,” he said. “The amplifier, i.e., the central nervous system, is set too high.”

Researchers have found that people who have severe OA of the knee on x-ray but do not experience pain “have a very low amplifier setting,” he said. That is, they are nontender and less sensitive to pain. Most of these patients are men. “On average, men have a much lower amplifier setting than women,” he said. “This is also why ... women have 1.5 to 2 times the rate of any type of chronic pain than men, because on average women have a higher amplifier setting. ... In OA, at any given age, men and women have the exact same percentage of radiographic OA. But if you look at the clinical condition of OA, it is always two-thirds women, one-third men.”
 

Opioid responsiveness

To examine whether fibromyalgia survey results correlate with outcomes after knee and hip arthroplasty, Dr. Clauw and colleagues conducted a prospective, observational cohort study that included approximately 500 people. Patients completed the questionnaire on the day of surgery.

Patients with higher levels of fibromyalgia were less responsive to opioids. “For each 1-point increase in the fibromyalgia score, people needed about one more hydrocodone tablet in the first 24-48 hours to control their pain,” he said (Anesthesiology. 2013 Dec;119[6]:1434-43). In addition, each 1-point increase in the fibromyalgia score made people about 25% less likely to have a 50% improvement in knee pain level after 6 months (Arthritis Rheumatol. 2015 May;67[5]:1386-94). The correlations were independent of psychological factors. In addition, the associations were linear. “There was nothing magical about a fibromyalgia score of 13,” Dr. Clauw said.

Dr. Clauw is a coauthor of a study to be presented at the 2019 American College of Rheumatology/Association of Rheumatology Professionals annual meeting that found pain centralization in patients with RA is associated with poor response to disease-modifying antirheumatic drugs (DMARDs).

Prior studies in patients with RA have found that the degree of fibromyalgia is a better predictor of pain and disability than erythrocyte sedimentation rate or the number of swollen joints.
 

Diagnosed cases are the “tip of the iceberg”

Researchers at Dr. Clauw’s institution have identified dozens of patients undergoing knee surgery who met criteria for fibromyalgia but had not received the diagnosis. “This is at the University of Michigan, which is the epicenter for fibromyalgia research. If we are not seeing fibromyalgia superimposed on OA in our patients, no one is seeing it,” he said.

Patients with diagnosed fibromyalgia are “the tip of the iceberg,” he said. “There are far greater numbers of individuals whose primary diagnosis is OA, RA, lupus, ankylosing spondylitis, cancer pain, or sickle cell disease that have the same fundamental problem as fibromyalgia patients. But you do not see it because you label them as having an autoimmune disease or osteoarthritis. And that is at your peril and at their peril. Because treating that individual as if all of their pain and other symptoms are due to a problem out on the periphery will not make that person better.”

Patients with high levels of centralized pain may be less responsive to peripherally directed therapies such as surgery or injections, Dr. Clauw said. Pharmacologic options for patients with centralized pain include gabapentinoids (e.g., pregabalin and gabapentin), serotonin-norepinephrine reuptake inhibitors (e.g., duloxetine and milnacipran), and tricyclic compounds (e.g., amitriptyline and cyclobenzaprine), he said. “Opioids are going to be quite unlikely to help these individuals,” he said. “In fact, it is likely that opioids will make this kind of pain worse.”

Dr. Clauw is a consultant for Aptinyx, Daiichi Sankyo, Eli Lilly, Intec Pharma, Pfizer, Samumed, Theravance, Tonix, and Zynerba Pharma. He has received grant or research support from Aptinyx and Pfizer and is an expert witness.

Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

New results for secukinumab (Cosentyx) in the PREVENT trial continue its promising trend for treatment of the full spectrum of axial spondyloarthritis (axSpA), according to a release from Novartis. The PREVENT trial is assessing this therapy in nonradiographic axSpA (nr-axSpA); it’s already approved in ankylosing spondylitis.

Results of 16-week data were presented in mid-September, and the new results represent 52-week data. Full details and data will be revealed at an upcoming scientific congress.

The PREVENT trial is an ongoing, 2-year trial with a 2-year extension phase; it enrolled 550 men and women with nr-axSpA and assessed their response to secukinumab with an induction phase, to it without induction, or to placebo. The trial met its primary endpoint of 40% improvement in Assessment in Spondyloarthritis International Society (ASAS40) criteria at 16 and 52 weeks, which indicates meaningful and sustained improvement. ASAS40 is defined as an improvement of at least 40% and both 10 out of 100 points in three of four domains (patient global assessment, pain, function, and inflammation) and no worsening in the remaining one. The safety profile in this trial was consistent with those seen in previous trials.

Overall, the most common adverse reactions seen with this interleukin-17A antagonist are nasopharyngitis, diarrhea, and upper respiratory tract infections. Patients should be evaluated for tuberculosis before initiating treatment. Serious infections have been observed, so be mindful of patients with chronic infections and discontinue secukinumab in patients who develop infections. Caution should be exercised when prescribing to patients with inflammatory bowel disease. Full prescribing information can be found on the Novartis website.

[email protected]

New results for secukinumab (Cosentyx) in the PREVENT trial continue its promising trend for treatment of the full spectrum of axial spondyloarthritis (axSpA), according to a release from Novartis. The PREVENT trial is assessing this therapy in nonradiographic axSpA (nr-axSpA); it’s already approved in ankylosing spondylitis.

Results of 16-week data were presented in mid-September, and the new results represent 52-week data. Full details and data will be revealed at an upcoming scientific congress.

The PREVENT trial is an ongoing, 2-year trial with a 2-year extension phase; it enrolled 550 men and women with nr-axSpA and assessed their response to secukinumab with an induction phase, to it without induction, or to placebo. The trial met its primary endpoint of 40% improvement in Assessment in Spondyloarthritis International Society (ASAS40) criteria at 16 and 52 weeks, which indicates meaningful and sustained improvement. ASAS40 is defined as an improvement of at least 40% and both 10 out of 100 points in three of four domains (patient global assessment, pain, function, and inflammation) and no worsening in the remaining one. The safety profile in this trial was consistent with those seen in previous trials.

Overall, the most common adverse reactions seen with this interleukin-17A antagonist are nasopharyngitis, diarrhea, and upper respiratory tract infections. Patients should be evaluated for tuberculosis before initiating treatment. Serious infections have been observed, so be mindful of patients with chronic infections and discontinue secukinumab in patients who develop infections. Caution should be exercised when prescribing to patients with inflammatory bowel disease. Full prescribing information can be found on the Novartis website.

[email protected]

New results for secukinumab (Cosentyx) in the PREVENT trial continue its promising trend for treatment of the full spectrum of axial spondyloarthritis (axSpA), according to a release from Novartis. The PREVENT trial is assessing this therapy in nonradiographic axSpA (nr-axSpA); it’s already approved in ankylosing spondylitis.

Results of 16-week data were presented in mid-September, and the new results represent 52-week data. Full details and data will be revealed at an upcoming scientific congress.

The PREVENT trial is an ongoing, 2-year trial with a 2-year extension phase; it enrolled 550 men and women with nr-axSpA and assessed their response to secukinumab with an induction phase, to it without induction, or to placebo. The trial met its primary endpoint of 40% improvement in Assessment in Spondyloarthritis International Society (ASAS40) criteria at 16 and 52 weeks, which indicates meaningful and sustained improvement. ASAS40 is defined as an improvement of at least 40% and both 10 out of 100 points in three of four domains (patient global assessment, pain, function, and inflammation) and no worsening in the remaining one. The safety profile in this trial was consistent with those seen in previous trials.

Overall, the most common adverse reactions seen with this interleukin-17A antagonist are nasopharyngitis, diarrhea, and upper respiratory tract infections. Patients should be evaluated for tuberculosis before initiating treatment. Serious infections have been observed, so be mindful of patients with chronic infections and discontinue secukinumab in patients who develop infections. Caution should be exercised when prescribing to patients with inflammatory bowel disease. Full prescribing information can be found on the Novartis website.

[email protected]

Continuous use of NSAIDs could increase the risk of incident hypertension among patients with ankylosing spondylitis (AS), according to findings from a recent prospective study.

dolgachov/Thinkstock

Against expectations, data also suggested that tumor necrosis factor inhibitor (TNFi) therapy could increase blood pressure, although this finding was not significant across all methods of analysis, reported lead author Jean W. Liew, MD, of the University of Washington, Seattle, and colleagues.

The investigators noted that patients with AS already have a greater risk of cardiovascular disease than that of the general population, making any added risks that much more concerning.

“[T]he evidence for increased cardiovascular disease burden and cardiovascular risk in patients with inflammatory rheumatic diseases is well recognized,” the investigators wrote in Arthritis Care & Research. “Multiple population-based studies have demonstrated increased cardiovascular events and cardiovascular-related mortality in AS. There is a high prevalence of cardiovascular risk factors among individuals with AS, particularly hypertension.”

Exacerbation of this risk by NSAIDs has been previously studied with mixed results, according to the investigators. Meta-analyses have suggested that NSAIDs increase blood pressure in normotensive and hypertensive individuals, but some data point to a cardioprotective effect among those with AS, possibly as a consequence of dampened inflammation, and/or improved physical activity, which could lead to a secondary CV benefit. Still, the relationship between NSAIDs and CV risk was unclear, prompting the current study.

The investigators enrolled 1,282 patients with AS at five centers in the United States and Australia. Using a combination of clinical evaluations and self-reporting, enrollees were monitored at regular intervals. Disease activity was tracked with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), while the Bath Ankylosing Spondylitis Functional Index (BASFI) was used for functional impairments. Patients were also checked for a variety of comorbidities such as hypertension, coronary artery disease, mental health conditions, and renal disorders. Medication data included type, dosage, frequency, duration, and number of missed doses.

Including only baseline normotensive patients with at least 1 year of follow-up, 628 participants were eligible for analysis, of whom 200 used NSAIDs continuously. After a median of 7 years follow-up, 129 out of 628 patients developed hypertension. This translated to a hazard ratio (HR) for incident hypertension of 1.12 (95% confidence interval, 1.04-1.20), compared with nonusers or those who took NSAIDs intermittently. This relationship did not differ across subgroups defined by age, disease activity, body mass index, or TNFi use. Multiple sensitivity analyses added support to the association between continuous NSAID use and hypertension.

“The association of NSAIDs and incident hypertension remains particularly concerning, as the early development of hypertension may portend a higher risk of premature CV events due to cumulative exposure,” the investigators wrote.

In contrast with NSAIDs, TNFi therapy was not associated with hypertension across all models; however, against expectations, two models of analysis pointed to an 8% increased risk.

“Although TNFi use did not reach statistical significance in the main model, the direction of association was opposite that hypothesized based on prior data, specifically that TNFi use reduces CV risk by suppressing chronic inflammation,” the investigators wrote.

Considering the present findings, and previous studies, which have reported conflicting associations between TNFi use and hypertension, the investigators suggested that more research is needed, and offered specific methods to approach the topic.

“The association of TNFi use and incident hypertension requires further clarification in future studies,” they wrote, “which may be done by applying a marginal structural modeling (MSM) framework and inverse probability of treatment weighting (IPTW) statistical analyses to account for the relationships between TNFi use, disease activity, and NSAID use.”

In their concluding remarks, the investigators further emphasized the current knowledge gap in this area.

“There is an unmet need to clarify how treatment choices, particularly the use of NSAIDs and TNFi, impact CV risk factors and CV events in AS,” they wrote. “Further studies are needed to focus on precision medicine and predicting risk and benefit for patients in whom continuous NSAIDs are being considered. These further studies can inform the revision of guidelines to address the management of CV risk factors and CV disease in AS and axial spondyloarthritis more broadly.”

The investigators reported funding from the National Institutes of Health, the Assessment of Spondyloarthritis International Society, the Spondylitis Association of America, and the Russel Engleman Rheumatology Research Center at the University of California, San Francisco. Some authors reported ties with Eli Lilly, Novartis, and other pharmaceutical companies..

SOURCE: Liew et al. Arthritis Care Res. 2019 Sep 17. doi: 10.1002/acr.24070.

Continuous use of NSAIDs could increase the risk of incident hypertension among patients with ankylosing spondylitis (AS), according to findings from a recent prospective study.

dolgachov/Thinkstock

Against expectations, data also suggested that tumor necrosis factor inhibitor (TNFi) therapy could increase blood pressure, although this finding was not significant across all methods of analysis, reported lead author Jean W. Liew, MD, of the University of Washington, Seattle, and colleagues.

The investigators noted that patients with AS already have a greater risk of cardiovascular disease than that of the general population, making any added risks that much more concerning.

“[T]he evidence for increased cardiovascular disease burden and cardiovascular risk in patients with inflammatory rheumatic diseases is well recognized,” the investigators wrote in Arthritis Care & Research. “Multiple population-based studies have demonstrated increased cardiovascular events and cardiovascular-related mortality in AS. There is a high prevalence of cardiovascular risk factors among individuals with AS, particularly hypertension.”

Exacerbation of this risk by NSAIDs has been previously studied with mixed results, according to the investigators. Meta-analyses have suggested that NSAIDs increase blood pressure in normotensive and hypertensive individuals, but some data point to a cardioprotective effect among those with AS, possibly as a consequence of dampened inflammation, and/or improved physical activity, which could lead to a secondary CV benefit. Still, the relationship between NSAIDs and CV risk was unclear, prompting the current study.

The investigators enrolled 1,282 patients with AS at five centers in the United States and Australia. Using a combination of clinical evaluations and self-reporting, enrollees were monitored at regular intervals. Disease activity was tracked with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), while the Bath Ankylosing Spondylitis Functional Index (BASFI) was used for functional impairments. Patients were also checked for a variety of comorbidities such as hypertension, coronary artery disease, mental health conditions, and renal disorders. Medication data included type, dosage, frequency, duration, and number of missed doses.

Including only baseline normotensive patients with at least 1 year of follow-up, 628 participants were eligible for analysis, of whom 200 used NSAIDs continuously. After a median of 7 years follow-up, 129 out of 628 patients developed hypertension. This translated to a hazard ratio (HR) for incident hypertension of 1.12 (95% confidence interval, 1.04-1.20), compared with nonusers or those who took NSAIDs intermittently. This relationship did not differ across subgroups defined by age, disease activity, body mass index, or TNFi use. Multiple sensitivity analyses added support to the association between continuous NSAID use and hypertension.

“The association of NSAIDs and incident hypertension remains particularly concerning, as the early development of hypertension may portend a higher risk of premature CV events due to cumulative exposure,” the investigators wrote.

In contrast with NSAIDs, TNFi therapy was not associated with hypertension across all models; however, against expectations, two models of analysis pointed to an 8% increased risk.

“Although TNFi use did not reach statistical significance in the main model, the direction of association was opposite that hypothesized based on prior data, specifically that TNFi use reduces CV risk by suppressing chronic inflammation,” the investigators wrote.

Considering the present findings, and previous studies, which have reported conflicting associations between TNFi use and hypertension, the investigators suggested that more research is needed, and offered specific methods to approach the topic.

“The association of TNFi use and incident hypertension requires further clarification in future studies,” they wrote, “which may be done by applying a marginal structural modeling (MSM) framework and inverse probability of treatment weighting (IPTW) statistical analyses to account for the relationships between TNFi use, disease activity, and NSAID use.”

In their concluding remarks, the investigators further emphasized the current knowledge gap in this area.

“There is an unmet need to clarify how treatment choices, particularly the use of NSAIDs and TNFi, impact CV risk factors and CV events in AS,” they wrote. “Further studies are needed to focus on precision medicine and predicting risk and benefit for patients in whom continuous NSAIDs are being considered. These further studies can inform the revision of guidelines to address the management of CV risk factors and CV disease in AS and axial spondyloarthritis more broadly.”

The investigators reported funding from the National Institutes of Health, the Assessment of Spondyloarthritis International Society, the Spondylitis Association of America, and the Russel Engleman Rheumatology Research Center at the University of California, San Francisco. Some authors reported ties with Eli Lilly, Novartis, and other pharmaceutical companies..

SOURCE: Liew et al. Arthritis Care Res. 2019 Sep 17. doi: 10.1002/acr.24070.

Continuous use of NSAIDs could increase the risk of incident hypertension among patients with ankylosing spondylitis (AS), according to findings from a recent prospective study.

dolgachov/Thinkstock

Against expectations, data also suggested that tumor necrosis factor inhibitor (TNFi) therapy could increase blood pressure, although this finding was not significant across all methods of analysis, reported lead author Jean W. Liew, MD, of the University of Washington, Seattle, and colleagues.

The investigators noted that patients with AS already have a greater risk of cardiovascular disease than that of the general population, making any added risks that much more concerning.

“[T]he evidence for increased cardiovascular disease burden and cardiovascular risk in patients with inflammatory rheumatic diseases is well recognized,” the investigators wrote in Arthritis Care & Research. “Multiple population-based studies have demonstrated increased cardiovascular events and cardiovascular-related mortality in AS. There is a high prevalence of cardiovascular risk factors among individuals with AS, particularly hypertension.”

Exacerbation of this risk by NSAIDs has been previously studied with mixed results, according to the investigators. Meta-analyses have suggested that NSAIDs increase blood pressure in normotensive and hypertensive individuals, but some data point to a cardioprotective effect among those with AS, possibly as a consequence of dampened inflammation, and/or improved physical activity, which could lead to a secondary CV benefit. Still, the relationship between NSAIDs and CV risk was unclear, prompting the current study.

The investigators enrolled 1,282 patients with AS at five centers in the United States and Australia. Using a combination of clinical evaluations and self-reporting, enrollees were monitored at regular intervals. Disease activity was tracked with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), while the Bath Ankylosing Spondylitis Functional Index (BASFI) was used for functional impairments. Patients were also checked for a variety of comorbidities such as hypertension, coronary artery disease, mental health conditions, and renal disorders. Medication data included type, dosage, frequency, duration, and number of missed doses.

Including only baseline normotensive patients with at least 1 year of follow-up, 628 participants were eligible for analysis, of whom 200 used NSAIDs continuously. After a median of 7 years follow-up, 129 out of 628 patients developed hypertension. This translated to a hazard ratio (HR) for incident hypertension of 1.12 (95% confidence interval, 1.04-1.20), compared with nonusers or those who took NSAIDs intermittently. This relationship did not differ across subgroups defined by age, disease activity, body mass index, or TNFi use. Multiple sensitivity analyses added support to the association between continuous NSAID use and hypertension.

“The association of NSAIDs and incident hypertension remains particularly concerning, as the early development of hypertension may portend a higher risk of premature CV events due to cumulative exposure,” the investigators wrote.

In contrast with NSAIDs, TNFi therapy was not associated with hypertension across all models; however, against expectations, two models of analysis pointed to an 8% increased risk.

“Although TNFi use did not reach statistical significance in the main model, the direction of association was opposite that hypothesized based on prior data, specifically that TNFi use reduces CV risk by suppressing chronic inflammation,” the investigators wrote.

Considering the present findings, and previous studies, which have reported conflicting associations between TNFi use and hypertension, the investigators suggested that more research is needed, and offered specific methods to approach the topic.

“The association of TNFi use and incident hypertension requires further clarification in future studies,” they wrote, “which may be done by applying a marginal structural modeling (MSM) framework and inverse probability of treatment weighting (IPTW) statistical analyses to account for the relationships between TNFi use, disease activity, and NSAID use.”

In their concluding remarks, the investigators further emphasized the current knowledge gap in this area.

“There is an unmet need to clarify how treatment choices, particularly the use of NSAIDs and TNFi, impact CV risk factors and CV events in AS,” they wrote. “Further studies are needed to focus on precision medicine and predicting risk and benefit for patients in whom continuous NSAIDs are being considered. These further studies can inform the revision of guidelines to address the management of CV risk factors and CV disease in AS and axial spondyloarthritis more broadly.”

The investigators reported funding from the National Institutes of Health, the Assessment of Spondyloarthritis International Society, the Spondylitis Association of America, and the Russel Engleman Rheumatology Research Center at the University of California, San Francisco. Some authors reported ties with Eli Lilly, Novartis, and other pharmaceutical companies..

SOURCE: Liew et al. Arthritis Care Res. 2019 Sep 17. doi: 10.1002/acr.24070.

A new study has found that a group of four collagen metabolites are promising biomarkers for axial spondyloarthritis (axSpA) that could potentially distinguish patients without radiographic signs of disease and those with ankylosing spondylitis.

“This current study illustrates the potential of serological metabolites of tissue destruction as novel disease activity biomarkers in axSpA,” wrote Markéta Hušáková, PhD, of the Institute of Rheumatology and Department of Rheumatology at First Faculty of Medicine Charles University in Prague and coauthors. The study was published in Scientific Reports.

To determine if certain collagen metabolites could indicate axSpA disease activity and distinguish nonradiographic axial spondyloarthritis (nr-axSpA) from ankylosing spondylitis (AS), the researchers examined 193 recently diagnosed axSpA patients and 100 asymptomatic controls. Of the 193 patients, 121 had nr-axSpA and 72 had AS.

The researchers found that four collagen metabolites occurred at significantly higher serum levels in both subtypes of axSpA patients, compared with controls: for C1M, a mean of 43.4 ng/mL for AS and 34.6 ng/mL for nr-axSpA versus 24.5 ng/mL for controls; for C2M, 0.35 and 0.36 versus 0.26; for C3M, 15.4 and 12.8 versus 7.8; and for C4M2, 27.8 and 22.4 versus 15.2. Mean serum levels of C1M, C3M, and C4M2 were significantly higher in AS patients when compared with nr-axSpA patients. Of the four collagen metabolites, C3M was the best for differentiating between axSpA patients and asymptomatic controls (area under receiver operator characteristics curve, 0.95; specificity, 92.0; sensitivity, 83.4) and between nr-axSpA patients and controls (AUC, 0.93; specificity, 80.0; sensitivity, 92.6) and AS patients (AUC, 0.98; specificity, 92.0; sensitivity, 91.7).

The authors acknowledged their study’s limitations, including the inability to investigate changes in biomarker levels and disease activity over time. In addition, there was a lack of clinical information about cardiovascular or other systemic complications, as well as no clinical or radiographic examination of the asymptomatic individuals, which could have revealed factors influencing their metabolite levels.

Two of the authors acknowledged being employees of fibrosis biomarker developer Nordic Bioscience; another researcher acknowledged being a stockholder. No additional conflicts of interest were reported.

SOURCE: Hušáková M et al. Sci Rep. 2019 Aug 2. doi: 10.1038/s41598-019-47502-z.

A new study has found that a group of four collagen metabolites are promising biomarkers for axial spondyloarthritis (axSpA) that could potentially distinguish patients without radiographic signs of disease and those with ankylosing spondylitis.

“This current study illustrates the potential of serological metabolites of tissue destruction as novel disease activity biomarkers in axSpA,” wrote Markéta Hušáková, PhD, of the Institute of Rheumatology and Department of Rheumatology at First Faculty of Medicine Charles University in Prague and coauthors. The study was published in Scientific Reports.

To determine if certain collagen metabolites could indicate axSpA disease activity and distinguish nonradiographic axial spondyloarthritis (nr-axSpA) from ankylosing spondylitis (AS), the researchers examined 193 recently diagnosed axSpA patients and 100 asymptomatic controls. Of the 193 patients, 121 had nr-axSpA and 72 had AS.

The researchers found that four collagen metabolites occurred at significantly higher serum levels in both subtypes of axSpA patients, compared with controls: for C1M, a mean of 43.4 ng/mL for AS and 34.6 ng/mL for nr-axSpA versus 24.5 ng/mL for controls; for C2M, 0.35 and 0.36 versus 0.26; for C3M, 15.4 and 12.8 versus 7.8; and for C4M2, 27.8 and 22.4 versus 15.2. Mean serum levels of C1M, C3M, and C4M2 were significantly higher in AS patients when compared with nr-axSpA patients. Of the four collagen metabolites, C3M was the best for differentiating between axSpA patients and asymptomatic controls (area under receiver operator characteristics curve, 0.95; specificity, 92.0; sensitivity, 83.4) and between nr-axSpA patients and controls (AUC, 0.93; specificity, 80.0; sensitivity, 92.6) and AS patients (AUC, 0.98; specificity, 92.0; sensitivity, 91.7).

The authors acknowledged their study’s limitations, including the inability to investigate changes in biomarker levels and disease activity over time. In addition, there was a lack of clinical information about cardiovascular or other systemic complications, as well as no clinical or radiographic examination of the asymptomatic individuals, which could have revealed factors influencing their metabolite levels.

Two of the authors acknowledged being employees of fibrosis biomarker developer Nordic Bioscience; another researcher acknowledged being a stockholder. No additional conflicts of interest were reported.

SOURCE: Hušáková M et al. Sci Rep. 2019 Aug 2. doi: 10.1038/s41598-019-47502-z.

A new study has found that a group of four collagen metabolites are promising biomarkers for axial spondyloarthritis (axSpA) that could potentially distinguish patients without radiographic signs of disease and those with ankylosing spondylitis.

“This current study illustrates the potential of serological metabolites of tissue destruction as novel disease activity biomarkers in axSpA,” wrote Markéta Hušáková, PhD, of the Institute of Rheumatology and Department of Rheumatology at First Faculty of Medicine Charles University in Prague and coauthors. The study was published in Scientific Reports.

To determine if certain collagen metabolites could indicate axSpA disease activity and distinguish nonradiographic axial spondyloarthritis (nr-axSpA) from ankylosing spondylitis (AS), the researchers examined 193 recently diagnosed axSpA patients and 100 asymptomatic controls. Of the 193 patients, 121 had nr-axSpA and 72 had AS.

The researchers found that four collagen metabolites occurred at significantly higher serum levels in both subtypes of axSpA patients, compared with controls: for C1M, a mean of 43.4 ng/mL for AS and 34.6 ng/mL for nr-axSpA versus 24.5 ng/mL for controls; for C2M, 0.35 and 0.36 versus 0.26; for C3M, 15.4 and 12.8 versus 7.8; and for C4M2, 27.8 and 22.4 versus 15.2. Mean serum levels of C1M, C3M, and C4M2 were significantly higher in AS patients when compared with nr-axSpA patients. Of the four collagen metabolites, C3M was the best for differentiating between axSpA patients and asymptomatic controls (area under receiver operator characteristics curve, 0.95; specificity, 92.0; sensitivity, 83.4) and between nr-axSpA patients and controls (AUC, 0.93; specificity, 80.0; sensitivity, 92.6) and AS patients (AUC, 0.98; specificity, 92.0; sensitivity, 91.7).

The authors acknowledged their study’s limitations, including the inability to investigate changes in biomarker levels and disease activity over time. In addition, there was a lack of clinical information about cardiovascular or other systemic complications, as well as no clinical or radiographic examination of the asymptomatic individuals, which could have revealed factors influencing their metabolite levels.

Two of the authors acknowledged being employees of fibrosis biomarker developer Nordic Bioscience; another researcher acknowledged being a stockholder. No additional conflicts of interest were reported.

SOURCE: Hušáková M et al. Sci Rep. 2019 Aug 2. doi: 10.1038/s41598-019-47502-z.

Rheumatologist Zachary S. Wallace, MD, knew just how prior authorization requirements were impacting his staff time and work flow when he embarked on a study several years ago. Managing authorizations for infusible medications alone was about to become a full-time job for one of the administrative assistants in the rheumatology unit at Massachusetts General Hospital in Boston.

His research questions concerned patients. “There’s a lot of talk about how much onus prior authorization requirements put on providers and the practice,” Dr. Wallace said. ”I was interested in understanding what impact [these requirements] have on patients themselves.”

Dr. Wallace led a review of the EHRs of 225 patients for whom an infusible medication such as rituximab and infliximab was ordered by 1 of the 16 physicians in the rheumatology unit between July 2016 and June 2018. The findings – that patients who needed prior authorizations for infusible medications had a significantly longer time to treatment initiation and higher prednisone-equivalent glucocorticoid exposure – were reported online in Arthritis Care & Research.

Among patients whose authorizations were initially denied, these differences were “pretty drastic,” Dr. Wallace said. The median time to receiving a first infusion was 50 days, compared with 27 days when permission was not required, and glucocorticoid exposure during the 3 months following the request was 605 mg versus 160 mg.

Among patients whose authorizations were not denied, the median time to first infusion was 31 days, compared with 27 days when authorization was not required, and the mean glucocorticoid exposure over 3 months was 364 mg versus 160 mg.

“I hope that our findings will help facilitate discussions with insurance providers, pharmacy benefit managers, and state and federal legislators about the need to address the impact that prior authorization requirements have on patients and providers,” said Dr. Wallace, also of the clinical epidemiology program in the division of rheumatology, allergy and immunology at Massachusetts General, and an assistant professor of medicine at Harvard Medical School, Boston.

Of the 225 patients for whom an infusible medication was ordered, 71% required preauthorization. Of these, 79% were approved and 21% were denied after the first request. And in a finding that Dr. Wallace called “somewhat surprising,” 82% of the authorizations originally denied were approved after appeal.

All told, prior authorizations for infusible medications were eventually approved in all but a small number of cases. “We go through all this effort to get these prior authorizations approved, and 96% of the time, they were ultimately approved,” he said in an interview.

Christopher Phillips, MD, a community rheumatologist in Paducah, Ky., who serves as chair of the insurance subcommittee of the American College of Rheumatology’s committee on rheumatologic care, said the findings “give further credence” to rheumatologists’ concerns. “We know [from our own experiences] that prior authorizations delay care, and we know that delays can cause harm to patients. We now have hard data backing up this assertion.”

Regarding the high number of authorization approvals, “there’s an argument to be made that for certain treatments and certain conditions where the success rate of appeals is high enough, you shouldn’t be subjecting these treatments to these [preauthorization] policies,” he said.

Calls for prior authorization reform

Most patients in the study (71%) had private insurance. But the findings also have implications for Medicare, Dr. Wallace said, as recent federal policies have expanded Medicare Advantage plans’ authority to use prior authorization in conjunction with step therapy for medications administered under Part B. Step therapy favors primary use of what insurers deem the most cost-effective therapies.

The ACR is one of almost 370 physician, patient, and health care organizations that are urging Congress to pass a bipartisan bill aimed at streamlining and standardizing prior authorization under the Medicare Advantage program. The legislation – Improving Seniors’ Timely Access to Care Act of 2019 (H.R. 3107) – was introduced by Reps. Suzan DelBene (D-Wash.), Mike Kelly (R-Pa.), Roger Marshall, MD (R-Kan.), and Ami Bera, MD (D-Calif.).

The bill calls for the creation of an electronic prior authorization program and a “real-time process for items and services that are routinely approved,” as well as greater Centers for Medicare & Medicaid Services oversight on how Medicare Advantage plans use prior authorization. Plans would be required to report to the CMS on the extent of their use of prior authorization and the rate of approvals or denials. They would also be held accountable for making timely prior authorization determinations and providing rationales for denials, according to a letter to Congress cosigned by the ACR.

In a press release about the legislation, Paula Marchetta, MD, president of the ACR, said that “the unregulated use of prior authorization has devolved into a time-consuming and obstructive process that often stalls or outright revokes patient access to medically necessary therapies.” She added that “many health care plans now use prior authorization indiscriminately.”

Cathryn Donaldson, director of communications for America’s Health Insurance Plans (AHIP), said in an email that prior authorization is used for less than 15% of covered services, and that, along with step therapy, it “helps ensure that patients receive care that is safe, effective, and necessary.” AHIP “knows that prior authorization can be improved,” she said, and is committed to streamlining the process.

A demonstration project on the automation of various parts of prior authorization is being coordinated with health information technology companies, plans, and providers, she noted.

The federal legislation is based at least partly on a consensus statement drafted by AHIP, the American Medical Association, and four other organizations representing hospitals, medical groups, and health plans on ways to improve the prior authorization process. Among the items mentioned in the statement is that “regular review” of services subject to prior authorization could help identify therapies that “no longer warrant” prior authorization because of low denial rates.

Outside of Medicare Advantage, the AMA is aware of at least 85 bills being introduced in states this year that address utilization management in commercial plans. Nearly all these bills attempt to reform prior authorization programs in some way, according to R. J. Mills, media relations coordinator for the AMA.

Rheumatologic patients hard hit

Off-label medication use was the most common reason (82%) for a prior authorization denial in the Massachusetts General study, even though 78% of the patients for whom infusible medications were prescribed had a condition with no Food and Drug Administration–approved treatment. Having such a condition was associated with 120% or 190% higher odds of having a denial in unadjusted and adjusted (for age and sex) analyses, Dr. Wallace and colleagues reported.

Moreover, nearly half (48%) of the patients with denials had already tried or were currently taking an oral disease-modifying antirheumatic drug, such as methotrexate.

The majority of denials were for the use of rituximab (70%), followed by infliximab (12%) and tocilizumab (12%). Most of the denials (79%) were appealed successfully through a peer-to-peer discussion. In five cases, the insurer’s preferred drug (for example, adalimumab) had to be used rather than the requested infusion (for example, infliximab).

Infused medications, many of which are biologics, are among the most expensive drugs prescribed for patients with rheumatic diseases. They were easiest for Dr. Wallace to study because of the way prior authorizations are handled in his unit, but prior authorization requirements are “widespread” in rheumatology practices across treatment types, he and Dr. Phillips said.

“Some of our relatively inexpensive treatments are subject to prior authorization requirements,” Dr. Phillips said. “We hear stories about prednisone needing a prior authorization sometimes.”

With respect to infusible medications, the insurance subcommittee is hearing from ACR members about seemingly increasing numbers of both clinical coverage reviews – for example, reviews of prior treatments – and site-of-care restrictions, Dr. Phillips noted. “Some carriers are insisting on infusions in non-hospital-based settings, for cost savings, or on home infusions, which are concerning because of [possible] infusion reactions and medical service availability.”

The application of step therapy to rheumatologic patients is troubling because of the “often unique medical circumstances of the patient,” Dr. Phillips said. “There are enough differences among the [tumor necrosis factor] antagonists, for instance, that make one more appropriate for a certain patient than another. Those differences are not brought into consideration with these policies.”

There are other ways in which prior authorization processes “are not well informed medically,” he said, recalling a case brought to the attention of the subcommittee in which a patient prescribed a biologic drug for psoriatic arthritis was denied authorization because “the documentation did not include a [disease activity measure] that is specific to RA and not used for psoriatic arthritis.”

It is not uncommon for authorizations for infusible medications to take 2 weeks or longer to secure – even when initially approved. In the AMA’s 2018 Prior Authorization Physician Survey, 65% reported waiting at least 1 business day for a decision and 26% reported waiting at least 3 business days for responses. “With infusibles, we’re absolutely dealing with a much longer time,” Dr. Phillips said.

In Dr. Wallace’s study, the finding that prior authorizations facilitated greater prednisone-equivalent glucocorticoid exposure is important, he and his colleagues wrote, because these medications may put patients at higher risk of infection, cardiovascular disease, and diabetes – even in low doses and with short-term use. Notably, the median delay to the initiation of treatment was 29 days, regardless of prior authorization requirements. Dr. Wallace said the delays “likely reflect a combination of factors” – including infusion center waiting lists and patient-level factors – and that his team is “thinking about how to facilitate better access [to their practice’s infusion center] for those who are approved for treatment.”

The most common conditions for which infused medication was ordered were inflammatory arthritis (32%), vasculitis (23%), and IgG4-related disease (17%). The 225 patients in the study had an average age of 53 years.

Dr. Wallace reported that he has no relevant financial disclosures.

SOURCE: Wallace ZS et al. Arthritis Care Res. 2019 Sep 10. doi: 10.1002/acr.24062.

Rheumatologist Zachary S. Wallace, MD, knew just how prior authorization requirements were impacting his staff time and work flow when he embarked on a study several years ago. Managing authorizations for infusible medications alone was about to become a full-time job for one of the administrative assistants in the rheumatology unit at Massachusetts General Hospital in Boston.

His research questions concerned patients. “There’s a lot of talk about how much onus prior authorization requirements put on providers and the practice,” Dr. Wallace said. ”I was interested in understanding what impact [these requirements] have on patients themselves.”

Dr. Wallace led a review of the EHRs of 225 patients for whom an infusible medication such as rituximab and infliximab was ordered by 1 of the 16 physicians in the rheumatology unit between July 2016 and June 2018. The findings – that patients who needed prior authorizations for infusible medications had a significantly longer time to treatment initiation and higher prednisone-equivalent glucocorticoid exposure – were reported online in Arthritis Care & Research.

Among patients whose authorizations were initially denied, these differences were “pretty drastic,” Dr. Wallace said. The median time to receiving a first infusion was 50 days, compared with 27 days when permission was not required, and glucocorticoid exposure during the 3 months following the request was 605 mg versus 160 mg.

Among patients whose authorizations were not denied, the median time to first infusion was 31 days, compared with 27 days when authorization was not required, and the mean glucocorticoid exposure over 3 months was 364 mg versus 160 mg.

“I hope that our findings will help facilitate discussions with insurance providers, pharmacy benefit managers, and state and federal legislators about the need to address the impact that prior authorization requirements have on patients and providers,” said Dr. Wallace, also of the clinical epidemiology program in the division of rheumatology, allergy and immunology at Massachusetts General, and an assistant professor of medicine at Harvard Medical School, Boston.

Of the 225 patients for whom an infusible medication was ordered, 71% required preauthorization. Of these, 79% were approved and 21% were denied after the first request. And in a finding that Dr. Wallace called “somewhat surprising,” 82% of the authorizations originally denied were approved after appeal.

All told, prior authorizations for infusible medications were eventually approved in all but a small number of cases. “We go through all this effort to get these prior authorizations approved, and 96% of the time, they were ultimately approved,” he said in an interview.

Christopher Phillips, MD, a community rheumatologist in Paducah, Ky., who serves as chair of the insurance subcommittee of the American College of Rheumatology’s committee on rheumatologic care, said the findings “give further credence” to rheumatologists’ concerns. “We know [from our own experiences] that prior authorizations delay care, and we know that delays can cause harm to patients. We now have hard data backing up this assertion.”

Regarding the high number of authorization approvals, “there’s an argument to be made that for certain treatments and certain conditions where the success rate of appeals is high enough, you shouldn’t be subjecting these treatments to these [preauthorization] policies,” he said.

Calls for prior authorization reform

Most patients in the study (71%) had private insurance. But the findings also have implications for Medicare, Dr. Wallace said, as recent federal policies have expanded Medicare Advantage plans’ authority to use prior authorization in conjunction with step therapy for medications administered under Part B. Step therapy favors primary use of what insurers deem the most cost-effective therapies.

The ACR is one of almost 370 physician, patient, and health care organizations that are urging Congress to pass a bipartisan bill aimed at streamlining and standardizing prior authorization under the Medicare Advantage program. The legislation – Improving Seniors’ Timely Access to Care Act of 2019 (H.R. 3107) – was introduced by Reps. Suzan DelBene (D-Wash.), Mike Kelly (R-Pa.), Roger Marshall, MD (R-Kan.), and Ami Bera, MD (D-Calif.).

The bill calls for the creation of an electronic prior authorization program and a “real-time process for items and services that are routinely approved,” as well as greater Centers for Medicare & Medicaid Services oversight on how Medicare Advantage plans use prior authorization. Plans would be required to report to the CMS on the extent of their use of prior authorization and the rate of approvals or denials. They would also be held accountable for making timely prior authorization determinations and providing rationales for denials, according to a letter to Congress cosigned by the ACR.

In a press release about the legislation, Paula Marchetta, MD, president of the ACR, said that “the unregulated use of prior authorization has devolved into a time-consuming and obstructive process that often stalls or outright revokes patient access to medically necessary therapies.” She added that “many health care plans now use prior authorization indiscriminately.”

Cathryn Donaldson, director of communications for America’s Health Insurance Plans (AHIP), said in an email that prior authorization is used for less than 15% of covered services, and that, along with step therapy, it “helps ensure that patients receive care that is safe, effective, and necessary.” AHIP “knows that prior authorization can be improved,” she said, and is committed to streamlining the process.

A demonstration project on the automation of various parts of prior authorization is being coordinated with health information technology companies, plans, and providers, she noted.

The federal legislation is based at least partly on a consensus statement drafted by AHIP, the American Medical Association, and four other organizations representing hospitals, medical groups, and health plans on ways to improve the prior authorization process. Among the items mentioned in the statement is that “regular review” of services subject to prior authorization could help identify therapies that “no longer warrant” prior authorization because of low denial rates.

Outside of Medicare Advantage, the AMA is aware of at least 85 bills being introduced in states this year that address utilization management in commercial plans. Nearly all these bills attempt to reform prior authorization programs in some way, according to R. J. Mills, media relations coordinator for the AMA.

Rheumatologic patients hard hit

Off-label medication use was the most common reason (82%) for a prior authorization denial in the Massachusetts General study, even though 78% of the patients for whom infusible medications were prescribed had a condition with no Food and Drug Administration–approved treatment. Having such a condition was associated with 120% or 190% higher odds of having a denial in unadjusted and adjusted (for age and sex) analyses, Dr. Wallace and colleagues reported.

Moreover, nearly half (48%) of the patients with denials had already tried or were currently taking an oral disease-modifying antirheumatic drug, such as methotrexate.

The majority of denials were for the use of rituximab (70%), followed by infliximab (12%) and tocilizumab (12%). Most of the denials (79%) were appealed successfully through a peer-to-peer discussion. In five cases, the insurer’s preferred drug (for example, adalimumab) had to be used rather than the requested infusion (for example, infliximab).

Infused medications, many of which are biologics, are among the most expensive drugs prescribed for patients with rheumatic diseases. They were easiest for Dr. Wallace to study because of the way prior authorizations are handled in his unit, but prior authorization requirements are “widespread” in rheumatology practices across treatment types, he and Dr. Phillips said.

“Some of our relatively inexpensive treatments are subject to prior authorization requirements,” Dr. Phillips said. “We hear stories about prednisone needing a prior authorization sometimes.”

With respect to infusible medications, the insurance subcommittee is hearing from ACR members about seemingly increasing numbers of both clinical coverage reviews – for example, reviews of prior treatments – and site-of-care restrictions, Dr. Phillips noted. “Some carriers are insisting on infusions in non-hospital-based settings, for cost savings, or on home infusions, which are concerning because of [possible] infusion reactions and medical service availability.”

The application of step therapy to rheumatologic patients is troubling because of the “often unique medical circumstances of the patient,” Dr. Phillips said. “There are enough differences among the [tumor necrosis factor] antagonists, for instance, that make one more appropriate for a certain patient than another. Those differences are not brought into consideration with these policies.”

There are other ways in which prior authorization processes “are not well informed medically,” he said, recalling a case brought to the attention of the subcommittee in which a patient prescribed a biologic drug for psoriatic arthritis was denied authorization because “the documentation did not include a [disease activity measure] that is specific to RA and not used for psoriatic arthritis.”

It is not uncommon for authorizations for infusible medications to take 2 weeks or longer to secure – even when initially approved. In the AMA’s 2018 Prior Authorization Physician Survey, 65% reported waiting at least 1 business day for a decision and 26% reported waiting at least 3 business days for responses. “With infusibles, we’re absolutely dealing with a much longer time,” Dr. Phillips said.

In Dr. Wallace’s study, the finding that prior authorizations facilitated greater prednisone-equivalent glucocorticoid exposure is important, he and his colleagues wrote, because these medications may put patients at higher risk of infection, cardiovascular disease, and diabetes – even in low doses and with short-term use. Notably, the median delay to the initiation of treatment was 29 days, regardless of prior authorization requirements. Dr. Wallace said the delays “likely reflect a combination of factors” – including infusion center waiting lists and patient-level factors – and that his team is “thinking about how to facilitate better access [to their practice’s infusion center] for those who are approved for treatment.”

The most common conditions for which infused medication was ordered were inflammatory arthritis (32%), vasculitis (23%), and IgG4-related disease (17%). The 225 patients in the study had an average age of 53 years.

Dr. Wallace reported that he has no relevant financial disclosures.

SOURCE: Wallace ZS et al. Arthritis Care Res. 2019 Sep 10. doi: 10.1002/acr.24062.

Rheumatologist Zachary S. Wallace, MD, knew just how prior authorization requirements were impacting his staff time and work flow when he embarked on a study several years ago. Managing authorizations for infusible medications alone was about to become a full-time job for one of the administrative assistants in the rheumatology unit at Massachusetts General Hospital in Boston.

His research questions concerned patients. “There’s a lot of talk about how much onus prior authorization requirements put on providers and the practice,” Dr. Wallace said. ”I was interested in understanding what impact [these requirements] have on patients themselves.”

Dr. Wallace led a review of the EHRs of 225 patients for whom an infusible medication such as rituximab and infliximab was ordered by 1 of the 16 physicians in the rheumatology unit between July 2016 and June 2018. The findings – that patients who needed prior authorizations for infusible medications had a significantly longer time to treatment initiation and higher prednisone-equivalent glucocorticoid exposure – were reported online in Arthritis Care & Research.

Among patients whose authorizations were initially denied, these differences were “pretty drastic,” Dr. Wallace said. The median time to receiving a first infusion was 50 days, compared with 27 days when permission was not required, and glucocorticoid exposure during the 3 months following the request was 605 mg versus 160 mg.

Among patients whose authorizations were not denied, the median time to first infusion was 31 days, compared with 27 days when authorization was not required, and the mean glucocorticoid exposure over 3 months was 364 mg versus 160 mg.

“I hope that our findings will help facilitate discussions with insurance providers, pharmacy benefit managers, and state and federal legislators about the need to address the impact that prior authorization requirements have on patients and providers,” said Dr. Wallace, also of the clinical epidemiology program in the division of rheumatology, allergy and immunology at Massachusetts General, and an assistant professor of medicine at Harvard Medical School, Boston.

Of the 225 patients for whom an infusible medication was ordered, 71% required preauthorization. Of these, 79% were approved and 21% were denied after the first request. And in a finding that Dr. Wallace called “somewhat surprising,” 82% of the authorizations originally denied were approved after appeal.

All told, prior authorizations for infusible medications were eventually approved in all but a small number of cases. “We go through all this effort to get these prior authorizations approved, and 96% of the time, they were ultimately approved,” he said in an interview.

Christopher Phillips, MD, a community rheumatologist in Paducah, Ky., who serves as chair of the insurance subcommittee of the American College of Rheumatology’s committee on rheumatologic care, said the findings “give further credence” to rheumatologists’ concerns. “We know [from our own experiences] that prior authorizations delay care, and we know that delays can cause harm to patients. We now have hard data backing up this assertion.”

Regarding the high number of authorization approvals, “there’s an argument to be made that for certain treatments and certain conditions where the success rate of appeals is high enough, you shouldn’t be subjecting these treatments to these [preauthorization] policies,” he said.

Calls for prior authorization reform

Most patients in the study (71%) had private insurance. But the findings also have implications for Medicare, Dr. Wallace said, as recent federal policies have expanded Medicare Advantage plans’ authority to use prior authorization in conjunction with step therapy for medications administered under Part B. Step therapy favors primary use of what insurers deem the most cost-effective therapies.

The ACR is one of almost 370 physician, patient, and health care organizations that are urging Congress to pass a bipartisan bill aimed at streamlining and standardizing prior authorization under the Medicare Advantage program. The legislation – Improving Seniors’ Timely Access to Care Act of 2019 (H.R. 3107) – was introduced by Reps. Suzan DelBene (D-Wash.), Mike Kelly (R-Pa.), Roger Marshall, MD (R-Kan.), and Ami Bera, MD (D-Calif.).

The bill calls for the creation of an electronic prior authorization program and a “real-time process for items and services that are routinely approved,” as well as greater Centers for Medicare & Medicaid Services oversight on how Medicare Advantage plans use prior authorization. Plans would be required to report to the CMS on the extent of their use of prior authorization and the rate of approvals or denials. They would also be held accountable for making timely prior authorization determinations and providing rationales for denials, according to a letter to Congress cosigned by the ACR.

In a press release about the legislation, Paula Marchetta, MD, president of the ACR, said that “the unregulated use of prior authorization has devolved into a time-consuming and obstructive process that often stalls or outright revokes patient access to medically necessary therapies.” She added that “many health care plans now use prior authorization indiscriminately.”

Cathryn Donaldson, director of communications for America’s Health Insurance Plans (AHIP), said in an email that prior authorization is used for less than 15% of covered services, and that, along with step therapy, it “helps ensure that patients receive care that is safe, effective, and necessary.” AHIP “knows that prior authorization can be improved,” she said, and is committed to streamlining the process.

A demonstration project on the automation of various parts of prior authorization is being coordinated with health information technology companies, plans, and providers, she noted.

The federal legislation is based at least partly on a consensus statement drafted by AHIP, the American Medical Association, and four other organizations representing hospitals, medical groups, and health plans on ways to improve the prior authorization process. Among the items mentioned in the statement is that “regular review” of services subject to prior authorization could help identify therapies that “no longer warrant” prior authorization because of low denial rates.

Outside of Medicare Advantage, the AMA is aware of at least 85 bills being introduced in states this year that address utilization management in commercial plans. Nearly all these bills attempt to reform prior authorization programs in some way, according to R. J. Mills, media relations coordinator for the AMA.

Rheumatologic patients hard hit

Off-label medication use was the most common reason (82%) for a prior authorization denial in the Massachusetts General study, even though 78% of the patients for whom infusible medications were prescribed had a condition with no Food and Drug Administration–approved treatment. Having such a condition was associated with 120% or 190% higher odds of having a denial in unadjusted and adjusted (for age and sex) analyses, Dr. Wallace and colleagues reported.

Moreover, nearly half (48%) of the patients with denials had already tried or were currently taking an oral disease-modifying antirheumatic drug, such as methotrexate.

The majority of denials were for the use of rituximab (70%), followed by infliximab (12%) and tocilizumab (12%). Most of the denials (79%) were appealed successfully through a peer-to-peer discussion. In five cases, the insurer’s preferred drug (for example, adalimumab) had to be used rather than the requested infusion (for example, infliximab).

Infused medications, many of which are biologics, are among the most expensive drugs prescribed for patients with rheumatic diseases. They were easiest for Dr. Wallace to study because of the way prior authorizations are handled in his unit, but prior authorization requirements are “widespread” in rheumatology practices across treatment types, he and Dr. Phillips said.

“Some of our relatively inexpensive treatments are subject to prior authorization requirements,” Dr. Phillips said. “We hear stories about prednisone needing a prior authorization sometimes.”

With respect to infusible medications, the insurance subcommittee is hearing from ACR members about seemingly increasing numbers of both clinical coverage reviews – for example, reviews of prior treatments – and site-of-care restrictions, Dr. Phillips noted. “Some carriers are insisting on infusions in non-hospital-based settings, for cost savings, or on home infusions, which are concerning because of [possible] infusion reactions and medical service availability.”

The application of step therapy to rheumatologic patients is troubling because of the “often unique medical circumstances of the patient,” Dr. Phillips said. “There are enough differences among the [tumor necrosis factor] antagonists, for instance, that make one more appropriate for a certain patient than another. Those differences are not brought into consideration with these policies.”

There are other ways in which prior authorization processes “are not well informed medically,” he said, recalling a case brought to the attention of the subcommittee in which a patient prescribed a biologic drug for psoriatic arthritis was denied authorization because “the documentation did not include a [disease activity measure] that is specific to RA and not used for psoriatic arthritis.”

It is not uncommon for authorizations for infusible medications to take 2 weeks or longer to secure – even when initially approved. In the AMA’s 2018 Prior Authorization Physician Survey, 65% reported waiting at least 1 business day for a decision and 26% reported waiting at least 3 business days for responses. “With infusibles, we’re absolutely dealing with a much longer time,” Dr. Phillips said.

In Dr. Wallace’s study, the finding that prior authorizations facilitated greater prednisone-equivalent glucocorticoid exposure is important, he and his colleagues wrote, because these medications may put patients at higher risk of infection, cardiovascular disease, and diabetes – even in low doses and with short-term use. Notably, the median delay to the initiation of treatment was 29 days, regardless of prior authorization requirements. Dr. Wallace said the delays “likely reflect a combination of factors” – including infusion center waiting lists and patient-level factors – and that his team is “thinking about how to facilitate better access [to their practice’s infusion center] for those who are approved for treatment.”

The most common conditions for which infused medication was ordered were inflammatory arthritis (32%), vasculitis (23%), and IgG4-related disease (17%). The 225 patients in the study had an average age of 53 years.

Dr. Wallace reported that he has no relevant financial disclosures.

SOURCE: Wallace ZS et al. Arthritis Care Res. 2019 Sep 10. doi: 10.1002/acr.24062.

While ankylosing spondylitis may be more common among whites, black patients have more comorbidities and express higher disease activity, Dilpreet Kaur Singh, MD, and Marina Magrey, MBBS, reported in The Journal of Rheumatology.

A retrospective review of a large U.S. medical database conducted by Dr. Singh and Dr. Magrey of MetroHealth Medical Center, Cleveland, found that black patients had higher erythrocyte sedimentation rates and C-reactive protein, and a higher prevalence of anterior uveitis, hypertension, diabetes, and depression, compared with white patients. (Dr. Singh, who was a rheumatology fellow at MetroHealth at the time of the study, is now a practicing rheumatologist in Springfield, Mass.)

Disease severity in AS is “thought to be genetically mediated but cultural, social, or economic factors may also be contributing to this racial disparity,” the investigators wrote. “Further research is needed to determine the role of factors other than genetic factors like HLA-B27 positivity that contribute to worsening disease severity.”

The authors extracted data recorded during 1999-2017 from the Explorys platform, a clinical research informatics tool with data from more than 50 million patients in 26 major integrated health care systems in the United States.

The current study comprised 10,990 AS patients with at least two visits to a rheumatologist. Most (84%) were white; 8% were black. Sex was equally distributed in both groups. Positivity for HLA-B27 was similar among whites (26%) and blacks (20%). A majority of patients smoked (65%), and smoking was more common among whites than among blacks (67% vs. 59%).

Disease characteristics suggested that AS was more severe among blacks. Significantly greater proportions of black patients had elevated erythrocyte sedimentation rate (62% vs. 48% of whites) and C-reactive protein (68% vs. 54%). Blacks also experienced significantly greater rates of anterior uveitis (8% vs. 4%), hypertension (29% vs. 22%), diabetes (27% vs. 17%), and depression (36% vs. 32%).

Blacks experienced higher rates of peripheral arthritis, enthesopathy, dactylitis, and inflammatory bowel disease, although these differences were not statistically significant when compared with whites.

Whites, however, had significantly higher rates of psoriasis (10% vs. 6.5%).

Most of the cohort (87%) received NSAIDs; 39% used tumor necrosis factor inhibitors. There were no significant between-group treatment differences.

The authors reported no potential conflicts of interest and no source of financial support.

[email protected]

SOURCE: Singh DK et al. J Rheumatol. 2019 Sep 1. doi: 10.3899/jrheum.181019.

While ankylosing spondylitis may be more common among whites, black patients have more comorbidities and express higher disease activity, Dilpreet Kaur Singh, MD, and Marina Magrey, MBBS, reported in The Journal of Rheumatology.

A retrospective review of a large U.S. medical database conducted by Dr. Singh and Dr. Magrey of MetroHealth Medical Center, Cleveland, found that black patients had higher erythrocyte sedimentation rates and C-reactive protein, and a higher prevalence of anterior uveitis, hypertension, diabetes, and depression, compared with white patients. (Dr. Singh, who was a rheumatology fellow at MetroHealth at the time of the study, is now a practicing rheumatologist in Springfield, Mass.)

Disease severity in AS is “thought to be genetically mediated but cultural, social, or economic factors may also be contributing to this racial disparity,” the investigators wrote. “Further research is needed to determine the role of factors other than genetic factors like HLA-B27 positivity that contribute to worsening disease severity.”

The authors extracted data recorded during 1999-2017 from the Explorys platform, a clinical research informatics tool with data from more than 50 million patients in 26 major integrated health care systems in the United States.

The current study comprised 10,990 AS patients with at least two visits to a rheumatologist. Most (84%) were white; 8% were black. Sex was equally distributed in both groups. Positivity for HLA-B27 was similar among whites (26%) and blacks (20%). A majority of patients smoked (65%), and smoking was more common among whites than among blacks (67% vs. 59%).

Disease characteristics suggested that AS was more severe among blacks. Significantly greater proportions of black patients had elevated erythrocyte sedimentation rate (62% vs. 48% of whites) and C-reactive protein (68% vs. 54%). Blacks also experienced significantly greater rates of anterior uveitis (8% vs. 4%), hypertension (29% vs. 22%), diabetes (27% vs. 17%), and depression (36% vs. 32%).

Blacks experienced higher rates of peripheral arthritis, enthesopathy, dactylitis, and inflammatory bowel disease, although these differences were not statistically significant when compared with whites.

Whites, however, had significantly higher rates of psoriasis (10% vs. 6.5%).

Most of the cohort (87%) received NSAIDs; 39% used tumor necrosis factor inhibitors. There were no significant between-group treatment differences.

The authors reported no potential conflicts of interest and no source of financial support.

[email protected]

SOURCE: Singh DK et al. J Rheumatol. 2019 Sep 1. doi: 10.3899/jrheum.181019.

While ankylosing spondylitis may be more common among whites, black patients have more comorbidities and express higher disease activity, Dilpreet Kaur Singh, MD, and Marina Magrey, MBBS, reported in The Journal of Rheumatology.

A retrospective review of a large U.S. medical database conducted by Dr. Singh and Dr. Magrey of MetroHealth Medical Center, Cleveland, found that black patients had higher erythrocyte sedimentation rates and C-reactive protein, and a higher prevalence of anterior uveitis, hypertension, diabetes, and depression, compared with white patients. (Dr. Singh, who was a rheumatology fellow at MetroHealth at the time of the study, is now a practicing rheumatologist in Springfield, Mass.)

Disease severity in AS is “thought to be genetically mediated but cultural, social, or economic factors may also be contributing to this racial disparity,” the investigators wrote. “Further research is needed to determine the role of factors other than genetic factors like HLA-B27 positivity that contribute to worsening disease severity.”

The authors extracted data recorded during 1999-2017 from the Explorys platform, a clinical research informatics tool with data from more than 50 million patients in 26 major integrated health care systems in the United States.

The current study comprised 10,990 AS patients with at least two visits to a rheumatologist. Most (84%) were white; 8% were black. Sex was equally distributed in both groups. Positivity for HLA-B27 was similar among whites (26%) and blacks (20%). A majority of patients smoked (65%), and smoking was more common among whites than among blacks (67% vs. 59%).

Disease characteristics suggested that AS was more severe among blacks. Significantly greater proportions of black patients had elevated erythrocyte sedimentation rate (62% vs. 48% of whites) and C-reactive protein (68% vs. 54%). Blacks also experienced significantly greater rates of anterior uveitis (8% vs. 4%), hypertension (29% vs. 22%), diabetes (27% vs. 17%), and depression (36% vs. 32%).

Blacks experienced higher rates of peripheral arthritis, enthesopathy, dactylitis, and inflammatory bowel disease, although these differences were not statistically significant when compared with whites.

Whites, however, had significantly higher rates of psoriasis (10% vs. 6.5%).

Most of the cohort (87%) received NSAIDs; 39% used tumor necrosis factor inhibitors. There were no significant between-group treatment differences.

The authors reported no potential conflicts of interest and no source of financial support.

[email protected]

SOURCE: Singh DK et al. J Rheumatol. 2019 Sep 1. doi: 10.3899/jrheum.181019.

Approximately two-thirds of adults with uveitis achieved inflammation control after 6 months on either methotrexate or mycophenolate alongside a reduction in corticosteroid use in an international, multicenter, open-label, randomized trial.

“The findings of this trial have implications for clinical practice because they provide scientific justification that mycophenolate mofetil is not more effective than methotrexate as a corticosteroid-sparing immunosuppressive therapy for uveitis,” wrote S.R. Rathinam, MD, PhD, of Aravind Eye Hospital and Postgraduate Institute of Ophthalmology, Madurai, India, and colleagues.

Although corticosteroid therapy is the first-line treatment for uveitis, adverse effects limit long-term use. Mycophenolate mofetil and methotrexate are options for corticosteroid-sparing immunosuppressive therapy for uveitis, but their effectiveness has not been compared until the current study, they said.

In the First-line Antimetabolites as Steroid-sparing Treatment (FAST) trial published Sept. 10 in JAMA, the researchers randomized 216 adults with uveitis (a total of 407 eyes with uveitis) to 25 mg of weekly oral methotrexate or 1.5 g of twice-daily oral mycophenolate mofetil at nine referral eye care centers in India, the United States, Australia, Saudi Arabia, and Mexico; the investigators were masked to the treatment assignment.

Patients with treatment success continued taking their randomized medication for another 6 months. If treatment failed, patients switched to the other antimetabolite with another 6-month follow-up. Overall, 84%-93% in each group had bilateral uveitis. Forty-six patients (21%) had intermediate uveitis only or anterior uveitis and intermediate uveitis, and 170 patients (79%) had posterior uveitis or panuveitis. The median age of the patients was 36 years in the methotrexate group and 41 years in the mycophenolate group; other demographic characteristics were similar between the groups.

SOURCE: Rathinam SR et al. JAMA. 2019;322(10):936-45. doi: 10.1001/jama.2019.12618.

Approximately two-thirds of adults with uveitis achieved inflammation control after 6 months on either methotrexate or mycophenolate alongside a reduction in corticosteroid use in an international, multicenter, open-label, randomized trial.

“The findings of this trial have implications for clinical practice because they provide scientific justification that mycophenolate mofetil is not more effective than methotrexate as a corticosteroid-sparing immunosuppressive therapy for uveitis,” wrote S.R. Rathinam, MD, PhD, of Aravind Eye Hospital and Postgraduate Institute of Ophthalmology, Madurai, India, and colleagues.

Although corticosteroid therapy is the first-line treatment for uveitis, adverse effects limit long-term use. Mycophenolate mofetil and methotrexate are options for corticosteroid-sparing immunosuppressive therapy for uveitis, but their effectiveness has not been compared until the current study, they said.

In the First-line Antimetabolites as Steroid-sparing Treatment (FAST) trial published Sept. 10 in JAMA, the researchers randomized 216 adults with uveitis (a total of 407 eyes with uveitis) to 25 mg of weekly oral methotrexate or 1.5 g of twice-daily oral mycophenolate mofetil at nine referral eye care centers in India, the United States, Australia, Saudi Arabia, and Mexico; the investigators were masked to the treatment assignment.

Patients with treatment success continued taking their randomized medication for another 6 months. If treatment failed, patients switched to the other antimetabolite with another 6-month follow-up. Overall, 84%-93% in each group had bilateral uveitis. Forty-six patients (21%) had intermediate uveitis only or anterior uveitis and intermediate uveitis, and 170 patients (79%) had posterior uveitis or panuveitis. The median age of the patients was 36 years in the methotrexate group and 41 years in the mycophenolate group; other demographic characteristics were similar between the groups.

SOURCE: Rathinam SR et al. JAMA. 2019;322(10):936-45. doi: 10.1001/jama.2019.12618.

Approximately two-thirds of adults with uveitis achieved inflammation control after 6 months on either methotrexate or mycophenolate alongside a reduction in corticosteroid use in an international, multicenter, open-label, randomized trial.

“The findings of this trial have implications for clinical practice because they provide scientific justification that mycophenolate mofetil is not more effective than methotrexate as a corticosteroid-sparing immunosuppressive therapy for uveitis,” wrote S.R. Rathinam, MD, PhD, of Aravind Eye Hospital and Postgraduate Institute of Ophthalmology, Madurai, India, and colleagues.

Although corticosteroid therapy is the first-line treatment for uveitis, adverse effects limit long-term use. Mycophenolate mofetil and methotrexate are options for corticosteroid-sparing immunosuppressive therapy for uveitis, but their effectiveness has not been compared until the current study, they said.

In the First-line Antimetabolites as Steroid-sparing Treatment (FAST) trial published Sept. 10 in JAMA, the researchers randomized 216 adults with uveitis (a total of 407 eyes with uveitis) to 25 mg of weekly oral methotrexate or 1.5 g of twice-daily oral mycophenolate mofetil at nine referral eye care centers in India, the United States, Australia, Saudi Arabia, and Mexico; the investigators were masked to the treatment assignment.

Patients with treatment success continued taking their randomized medication for another 6 months. If treatment failed, patients switched to the other antimetabolite with another 6-month follow-up. Overall, 84%-93% in each group had bilateral uveitis. Forty-six patients (21%) had intermediate uveitis only or anterior uveitis and intermediate uveitis, and 170 patients (79%) had posterior uveitis or panuveitis. The median age of the patients was 36 years in the methotrexate group and 41 years in the mycophenolate group; other demographic characteristics were similar between the groups.

SOURCE: Rathinam SR et al. JAMA. 2019;322(10):936-45. doi: 10.1001/jama.2019.12618.

A number of medications commonly prescribed by rheumatologists may interact with cannabidiol oil, investigators at the Imperial College Healthcare NHS Trust, London, reported.

“Patients are increasingly requesting information concerning the safety of CBD oil,” Taryn Youngstein, MD, and associates said in letter to the editor in Rheumatology, but current guidelines on the use of medical cannabis do “not address the potential interactions between CBD oil and medicines frequently used in the rheumatology clinic.”

The most important potential CBD interaction, they suggested, may be with corticosteroids. Hydrocortisone and prednisolone both inhibit the cytochrome P450 enzyme CYP3A, but CBD is a potent inhibitor of CYP3A, so “concomitant use may decrease glucocorticoid clearance and increase risk of systemic [corticosteroid] side effects,” the investigators wrote.

CBD also is known to inhibit the cytochrome P450 isozymes CYP2C9, CYP2D6, CYP2C19, CYP3A4, and CYP1A2, which, alone or in combination, are involved in the metabolization of naproxen, tramadol, amitriptyline, and tofacitinib (Xeljanz), according to a literature search done via the college’s medicine information department that also used the British National Formulary and the Natural Medicines online interaction checker.

The Janus kinase inhibitor tofacitinib is included among the possible interactions, but the other Food and Drug Administration–approved JAK inhibitor, baricitinib (Olumiant), is primarily metabolized by the kidneys and should not have significant interaction with CBD, Dr. Youngstein and associates said. Most of the conventional synthetic and biologic disease-modifying antirheumatic drugs, including methotrexate, hydroxychloroquine, adalimumab (Humira), and abatacept (Orencia), also are expected to be relatively free from CBD interactions.

This first published report on interactions between CBD oil and common rheumatology medications “highlights the importance of taking comprehensive drug histories, by asking directly about drugs considered alternative medicines and food supplements,” they said.

The investigators declared no conflicts of interest, and there was no specific funding for the study.

[email protected]

SOURCE: Wilson-Morkeh H et al. Rheumatology. 2019 July 29. doi: 10.1093/rheumatology/kez304.

A number of medications commonly prescribed by rheumatologists may interact with cannabidiol oil, investigators at the Imperial College Healthcare NHS Trust, London, reported.

“Patients are increasingly requesting information concerning the safety of CBD oil,” Taryn Youngstein, MD, and associates said in letter to the editor in Rheumatology, but current guidelines on the use of medical cannabis do “not address the potential interactions between CBD oil and medicines frequently used in the rheumatology clinic.”

The most important potential CBD interaction, they suggested, may be with corticosteroids. Hydrocortisone and prednisolone both inhibit the cytochrome P450 enzyme CYP3A, but CBD is a potent inhibitor of CYP3A, so “concomitant use may decrease glucocorticoid clearance and increase risk of systemic [corticosteroid] side effects,” the investigators wrote.

CBD also is known to inhibit the cytochrome P450 isozymes CYP2C9, CYP2D6, CYP2C19, CYP3A4, and CYP1A2, which, alone or in combination, are involved in the metabolization of naproxen, tramadol, amitriptyline, and tofacitinib (Xeljanz), according to a literature search done via the college’s medicine information department that also used the British National Formulary and the Natural Medicines online interaction checker.

The Janus kinase inhibitor tofacitinib is included among the possible interactions, but the other Food and Drug Administration–approved JAK inhibitor, baricitinib (Olumiant), is primarily metabolized by the kidneys and should not have significant interaction with CBD, Dr. Youngstein and associates said. Most of the conventional synthetic and biologic disease-modifying antirheumatic drugs, including methotrexate, hydroxychloroquine, adalimumab (Humira), and abatacept (Orencia), also are expected to be relatively free from CBD interactions.

This first published report on interactions between CBD oil and common rheumatology medications “highlights the importance of taking comprehensive drug histories, by asking directly about drugs considered alternative medicines and food supplements,” they said.

The investigators declared no conflicts of interest, and there was no specific funding for the study.

[email protected]

SOURCE: Wilson-Morkeh H et al. Rheumatology. 2019 July 29. doi: 10.1093/rheumatology/kez304.

A number of medications commonly prescribed by rheumatologists may interact with cannabidiol oil, investigators at the Imperial College Healthcare NHS Trust, London, reported.

“Patients are increasingly requesting information concerning the safety of CBD oil,” Taryn Youngstein, MD, and associates said in letter to the editor in Rheumatology, but current guidelines on the use of medical cannabis do “not address the potential interactions between CBD oil and medicines frequently used in the rheumatology clinic.”

The most important potential CBD interaction, they suggested, may be with corticosteroids. Hydrocortisone and prednisolone both inhibit the cytochrome P450 enzyme CYP3A, but CBD is a potent inhibitor of CYP3A, so “concomitant use may decrease glucocorticoid clearance and increase risk of systemic [corticosteroid] side effects,” the investigators wrote.

CBD also is known to inhibit the cytochrome P450 isozymes CYP2C9, CYP2D6, CYP2C19, CYP3A4, and CYP1A2, which, alone or in combination, are involved in the metabolization of naproxen, tramadol, amitriptyline, and tofacitinib (Xeljanz), according to a literature search done via the college’s medicine information department that also used the British National Formulary and the Natural Medicines online interaction checker.

The Janus kinase inhibitor tofacitinib is included among the possible interactions, but the other Food and Drug Administration–approved JAK inhibitor, baricitinib (Olumiant), is primarily metabolized by the kidneys and should not have significant interaction with CBD, Dr. Youngstein and associates said. Most of the conventional synthetic and biologic disease-modifying antirheumatic drugs, including methotrexate, hydroxychloroquine, adalimumab (Humira), and abatacept (Orencia), also are expected to be relatively free from CBD interactions.

This first published report on interactions between CBD oil and common rheumatology medications “highlights the importance of taking comprehensive drug histories, by asking directly about drugs considered alternative medicines and food supplements,” they said.

The investigators declared no conflicts of interest, and there was no specific funding for the study.

[email protected]

SOURCE: Wilson-Morkeh H et al. Rheumatology. 2019 July 29. doi: 10.1093/rheumatology/kez304.

The American College of Rheumatology, Spondylitis Association of America, and Spondyloarthritis Research and Treatment Network have updated their guidelines on management of ankylosing spondylitis and nonradiographic axial spondyloarthritis.

These guidelines serve as an update to the previous guidelines that were first published in 2015 (Arthritis Care Res. 2016;68:151–66). While the new guidelines did not review all recommendations from the 2015 guidelines, 20 questions on pharmacologic treatment were re-reviewed in addition to 26 new questions and recommendations.

Michael M. Ward, MD, chief of the Clinical Trials and Outcomes Branch at the National Institute of Arthritis and Musculoskeletal and Skin Diseases, said in an interview that the availability of new medications to treat axial spondyloarthritis (axSpA) prompted the updated guidelines.

“We took the opportunity to revisit some previous recommendations for which substantial new evidence was available, and also included new recommendations on some other topics, such as imaging,” said Dr. Ward, who is also first author of the new guidelines.

The panel that developed the questions focused on scenarios that a clinician would likely encounter in clinical practice, or situations in which how to manage a case is not clear. “Given this perspective, there were many questions that had limited evidence, but recommendations were made for all questions. For those questions that had less evidence in the literature, we relied more on the expertise of the panel,” Dr. Ward said.

The questions and recommendations for ankylosing spondylitis (AS) and nonradiographic axSpA centered around use of interleukin-17 (IL-17) inhibitors, tofacitinib (Xeljanz), and biosimilars of tumor necrosis factor-alpha inhibitors (TNFi), as well as when to taper and discontinue these medications.

Strong recommendations for patients with AS included using NSAIDs (low level of evidence), using TNFi when active disease remains despite NSAID treatment (high level of evidence), and using secukinumab (Cosentyx) or ixekizumab (Taltz) when active disease remains despite NSAID treatment over no treatment (high level of evidence). The guidelines also strongly recommend the use of physical therapy for adults with stable AS over no physical therapy (low level of evidence), as well as total hip arthroplasty in cases of advanced hip arthritis. The writing panel also strongly advised that adults with AS-related comorbidities should receive treatment by an ophthalmologist in cases of acute iritis. Strong recommendations were made against switching to a biosimilar of a TNFi after receiving treatment with an originator TNFi (regardless of whether it is for active or stable AS), use of systemic glucocorticoids in adults with active AS, treatment with spinal manipulation in patients with spinal fusion or advanced spinal osteoporosis, and screening for cardiac conduction defects and valvular heart disease with electrocardiograms.

Strong recommendations for nonradiographic axSpA were similar to those made for patients with AS, and the panel made strong recommendations for use of NSAIDs in patients with active disease; for TNFi treatment when NSAIDs fail; against switching to a biosimilar of a TNFi after starting the originator TNFi; against using systemic glucocorticoids; and in favor of using physical therapy rather than not.

The panel also made a number of conditional recommendations for AS and nonradiographic axSpA patients with regard to biologic preference and imaging. TNFis were conditionally recommended over secukinumab or ixekizumab in patients with active disease despite NSAIDs treatment, and in cases where a patient is not responding to a first TNFi treatment, the panel conditionally recommended secukinumab or ixekizumab over a second TNFi (very low evidence for all). Secukinumab or ixekizumab were also conditionally recommended over tofacitinib (very low evidence). Sulfasalazine, methotrexate, and tofacitinib were conditionally recommended in cases where patients had prominent peripheral arthritis or when TNFis are not available (very low to moderate evidence). The panel recommended against adding sulfasalazine or methotrexate to existing TNFi treatment (very low evidence), and they also advised against tapering as a standard treatment approach or discontinuing the biologic (very low evidence). MRI of the spine or pelvis was conditionally recommended to examine disease activity in unclear cases, but the panel recommended against ordering MRI scans to monitor disease inactivity (very low evidence).

“Most of the recommendations are conditional, primarily because of the relatively low level of evidence in the literature that addressed many of the questions,” while stronger recommendations came from larger clinical trials, Dr. Ward said. “The need for this update demonstrates the rapid progress in treatment that is occurring in axial spondyloarthritis, but the low level of evidence for many questions indicates that much more research is needed.”

Nine authors reported personal and institutional relationships in the form of consultancies, educational advisory board memberships, and site investigator appointments for AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, Galapagos, Janssen, Novartis, Pfizer, and UCB. The other authors reported no relevant conflicts of interest.

SOURCE: Ward MM et al. Arthritis Care Res. 2019 Aug 21. doi: 10.1002/acr.24025.

The American College of Rheumatology, Spondylitis Association of America, and Spondyloarthritis Research and Treatment Network have updated their guidelines on management of ankylosing spondylitis and nonradiographic axial spondyloarthritis.

These guidelines serve as an update to the previous guidelines that were first published in 2015 (Arthritis Care Res. 2016;68:151–66). While the new guidelines did not review all recommendations from the 2015 guidelines, 20 questions on pharmacologic treatment were re-reviewed in addition to 26 new questions and recommendations.

Michael M. Ward, MD, chief of the Clinical Trials and Outcomes Branch at the National Institute of Arthritis and Musculoskeletal and Skin Diseases, said in an interview that the availability of new medications to treat axial spondyloarthritis (axSpA) prompted the updated guidelines.

“We took the opportunity to revisit some previous recommendations for which substantial new evidence was available, and also included new recommendations on some other topics, such as imaging,” said Dr. Ward, who is also first author of the new guidelines.

The panel that developed the questions focused on scenarios that a clinician would likely encounter in clinical practice, or situations in which how to manage a case is not clear. “Given this perspective, there were many questions that had limited evidence, but recommendations were made for all questions. For those questions that had less evidence in the literature, we relied more on the expertise of the panel,” Dr. Ward said.

The questions and recommendations for ankylosing spondylitis (AS) and nonradiographic axSpA centered around use of interleukin-17 (IL-17) inhibitors, tofacitinib (Xeljanz), and biosimilars of tumor necrosis factor-alpha inhibitors (TNFi), as well as when to taper and discontinue these medications.

Strong recommendations for patients with AS included using NSAIDs (low level of evidence), using TNFi when active disease remains despite NSAID treatment (high level of evidence), and using secukinumab (Cosentyx) or ixekizumab (Taltz) when active disease remains despite NSAID treatment over no treatment (high level of evidence). The guidelines also strongly recommend the use of physical therapy for adults with stable AS over no physical therapy (low level of evidence), as well as total hip arthroplasty in cases of advanced hip arthritis. The writing panel also strongly advised that adults with AS-related comorbidities should receive treatment by an ophthalmologist in cases of acute iritis. Strong recommendations were made against switching to a biosimilar of a TNFi after receiving treatment with an originator TNFi (regardless of whether it is for active or stable AS), use of systemic glucocorticoids in adults with active AS, treatment with spinal manipulation in patients with spinal fusion or advanced spinal osteoporosis, and screening for cardiac conduction defects and valvular heart disease with electrocardiograms.

Strong recommendations for nonradiographic axSpA were similar to those made for patients with AS, and the panel made strong recommendations for use of NSAIDs in patients with active disease; for TNFi treatment when NSAIDs fail; against switching to a biosimilar of a TNFi after starting the originator TNFi; against using systemic glucocorticoids; and in favor of using physical therapy rather than not.

The panel also made a number of conditional recommendations for AS and nonradiographic axSpA patients with regard to biologic preference and imaging. TNFis were conditionally recommended over secukinumab or ixekizumab in patients with active disease despite NSAIDs treatment, and in cases where a patient is not responding to a first TNFi treatment, the panel conditionally recommended secukinumab or ixekizumab over a second TNFi (very low evidence for all). Secukinumab or ixekizumab were also conditionally recommended over tofacitinib (very low evidence). Sulfasalazine, methotrexate, and tofacitinib were conditionally recommended in cases where patients had prominent peripheral arthritis or when TNFis are not available (very low to moderate evidence). The panel recommended against adding sulfasalazine or methotrexate to existing TNFi treatment (very low evidence), and they also advised against tapering as a standard treatment approach or discontinuing the biologic (very low evidence). MRI of the spine or pelvis was conditionally recommended to examine disease activity in unclear cases, but the panel recommended against ordering MRI scans to monitor disease inactivity (very low evidence).

“Most of the recommendations are conditional, primarily because of the relatively low level of evidence in the literature that addressed many of the questions,” while stronger recommendations came from larger clinical trials, Dr. Ward said. “The need for this update demonstrates the rapid progress in treatment that is occurring in axial spondyloarthritis, but the low level of evidence for many questions indicates that much more research is needed.”

Nine authors reported personal and institutional relationships in the form of consultancies, educational advisory board memberships, and site investigator appointments for AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, Galapagos, Janssen, Novartis, Pfizer, and UCB. The other authors reported no relevant conflicts of interest.

SOURCE: Ward MM et al. Arthritis Care Res. 2019 Aug 21. doi: 10.1002/acr.24025.

The American College of Rheumatology, Spondylitis Association of America, and Spondyloarthritis Research and Treatment Network have updated their guidelines on management of ankylosing spondylitis and nonradiographic axial spondyloarthritis.

These guidelines serve as an update to the previous guidelines that were first published in 2015 (Arthritis Care Res. 2016;68:151–66). While the new guidelines did not review all recommendations from the 2015 guidelines, 20 questions on pharmacologic treatment were re-reviewed in addition to 26 new questions and recommendations.

Michael M. Ward, MD, chief of the Clinical Trials and Outcomes Branch at the National Institute of Arthritis and Musculoskeletal and Skin Diseases, said in an interview that the availability of new medications to treat axial spondyloarthritis (axSpA) prompted the updated guidelines.

“We took the opportunity to revisit some previous recommendations for which substantial new evidence was available, and also included new recommendations on some other topics, such as imaging,” said Dr. Ward, who is also first author of the new guidelines.

The panel that developed the questions focused on scenarios that a clinician would likely encounter in clinical practice, or situations in which how to manage a case is not clear. “Given this perspective, there were many questions that had limited evidence, but recommendations were made for all questions. For those questions that had less evidence in the literature, we relied more on the expertise of the panel,” Dr. Ward said.

The questions and recommendations for ankylosing spondylitis (AS) and nonradiographic axSpA centered around use of interleukin-17 (IL-17) inhibitors, tofacitinib (Xeljanz), and biosimilars of tumor necrosis factor-alpha inhibitors (TNFi), as well as when to taper and discontinue these medications.

Strong recommendations for patients with AS included using NSAIDs (low level of evidence), using TNFi when active disease remains despite NSAID treatment (high level of evidence), and using secukinumab (Cosentyx) or ixekizumab (Taltz) when active disease remains despite NSAID treatment over no treatment (high level of evidence). The guidelines also strongly recommend the use of physical therapy for adults with stable AS over no physical therapy (low level of evidence), as well as total hip arthroplasty in cases of advanced hip arthritis. The writing panel also strongly advised that adults with AS-related comorbidities should receive treatment by an ophthalmologist in cases of acute iritis. Strong recommendations were made against switching to a biosimilar of a TNFi after receiving treatment with an originator TNFi (regardless of whether it is for active or stable AS), use of systemic glucocorticoids in adults with active AS, treatment with spinal manipulation in patients with spinal fusion or advanced spinal osteoporosis, and screening for cardiac conduction defects and valvular heart disease with electrocardiograms.

Strong recommendations for nonradiographic axSpA were similar to those made for patients with AS, and the panel made strong recommendations for use of NSAIDs in patients with active disease; for TNFi treatment when NSAIDs fail; against switching to a biosimilar of a TNFi after starting the originator TNFi; against using systemic glucocorticoids; and in favor of using physical therapy rather than not.

The panel also made a number of conditional recommendations for AS and nonradiographic axSpA patients with regard to biologic preference and imaging. TNFis were conditionally recommended over secukinumab or ixekizumab in patients with active disease despite NSAIDs treatment, and in cases where a patient is not responding to a first TNFi treatment, the panel conditionally recommended secukinumab or ixekizumab over a second TNFi (very low evidence for all). Secukinumab or ixekizumab were also conditionally recommended over tofacitinib (very low evidence). Sulfasalazine, methotrexate, and tofacitinib were conditionally recommended in cases where patients had prominent peripheral arthritis or when TNFis are not available (very low to moderate evidence). The panel recommended against adding sulfasalazine or methotrexate to existing TNFi treatment (very low evidence), and they also advised against tapering as a standard treatment approach or discontinuing the biologic (very low evidence). MRI of the spine or pelvis was conditionally recommended to examine disease activity in unclear cases, but the panel recommended against ordering MRI scans to monitor disease inactivity (very low evidence).

“Most of the recommendations are conditional, primarily because of the relatively low level of evidence in the literature that addressed many of the questions,” while stronger recommendations came from larger clinical trials, Dr. Ward said. “The need for this update demonstrates the rapid progress in treatment that is occurring in axial spondyloarthritis, but the low level of evidence for many questions indicates that much more research is needed.”

Nine authors reported personal and institutional relationships in the form of consultancies, educational advisory board memberships, and site investigator appointments for AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, Galapagos, Janssen, Novartis, Pfizer, and UCB. The other authors reported no relevant conflicts of interest.

SOURCE: Ward MM et al. Arthritis Care Res. 2019 Aug 21. doi: 10.1002/acr.24025.

The Food and Drug Administration has approved a subcutaneous injection formulation of ixekizumab (Taltz) at 80 mg/mL for the treatment of adult patients with active ankylosing spondylitis (AS), according to a press release from Eli Lilly.

Olivier Le Moal/Getty Images

AS is the third indication for ixekizumab, along with moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and active psoriatic arthritis in adults.

Approval of the humanized interleukin-17A antagonist was based on results from a pair of randomized, double-blind, placebo-controlled, phase 3 studies involving 657 adult patients with active AS: the COAST-V trial in those naive to biologic disease-modifying antirheumatic drugs (bDMARDs) and the COAST-W trial in those who were intolerant or had inadequate response to tumor necrosis factor (TNF) inhibitors. The primary endpoint in both trials was achievement of 40% improvement in Assessment of Spondyloarthritis International Society criteria (ASAS40) at 16 weeks, compared with placebo.

In COAST-V, 48% of patients who received ixekizumab achieved ASAS40, compared with 18% of controls (P less than .0001). In COAST-W, 25% of patients who received ixekizumab achieved ASAS40 versus 13% of controls (P less than .05). The adverse events reported during both trials were consistent with the safety profile in patients who receive ixekizumab for the treatment of plaque psoriasis, including injection-site reactions, upper respiratory tract infections, nausea, and tinea infections.

“Results from the phase 3 clinical trial program in ankylosing spondylitis show that Taltz helped reduce pain and inflammation and improve function in patients who had never been treated with a bDMARD as well as those who previously failed TNF inhibitors. This approval is an important milestone for patients and physicians who are looking for a much-needed alternative to address symptoms of AS,” said Philip Mease, MD, of Providence St. Joseph Health and the University of Washington, both in Seattle.

[email protected]

The Food and Drug Administration has approved a subcutaneous injection formulation of ixekizumab (Taltz) at 80 mg/mL for the treatment of adult patients with active ankylosing spondylitis (AS), according to a press release from Eli Lilly.

Olivier Le Moal/Getty Images

AS is the third indication for ixekizumab, along with moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and active psoriatic arthritis in adults.

Approval of the humanized interleukin-17A antagonist was based on results from a pair of randomized, double-blind, placebo-controlled, phase 3 studies involving 657 adult patients with active AS: the COAST-V trial in those naive to biologic disease-modifying antirheumatic drugs (bDMARDs) and the COAST-W trial in those who were intolerant or had inadequate response to tumor necrosis factor (TNF) inhibitors. The primary endpoint in both trials was achievement of 40% improvement in Assessment of Spondyloarthritis International Society criteria (ASAS40) at 16 weeks, compared with placebo.

In COAST-V, 48% of patients who received ixekizumab achieved ASAS40, compared with 18% of controls (P less than .0001). In COAST-W, 25% of patients who received ixekizumab achieved ASAS40 versus 13% of controls (P less than .05). The adverse events reported during both trials were consistent with the safety profile in patients who receive ixekizumab for the treatment of plaque psoriasis, including injection-site reactions, upper respiratory tract infections, nausea, and tinea infections.

“Results from the phase 3 clinical trial program in ankylosing spondylitis show that Taltz helped reduce pain and inflammation and improve function in patients who had never been treated with a bDMARD as well as those who previously failed TNF inhibitors. This approval is an important milestone for patients and physicians who are looking for a much-needed alternative to address symptoms of AS,” said Philip Mease, MD, of Providence St. Joseph Health and the University of Washington, both in Seattle.

[email protected]

The Food and Drug Administration has approved a subcutaneous injection formulation of ixekizumab (Taltz) at 80 mg/mL for the treatment of adult patients with active ankylosing spondylitis (AS), according to a press release from Eli Lilly.

Olivier Le Moal/Getty Images

AS is the third indication for ixekizumab, along with moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and active psoriatic arthritis in adults.

Approval of the humanized interleukin-17A antagonist was based on results from a pair of randomized, double-blind, placebo-controlled, phase 3 studies involving 657 adult patients with active AS: the COAST-V trial in those naive to biologic disease-modifying antirheumatic drugs (bDMARDs) and the COAST-W trial in those who were intolerant or had inadequate response to tumor necrosis factor (TNF) inhibitors. The primary endpoint in both trials was achievement of 40% improvement in Assessment of Spondyloarthritis International Society criteria (ASAS40) at 16 weeks, compared with placebo.

In COAST-V, 48% of patients who received ixekizumab achieved ASAS40, compared with 18% of controls (P less than .0001). In COAST-W, 25% of patients who received ixekizumab achieved ASAS40 versus 13% of controls (P less than .05). The adverse events reported during both trials were consistent with the safety profile in patients who receive ixekizumab for the treatment of plaque psoriasis, including injection-site reactions, upper respiratory tract infections, nausea, and tinea infections.

“Results from the phase 3 clinical trial program in ankylosing spondylitis show that Taltz helped reduce pain and inflammation and improve function in patients who had never been treated with a bDMARD as well as those who previously failed TNF inhibitors. This approval is an important milestone for patients and physicians who are looking for a much-needed alternative to address symptoms of AS,” said Philip Mease, MD, of Providence St. Joseph Health and the University of Washington, both in Seattle.

[email protected]