Nicola Garrett

Switching to rituximab may be more efficacious than switching anti–tumor necrosis factor agents in patients with moderate to severe rheumatoid arthritis and prior exposure to anti-TNF agents, data from the observational Corrona registry show.

In an adjusted analyses of two drug exposure cohorts categorized using propensity scores, patients treated with rituximab were 35%-50% more likely to achieve low disease activity or remission (primary outcome) than were those treated with a subsequent anti-TNF agent, reported Dr. Leslie Harrold of the University of Massachusetts, Worcester, and associates. However, this finding was not statistically significant in patients who fell outside the area of common support (trimmed population), the authors noted (Arthritis Res Ther. 2015;17:256).

Patients treated with rituximab also were more likely to achieve the study’s secondary outcomes of modified American College of Rheumatology (mACR) 20 and mACR 50 responses (trimmed population only) and demonstrate clinically meaningful improvement in modified Health Assessment Questionnaire scores than were those treated with a subsequent anti-TNF.

Overall, 265 rituximab users and 737 patients on anti-TNF agents were included in the analysis. Approximately 16.2% of rituximab users and 29.4% of users of anti-TNF agents switched to another biologic during the study period.

An analysis of safety events over the 12-month study showed the rate of new adverse events per 100 patient years was similar between groups.

The results of the study reinforce important observations from European studies that switching to rituximab is superior to receiving another anti-TNF agent and expand upon the findings with a rigorous evaluation of the comparative safety of these two drug classes, the study authors said. “This is important because patients and the rheumatologists treating them need a comprehensive evaluation of the benefit-risk profiles of different biologic agents to optimize decision making,” they wrote.

“Taken together, these results suggest that in a clinical practice, rituximab may be more efficacious than a subsequent anti-TNF agent in patients with moderately active to severely active RA and prior exposure to anti-TNF agents,” they concluded.

Corrona LLC sponsored the study. The Corrona registry has been supported by several pharmaceutical companies. Two authors are employees of Genentech.

Switching to rituximab may be more efficacious than switching anti–tumor necrosis factor agents in patients with moderate to severe rheumatoid arthritis and prior exposure to anti-TNF agents, data from the observational Corrona registry show.

In an adjusted analyses of two drug exposure cohorts categorized using propensity scores, patients treated with rituximab were 35%-50% more likely to achieve low disease activity or remission (primary outcome) than were those treated with a subsequent anti-TNF agent, reported Dr. Leslie Harrold of the University of Massachusetts, Worcester, and associates. However, this finding was not statistically significant in patients who fell outside the area of common support (trimmed population), the authors noted (Arthritis Res Ther. 2015;17:256).

Patients treated with rituximab also were more likely to achieve the study’s secondary outcomes of modified American College of Rheumatology (mACR) 20 and mACR 50 responses (trimmed population only) and demonstrate clinically meaningful improvement in modified Health Assessment Questionnaire scores than were those treated with a subsequent anti-TNF.

Overall, 265 rituximab users and 737 patients on anti-TNF agents were included in the analysis. Approximately 16.2% of rituximab users and 29.4% of users of anti-TNF agents switched to another biologic during the study period.

An analysis of safety events over the 12-month study showed the rate of new adverse events per 100 patient years was similar between groups.

The results of the study reinforce important observations from European studies that switching to rituximab is superior to receiving another anti-TNF agent and expand upon the findings with a rigorous evaluation of the comparative safety of these two drug classes, the study authors said. “This is important because patients and the rheumatologists treating them need a comprehensive evaluation of the benefit-risk profiles of different biologic agents to optimize decision making,” they wrote.

“Taken together, these results suggest that in a clinical practice, rituximab may be more efficacious than a subsequent anti-TNF agent in patients with moderately active to severely active RA and prior exposure to anti-TNF agents,” they concluded.

Corrona LLC sponsored the study. The Corrona registry has been supported by several pharmaceutical companies. Two authors are employees of Genentech.

Switching to rituximab may be more efficacious than switching anti–tumor necrosis factor agents in patients with moderate to severe rheumatoid arthritis and prior exposure to anti-TNF agents, data from the observational Corrona registry show.

In an adjusted analyses of two drug exposure cohorts categorized using propensity scores, patients treated with rituximab were 35%-50% more likely to achieve low disease activity or remission (primary outcome) than were those treated with a subsequent anti-TNF agent, reported Dr. Leslie Harrold of the University of Massachusetts, Worcester, and associates. However, this finding was not statistically significant in patients who fell outside the area of common support (trimmed population), the authors noted (Arthritis Res Ther. 2015;17:256).

Patients treated with rituximab also were more likely to achieve the study’s secondary outcomes of modified American College of Rheumatology (mACR) 20 and mACR 50 responses (trimmed population only) and demonstrate clinically meaningful improvement in modified Health Assessment Questionnaire scores than were those treated with a subsequent anti-TNF.

Overall, 265 rituximab users and 737 patients on anti-TNF agents were included in the analysis. Approximately 16.2% of rituximab users and 29.4% of users of anti-TNF agents switched to another biologic during the study period.

An analysis of safety events over the 12-month study showed the rate of new adverse events per 100 patient years was similar between groups.

The results of the study reinforce important observations from European studies that switching to rituximab is superior to receiving another anti-TNF agent and expand upon the findings with a rigorous evaluation of the comparative safety of these two drug classes, the study authors said. “This is important because patients and the rheumatologists treating them need a comprehensive evaluation of the benefit-risk profiles of different biologic agents to optimize decision making,” they wrote.

“Taken together, these results suggest that in a clinical practice, rituximab may be more efficacious than a subsequent anti-TNF agent in patients with moderately active to severely active RA and prior exposure to anti-TNF agents,” they concluded.

Corrona LLC sponsored the study. The Corrona registry has been supported by several pharmaceutical companies. Two authors are employees of Genentech.

Three months marks a critical time point that determines whether a rheumatoid arthritis patient will reach a treatment target at 6 months, according to results of a study published in Annals of the Rheumatic Diseases.

Dr. Daniel Aletaha of the Medical University of Vienna and his associates performed a pooled analysis of clinical data from RA trials in the last decade. They found that, regardless of the starting point, 6-month success rates were clearly related to disease activity state reached at 3 months, and not so much to the number of disease activity categories improved.

©Suze777/Thinkstock.com

The results show that a response at 3 months can be used as a decision criterion in two clinical situations. Failure to achieve minor responses (for example, ACR 20, Simplified Disease Activity Index [SDAI] 50) at the 3-month mark had the potential to almost rule out successfully reaching the target at 6 months, the investigators wrote (Ann Rheum Dis. 2015. doi: 10.1136/annrheumdis-2015-208324).

Conversely, achievement of major response definitions at 3 months (for example, ACR 70, SDAI 85%) can reliably predict achievement of a good state at 6 months.

“It is also obvious therefore that for many patients in the gray zone between these response levels, the prediction may be less solid, and may – to a greater extent – rest on the physician’s decision,” they wrote.

The findings were in line with updated treat-to-target (T2T) recommendations that suggest a goal of significant improvement at 3 months and attainment of the treatment target at 6 months, they added.

The study results showed that in order to be at least 80% sensitive for achieving the low disease activity target at 6 months, a change of 58% in SDAI/Clinical Disease Activity Index needed to be observed at 3 months.

Patients who did not achieve the (minor) SDAI 50% response level had very low negative likelihood ratios of 0.28 for low disease activity and 0.07 for remission at 6 months. Patients who achieved the (major) SDAI 85% response had substantial positive likelihood ratios of 9.2 for reaching low disease activity and 6.2 for reaching remission at 6 months.

In logistic regression, the change at 3 months was significantly associated with reaching the target at 6 months.

Dr. Aletaha and one of his associates received consulting and/or speaking honoraria from AbbVie; Merck, Sharp & Dohme; Pfizer; and Roche.

Three months marks a critical time point that determines whether a rheumatoid arthritis patient will reach a treatment target at 6 months, according to results of a study published in Annals of the Rheumatic Diseases.

Dr. Daniel Aletaha of the Medical University of Vienna and his associates performed a pooled analysis of clinical data from RA trials in the last decade. They found that, regardless of the starting point, 6-month success rates were clearly related to disease activity state reached at 3 months, and not so much to the number of disease activity categories improved.

©Suze777/Thinkstock.com

The results show that a response at 3 months can be used as a decision criterion in two clinical situations. Failure to achieve minor responses (for example, ACR 20, Simplified Disease Activity Index [SDAI] 50) at the 3-month mark had the potential to almost rule out successfully reaching the target at 6 months, the investigators wrote (Ann Rheum Dis. 2015. doi: 10.1136/annrheumdis-2015-208324).

Conversely, achievement of major response definitions at 3 months (for example, ACR 70, SDAI 85%) can reliably predict achievement of a good state at 6 months.

“It is also obvious therefore that for many patients in the gray zone between these response levels, the prediction may be less solid, and may – to a greater extent – rest on the physician’s decision,” they wrote.

The findings were in line with updated treat-to-target (T2T) recommendations that suggest a goal of significant improvement at 3 months and attainment of the treatment target at 6 months, they added.

The study results showed that in order to be at least 80% sensitive for achieving the low disease activity target at 6 months, a change of 58% in SDAI/Clinical Disease Activity Index needed to be observed at 3 months.

Patients who did not achieve the (minor) SDAI 50% response level had very low negative likelihood ratios of 0.28 for low disease activity and 0.07 for remission at 6 months. Patients who achieved the (major) SDAI 85% response had substantial positive likelihood ratios of 9.2 for reaching low disease activity and 6.2 for reaching remission at 6 months.

In logistic regression, the change at 3 months was significantly associated with reaching the target at 6 months.

Dr. Aletaha and one of his associates received consulting and/or speaking honoraria from AbbVie; Merck, Sharp & Dohme; Pfizer; and Roche.

Three months marks a critical time point that determines whether a rheumatoid arthritis patient will reach a treatment target at 6 months, according to results of a study published in Annals of the Rheumatic Diseases.

Dr. Daniel Aletaha of the Medical University of Vienna and his associates performed a pooled analysis of clinical data from RA trials in the last decade. They found that, regardless of the starting point, 6-month success rates were clearly related to disease activity state reached at 3 months, and not so much to the number of disease activity categories improved.

©Suze777/Thinkstock.com

The results show that a response at 3 months can be used as a decision criterion in two clinical situations. Failure to achieve minor responses (for example, ACR 20, Simplified Disease Activity Index [SDAI] 50) at the 3-month mark had the potential to almost rule out successfully reaching the target at 6 months, the investigators wrote (Ann Rheum Dis. 2015. doi: 10.1136/annrheumdis-2015-208324).

Conversely, achievement of major response definitions at 3 months (for example, ACR 70, SDAI 85%) can reliably predict achievement of a good state at 6 months.

“It is also obvious therefore that for many patients in the gray zone between these response levels, the prediction may be less solid, and may – to a greater extent – rest on the physician’s decision,” they wrote.

The findings were in line with updated treat-to-target (T2T) recommendations that suggest a goal of significant improvement at 3 months and attainment of the treatment target at 6 months, they added.

The study results showed that in order to be at least 80% sensitive for achieving the low disease activity target at 6 months, a change of 58% in SDAI/Clinical Disease Activity Index needed to be observed at 3 months.

Patients who did not achieve the (minor) SDAI 50% response level had very low negative likelihood ratios of 0.28 for low disease activity and 0.07 for remission at 6 months. Patients who achieved the (major) SDAI 85% response had substantial positive likelihood ratios of 9.2 for reaching low disease activity and 6.2 for reaching remission at 6 months.

In logistic regression, the change at 3 months was significantly associated with reaching the target at 6 months.

Dr. Aletaha and one of his associates received consulting and/or speaking honoraria from AbbVie; Merck, Sharp & Dohme; Pfizer; and Roche.

The power of the central sensitization analogy – the idea that pain is best thought about as a stereo with the volume turned up – has led to the science of fibromyalgia becoming “lost in translation,” according to Dr. Brian Walitt.

This problem has appeared because the priorities of basic scientists and those of translational scientists are different, Dr. Walitt said at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

©Zerbor/thinkstockphotos.com

“For a basic scientist, anything that’s real is interesting because who knows what you may find, but a translational scientist is trying to help people,” he explained. “A lot of the time, things that we’re trying to find in basic science are up-translated into being meaningful when they may not be,” and then used to fit an analogy that is probably not true, said Dr. Walitt, director of clinical pain research at the National Center for Complementary and Integrative Health, Bethesda, Md.

Proponents of the popular central sensitization analogy have put forward five types of evidence – psychophysical, neuroimaging, genetic, neurotransmitters, and treatments – to support their view, but Dr. Walitt said that the evidence is weak, doesn’t prove anything, or seem legitimate. For instance, none of the treatments for fibromyalgia are particularly effective, at best giving a minimally clinically important difference that does not change patient outcomes.

Another issue with the analogy is that it is not possible to disprove the hypothesis. Any central nervous system measurements that correlate with differences in subjective pain reports can be presented as “mounting evidence” but not definite proof, he said. If the idea was changed from amplification of pain signals to distortion, the same data could be used to prove that, too. “Distortion is also bogus. It’s just another idea, another way of talking about it that shows that whatever you pick you can find ways to make a story that fits all the data,” Dr. Walitt said. However, analogies can be powerful, particularly if they wash away the complexity and difficulty in understanding neuroscience.

“But the truth of the matter, at least to me, is there is no analogy for pain and any analogy that we use is going to fall flat,” he said. “When we try to fit science to an idea or a story it can mislead us. Sometimes we’re better off letting the science speak for itself than try to make it fit a particular story.”

Dr. Walitt, however, acknowledged a caveat – that fibromyalgia is a very hard problem and that, even if we hadn’t been chasing analogies we may still not be better off. “If we don’t understand why we feel things to begin with, it means we may be further away than we think,” he said.

Dr. Walitt said he has no financial conflicts of interest to report. Global Academy for Medical Education and this news organization are owned by the same parent company.

The power of the central sensitization analogy – the idea that pain is best thought about as a stereo with the volume turned up – has led to the science of fibromyalgia becoming “lost in translation,” according to Dr. Brian Walitt.

This problem has appeared because the priorities of basic scientists and those of translational scientists are different, Dr. Walitt said at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

©Zerbor/thinkstockphotos.com

“For a basic scientist, anything that’s real is interesting because who knows what you may find, but a translational scientist is trying to help people,” he explained. “A lot of the time, things that we’re trying to find in basic science are up-translated into being meaningful when they may not be,” and then used to fit an analogy that is probably not true, said Dr. Walitt, director of clinical pain research at the National Center for Complementary and Integrative Health, Bethesda, Md.

Proponents of the popular central sensitization analogy have put forward five types of evidence – psychophysical, neuroimaging, genetic, neurotransmitters, and treatments – to support their view, but Dr. Walitt said that the evidence is weak, doesn’t prove anything, or seem legitimate. For instance, none of the treatments for fibromyalgia are particularly effective, at best giving a minimally clinically important difference that does not change patient outcomes.

Another issue with the analogy is that it is not possible to disprove the hypothesis. Any central nervous system measurements that correlate with differences in subjective pain reports can be presented as “mounting evidence” but not definite proof, he said. If the idea was changed from amplification of pain signals to distortion, the same data could be used to prove that, too. “Distortion is also bogus. It’s just another idea, another way of talking about it that shows that whatever you pick you can find ways to make a story that fits all the data,” Dr. Walitt said. However, analogies can be powerful, particularly if they wash away the complexity and difficulty in understanding neuroscience.

“But the truth of the matter, at least to me, is there is no analogy for pain and any analogy that we use is going to fall flat,” he said. “When we try to fit science to an idea or a story it can mislead us. Sometimes we’re better off letting the science speak for itself than try to make it fit a particular story.”

Dr. Walitt, however, acknowledged a caveat – that fibromyalgia is a very hard problem and that, even if we hadn’t been chasing analogies we may still not be better off. “If we don’t understand why we feel things to begin with, it means we may be further away than we think,” he said.

Dr. Walitt said he has no financial conflicts of interest to report. Global Academy for Medical Education and this news organization are owned by the same parent company.

The power of the central sensitization analogy – the idea that pain is best thought about as a stereo with the volume turned up – has led to the science of fibromyalgia becoming “lost in translation,” according to Dr. Brian Walitt.

This problem has appeared because the priorities of basic scientists and those of translational scientists are different, Dr. Walitt said at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

©Zerbor/thinkstockphotos.com

“For a basic scientist, anything that’s real is interesting because who knows what you may find, but a translational scientist is trying to help people,” he explained. “A lot of the time, things that we’re trying to find in basic science are up-translated into being meaningful when they may not be,” and then used to fit an analogy that is probably not true, said Dr. Walitt, director of clinical pain research at the National Center for Complementary and Integrative Health, Bethesda, Md.

Proponents of the popular central sensitization analogy have put forward five types of evidence – psychophysical, neuroimaging, genetic, neurotransmitters, and treatments – to support their view, but Dr. Walitt said that the evidence is weak, doesn’t prove anything, or seem legitimate. For instance, none of the treatments for fibromyalgia are particularly effective, at best giving a minimally clinically important difference that does not change patient outcomes.

Another issue with the analogy is that it is not possible to disprove the hypothesis. Any central nervous system measurements that correlate with differences in subjective pain reports can be presented as “mounting evidence” but not definite proof, he said. If the idea was changed from amplification of pain signals to distortion, the same data could be used to prove that, too. “Distortion is also bogus. It’s just another idea, another way of talking about it that shows that whatever you pick you can find ways to make a story that fits all the data,” Dr. Walitt said. However, analogies can be powerful, particularly if they wash away the complexity and difficulty in understanding neuroscience.

“But the truth of the matter, at least to me, is there is no analogy for pain and any analogy that we use is going to fall flat,” he said. “When we try to fit science to an idea or a story it can mislead us. Sometimes we’re better off letting the science speak for itself than try to make it fit a particular story.”

Dr. Walitt, however, acknowledged a caveat – that fibromyalgia is a very hard problem and that, even if we hadn’t been chasing analogies we may still not be better off. “If we don’t understand why we feel things to begin with, it means we may be further away than we think,” he said.

Dr. Walitt said he has no financial conflicts of interest to report. Global Academy for Medical Education and this news organization are owned by the same parent company.

The power of the central sensitization analogy – the idea that pain is best thought about as a stereo with the volume turned up – has led to the science of fibromyalgia becoming “lost in translation,” according to Dr. Brian Walitt.

This problem has appeared because the priorities of basic scientists and those of translational scientists are different, Dr. Walitt said at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

©Zerbor/thinkstockphotos.com

“For a basic scientist, anything that’s real is interesting because who knows what you may find, but a translational scientist is trying to help people,” he explained. “A lot of the time, things that we’re trying to find in basic science are up-translated into being meaningful when they may not be,” and then used to fit an analogy that is probably not true, said Dr. Walitt, director of clinical pain research at the National Center for Complementary and Integrative Health, Bethesda, Md.

Proponents of the popular central sensitization analogy have put forward five types of evidence – psychophysical, neuroimaging, genetic, neurotransmitters, and treatments – to support their view, but Dr. Walitt said that the evidence is weak, doesn’t prove anything, or seem legitimate. For instance, none of the treatments for fibromyalgia are particularly effective, at best giving a minimally clinically important difference that does not change patient outcomes.

Another issue with the analogy is that it is not possible to disprove the hypothesis. Any central nervous system measurements that correlate with differences in subjective pain reports can be presented as “mounting evidence” but not definite proof, he said. If the idea was changed from amplification of pain signals to distortion, the same data could be used to prove that, too. “Distortion is also bogus. It’s just another idea, another way of talking about it that shows that whatever you pick you can find ways to make a story that fits all the data,” Dr. Walitt said. However, analogies can be powerful, particularly if they wash away the complexity and difficulty in understanding neuroscience.

“But the truth of the matter, at least to me, is there is no analogy for pain and any analogy that we use is going to fall flat,” he said. “When we try to fit science to an idea or a story it can mislead us. Sometimes we’re better off letting the science speak for itself than try to make it fit a particular story.”

Dr. Walitt, however, acknowledged a caveat – that fibromyalgia is a very hard problem and that, even if we hadn’t been chasing analogies we may still not be better off. “If we don’t understand why we feel things to begin with, it means we may be further away than we think,” he said.

Dr. Walitt said he has no financial conflicts of interest to report. Global Academy for Medical Education and this news organization are owned by the same parent company.

The power of the central sensitization analogy – the idea that pain is best thought about as a stereo with the volume turned up – has led to the science of fibromyalgia becoming “lost in translation,” according to Dr. Brian Walitt.

This problem has appeared because the priorities of basic scientists and those of translational scientists are different, Dr. Walitt said at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

©Zerbor/thinkstockphotos.com

“For a basic scientist, anything that’s real is interesting because who knows what you may find, but a translational scientist is trying to help people,” he explained. “A lot of the time, things that we’re trying to find in basic science are up-translated into being meaningful when they may not be,” and then used to fit an analogy that is probably not true, said Dr. Walitt, director of clinical pain research at the National Center for Complementary and Integrative Health, Bethesda, Md.

Proponents of the popular central sensitization analogy have put forward five types of evidence – psychophysical, neuroimaging, genetic, neurotransmitters, and treatments – to support their view, but Dr. Walitt said that the evidence is weak, doesn’t prove anything, or seem legitimate. For instance, none of the treatments for fibromyalgia are particularly effective, at best giving a minimally clinically important difference that does not change patient outcomes.

Another issue with the analogy is that it is not possible to disprove the hypothesis. Any central nervous system measurements that correlate with differences in subjective pain reports can be presented as “mounting evidence” but not definite proof, he said. If the idea was changed from amplification of pain signals to distortion, the same data could be used to prove that, too. “Distortion is also bogus. It’s just another idea, another way of talking about it that shows that whatever you pick you can find ways to make a story that fits all the data,” Dr. Walitt said. However, analogies can be powerful, particularly if they wash away the complexity and difficulty in understanding neuroscience.

“But the truth of the matter, at least to me, is there is no analogy for pain and any analogy that we use is going to fall flat,” he said. “When we try to fit science to an idea or a story it can mislead us. Sometimes we’re better off letting the science speak for itself than try to make it fit a particular story.”

Dr. Walitt, however, acknowledged a caveat – that fibromyalgia is a very hard problem and that, even if we hadn’t been chasing analogies we may still not be better off. “If we don’t understand why we feel things to begin with, it means we may be further away than we think,” he said.

Dr. Walitt said he has no financial conflicts of interest to report. Global Academy for Medical Education and this news organization are owned by the same parent company.

The power of the central sensitization analogy – the idea that pain is best thought about as a stereo with the volume turned up – has led to the science of fibromyalgia becoming “lost in translation,” according to Dr. Brian Walitt.

This problem has appeared because the priorities of basic scientists and those of translational scientists are different, Dr. Walitt said at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

©Zerbor/thinkstockphotos.com

“For a basic scientist, anything that’s real is interesting because who knows what you may find, but a translational scientist is trying to help people,” he explained. “A lot of the time, things that we’re trying to find in basic science are up-translated into being meaningful when they may not be,” and then used to fit an analogy that is probably not true, said Dr. Walitt, director of clinical pain research at the National Center for Complementary and Integrative Health, Bethesda, Md.

Proponents of the popular central sensitization analogy have put forward five types of evidence – psychophysical, neuroimaging, genetic, neurotransmitters, and treatments – to support their view, but Dr. Walitt said that the evidence is weak, doesn’t prove anything, or seem legitimate. For instance, none of the treatments for fibromyalgia are particularly effective, at best giving a minimally clinically important difference that does not change patient outcomes.

Another issue with the analogy is that it is not possible to disprove the hypothesis. Any central nervous system measurements that correlate with differences in subjective pain reports can be presented as “mounting evidence” but not definite proof, he said. If the idea was changed from amplification of pain signals to distortion, the same data could be used to prove that, too. “Distortion is also bogus. It’s just another idea, another way of talking about it that shows that whatever you pick you can find ways to make a story that fits all the data,” Dr. Walitt said. However, analogies can be powerful, particularly if they wash away the complexity and difficulty in understanding neuroscience.

“But the truth of the matter, at least to me, is there is no analogy for pain and any analogy that we use is going to fall flat,” he said. “When we try to fit science to an idea or a story it can mislead us. Sometimes we’re better off letting the science speak for itself than try to make it fit a particular story.”

Dr. Walitt, however, acknowledged a caveat – that fibromyalgia is a very hard problem and that, even if we hadn’t been chasing analogies we may still not be better off. “If we don’t understand why we feel things to begin with, it means we may be further away than we think,” he said.

Dr. Walitt said he has no financial conflicts of interest to report. Global Academy for Medical Education and this news organization are owned by the same parent company.

Rheumatologists’ understanding of the spectrum of spondyloarthritis is undergoing an evolution that has revealed an underrecognition of the disease, particularly in women, but regulatory recognition of the spectrum of disease in the United States has yet to catch up with reality, according to Dr. Philip Mease.

More sophisticated imaging and laboratory techniques has meant that spondyloarthritis (SpA) is being discovered in up to twice as many people as originally thought, many of whom are women, said Dr. Mease, director of rheumatology research at Swedish Medical Center and clinical professor at the University of Washington, both in Seattle.

It’s not that SpA occurs as frequently in women as in men, but that it presents in a less-severe form with often little visible x-ray damage but with evidence of inflammation on MRI or in lab tests, he said at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

“These patients can be just as significantly impacted as patients with more ‘objective’ ankylosing spondylitis and can benefit as much from therapy such as anti-TNF [tumor necrosis factor] medications,” he said.

Evidence shows the prevalence of all spondyloarthritides in the United States is 0.346%-1.31%, compared with a rheumatoid arthritis prevalence of 0.6%-1.0%. Data from the German spondyloarthritis inception cohort has shown that the burden of disease in ankylosing spondylitis and nonradiographic axial SpA (nr-axSpA) is similar, Dr. Mease said.

The Assessment of SpondyloArthritis Society (ASAS) classification criteria (Ann Rheum Dis. 2009;68:777-83) have gone some way toward identifying patients earlier, he said, but the biggest controversy surrounding the management of nr-axSpA in the United States has been the Food and Drug Administration’s lack of recognition of the disease, making it difficult to treat patients early.

The FDA is concerned about the potential for misdiagnosis and inappropriate use of anti-TNFs for these noninflammatory conditions, he said. “They readily understand that patients who are MRI positive or CRP [C-reactive protein] elevated and x-ray negative exist and are significantly affected by their disease, but they are also aware that there can be similarity of symptomatology between these types of patients and patients with mechanical or degenerative spine disease and/or fibromyalgia.”

As such, there is a need for more information on the natural history of the disease from clinical registries and trials in order to gain more understanding on how to accurately diagnose patients, he said.

More education to U.S. physicians is also needed, he added, noting that this particular controversy is not present in other parts of the world, such as the European Union, where etanercept, adalimumab, and certolizumab pegol have been approved by the European Medicines Agency for the treatment of nr-axSpA.

“There is need for better understanding about this patient population and better education of health-care providers to get them to think about this condition and refer their patients to rheumatologists for evaluation and appropriate therapy,” he added.

Dr. Mease disclosed that he has received research grants, consultation fees, and/or speaker honoraria from AbbVie, Amgen, Biogen, Bristol-Myers Squibb, Celgene, Genentech, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, and UCB. Global Academy for Medical Education and this news organization are owned by the same parent company.

Rheumatologists’ understanding of the spectrum of spondyloarthritis is undergoing an evolution that has revealed an underrecognition of the disease, particularly in women, but regulatory recognition of the spectrum of disease in the United States has yet to catch up with reality, according to Dr. Philip Mease.

More sophisticated imaging and laboratory techniques has meant that spondyloarthritis (SpA) is being discovered in up to twice as many people as originally thought, many of whom are women, said Dr. Mease, director of rheumatology research at Swedish Medical Center and clinical professor at the University of Washington, both in Seattle.

It’s not that SpA occurs as frequently in women as in men, but that it presents in a less-severe form with often little visible x-ray damage but with evidence of inflammation on MRI or in lab tests, he said at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

“These patients can be just as significantly impacted as patients with more ‘objective’ ankylosing spondylitis and can benefit as much from therapy such as anti-TNF [tumor necrosis factor] medications,” he said.

Evidence shows the prevalence of all spondyloarthritides in the United States is 0.346%-1.31%, compared with a rheumatoid arthritis prevalence of 0.6%-1.0%. Data from the German spondyloarthritis inception cohort has shown that the burden of disease in ankylosing spondylitis and nonradiographic axial SpA (nr-axSpA) is similar, Dr. Mease said.

The Assessment of SpondyloArthritis Society (ASAS) classification criteria (Ann Rheum Dis. 2009;68:777-83) have gone some way toward identifying patients earlier, he said, but the biggest controversy surrounding the management of nr-axSpA in the United States has been the Food and Drug Administration’s lack of recognition of the disease, making it difficult to treat patients early.

The FDA is concerned about the potential for misdiagnosis and inappropriate use of anti-TNFs for these noninflammatory conditions, he said. “They readily understand that patients who are MRI positive or CRP [C-reactive protein] elevated and x-ray negative exist and are significantly affected by their disease, but they are also aware that there can be similarity of symptomatology between these types of patients and patients with mechanical or degenerative spine disease and/or fibromyalgia.”

As such, there is a need for more information on the natural history of the disease from clinical registries and trials in order to gain more understanding on how to accurately diagnose patients, he said.

More education to U.S. physicians is also needed, he added, noting that this particular controversy is not present in other parts of the world, such as the European Union, where etanercept, adalimumab, and certolizumab pegol have been approved by the European Medicines Agency for the treatment of nr-axSpA.

“There is need for better understanding about this patient population and better education of health-care providers to get them to think about this condition and refer their patients to rheumatologists for evaluation and appropriate therapy,” he added.

Dr. Mease disclosed that he has received research grants, consultation fees, and/or speaker honoraria from AbbVie, Amgen, Biogen, Bristol-Myers Squibb, Celgene, Genentech, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, and UCB. Global Academy for Medical Education and this news organization are owned by the same parent company.

Rheumatologists’ understanding of the spectrum of spondyloarthritis is undergoing an evolution that has revealed an underrecognition of the disease, particularly in women, but regulatory recognition of the spectrum of disease in the United States has yet to catch up with reality, according to Dr. Philip Mease.

More sophisticated imaging and laboratory techniques has meant that spondyloarthritis (SpA) is being discovered in up to twice as many people as originally thought, many of whom are women, said Dr. Mease, director of rheumatology research at Swedish Medical Center and clinical professor at the University of Washington, both in Seattle.

It’s not that SpA occurs as frequently in women as in men, but that it presents in a less-severe form with often little visible x-ray damage but with evidence of inflammation on MRI or in lab tests, he said at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

“These patients can be just as significantly impacted as patients with more ‘objective’ ankylosing spondylitis and can benefit as much from therapy such as anti-TNF [tumor necrosis factor] medications,” he said.

Evidence shows the prevalence of all spondyloarthritides in the United States is 0.346%-1.31%, compared with a rheumatoid arthritis prevalence of 0.6%-1.0%. Data from the German spondyloarthritis inception cohort has shown that the burden of disease in ankylosing spondylitis and nonradiographic axial SpA (nr-axSpA) is similar, Dr. Mease said.

The Assessment of SpondyloArthritis Society (ASAS) classification criteria (Ann Rheum Dis. 2009;68:777-83) have gone some way toward identifying patients earlier, he said, but the biggest controversy surrounding the management of nr-axSpA in the United States has been the Food and Drug Administration’s lack of recognition of the disease, making it difficult to treat patients early.

The FDA is concerned about the potential for misdiagnosis and inappropriate use of anti-TNFs for these noninflammatory conditions, he said. “They readily understand that patients who are MRI positive or CRP [C-reactive protein] elevated and x-ray negative exist and are significantly affected by their disease, but they are also aware that there can be similarity of symptomatology between these types of patients and patients with mechanical or degenerative spine disease and/or fibromyalgia.”

As such, there is a need for more information on the natural history of the disease from clinical registries and trials in order to gain more understanding on how to accurately diagnose patients, he said.

More education to U.S. physicians is also needed, he added, noting that this particular controversy is not present in other parts of the world, such as the European Union, where etanercept, adalimumab, and certolizumab pegol have been approved by the European Medicines Agency for the treatment of nr-axSpA.

“There is need for better understanding about this patient population and better education of health-care providers to get them to think about this condition and refer their patients to rheumatologists for evaluation and appropriate therapy,” he added.

Dr. Mease disclosed that he has received research grants, consultation fees, and/or speaker honoraria from AbbVie, Amgen, Biogen, Bristol-Myers Squibb, Celgene, Genentech, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, and UCB. Global Academy for Medical Education and this news organization are owned by the same parent company.

A single intradermal injection of autologous modified dendritic cells exposed to citrullinated peptides is safe and has immunoregulatory and anti-inflammatory effects, results of a phase I first in-human trial showed.

Dr. Helen Benham of the University of Queensland Diamantina Institute, Woolloongabba, Australia, and her colleagues gave 34 anticitrullinated peptide antibody (ACPA)-positive RA patients carrying HLA-DRB1 shared epitope alleles the immunotherapy treatment Rheumavax at either a high or low dose. They then compared results 1 month after treatment with 16 RA patients who served as controls.

Patients who received the treatment had a reduced number of effector T cells and a decreased production of proinflammatory cytokines, compared with controls, the researchers reported (Sci. Transl. Med. 2015;7:290ra87 [doi: 10.1126/scitranslmed.aaa9301]).

University of Queensland

Rheumavax did not induce disease flares in patients recruited with minimal disease activity, and the 28-joint disease activity score (DAS28) decreased in treated patients with active disease. Adverse events were a grade 1 out of a maximum of 4 and were similar between the low- and high-dose groups.

“The exploratory study demonstrates safety and biological activity of a single intradermal injection of autologous modified dendritic cells exposed to citrullinated peptides and provides rationale for further studies to assess clinical efficacy and antigen specific effects of autoantigen immunomodulatory therapy in RA,” concluded senior investigator Ranjeny Thomas, also of the University of Queensland, and associates.

All of the study patients were being treated with disease-modifying antirheumatic drugs. Median disease duration in the low-dose group was 3 years and baseline DAS28 based on C-reactive protein was 2.43. The high-dose group had a median disease duration of 2 years and a DAS28-CRP score of 2.2.

The authors reported no conflicts of interest.

[email protected]

A single intradermal injection of autologous modified dendritic cells exposed to citrullinated peptides is safe and has immunoregulatory and anti-inflammatory effects, results of a phase I first in-human trial showed.

Dr. Helen Benham of the University of Queensland Diamantina Institute, Woolloongabba, Australia, and her colleagues gave 34 anticitrullinated peptide antibody (ACPA)-positive RA patients carrying HLA-DRB1 shared epitope alleles the immunotherapy treatment Rheumavax at either a high or low dose. They then compared results 1 month after treatment with 16 RA patients who served as controls.

Patients who received the treatment had a reduced number of effector T cells and a decreased production of proinflammatory cytokines, compared with controls, the researchers reported (Sci. Transl. Med. 2015;7:290ra87 [doi: 10.1126/scitranslmed.aaa9301]).

University of Queensland

Rheumavax did not induce disease flares in patients recruited with minimal disease activity, and the 28-joint disease activity score (DAS28) decreased in treated patients with active disease. Adverse events were a grade 1 out of a maximum of 4 and were similar between the low- and high-dose groups.

“The exploratory study demonstrates safety and biological activity of a single intradermal injection of autologous modified dendritic cells exposed to citrullinated peptides and provides rationale for further studies to assess clinical efficacy and antigen specific effects of autoantigen immunomodulatory therapy in RA,” concluded senior investigator Ranjeny Thomas, also of the University of Queensland, and associates.

All of the study patients were being treated with disease-modifying antirheumatic drugs. Median disease duration in the low-dose group was 3 years and baseline DAS28 based on C-reactive protein was 2.43. The high-dose group had a median disease duration of 2 years and a DAS28-CRP score of 2.2.

The authors reported no conflicts of interest.

[email protected]

A single intradermal injection of autologous modified dendritic cells exposed to citrullinated peptides is safe and has immunoregulatory and anti-inflammatory effects, results of a phase I first in-human trial showed.

Dr. Helen Benham of the University of Queensland Diamantina Institute, Woolloongabba, Australia, and her colleagues gave 34 anticitrullinated peptide antibody (ACPA)-positive RA patients carrying HLA-DRB1 shared epitope alleles the immunotherapy treatment Rheumavax at either a high or low dose. They then compared results 1 month after treatment with 16 RA patients who served as controls.

Patients who received the treatment had a reduced number of effector T cells and a decreased production of proinflammatory cytokines, compared with controls, the researchers reported (Sci. Transl. Med. 2015;7:290ra87 [doi: 10.1126/scitranslmed.aaa9301]).

University of Queensland

Rheumavax did not induce disease flares in patients recruited with minimal disease activity, and the 28-joint disease activity score (DAS28) decreased in treated patients with active disease. Adverse events were a grade 1 out of a maximum of 4 and were similar between the low- and high-dose groups.

“The exploratory study demonstrates safety and biological activity of a single intradermal injection of autologous modified dendritic cells exposed to citrullinated peptides and provides rationale for further studies to assess clinical efficacy and antigen specific effects of autoantigen immunomodulatory therapy in RA,” concluded senior investigator Ranjeny Thomas, also of the University of Queensland, and associates.

All of the study patients were being treated with disease-modifying antirheumatic drugs. Median disease duration in the low-dose group was 3 years and baseline DAS28 based on C-reactive protein was 2.43. The high-dose group had a median disease duration of 2 years and a DAS28-CRP score of 2.2.

The authors reported no conflicts of interest.

[email protected]

Despite a similar relationship between lipid levels and cardiovascular disease risk in patients with or without rheumatoid arthritis, people with RA have an almost two-fold increased risk of having a major cardiovascular event, research shows.

The findings confirm that existing CV risk calculators are suboptimal for patients with RA and that improved methods of measuring risk in this population are needed, say the study authors from the Brigham and Women’s Hospital in Boston. They also show that there may be potential benefit in considering both LDL-C and HDL-C levels when estimating CV risk in RA, according to Dr. Katherine P. Liao and her associates from Brigham and Women’s Hospital, Boston (Arthritis & Rheumatology 2015; [doi: 10.1002/art.39165]).

While there have been many studies examining the relationship between low density lipoprotein cholesterol levels (LDL-C) and CV risk, only one study described the relationship between high density lipoprotein cholesterol levels (HDL-C) with CV risk among RA patients. It found higher levels of HDL-C were associated with lower CV risk in people with RA, consistent with the general population. “[This] suggests that HDL-C levels may provide important information for estimating CV risk independent of LDL-C,” according to Dr. Liao and her associates.

To assess the relationship between LDL-C and HDL-C with CV risk in RA patients compared with the general population, the researchers compared 16,085 RA patients with 48,499 matched controls without RA from the United Healthcare database. In line with other studies the researchers found evidence of the “lipid paradox” – where low and high LDL-C levels confer a similar CV risk – in both groups.

Looking at HDL-C levels, the risk of a major cardiovascular event (MACE) was highest among patients with lower levels compared with higher levels in both RA and non-RA subjects. For example subjects in the highest quintile had a 55% lower risk for MACE (hazard ratio, 0.45; 95% confidence interval, 0.48-0.72) compared with the lowest quintile after adjusting for CV risk factors. However,in a model that included both LDL-C and HDL-C levels, patients with RA had an elevated risk of MACE (HR 1.7; 95% CI, 1.5-1.9) independent of LDL-C levels.

“This magnitude of increased CV risk is similar to studies published a decade ago, suggesting that current practice and new RA therapies have not closed the gap between CV risk in RA compared to non-RA,” the researchers wrote. The finding also highlighted the potential benefit of considering both LDL-C and HDL-C levels when estimating CV risk in RA,” they said. One potential explanation for the independent significant association between HDL-C levels and CV-risk was that HDL-C levels appeared to remain relatively stable throughout changes in inflammation and may correlate better than LDL-C for CV risk, they suggested.

Overall the findings supported the notion that LDL-C levels may be a suboptimal measure for CV risk assessment in RA and demonstrated the need for improved methods for CV risk assessment, they said. The TransAtlantic cardiovascular risk calculator is under development to address this “major need in optimizing care for RA patients,” they added.

Despite a similar relationship between lipid levels and cardiovascular disease risk in patients with or without rheumatoid arthritis, people with RA have an almost two-fold increased risk of having a major cardiovascular event, research shows.

The findings confirm that existing CV risk calculators are suboptimal for patients with RA and that improved methods of measuring risk in this population are needed, say the study authors from the Brigham and Women’s Hospital in Boston. They also show that there may be potential benefit in considering both LDL-C and HDL-C levels when estimating CV risk in RA, according to Dr. Katherine P. Liao and her associates from Brigham and Women’s Hospital, Boston (Arthritis & Rheumatology 2015; [doi: 10.1002/art.39165]).

While there have been many studies examining the relationship between low density lipoprotein cholesterol levels (LDL-C) and CV risk, only one study described the relationship between high density lipoprotein cholesterol levels (HDL-C) with CV risk among RA patients. It found higher levels of HDL-C were associated with lower CV risk in people with RA, consistent with the general population. “[This] suggests that HDL-C levels may provide important information for estimating CV risk independent of LDL-C,” according to Dr. Liao and her associates.

To assess the relationship between LDL-C and HDL-C with CV risk in RA patients compared with the general population, the researchers compared 16,085 RA patients with 48,499 matched controls without RA from the United Healthcare database. In line with other studies the researchers found evidence of the “lipid paradox” – where low and high LDL-C levels confer a similar CV risk – in both groups.

Looking at HDL-C levels, the risk of a major cardiovascular event (MACE) was highest among patients with lower levels compared with higher levels in both RA and non-RA subjects. For example subjects in the highest quintile had a 55% lower risk for MACE (hazard ratio, 0.45; 95% confidence interval, 0.48-0.72) compared with the lowest quintile after adjusting for CV risk factors. However,in a model that included both LDL-C and HDL-C levels, patients with RA had an elevated risk of MACE (HR 1.7; 95% CI, 1.5-1.9) independent of LDL-C levels.

“This magnitude of increased CV risk is similar to studies published a decade ago, suggesting that current practice and new RA therapies have not closed the gap between CV risk in RA compared to non-RA,” the researchers wrote. The finding also highlighted the potential benefit of considering both LDL-C and HDL-C levels when estimating CV risk in RA,” they said. One potential explanation for the independent significant association between HDL-C levels and CV-risk was that HDL-C levels appeared to remain relatively stable throughout changes in inflammation and may correlate better than LDL-C for CV risk, they suggested.

Overall the findings supported the notion that LDL-C levels may be a suboptimal measure for CV risk assessment in RA and demonstrated the need for improved methods for CV risk assessment, they said. The TransAtlantic cardiovascular risk calculator is under development to address this “major need in optimizing care for RA patients,” they added.

Despite a similar relationship between lipid levels and cardiovascular disease risk in patients with or without rheumatoid arthritis, people with RA have an almost two-fold increased risk of having a major cardiovascular event, research shows.

The findings confirm that existing CV risk calculators are suboptimal for patients with RA and that improved methods of measuring risk in this population are needed, say the study authors from the Brigham and Women’s Hospital in Boston. They also show that there may be potential benefit in considering both LDL-C and HDL-C levels when estimating CV risk in RA, according to Dr. Katherine P. Liao and her associates from Brigham and Women’s Hospital, Boston (Arthritis & Rheumatology 2015; [doi: 10.1002/art.39165]).

While there have been many studies examining the relationship between low density lipoprotein cholesterol levels (LDL-C) and CV risk, only one study described the relationship between high density lipoprotein cholesterol levels (HDL-C) with CV risk among RA patients. It found higher levels of HDL-C were associated with lower CV risk in people with RA, consistent with the general population. “[This] suggests that HDL-C levels may provide important information for estimating CV risk independent of LDL-C,” according to Dr. Liao and her associates.

To assess the relationship between LDL-C and HDL-C with CV risk in RA patients compared with the general population, the researchers compared 16,085 RA patients with 48,499 matched controls without RA from the United Healthcare database. In line with other studies the researchers found evidence of the “lipid paradox” – where low and high LDL-C levels confer a similar CV risk – in both groups.

Looking at HDL-C levels, the risk of a major cardiovascular event (MACE) was highest among patients with lower levels compared with higher levels in both RA and non-RA subjects. For example subjects in the highest quintile had a 55% lower risk for MACE (hazard ratio, 0.45; 95% confidence interval, 0.48-0.72) compared with the lowest quintile after adjusting for CV risk factors. However,in a model that included both LDL-C and HDL-C levels, patients with RA had an elevated risk of MACE (HR 1.7; 95% CI, 1.5-1.9) independent of LDL-C levels.

“This magnitude of increased CV risk is similar to studies published a decade ago, suggesting that current practice and new RA therapies have not closed the gap between CV risk in RA compared to non-RA,” the researchers wrote. The finding also highlighted the potential benefit of considering both LDL-C and HDL-C levels when estimating CV risk in RA,” they said. One potential explanation for the independent significant association between HDL-C levels and CV-risk was that HDL-C levels appeared to remain relatively stable throughout changes in inflammation and may correlate better than LDL-C for CV risk, they suggested.

Overall the findings supported the notion that LDL-C levels may be a suboptimal measure for CV risk assessment in RA and demonstrated the need for improved methods for CV risk assessment, they said. The TransAtlantic cardiovascular risk calculator is under development to address this “major need in optimizing care for RA patients,” they added.

Naive lymphopenia may be a B cell–specific marker of disease activity in ANCA-associated vasculitis that could help guide when to retreat patients with B cell depletion–therapy, researchers report.

In a study of 35 patients with severe ANCA associated vasculitis (AAV) who were treated with B cell depletion therapy with rituximab, relapse was more likely in those patients who did not experience naive B cell repopulation at 6 months, the researchers reported in the Annals of the Rheumatic Diseases (Ann. Rheum. Dis. 2015; [doi: 10.1136/annrheumdis-2014-206496]).

A single cycle of B cell depletion with rituximab has been effective for inducing remission in patients with AAV, but an optimal long-term strategy had not yet been established. In rheumatoid arthritis, repeat cycles were often given when patients developed clinical relapse, but this approach may be riskier in AAV since relapses may cause life or organ threatening disease, according to Dr. Paul Emery of the Leeds Institute of Rheumatic and Musculoskeletal Diseases and his associates.

“An alternative approach is to use pre-emptive treatment either based on reconstitution of B cells or fixed intervals,” they wrote. However the identification of biomarkers that could guide these decisions would be very valuable, they said.

The study of 35 patients with AAV received treatment with two infusions of rituximab at a dose of 1,000 mg that was repeated 2 weeks later; the treatment was then repeated in patients with clinical relapse for up to five cycles. Disease activity was assessed at baseline and every 3 months using the Birmingham Vasculitis Activity Score (BVAS). Peripheral B cell subsets were measured using highly sensitive flow cytometry (HSFC) at week 0, 6, and 26 without knowledge of clinical status other than time since rituximab.

Complete response was defined as a BVAS score of zero, and partial response was defined as 50% improvement in BVAS from baseline at week 26. Response rates for cycle 1 to cycle 5 were 94%, 100%, 85%, 85%, and 83%, respectively, the study authors reported. Patients with early relapse failed to develop naive B cells, a finding that differed from results seen in SLE, the authors noted.

However, repopulation of naive B cell at 6 months was associated with a reduced risk of relapse (hazard ratio, 0.326; 95% confidence interval, 0.114-0.930, P = .036). Relapse rates at 12 and 18 months were 0% and 14% with naive repopulation at 6 months, and 31% and 54% without naive repopulation. “Patients with undetectable naive B cells at 6 months may be suited for earlier retreatment due to 30% relapse rate observed at 12 months,” they said.

The results suggest that evaluation of naive B cell numbers in very early repopulation using HSFC may have value in guiding retreatment decisions for the most effective and efficient use of rituximab in AAV, the study authors concluded. The results warranted validation in larger cohorts, they added.

Naive lymphopenia may be a B cell–specific marker of disease activity in ANCA-associated vasculitis that could help guide when to retreat patients with B cell depletion–therapy, researchers report.

In a study of 35 patients with severe ANCA associated vasculitis (AAV) who were treated with B cell depletion therapy with rituximab, relapse was more likely in those patients who did not experience naive B cell repopulation at 6 months, the researchers reported in the Annals of the Rheumatic Diseases (Ann. Rheum. Dis. 2015; [doi: 10.1136/annrheumdis-2014-206496]).

A single cycle of B cell depletion with rituximab has been effective for inducing remission in patients with AAV, but an optimal long-term strategy had not yet been established. In rheumatoid arthritis, repeat cycles were often given when patients developed clinical relapse, but this approach may be riskier in AAV since relapses may cause life or organ threatening disease, according to Dr. Paul Emery of the Leeds Institute of Rheumatic and Musculoskeletal Diseases and his associates.

“An alternative approach is to use pre-emptive treatment either based on reconstitution of B cells or fixed intervals,” they wrote. However the identification of biomarkers that could guide these decisions would be very valuable, they said.

The study of 35 patients with AAV received treatment with two infusions of rituximab at a dose of 1,000 mg that was repeated 2 weeks later; the treatment was then repeated in patients with clinical relapse for up to five cycles. Disease activity was assessed at baseline and every 3 months using the Birmingham Vasculitis Activity Score (BVAS). Peripheral B cell subsets were measured using highly sensitive flow cytometry (HSFC) at week 0, 6, and 26 without knowledge of clinical status other than time since rituximab.

Complete response was defined as a BVAS score of zero, and partial response was defined as 50% improvement in BVAS from baseline at week 26. Response rates for cycle 1 to cycle 5 were 94%, 100%, 85%, 85%, and 83%, respectively, the study authors reported. Patients with early relapse failed to develop naive B cells, a finding that differed from results seen in SLE, the authors noted.

However, repopulation of naive B cell at 6 months was associated with a reduced risk of relapse (hazard ratio, 0.326; 95% confidence interval, 0.114-0.930, P = .036). Relapse rates at 12 and 18 months were 0% and 14% with naive repopulation at 6 months, and 31% and 54% without naive repopulation. “Patients with undetectable naive B cells at 6 months may be suited for earlier retreatment due to 30% relapse rate observed at 12 months,” they said.

The results suggest that evaluation of naive B cell numbers in very early repopulation using HSFC may have value in guiding retreatment decisions for the most effective and efficient use of rituximab in AAV, the study authors concluded. The results warranted validation in larger cohorts, they added.

Naive lymphopenia may be a B cell–specific marker of disease activity in ANCA-associated vasculitis that could help guide when to retreat patients with B cell depletion–therapy, researchers report.

In a study of 35 patients with severe ANCA associated vasculitis (AAV) who were treated with B cell depletion therapy with rituximab, relapse was more likely in those patients who did not experience naive B cell repopulation at 6 months, the researchers reported in the Annals of the Rheumatic Diseases (Ann. Rheum. Dis. 2015; [doi: 10.1136/annrheumdis-2014-206496]).

A single cycle of B cell depletion with rituximab has been effective for inducing remission in patients with AAV, but an optimal long-term strategy had not yet been established. In rheumatoid arthritis, repeat cycles were often given when patients developed clinical relapse, but this approach may be riskier in AAV since relapses may cause life or organ threatening disease, according to Dr. Paul Emery of the Leeds Institute of Rheumatic and Musculoskeletal Diseases and his associates.

“An alternative approach is to use pre-emptive treatment either based on reconstitution of B cells or fixed intervals,” they wrote. However the identification of biomarkers that could guide these decisions would be very valuable, they said.

The study of 35 patients with AAV received treatment with two infusions of rituximab at a dose of 1,000 mg that was repeated 2 weeks later; the treatment was then repeated in patients with clinical relapse for up to five cycles. Disease activity was assessed at baseline and every 3 months using the Birmingham Vasculitis Activity Score (BVAS). Peripheral B cell subsets were measured using highly sensitive flow cytometry (HSFC) at week 0, 6, and 26 without knowledge of clinical status other than time since rituximab.

Complete response was defined as a BVAS score of zero, and partial response was defined as 50% improvement in BVAS from baseline at week 26. Response rates for cycle 1 to cycle 5 were 94%, 100%, 85%, 85%, and 83%, respectively, the study authors reported. Patients with early relapse failed to develop naive B cells, a finding that differed from results seen in SLE, the authors noted.

However, repopulation of naive B cell at 6 months was associated with a reduced risk of relapse (hazard ratio, 0.326; 95% confidence interval, 0.114-0.930, P = .036). Relapse rates at 12 and 18 months were 0% and 14% with naive repopulation at 6 months, and 31% and 54% without naive repopulation. “Patients with undetectable naive B cells at 6 months may be suited for earlier retreatment due to 30% relapse rate observed at 12 months,” they said.

The results suggest that evaluation of naive B cell numbers in very early repopulation using HSFC may have value in guiding retreatment decisions for the most effective and efficient use of rituximab in AAV, the study authors concluded. The results warranted validation in larger cohorts, they added.