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Two recent reports that provide opposing evidence about the potential for inflammatory bowel disease patients to develop articular manifestations after starting vedolizumab raise questions for future studies to answer in regard to a plausible mechanism for the adverse event and its relative importance.
The two reports, one a case series of 5 patients with inflammatory bowel disease (IBD) who developed articular manifestations after beginning vedolizumab (Entyvio) and the other a prospective cohort study of 53 patients with IBD who started vedolizumab without any subsequent cases of induction or flare of arthritis and/or sacroiliitis, came to somewhat different conclusions about the beneficial or paradoxical effects of vedolizumab’s blockade of the alpha4beta7 receptor on articular manifestations of IBD.
The five-patient cases series reported by Gaëlle Varkas, MD, a doctoral student at the University of Ghent, Belgium, and her colleagues consisted of five IBD patients, aged 26-50 years, who developed either new onset or an exacerbation of sacroiliitis or arthritis soon after starting vedolizumab. All but one of the patients was female (Ann Rheum Dis. 2016 Nov 29. doi: 10.1136/annrheumdis-2016-210233). In these patients, the investigators said, vedolizumab did not “seem to show any efficacy in and might even induce arthritis and/or sacroiliitis.”
The first was a 50-year-old woman who had progressive back pain with MRI-confirmed bilateral sacroiliitis about 2 months after beginning vedolizumab. The second patient, a 28-year-old woman with no previous history of spondyloarthropathy, had lower limb pain, a painful left shoulder, and arthritis of one wrist. Ultrasound examination confirmed intercarpal effusions and synovial hyperproliferation.
The third patient was 30 years old and male. He had both ankylosing spondylitis and Crohn’s disease, and experienced arthralgias, elevated C-reactive protein, and MRI-confirmed axial skeletal inflammation 4 weeks after starting vedolizumab.
The fourth patient was a 47-year-old woman with no previous history of spondyloarthropathy who developed MRI-confirmed sacroiliitis after beginning vedolizumab. The fifth patient, a 26-year-old woman, developed polyarticular joint pain after starting vedolizumab. Examination of this patient showed synovitis and enthesitis of multiple joints of the appendicular skeleton.
In discussion, Dr. Varkas and her colleagues noted that “one of the many hypotheses is that integrins and adhesion molecules play a role in the interception of recirculating activated lymphocytes between the gut and the synovial membrane due to the inhibition of the alpha4beta7 integrin homing at the level of the gut.” However, the investigators also acknowledged that other hypotheses may also account for their findings. “Alternatively, in the presence of vedolizumab, cellular recruitment may be mediated by yet to be determined adhesion molecules. This recirculation theory might explain the short mean interval of 64 days between vedolizumab initiation and the expression of symptoms.”
Another group, publishing its prospective cohort study in a letter, had different findings (Ann Rheum Dis. 2017 Jan 17. doi: 10.1136/annrheumdis-2016-211011).
“Although the hypotheses proposed by the authors to explain such events sounds reasonable,” wrote Ambrogio Orlando, MD, and his coauthors, their experience of the effect of vedolizumab on spondyloarthritis differed.
In the report on 53 patients who began treatment with vedolizumab at Villa Sofia-Cervello Hospital, Palermo, Italy, where Dr. Orlando and his associates work, almost all (96%) had been steroid dependent and 81% had been treated with at least one tumor necrosis factor inhibitor. About two-thirds had completed the induction phase of vedolizumab treatment during follow-up, which lasted a mean of 2.6 months. Of the 14 patients (26%) who had active IBD-associated spondyloarthropathy when starting vedolizumab, 6 (46.2%) saw “a sharp clinical benefit after the initiation of vedolizumab,” wrote Dr. Orlando and his colleagues. Five of these six patients experienced clinical remission of gut symptoms by 12 weeks of therapy.
Dr. Orlando and his colleagues wrote that “our preliminary prospective data indicate a potential benefit of vedolizumab on IBD-associated spondyloarthropathy.”
Looking for mechanistic reasons for this apparent benefit, Dr. Orlando and his collaborators wrote that “the previous demonstration of alpha4beta7 in the joint and the recent evidence of the upregulation of mucosal vascular address in cell adhesion molecule (MadCAM-1) in the high endothelial venules of bone marrow in patients with active axial SpA seem to strengthen the hypothesis of a beneficial rather than a paradoxical effect of alpha4beta7 blockade on articular manifestations of IBD.”
Two authors of the case series reported relationships with multiple pharmaceutical companies, as did Dr. Orlando and two other authors of the letter describing the prospective study.
[email protected]
On Twitter @karioakes
Vedolizumab is gut-selective, and therefore a question that’s been raised is whether it would uncover extra-intestinal manifestations of inflammatory bowel disease (IBD).
When extra-intestinal manifestations of IBD occur with new treatments, we try to discern whether there is still active disease in the bowel. If the bowel is responding, we try to determine if the extra-intestinal symptoms are occurring in parallel to the bowel disease or if they represent a unique side effect of the medication.
In February 2017, at ECCO [the annual meeting of the European Crohn’s and Colitis Organisation], we will be presenting a post hoc analysis of the data from the vedolizumab pivotal clinical trial that examines whether joint pain was independently associated with administration of vedolizumab.
The individual case reports of joint pain with vedolizumab have not limited our using the drug for the patients who need it. It’s a matter of weighing risks and benefits, and the safety profile of this medication is overall so good that we don’t hesitate to use it. In our clinic, we have treated more than 400 IBD patients with vedolizumab, and I can only recall one patient who had to stop using it due to joint pain.
David Rubin, MD, is professor of medicine and chief of the gastroenterology, hepatology, and nutrition section of the University of Chicago. He reported that he is a consultant for and has received grant support from Takeda Pharmaceuticals. These remarks were drawn from an interview.
Vedolizumab is gut-selective, and therefore a question that’s been raised is whether it would uncover extra-intestinal manifestations of inflammatory bowel disease (IBD).
When extra-intestinal manifestations of IBD occur with new treatments, we try to discern whether there is still active disease in the bowel. If the bowel is responding, we try to determine if the extra-intestinal symptoms are occurring in parallel to the bowel disease or if they represent a unique side effect of the medication.
In February 2017, at ECCO [the annual meeting of the European Crohn’s and Colitis Organisation], we will be presenting a post hoc analysis of the data from the vedolizumab pivotal clinical trial that examines whether joint pain was independently associated with administration of vedolizumab.
The individual case reports of joint pain with vedolizumab have not limited our using the drug for the patients who need it. It’s a matter of weighing risks and benefits, and the safety profile of this medication is overall so good that we don’t hesitate to use it. In our clinic, we have treated more than 400 IBD patients with vedolizumab, and I can only recall one patient who had to stop using it due to joint pain.
David Rubin, MD, is professor of medicine and chief of the gastroenterology, hepatology, and nutrition section of the University of Chicago. He reported that he is a consultant for and has received grant support from Takeda Pharmaceuticals. These remarks were drawn from an interview.
Vedolizumab is gut-selective, and therefore a question that’s been raised is whether it would uncover extra-intestinal manifestations of inflammatory bowel disease (IBD).
When extra-intestinal manifestations of IBD occur with new treatments, we try to discern whether there is still active disease in the bowel. If the bowel is responding, we try to determine if the extra-intestinal symptoms are occurring in parallel to the bowel disease or if they represent a unique side effect of the medication.
In February 2017, at ECCO [the annual meeting of the European Crohn’s and Colitis Organisation], we will be presenting a post hoc analysis of the data from the vedolizumab pivotal clinical trial that examines whether joint pain was independently associated with administration of vedolizumab.
The individual case reports of joint pain with vedolizumab have not limited our using the drug for the patients who need it. It’s a matter of weighing risks and benefits, and the safety profile of this medication is overall so good that we don’t hesitate to use it. In our clinic, we have treated more than 400 IBD patients with vedolizumab, and I can only recall one patient who had to stop using it due to joint pain.
David Rubin, MD, is professor of medicine and chief of the gastroenterology, hepatology, and nutrition section of the University of Chicago. He reported that he is a consultant for and has received grant support from Takeda Pharmaceuticals. These remarks were drawn from an interview.
Two recent reports that provide opposing evidence about the potential for inflammatory bowel disease patients to develop articular manifestations after starting vedolizumab raise questions for future studies to answer in regard to a plausible mechanism for the adverse event and its relative importance.
The two reports, one a case series of 5 patients with inflammatory bowel disease (IBD) who developed articular manifestations after beginning vedolizumab (Entyvio) and the other a prospective cohort study of 53 patients with IBD who started vedolizumab without any subsequent cases of induction or flare of arthritis and/or sacroiliitis, came to somewhat different conclusions about the beneficial or paradoxical effects of vedolizumab’s blockade of the alpha4beta7 receptor on articular manifestations of IBD.
The five-patient cases series reported by Gaëlle Varkas, MD, a doctoral student at the University of Ghent, Belgium, and her colleagues consisted of five IBD patients, aged 26-50 years, who developed either new onset or an exacerbation of sacroiliitis or arthritis soon after starting vedolizumab. All but one of the patients was female (Ann Rheum Dis. 2016 Nov 29. doi: 10.1136/annrheumdis-2016-210233). In these patients, the investigators said, vedolizumab did not “seem to show any efficacy in and might even induce arthritis and/or sacroiliitis.”
The first was a 50-year-old woman who had progressive back pain with MRI-confirmed bilateral sacroiliitis about 2 months after beginning vedolizumab. The second patient, a 28-year-old woman with no previous history of spondyloarthropathy, had lower limb pain, a painful left shoulder, and arthritis of one wrist. Ultrasound examination confirmed intercarpal effusions and synovial hyperproliferation.
The third patient was 30 years old and male. He had both ankylosing spondylitis and Crohn’s disease, and experienced arthralgias, elevated C-reactive protein, and MRI-confirmed axial skeletal inflammation 4 weeks after starting vedolizumab.
The fourth patient was a 47-year-old woman with no previous history of spondyloarthropathy who developed MRI-confirmed sacroiliitis after beginning vedolizumab. The fifth patient, a 26-year-old woman, developed polyarticular joint pain after starting vedolizumab. Examination of this patient showed synovitis and enthesitis of multiple joints of the appendicular skeleton.
In discussion, Dr. Varkas and her colleagues noted that “one of the many hypotheses is that integrins and adhesion molecules play a role in the interception of recirculating activated lymphocytes between the gut and the synovial membrane due to the inhibition of the alpha4beta7 integrin homing at the level of the gut.” However, the investigators also acknowledged that other hypotheses may also account for their findings. “Alternatively, in the presence of vedolizumab, cellular recruitment may be mediated by yet to be determined adhesion molecules. This recirculation theory might explain the short mean interval of 64 days between vedolizumab initiation and the expression of symptoms.”
Another group, publishing its prospective cohort study in a letter, had different findings (Ann Rheum Dis. 2017 Jan 17. doi: 10.1136/annrheumdis-2016-211011).
“Although the hypotheses proposed by the authors to explain such events sounds reasonable,” wrote Ambrogio Orlando, MD, and his coauthors, their experience of the effect of vedolizumab on spondyloarthritis differed.
In the report on 53 patients who began treatment with vedolizumab at Villa Sofia-Cervello Hospital, Palermo, Italy, where Dr. Orlando and his associates work, almost all (96%) had been steroid dependent and 81% had been treated with at least one tumor necrosis factor inhibitor. About two-thirds had completed the induction phase of vedolizumab treatment during follow-up, which lasted a mean of 2.6 months. Of the 14 patients (26%) who had active IBD-associated spondyloarthropathy when starting vedolizumab, 6 (46.2%) saw “a sharp clinical benefit after the initiation of vedolizumab,” wrote Dr. Orlando and his colleagues. Five of these six patients experienced clinical remission of gut symptoms by 12 weeks of therapy.
Dr. Orlando and his colleagues wrote that “our preliminary prospective data indicate a potential benefit of vedolizumab on IBD-associated spondyloarthropathy.”
Looking for mechanistic reasons for this apparent benefit, Dr. Orlando and his collaborators wrote that “the previous demonstration of alpha4beta7 in the joint and the recent evidence of the upregulation of mucosal vascular address in cell adhesion molecule (MadCAM-1) in the high endothelial venules of bone marrow in patients with active axial SpA seem to strengthen the hypothesis of a beneficial rather than a paradoxical effect of alpha4beta7 blockade on articular manifestations of IBD.”
Two authors of the case series reported relationships with multiple pharmaceutical companies, as did Dr. Orlando and two other authors of the letter describing the prospective study.
[email protected]
On Twitter @karioakes
Two recent reports that provide opposing evidence about the potential for inflammatory bowel disease patients to develop articular manifestations after starting vedolizumab raise questions for future studies to answer in regard to a plausible mechanism for the adverse event and its relative importance.
The two reports, one a case series of 5 patients with inflammatory bowel disease (IBD) who developed articular manifestations after beginning vedolizumab (Entyvio) and the other a prospective cohort study of 53 patients with IBD who started vedolizumab without any subsequent cases of induction or flare of arthritis and/or sacroiliitis, came to somewhat different conclusions about the beneficial or paradoxical effects of vedolizumab’s blockade of the alpha4beta7 receptor on articular manifestations of IBD.
The five-patient cases series reported by Gaëlle Varkas, MD, a doctoral student at the University of Ghent, Belgium, and her colleagues consisted of five IBD patients, aged 26-50 years, who developed either new onset or an exacerbation of sacroiliitis or arthritis soon after starting vedolizumab. All but one of the patients was female (Ann Rheum Dis. 2016 Nov 29. doi: 10.1136/annrheumdis-2016-210233). In these patients, the investigators said, vedolizumab did not “seem to show any efficacy in and might even induce arthritis and/or sacroiliitis.”
The first was a 50-year-old woman who had progressive back pain with MRI-confirmed bilateral sacroiliitis about 2 months after beginning vedolizumab. The second patient, a 28-year-old woman with no previous history of spondyloarthropathy, had lower limb pain, a painful left shoulder, and arthritis of one wrist. Ultrasound examination confirmed intercarpal effusions and synovial hyperproliferation.
The third patient was 30 years old and male. He had both ankylosing spondylitis and Crohn’s disease, and experienced arthralgias, elevated C-reactive protein, and MRI-confirmed axial skeletal inflammation 4 weeks after starting vedolizumab.
The fourth patient was a 47-year-old woman with no previous history of spondyloarthropathy who developed MRI-confirmed sacroiliitis after beginning vedolizumab. The fifth patient, a 26-year-old woman, developed polyarticular joint pain after starting vedolizumab. Examination of this patient showed synovitis and enthesitis of multiple joints of the appendicular skeleton.
In discussion, Dr. Varkas and her colleagues noted that “one of the many hypotheses is that integrins and adhesion molecules play a role in the interception of recirculating activated lymphocytes between the gut and the synovial membrane due to the inhibition of the alpha4beta7 integrin homing at the level of the gut.” However, the investigators also acknowledged that other hypotheses may also account for their findings. “Alternatively, in the presence of vedolizumab, cellular recruitment may be mediated by yet to be determined adhesion molecules. This recirculation theory might explain the short mean interval of 64 days between vedolizumab initiation and the expression of symptoms.”
Another group, publishing its prospective cohort study in a letter, had different findings (Ann Rheum Dis. 2017 Jan 17. doi: 10.1136/annrheumdis-2016-211011).
“Although the hypotheses proposed by the authors to explain such events sounds reasonable,” wrote Ambrogio Orlando, MD, and his coauthors, their experience of the effect of vedolizumab on spondyloarthritis differed.
In the report on 53 patients who began treatment with vedolizumab at Villa Sofia-Cervello Hospital, Palermo, Italy, where Dr. Orlando and his associates work, almost all (96%) had been steroid dependent and 81% had been treated with at least one tumor necrosis factor inhibitor. About two-thirds had completed the induction phase of vedolizumab treatment during follow-up, which lasted a mean of 2.6 months. Of the 14 patients (26%) who had active IBD-associated spondyloarthropathy when starting vedolizumab, 6 (46.2%) saw “a sharp clinical benefit after the initiation of vedolizumab,” wrote Dr. Orlando and his colleagues. Five of these six patients experienced clinical remission of gut symptoms by 12 weeks of therapy.
Dr. Orlando and his colleagues wrote that “our preliminary prospective data indicate a potential benefit of vedolizumab on IBD-associated spondyloarthropathy.”
Looking for mechanistic reasons for this apparent benefit, Dr. Orlando and his collaborators wrote that “the previous demonstration of alpha4beta7 in the joint and the recent evidence of the upregulation of mucosal vascular address in cell adhesion molecule (MadCAM-1) in the high endothelial venules of bone marrow in patients with active axial SpA seem to strengthen the hypothesis of a beneficial rather than a paradoxical effect of alpha4beta7 blockade on articular manifestations of IBD.”
Two authors of the case series reported relationships with multiple pharmaceutical companies, as did Dr. Orlando and two other authors of the letter describing the prospective study.
[email protected]
On Twitter @karioakes
FROM ANNALS OF THE RHEUMATIC DISEASES
Key clinical point:
Major finding: Imaging-confirmed arthritis or sacroiliitis after starting vedolizumab was seen in a case series of 5 patients; a prospective study of 53 patients saw zero new-onset cases of joint pain.
Data source: Case series of 5 IBD patients starting vedolizumab, and prospective surveillance at another facility of 53 IBD patients receiving vedolizumab.
Disclosures: Two authors of the case series reported multiple relationships with pharmaceutical companies, as did three authors of a letter describing a prospective study.