Considerable uncertainty surrounds whether people with axial spondyloarthritis (axSpA) who are treated with biologic drugs have an increased risk for developing inflammatory bowel disease (IBD) that is higher than if they receive other treatments, according to data reported at the annual meeting of the British Society for Rheumatology.
“We noticed two patterns,” Gary Macfarlane, MD, PhD, Dsc, of the University of Aberdeen (Scotland) said in presenting findings from an analysis of the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS) and a meta-analysis of available studies.
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There was a “large excess risk in observational studies associated with biologic therapies, which was not replicated in RCTs [randomized, controlled trials],” he said, “and trials under extensions suggested a small absolute increased risk associated with etanercept and with [interleukin]-17 [inhibitors], although again with considerable uncertainty.”
While these data make it difficult to draw any firm conclusions, “we should be reassured that the patient groups receiving these specific biologics in routine clinical care have not demonstrated an excess risk of IBD,” Dr. Macfarlane told delegates at the meeting.
Addressing clinical questions
IBD is a known extra-articular manifestation of axSpA, with an estimated prevalence of about 7%, according to a 2015 meta-analysis of 69 studies involving more than 30,000 patients.
The idea that people being treated with biologics may be at higher risk for developing IBD than those taking other treatments was suggested by the results of a large (n = 80,326) Danish study in which patients who were treated with an anti–tumor necrosis factor (TNF)–alpha medication were found to be more likely to develop de novo ulcerative colitis or Crohn’s disease than were patients who did not receive biologics.
Notably, the risk for IBD seemed higher with etanercept than with other anti–TNF-alpha agents, such as infliximab and adalimumab.
The aim of the analyses that Dr. Macfarlane presented was therefore to see if there was a difference in IBD risk among patients treated with biologic agents versus other agents, and if etanercept really did pose a greater cause for concern.
“The reason that we are asking this question is that a clinician called us up and asked us if we had any data on it,” Dr. Macfarlane said. “I think that’s really important to say that one of the things the registers are designed for are to answer questions that clinicians may have.”
Looking for new-onset IBD
Although no longer recruiting patients, the BSRBR-AS provides a wealth of data on the real-life management of patients with axSpA who were or were not taking a biologic. Patients were recruited into the register between 2012 and 2017, with follow-up until 2018. Data analyses are still ongoing and expected to continue for another couple of years.
The current analysis of data from the BSRBR-AS included patients who did not already have IBD at enrollment into the register, and patients who had been treated with a biologic could have been treated only with a single agent. Of just over 1,800 eligible patients, 793 had been treated with a biologic and 1,058 had been given nonbiologic treatment.
As expected, there were some differences between the two groups of patients studied, with biologic-treated patients having a younger age than non–biologic-treated patients. Those who took a biologic also had higher disease activity, inflammatory scores, and rates of psoriasis, enthesitis, and peripheral joint involvement.
Incidence rates for new-onset IBD per 1,000 person-years of treatment were calculated as 17 (95% confidence interval, 10.7-25.8) for patients taking a biologic and 5.1 (95% CI, 2.7-8.7) for those not taking a biologic, giving an incidence rate difference of 11.9 (95% CI, 4.3-19.6).
There was some observed differences in the incidence of new-onset IBD associated with specific agents. Etanercept did not have a higher rate (13.9/1,000 patient-years; 95% CI, 5.1-30.3) than did other agents. But in comparison, the incidence of new-onset IBD for adalimumab was 20.4 (95% CI, 11.7-33.1) and zero for other anti-TNF agents such as certolizumab pegol and infliximab, although the duration of exposure to these drugs was much lower.
The IRDs for etanercept versus nonbiologic treatment and versus other anti-TNFs were 8.8 (95% CI, –2.7 to 20.3) and -6.4 (95% CI, –21.3 to 8.5), but with “considerable uncertainty” because the confidence intervals were very wide.