Among patients with ankylosing spondylitis or undifferentiated spondyloarthritis, risk for anterior uveitis may hinge on the choice of biologic disease-modifying antirheumatic drug (bDMARD), a large Swedish cohort study suggests.
Dr. Ulf Lindström
Study results were reported in the opening plenary abstract session at the annual European Congress of Rheumatology, held online this year due to COVID-19.
“Randomized, controlled trials indicate that compared to tumor necrosis factor (TNF) inhibitors, secukinumab has similar efficacy regarding axial inflammation in spondyloarthritis and better efficacy regarding cutaneous psoriasis, but is inferior in inflammatory bowel disease,” noted lead investigator Ulf Lindström, MD, PhD, of the department of rheumatology and inflammation research in the Institute of Medicine at the University of Gothenburg (Sweden). “However, the efficacy of secukinumab, compared to TNF inhibitors, in anterior uveitis has not been extensively studied.”
The investigators used national registry data to study 3,568 patients with ankylosing spondylitis or undifferentiated spondyloarthritis who started bDMARDs in 2005-2018. They considered four agents: the anti–interleukin-17A antibody secukinumab (Cosentyx) and the TNF inhibitors etanercept (Enbrel), adalimumab (Humira), and infliximab (Remicade).
Analyses based on 4,523 treatment episodes showed that after excluding the 23% of patients who had previously experienced anterior uveitis, merely 0.9% of patients experienced new-onset anterior uveitis while on their bDMARD, Dr. Lindström reported.
There was confounding by indication, whereby patients with previous anterior uveitis were channeled toward adalimumab and infliximab, and away from secukinumab and etanercept. In addition, there was confounding by line of treatment, with secukinumab usually used in the third line.
After excluding patients who had experienced anterior uveitis in the past year to partly address confounding, the adjusted risk for first on-treatment anterior uveitis was about twice as high with secukinumab and with etanercept as compared with adalimumab. After additionally excluding all biologic treatment episodes beyond the third line, elevation of risk remained significant only for etanercept.
“There is probably a higher occurrence of anterior uveitis on treatment with secukinumab, compared to adalimumab, but there may still be residual confounding and bias that we need to consider,” Dr. Lindström concluded. “As seen previously, there is a higher occurrence of anterior uveitis on etanercept compared to adalimumab or infliximab.”
Findings in context
“These results are not surprising as we have known that secukinumab and etanercept are not good for controlling recurrent and chronic uveitis,” Nigil Haroon MD, PhD, DM, commented in an interview. However, “a single episode of uveitis or infrequent episodes are not usually considered a contraindication to starting these drugs.”
Dr. Nigil Haroon
Study caveats included lack of adjustment for uveitis severity and potentially missed uveitis episodes in patients who treated it themselves with steroid eyedrops, he said. “Standard practice is to keep drops with them to start at the earliest possible time point.”
“It would be useful to know the number of patients who stopped medications as a result of uveitis,” added Dr. Haroon, who is codirector of the spondylitis program at the University Health Network and associate professor of medicine and rheumatology at the University of Toronto. “Time-to-event analysis may also be interesting.”
“The study raises an important point regarding channeling bias, and this is important to consider when interpreting clinical trial data as well. Investigators are unlikely to include patients with history of uveitis (or strong family history of inflammatory bowel disease or personal history of gut symptoms) in studies with IL-17 inhibitors and etanercept. Hence, the results have to be interpreted with caution.”