Although the risk of developing inflammatory bowel disease (IBD) is low in patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS) initiating secukinumab, the risk for IBD flares is higher among patients with AS vs PsA, according to study results published in Rheumatology.
Selective interleukin (IL)-17A inhibitor secukinumab has been considered an effective treatment option for PsA and AS, conditions which are associated with a significantly increased risk of developing IBD. Previous studies have suggested that treatment with secukinumab may worsen IBD symptoms, but data are limited.
The objective of the current study was to report real-world data of secukinumab in routine care, and the rates and predictors of gastrointestinal-related adverse events in patients with PsA and AS initiating secukinumab.
Using electronic and paper records from 10 UK centers on patients who initiated treatment with secukinumab between 2016 and 2019, the researchers of the study collected data on gastrointestinal-related adverse events. Gastrointestinal-related adverse events were classified as follows: definite (objective evidence of IBD [biopsy-proven], clear temporal association, resolution of symptoms on drug withdrawal, not alternative explanation felt more likely); probable (similar to definite, but without a biopsy confirmation); or possible (gastrointestinal symptoms not fulfilling definite or probable criteria).
The study cohort included 306 patients (124 with AS and 182 with PsA; mean age, 51 years; 49% men) who received at least 1 secukinumab dose. The study sample included 7 patients with confirmed IBD and 3 patients with suspected IBD, prior to initiation with secukinumab. During follow-up, 24 (15 AS and 9 PsA; 7.8%) patients had any gastrointestinal-related adverse events.
Risk for gastrointestinal-related adverse events was almost 3-fold higher in patients with AS compared with those with PsA (hazard ratio, 2.8; 95% CI, 1.2-6.7; P = .018). The cumulative probability of secukinumab withdrawal due to gastrointestinal-related adverse events was also higher among patients with AS vs PsA. While age and sex were not significant predictors, a pre-existing diagnosis of IBD was associated with a 14-fold increased risk for gastrointestinal-related adverse events (hazard ratio, 14.1; 95% CI, 5.9-33.3; P <.001). During a total follow-up of 331 patient-years, the incidence of IBD was 1.3 per 100 person-years, including 2 de novo cases of which 1 required surgical intervention.
Definite IBD was documented in 4 patients (1.3%), all of whom had AS and stopped treatment with secukinumab. Probable IBD was documented in 7 patients (2.2%; 4 with PsA and 3 with AS).
Of the 7 patients with a pre-existing diagnosis of IBD, 5 patients developed gastrointestinal-related adverse events after initiation with secukinumab; the patients who did not develop gastrointestinal-related adverse events had ulcerative colitis.
The study had several limitations, including the relatively small sample size, potential bias due to incomplete follow-up, the lack of assessment of some adverse events, and potential right censorship.
“Further research to evaluate the characteristics of patients [with] AS with no history of IBD should be considered in view of stratifying IBD risk prior to IL-17 inhibition,” the researchers concluded.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Onac IA, Clarke BD, Tacu C, et al. Secukinumab as a potential trigger of inflammatory bowel disease in ankylosing spondylitis or psoriatic arthritis patients. Rheumatology (Oxford). Published online March 2, 2021. doi:10.1093/rheumatology/keab193