London, United Kingdom—Inflammatory bowel disease (IBD) is often associated with psoriasis, psoriatic arthritis (PsA), and ankylosing spondylitis (AS), explained Stefan Schreiber, MD, Christian-Albrechts-University, Kiel, Germany. The risk for Crohn’s disease is approximately 4 times higher in patients with psoriasis, compared with the general population; it is even higher in patients with PsA and AS.
According to data Dr Schreiber presented at the 2016 annual meeting of the European League Against Rheumatism (EULAR), secukinumab does not increase the risk for IBD in patients with psoriasis, PsA, and AS.1
“These results suggest that secukinumab is a therapeutic option for patients with concomitant stable IBD who have good follow-up,” he added.
Secukinumab is an interleukin (IL)-17A inhibitor approved by the FDA for treatment of psoriasis, PsA, and AS. The monoclonal antibody is widely approved in other countries, and is the first IL-17A inhibitor with positive phase 3 results for the treatment of patients with active PsA and AS.
“There have been conflicting reports on the role of IL-17A in gastrointestinal health and disease,” Dr Schreiber continued. “Inhibiting 17A may have dual effects, reducing inflammation but also potentially interfering with repair and function of the epithelial barrier of the gut.”
Low Incidence of Crohn’s Disease, Ulcerative Colitis
The investigators evaluated data from a database of 14 phase 2 and 3 clinical trials of patients (N = 5550) treated with secukinumab. Of these trials, 10 were conducted in patients with moderate-to-severe psoriasis, and 2 phase 3 studies in patients with active PsA and AS, respectively.
Patients with a history of IBD were eligible for study inclusion, but not patients with active IBD. At baseline, patients’ ages ranged from 42 to 48 years; few (2.3%) patients had a history of IBD, with the highest percentage in AS. Patients were treated for 12 to 16 weeks, and then patients receiving placebo were switched to secukinumab over the longer term.
“Over 5200 patient-years of exposure to secukinumab, there was a very low incidence, under 1%, of any Crohn’s disease or ulcerative colitis event,” observed Dr Schreiber. “We did not see any pattern related to secukinumab exposure. We certainly did not see a wave of IBD triggered by this antibody.”
Twelve cases of Crohn’s disease events were identified: 6 new cases, and 6 exacerbations of previous cases. Some of these patients continued on drug treatment with secukinumab, and no temporal pattern was observed.
Nine cases of ulcerative colitis developed in the study patients: 5 new cases, and 4 exacerbations of previous ulcerative colitis. Most patients recovered, and some continued on secukinumab. Again, no temporal pattern was observed.
Factors associated with emerging IBD included a prior history of IBD, prior use of an anti–tumor necrosis factor inhibitor, and smoking.
“This comprehensive evaluation of patients with psoriasis, PsA, and AS treated with secukinumab showed that IBD occurred infrequently, with no evidence of increased new onset or exacerbated cases,” Dr Schreiber said. “With long-term secukinumab exposure, the rate of IBD was within the expected range.”
The rates of Crohn’s disease and ulcerative colitis observed in secukinumab-treated patients of this study are consistent with those reported in the literature in patients with psoriasis, PsA, and AS.
“This study provides important information for rheumatologists around the world,” emphasized session moderator Maxime Dougados, MD, René Descartes University and Hôpital Cochin in Paris, France.
MEASURE 1 Trial
According to a separate report presented at EULAR on the phase 3 MEASURE 1 trial, secukinumab prevented radiographic progression of the spine in patients with AS, which is important for preventing functional disability, according to experts.2
The investigators of the trial randomized 371 patients with AS to receive secukinumab or placebo. After 16 weeks of treatment, nonresponders to placebo crossed over to review secukinumab.
No radiographic progression was observed in 80% of the patients. At 2 years, the change in modified Stoke AS Spinal Score (SASSS) was .30 units in patients treated with placebo, compared with .45 units in patients taking placebo who were switched to the active drug.
“The change in modified SASSS with anti-TNF inhibitors was about 1 unit, suggesting that secukinumab slows progression a bit more,” noted the study’s lead author Juergen Braun, MD, Rheumazentrum Ruhrgebiet, Herne, Germany. “But we have to prove this in a head-to-head trial.”
- Schreiber S, Sands, BE, Deodhar A, et al. No increased incidence of inflammatory bowel disease among secukinumab-treated patients with moderate to severe psoriasis, psoriatic arthritis, or ankylosing spondylitis: data from 14 phase 2 and phase 3 clinical studies. Presented at: 2016 European League Against Rheumatism Annual Congress; June 8-10, 2016;London, United Kingdom.
- Braun J, Baraliakos X, Deodhar A, et al. Effect of secukinumab, an interleukin-17a inhibitor, on spinal radiographic changes through 2 years in patients with active ankylosing spondylitis: results of the phase 3 study, measure 1. Presented at: 2016 European League Against Rheumatism Annual Congress; June 8-10, 2016; London, United Kingdom.