Incidence rates of inflammatory bowel disease (IBD) among patients being treated with secukinumab (Cosentyx) for rheumatic inflammatory diseases were low, pooled clinical trial data indicated.
The exposure-adjusted incidence rates of IBD for patients receiving secukinumab for psoriasis ranged from 0.01 to 0.13 per 100 patient-years, according to Stefan Schreiber, MD, PhD, of University Hospital Schleswig Holstein in Kiel, Germany, and colleagues.
In addition, rates ranged from 0.05 to 0.08 per 100 for psoriatic arthritis (PsA) and from 0.1 to 0.4 per 100 for ankylosing spondylitis (AS), the researchers reported online in .
Patients with psoriasis, PsA, and AS have a recognized risk for developing IBD, with significant genetic overlap between the skin and joint disorders and the intestinal condition.
Secukinumab is a monoclonal antibody that targets interleukin (IL)-17A and is associated with rapid and significant improvements in psoriasis, PsA, and AS. However, "inhibition of IL-17A may have dual effects, reducing inflammation but also potentially impairing residual function of an already damaged [intestinal] epithelial barrier," the researchers wrote.
Moreover, have been reported among patients with these disorders being treated with IL-17 inhibitors.
Therefore, to examine the incidence and pattern of IBD among patients receiving secukinumab, Schreiber and colleagues pooled data from 21 randomized trials that included a total of 7,355 patients with cumulative exposure of 16,226.9 patient-years.
The analysis included 5,181 patients with psoriasis and exposure of 10,416.9 patient-years, 1,380 patients with PsA and 3,866.9 patient-years of exposure, and 794 patients with AS and 1,943.1 patient-years of exposure. Cases of IBD were defined as Crohn's disease, ulcerative colitis, or IBD-unclassified.
Two-thirds of patients with psoriasis and AS and half of those with PsA were men, and mean ages ranged from 42 to 49 years. Up to one-third of patients had previously used tumor necrosis factor inhibitors and were smokers, which are risk factors for the development of Crohn's disease.
A previous history of IBD was reported in 15 patients with psoriasis, in 14 of those with PsA, and in 25 of those with unclassified IBD.
During overall follow-up, 41 cases of IBD were reported. In the psoriasis group, there were 14 cases of ulcerative colitis, five cases of Crohn's disease, and one case of unclassified IBD, with 14 of the cases being new onset.
In the PsA group, there were three cases of ulcerative colitis, three of Crohn's disease, and two unclassified, with seven being new onset cases, and in the AS group, the respective number of cases were four, eight, and one, with nine being new onset.
Mean age at the time of the IBD diagnosis was 46.1 years, and two-thirds were men.
During post-marketing surveillance that exceeded 96,000 patient-years, the cumulative rate of events remained stable, at approximately 0.20 per 100 patient-years. "This is consistent with previously reported long-term secukinumab data, which demonstrated that the safety profile of secukinumab remains favorable through 5 years of psoriasis treatment with no increases in yearly adverse event rates," the authors noted.
The rates of IBD observed in this study "appear to be within the range of expected background incidence rates (per 100 patient-years) of Crohn's disease and ulcerative colitis in patients with psoriasis, PsA, and AS, which are approximately 0.1 in patients with PsA, 0.3 in psoriasis, and 0.7 in AS," the researchers noted.
Also reflecting the background incidence of IBD, the observed incidence rate for Crohn's disease was higher among patients with AS, at 0.4 per 100 patient-years, than in patients with psoriasis or PsA, both at 0.1 per 100. Rates of ulcerative colitis were similar for the three indications.
An area of considerable interest for further study is whether the etiology of IBD that develops in patients with inflammatory rheumatic diseases is the same as for IBD in general. "IBD is an extremely polygenic disease with a diverse range of pathophysiologies that are probably related to the individual genetic distortions in the patient. Genetic risk architecture in IBD, however, relates to the specific intestinal phenotype," they explained.
Longer term registry data could provide additional information about the occurrence of IBD in patients being treated with IL-17 blockers, they concluded.
Disclosures
The clinical trials analyzed in this study were funded by Novartis Pharma AG.
The authors reported financial relationships with Novartis, AbbVie, AstraZeneca/MedImmune, Boehringer Ingelheim, Celltrion, Ferring, Janssen, Merck Sharp & Dohme, Pfizer, Sanofi, Takeda, UCB, Amgen, Celgene, Genentech, Eli Lilly, Second Genome, Seres, Shire, Theradiag, Millennium, Tillotts, Centocor, Elan/Biogen, Bristol-Myers Squibb, ActoGenix, Weeth, Teva, Serono, Albireo, Given Imaging, Salix, Novo Nordisk, GlaxoSmithKline, Vertex, and Xenoport. Several are employees of Novartis.
Primary Source
Annals of the Rheumatic Diseases
Schreiber S, et al "Incidence rates of inflammatory bowel disease in patients with psoriasis, psoriatic arthritis and ankylosing spondylitis treated with secukinumab: a retrospective analysis of pooled data from 21 clinical trials" Ann Rheum Dis 2019; doi:10.1136/annrheumdis-2018-214273.