Real-world incidence of inflammatory bowel disease among patients with other chronic inflammatory diseases treated with interleukin-17a or phosphodiesterase 4 inhibitors

Abstract

Objectives: (1) To assess the real-world incidence of inflammatory bowel disease (IBD) in patients with or without other chronic inflammatory diseases (CIDs), and (2) to understand whether IBD incidence differs in CID patients receiving interleukin-17a signaling antagonists (anti-IL-17a) or phosphodiesterase 4 inhibitors (PDE4i) versus patients using a biologic not indicated for IBD or biologic-naïve patients.

Methods: The MarketScan Research Databases (January 2010–July 2017) were used. A CID population was created from patients with ankylosing spondylitis, psoriatic arthritis, psoriasis or rheumatoid arthritis (RA). The CID population was stratified into different cohorts based on the baseline treatments received: (1) anti-IL-17a, (2) PDE4i, (3) biologic-naïve, and (4) non-IBD-indicated biologic (i.e. biologics not indicated for the treatment of IBD and excluding anti-IL-17a and PDE4i); a non-CID cohort was also created. The 1 year incidence rate (IR) of IBD was compared between cohorts using a logistic regression model adjusting for baseline characteristics.

Results: CID cohorts included older patients than the non-CID cohort (mean age range: 48.4–54.4 versus 46.3 years). The 1 year IR of IBD was 1.41% in the anti-IL-17a cohort (N = 355), 0.68% in the PDE4i cohort (N = 2195), 0.47% in the biologic-naïve cohort (N = 424,767), 0.51% in the non-IBD-indicated biologic cohort (N = 56,317) cohort and 0.25% in the non-CID cohort (N = 1,008,436). After 1 year of follow-up, the odds of having IBD were 2.85 (p = .0213) and 1.42 (p = .1891) times higher in the anti-IL-17a and PDE4i cohorts, respectively, compared to the biologic-naïve cohort, and 2.86 (p = .0253) and 1.21 (p = .4978) times higher compared to the non-IBD-indicated biologic cohort. Similar results were observed in sensitivity analyses where patients with RA only were excluded (since anti-IL-17a and PDE4i agents are not indicated for RA).

Conclusions: Anti-IL-17a treatment was associated with a nearly three-fold higher risk of IBD in CID patients. Treatment decisions for patients with CIDs should take into account the risk of developing of IBD.

Keywords:

• Inflammatory bowel diseases
• interleukin-17
• PDE4
• phosphodiesterases
• incidence

Transparency

Declaration of funding

This work was supported by Janssen Scientific Affairs LLC, and the study sponsor was involved in all aspects of the research, including the conception and design of the study; the collection, analysis and interpretation of the data; writing of the report; and the decision to submit the report for publication.

Author contributions: All authors were involved in the following aspects of the research: the conception and design of the study, or analysis and interpretation of the data; drafting of the paper and revising it critically for intellectual content; and the decision to submit the manuscript for publication. All authors agree to be accountable for all aspects of the work.

Declaration of financial/other relationships

B.E. and P.L. have disclosed that they are employees of Analysis Group Inc., a consulting company that has provided paid consulting services to Janssen Scientific Affairs LLC, which funded the development and conduct of this study and manuscript. M.L. (currently working at Evidera) has disclosed that he was an employee of Analysis Group Inc. at the time the study was conducted. L.A.E. and S.D.C. have disclosed that they are current employees and stockholders of Johnson & Johnson. CMRO peer reviewers on this manuscript have received an honorarium from CMRO for their review work but have no relevant financial or other relationships to disclose.

Previous presentation: Part of the material in this manuscript was presented at the 2018 Academy of Managed Care Pharmacy (AMCP) Annual Meeting, 2018 Apr 23–26, Boston, MA; and at the American College of Rheumatology (ACR) 2018 Annual Meeting, 2018 Oct 19–24, Chicago, IL.

Acknowledgements

Medical writing assistance was provided by Samuel Rochette, an employee of Analysis Group Inc., which received consultancy fees from Janssen Scientific Affairs, LLC to conduct this study.