Factors Associated with Discontinuation of Anti-TNF Inhibitors Among Persons with IBD: A Population-Based Analysis

Antitumor necrosis factor (anti-TNF) medications are known to be highly efficacious in persons with moderate-to-severe inflammatory bowel disease (IBD). There is a paucity of data from population-based sources to elucidate persistence with these medications in the general population of IBD. Discontinuation of anti-TNF therapy is a marker of lack of effectiveness, intolerance, and patient/physician practice preferences.

We identified all persons with IBD in Manitoba who were dispensed infliximab (IFX) and adalimumab (ADA) between 2001 and 2014. Subjects were followed longitudinally to assess rates of completion of anti-TNF induction, duration of continued use, intraclass substitution, and dose adjustments. Cox proportional hazards models were used to test demographic and clinical factors associated with anti-TNF therapy discontinuation.

Overall, 925 of 8651 persons (10.7%) with IBD were prescribed an anti-TNF drug (705 Crohn's disease: 523 IFX and 182 ADA; 220 ulcerative colitis: 214 IFX and 6 ADA). Approximately four-fifths of persons starting on anti-TNF therapy completed induction. At 1 and 5 years, persistence rates with the original anti-TNF were approximately 60% and 40%, respectively. Immunomodulator use at the time of anti-TNF dispensation was associated with a decreased likelihood of anti-TNF discontinuation in both Crohn's disease and ulcerative colitis. ADA users with Crohn's disease who reached maintenance phase had a higher risk of discontinuation than IFX users (hazard ratio 1.64, 95% confidence interval 1.15-2.37).

Approximately two-fifths of anti-TNF users discontinue use within 1 year of initiation, and three-fifths will have discontinued at 5 years. Concomitant IM therapy has a modest effect on discontinuation rates.