Introduction: The armamentarium of medical therapies to treat inflammatory bowel disease (IBD) continues to grow, giving patients more options if they fail their first biologic. Currently, there are limited studies investigating the predictive value of first biologic primary nonresponse (PNR) on subsequent biologic success. Our objective was to determine if PNR to the first biologic for IBD is predictive to response to subsequent biologic therapy.
Methods: A multicenter retrospective study was performed on IBD patients that received two or more biologics. PNR was defined as no clinical or symptomatic improvement leading to cessation of drug. Patients who stopped their first biologic due to adverse side effects were classified in the intolerance group. Patients with initial significant response to biologic followed by a loss of response including antibody response to the biologic agent were classified as secondary loss of response (SLOR). Python was used for analysis.
Results: We identified 87 patients with PNR, 96 patients with SLOR, and 66 patients with intolerance to their first biologic exposure. In patients with PNR, there was a significantly (p=0.0344) higher percentage of patients with ulcerative colitis and indeterminate colitis (UC: 57.5%, IC: 10.3%) compared to Crohn’s disease (CD: 32.2%). Among patients who had PNR, SLOR, or intolerance of their first biologic, there was no significant difference in those that demonstrate non-response to their second biologic. Univariate and multivariate analyses showed no difference in rates of PNR to second biologic when switching intra-class or out of class. There was a trend towards significance of higher rates of PNR to adalimumab as second biologic when switching from infliximab (OR 0.36, CI: 0.09 – 1.55, p = 0.171), however the total sample size was low (n=60). Additionally, when analyzing Crohn’s disease and ulcerative colitis separately, there were no differences in response to second biologic after PNR to first biologic.
Discussion: Our results are reassuring that despite PNR to first biologic, there is a high chance of response to second biologic. Subanalyses evaluating intraclass and out of class medication switches showed similar success, however larger studies are required to better evaluate this. Ulcerative colitis and indeterminant colitis have higher rates of PNR compared to Crohn’s disease, but still have high response to second biologic agents.
