Retrospective Cohort Study on the Predictive Value of Primary Non-response to Initial Biologic for Future Biologic Use in Patients with Inflammatory Bowel Disease.

Abstract

Background: The armamentarium of medical therapies to treat inflammatory bowel disease (IBD) continues to grow, which has expanded treatment options, particularly after first biologic failure. Currently, there are limited studies investigating the predictive value of first biologic primary non-response (PNR) on subsequent biologic success. Our objective was to determine if PNR to the first biologic for IBD is predictive of response to subsequent biologic therapy.

Methods: A multicenter retrospective chart review study was performed with patients with IBD that received two or more biologics. PNR was defined as no clinical or symptomatic improvement after at least six weeks of treatment 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 were classified as secondary loss of response (SLOR). Data analysis was performed with Python and Excel.

Results: Of the 249 patients that met inclusion criteria, there were 87 patients with PNR, 96 patients with SLOR, and 66 patients with intolerance to their first biologic exposure. Patients with ulcerative colitis (UC: 41.3%, p = 0.0083) and IBD-unclassified (IC: 56.3%, p = 0.0099) were found to have a significantly higher rate of primary non-response compared to patients with Crohn's disease (CD: 25.0%). Patients on adalimumab for their first biologic had a significantly (p = 0.0014) higher rate of PNR (42.7%, UC: 50.0%, CD: 32.7%) compared to those on infliximab (23.0%, UC: 31.0%, CD: 12.1%). Patients with PNR did not have a higher rate of second biologic nonresponse when compared to patients who had SLOR or intolerance to their first biologic. Univariate analyses demonstrated no difference in rates of response to second biologic when switching intra-class or out-of-class.

Conclusion: Ulcerative colitis and IBDU have higher rates of PNR compared to Crohn's disease, but still have high response rates to second biologic agents. Adalimumab may be a suboptimal initial biologic given its higher PNR rate compared to infliximab. Our results support that there is an equally likely chance of response to second biologic after first biologic PNR. Subanalyses evaluating intraclass and out-of-class medication switching showed similar success.