Loss of Response to Anti‐Tumor Necrosis Factor Alpha Therapy in Patients With Inflammatory Bowel Disease: A Real‐World Comparison of Combination Therapy Versus Monotherapy

ABSTRACT Objectives The success of anti‐TNFα agents has changed the landscape of treatment for inflammatory bowel diseases (IBD). One major limitation to this success is the secondary loss of response (sLOR) phenomenon. Combination therapy with immunomodulating agents has been shown to be effective in reducing the sLOR process. The primary aim of this study was to evaluate the rates of sLOR to anti‐TNFα therapy in IBD patients on mono versus combination therapy, using real‐world data. Methods This was a retrospective study of 200 patients with IBD treated with anti‐TNFα agents from 2000 to 2023. Data was collected on patient demographics, IBD phenotype, drug therapy, clinical and biochemical response to treatment. Results Overall, there was no significant difference in median duration of response for infliximab (IFX) vs. adalimumab (ADA) (15 months, IQR 7–30 vs. 17 months, IQR 8–31; p = 0.53). In total, 41/200 (20.6%) of patients developed sLOR. Rates of sLOR were similar between IFX (23/106, 21.7%) and ADA (18/94, 19.1%, p = 0.76). Combination therapy (used in 69/200, 34.8% patients) was associated with a significantly lower risk of sLOR compared with monotherapy (HR 0.41, 95% CI: 0.19–0.87; p = 0.020). This effect was observed in patients receiving IFX (p = 0.0095), whilst no significant difference was seen with ADA (p = 0.15). Safety outcomes were comparable between both groups, with no signal for increased risk of infection or malignancy with combination therapy. Conclusion Combination therapy significantly reduced sLOR compared with monotherapy. There was no significant difference in sLOR between IFX and ADA.