Incidence Of Suboptimal Response To First-Line Anti-Tnf Therapy In Patients With Ibd In Argentina: Results From The Explore Study

BACKGROUND: While anti-TNFs have long been a mainstay in UC and CD management, a considerable proportion of patients experience treatment failure. The aim of this sub-analysis from the main EXPLORE study (NCT03090139) was to assess suboptimal response to anti-TNFs in Argentina. METHODS: Patients with Ulcerative Colitis (UC) and Crohn´s Disease (CD) who initiated first-line anti-TNF therapy between March 2010 and March 2015 from 5 centers in Argentina were enrolled. Anti-TNF dose escalation or discontinuation, IBD-related surgery or hospitalizations, and augmentation of non-biological therapy were considered indicators of suboptimal response to anti-TNF therapy. Primary non-response (PNR) was defined as suboptimal response that occurred within 4 months of anti-TNF initiation (index date), and secondary loss of response (SLOR) if this occurred > 4 months after initiation. The cumulative incidence (CI) of suboptimal response to first-line anti-TNF therapy was evaluated within 2 years after treatment initiation. RESULTS: A total of 78 first-line anti-TNF treated patients were analyzed (n = 40 CD, n = 38 UC). Females represented 45.0% and 52.6% in CD and UC, respectively. At diagnosis, over half of the CD patients had ileocolonic disease involvement (55.0%), while 47.4% and 39.5% of the UC patients showed a left-sided colitis and extensive involvement (including pancolitis), respectively. Median age at diagnosis was 31 years (range 13-67) and 29 years (range 11-80) for CD and UC, respectively. Median age at first-line anti-TNF treatment was 34.5 years (range 22-70 for CD and 19-81 for UC). About 36.9% of CD patients had a disease duration between 0 to < 2 years to index date, 33.3% ≥ 2 to 5 years, 10.3% ≥ 5 to < 8 years and 20.5% ≥ 8 years; the respective proportions were 50.0%, 15.8%, 13.2% and 21.0% in UC.Within 2 years of treatment initiation, PNR was 15.0% in CD (n = 6) and 10.5% in UC (n = 4), while SLOR was 42.5% in CD (n = 17) and 31.6% in UC (n = 12). The CI of suboptimal response for the first anti-TNF agent was 37.9% and 30.0% at 12 months and 49.2% and 44.5% at 24 months for CD and UC, respectively. Augmentation in non-biological therapy and dose escalation of the anti-TNF were the most frequent indicators of suboptimal response in both conditions (30.4% and 26.1% [CD]; 25.0% and 56.3% [UC]). CONCLUSION: In accordance with other real-world studies, almost half of first-line anti-TNF treated IBD patients evaluated in 5 centers in Argentina experienced suboptimal response to their first-line anti-TNF therapy within 2 years. Determining response-predictive biomarkers and the use of newer therapies may help improve treatment outcomes in IBD.