Early immunomodulator therapy reduces the risk of intestinal resection in Crohns disease: a systematic review and meta-analysis

Abstract Background The optimal timing for initiating immunomodulators (IMs) in Crohns disease (CD) remains unclear. We assessed whether early IM therapy reduces the risk of intestinal resection. Methods MEDLINE, EMBASE, and the Cochrane Library were systematically searched for studies comparing outcomes by timing of IM (thiopurines or methotrexate) initiation in CD. The primary outcome was intestinal resection. Pooled hazard ratios (HRs) with 95% CIs were calculated using a random-effects model. Results Seven cohort studies including 4297 patients were analyzed. Early IM initiation was associated with a 47% lower risk of intestinal resection compared with late or no IM therapy (pooled HR, 0.53; 95% CI, 0.44-0.65; I2 = 23%). This protective effect was consistent across subgroups, including studies in which all patients received IMs and early initiation was associated with a lower risk than late initiation (HR 0.59; 95% CI, 0.42-0.83). When early treatment was defined as initiation within 1-2 years of diagnosis, early IM use was associated with a lower risk of intestinal resection than late or no IM therapy, with no heterogeneity (HR 0.55; 95% CI, 0.43-0.70; I2 = 0%). A broader definition of early treatment as within 3 years of diagnosis also showed benefit compared with late or no IM therapy (HR, 0.52; 95% CI, 0.37-0.74) but with moderate heterogeneity (I2 = 57%). Conclusions Early IM therapy is associated with a substantially lower risk of intestinal resection in CD compared with later or no IM therapy. The most consistent benefit occurs when treatment is initiated within the first 1-2 years after diagnosis, supporting the concept of a therapeutic “window of opportunity” during which timely IM initiation may favorably alter the disease course.