Systematic review with meta-analysis: loss of response and requirement of anti-TNFα dose intensification in Crohn's disease.

<bold>Background: </bold>To review the frequency with which anti-TNF-α loses its effect and dose "intensification" is required for Crohn's disease (CD) treatment.<bold>Methods: </bold>Electronic databases were searched for eligible studies. Raw data from studies meeting inclusion criteria were pooled for effect estimates. Subgroup analyses were performed for exploration of heterogeneity regarding all outcomes.<bold>Results: </bold>Eighty-six eligible studies were included. Estimates of loss of response (LOR) incidence ranged from 8 to 71%. The random effects pooled incidence of LOR with a median follow-up of 1-year was 33% (95% CI 29-38, 55 studies, n = 6135). The effect estimate based on data from patients with infliximab was 33% (95% CI 27-40), 30% (95% CI 22-39) for adalimumab, and 41% (95% CI 30-53) for certolizumabpegol. Overall, the mean percentage of patients' LOR to anti-TNFs was 38.5%. The annual risk for LOR was 20.9% per patient-year. The random-effects pooled rate of need for dose intensification with a median follow-up of 1 year was 34% (95% CI 28-41, 38 studies, n = 10,690). The effect estimate for infliximab was 38% (95% CI 28-50), 36% (95% CI 30-43) for adalimumab, and 2% (95% CI 2-3) for certolizumab-pegol. The mean percentage of patients who needed an anti-TNF dose escalation was 23% with an annual risk of 18.5% per patient-year. There was no evidence of publication bias for incidence of LOR but not for the dose intensification (p = 0.001).<bold>Conclusions: </bold>Overall, around one-third of CD patients experience a LOR and required dose intensification in primary anti-TNF-α responders. [ABSTRACT FROM AUTHOR]