Predictors of drug survival: A cohort study comparing anti-tumour necrosis factor agents using the Swedish inflammatory bowel disease quality register.

Abstract

Whether long-term effectiveness differs between anti-tumour necrosis factor (anti-TNF) agents is unknown. To examine drug survival of first-line anti-TNF agents and identify predictors of discontinuation. To reduce channelling bias, we also compared drug survival of the second anti-TNF. Biologic-naïve patients (N=955) recorded in the Swedish IBD Quality Register (SWIBREG) were examined. We used propensity score matching, comparing drug survival over up to three years of follow-up. Cox regression estimated adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). In Crohn's disease, discontinuation because of lack/loss of response was 32% [95%CI=26%-38%] for infliximab versus 16% [95%CI=11%-21%] for adalimumab. Infliximab [vs adalimumab; aHR=1.96; 95%CI=1.20-3.21] and colonic disease (L2) [vs no L2; aHR=2.17; 95% CI=1.26-3.75] were associated with higher discontinuation rates, whereas normalised CRP at three months [aHR=0.40; 95% CI=0.19-0.81] with a lower rate. Consistently, patients who switched from adalimumab to infliximab (vs infliximab to adalimumab) had earlier discontinuation (P=0.04). Concomitant use of immunomodulators was associated with a lower adverse drug reaction-mediated discontinuation rate [aHR=0.46; 95% CI=0.28-0.77], in part explained by fewer infusion reactions [aHR=0.27; 95% CI=0.08-0.89]. In ulcerative colitis, the probability of discontinuation because of lack/loss of response was 40% [95% CI=33%-47%] for infliximab versus 37% [95% CI=21%-53%] for adalimumab. Disease duration ≥10years [aHR=0.25; 95% CI=0.10-0.58] and normalised CRP after three months [aHR=0.39; 95% CI=0.18-0.84] were associated with lower discontinuation rates. Clinical characterisation of patients may aid decision-making on anti-TNF treatment. The consistently shorter drug survival for infliximab (vs adalimumab) in Crohn's disease, suggests a potential difference between the two drugs.