Impact of Age on Efficacy and Safety of Advanced Therapies During Induction in Ulcerative Colitis: An Individual Patient Data Pooled Analysis from Randomized Controlled Trials.

BACKGROUND AND AIMS: We evaluated whether age modifies treatment efficacy and safety of advanced therapies in patients with moderate-to-severe ulcerative colitis (UC).

METHODS

Through an individual patient-level data (IPD) meta-analysis of 10 RCTs of advanced therapies (TNF antagonists: infliximab, adalimumab, golimumab; vedolizumab; ustekinumab; tofacitinib) in patients with moderate-to-severe UC, we compared the efficacy (induction of clinical remission, endoscopic improvement, endoscopic remission, and symptomatic remission) and safety (serious adverse events [SAEs] and infections) of induction therapy in older (≥ 60y) vs younger adults (< 60y). Modified Poisson regression was used to estimate the ratio of risk ratios (RRR) of treatment effects by age, adjusting for baseline endoscopic severity, disease duration, disease extent, prior biologic exposure, C-reactive protein, albumin, hemoglobin, concomitant corticosteroid use, and clustering effect by studies.

RESULTS

Among 6192 patients (mean age 39.6 years, 41% female), 634 (10.2%) were aged ≥ 60 years. Efficacy of all advanced therapies over placebo was similar in older vs younger adults, with no significant treatment effect modification (induction of clinical remission: TNF antagonists, RRR of older vs younger adults, 0.94 [95% CI, 0.41-2.15]; non-TNF-targeting agents, RRR, 1.26 [0.60-2.62]). However, older adults were significantly more likely to experience infections with advanced therapies vs placebo, compared with younger adults (TNF antagonists, RRR, 1.52 [1.12-2.05]; non-TNF-targeting agents, RRR, 2.04 [1.45-2.87]).

CONCLUSION

In patients with moderate-to-severe UC, older age did not modify the magnitude of efficacy but was associated with higher magnitude of infection during induction with advanced therapies.