Safety and Efficacy of Tumor Necrosis Factor Antagonists in Older Patients With Ulcerative Colitis: Patient-Level Pooled Analysis of Data From Randomized Trials.

BACKGROUND & AIMS: Treatment of older patients (more than 60 years) with ulcerative colitis (UC) can be a challenge, because they might be more vulnerable to adverse events (AEs). We determined the effects of age on the safety and efficacy of anti-tumor necrosis factor (TNF) therapy in a pooled analysis of data from randomized trials.

METHODS

We obtained individual patient-level data from 4 trials of anti-TNF therapy for patients with UC from the Yale Open Data Access Project. Participants were assigned to groups of older age (60 years or older) and younger age (younger than 60 years). The primary outcome was difference in serious AEs (SAEs), defined as death, life-threatening event, hospitalization, and/or significant disability. Secondary outcomes were severe infections, non-severe infections, neoplasms, and achievement of clinical remission, defined by trial investigators as Mayo score ≤ 2 with no sub-score >1 at the end of induction or maintenance therapy. A random effects logistic regression model was fitted to estimate the effect of anti-TNF therapy on safety and efficacy by age, adjusting for confounders and trial-level effects.

RESULTS

The study cohort included 2257 patients (231 60 years or older). Higher proportions of older patients receiving anti-TNF therapy had SAEs (20%) and hospitalizations (14.4%), compared with younger patients (10.2% had SAEs and 5.2% were hospitalized); there were no significant differences between groups in proportions with severe or non-severe infections. Compared with placebo, there was no significant difference in safety risks associated with anti-TNF therapy (SAEs reduced by 5.4% in older patients vs reduction of 2.4% in younger patients; hospitalizations reduced by 6.7% in older patients vs reduction of 2.5% in younger patients; severe infections reduced by 3.1% vs increase of 0.7% in younger patients). There was no significant difference in between older vs younger patients in efficacy of anti-TNF therapy in inducing remission (odds risk ratio, 1.05, 95% CI, 0.33-3.39) or in maintaining remission (odds risk ratio, 0.49; 95% CI, 0.18-1.33).

CONCLUSIONS

In a pooled analysis of data from randomized trials, we found that older patients with UC have an increased baseline increased risk of SAEs, but no increase in risk can be attributed to anti-TNF therapy in older vs younger patients.