COMPARISON OF RATES OF ACTIVE TUBERCULOSIS INFECTION IN THE PHASE 2 AND 3 CLINICAL TRIAL PROGRAMS FOR ANTI-IL12/23 AND ANTI-TNFS

Abstract

Background: Biologics are used to treat a variety of autoimmune diseases such as rheumatoid arthritis (RA), psoriasis (PsO), psoriatic arthritis (PsA), Crohn's disease (CD), ulcerative colitis (UC) and ankylosing spondylitis (AS). Patients treated with biologics are at increased risk of developing tuberculosis (TB). We compared the risk of active TB in patients who were treated with biologics having 2 different mechanisms of action, anti‐IL12/23 and anti‐TNF, using data from previous company‐sponsored randomized clinical trials. Methods: Using safety data from the Phase 2 and 3 adult clinical trial programs for anti‐IL 12/23 (ustekinumab) and representative anti‐TNFs (infliximab and golimumab), we compared incidence rates of active TB in patients who received treatment or placebo for RA, PsO, PsA, CD, UC, and AS. Here we report the incidence rates of active TB for these patients, both as absolute frequencies and adjusted for patient‐years of follow‐up. Results: The overall number of active TB cases in the randomized clinical trials using anti‐IL 12/23 (ustekinumab) were lower (2, <0.1%) than with the anti‐TNFs (58, 0.5%) (see Table). The duration of follow‐up varied among the clinical trials; therefore, the incidence rate of active TB cases per 100 patient‐years was compared between anti‐IL 12/23 and anti‐TNFs. When adjusted for patient‐years, the incidence rates of active TB for anti‐IL 12/23 were lower than those observed with anti‐TNFs: anti‐IL 12/23 0.02 (95% CI: 0.00, 0.06) vs anti‐TNFs 0.28 (95% CI: 0.21, 0.37); (cases per 100 patient‐years). This analysis presents data that compared incidence rates of active TB during company‐sponsored clinical trials and was adjusted only for patient‐years of follow‐up and not for other factors including disease indications, patient criteria, geographic regions, demographics, concomitant medication use (e g, methotrexate, and other immune modulators), etc. Conclusion: In this analysis with substantial biological clinical trial experience across indications, treatment with anti‐IL 12/23 was associated with a significantly lower rate of active TB cases compared to treatment with the 2 representative anti‐TNFs. (Figure Presented).