Efficacy and Safety of ABBV-154 for the Treatment of Active Rheumatoid Arthritis: A Phase 2b, Randomized, Placebo-Controlled Trial.

Abstract

Despite the availability of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) to treat rheumatoid arthritis (RA), many patients do not experience optimized disease control. Glucocorticoids are effective but have safety risks. ABBV-154, an antibody-drug conjugate, is made up of adalimumab linked to a glucocorticoid receptor modulator. This phase 2b study evaluated the efficacy and safety of ABBV-154 in patients with moderately to severely active RA receiving background methotrexate with inadequate response to at least one prior b/tsDMARD. Patients were randomized 1:1:1:1:1 to subcutaneous ABBV-154 40, 150, or 340 mg every other week; 340 mg every 4 weeks; or placebo. The primary endpoint was achieving 50% improvement in the American College of Rheumatology response criteria (ACR50) at week 12; secondary endpoints included achieving the ACR20 and ACR70 criteria. Treatment-emergent adverse events (TEAEs) were monitored. Clinical development of ABBV-154 was discontinued; the study was terminated early. Overall, 472 patients were treated. At week 12, more patients achieved ACR50 (primary endpoint) with ABBV-154 (25.5%-44.4% across dose groups) versus placebo (6.3%; all P < 0.001). ACR20 response rates were higher in all ABBV-154 treatment groups versus placebo (P < 0.001). Most ABBV-154 groups achieved the other secondary endpoints. For all ABBV-154 doses, TEAEs rates through week 12 were similar to placebo. Ten serious infection TEAEs occurred in the ABBV-154 groups. ABBV-154 demonstrated superior efficacy over placebo in patients with RA and inadequate response to prior b/tsDMARDs. TEAE rates in all ABBV-154 arms were comparable with placebo. These findings provide useful insights into the design of new antibody-drug conjugates for RA.