Efficacy and Safety of <scp>ABBV</scp> ‐154 for the Treatment of Active Rheumatoid Arthritis: A Phase 2b, Randomized, Placebo‐Controlled Trial
Frank Buttgereit, Atul Singhal, Alan Kivitz, Edit Drescher, Yoshinori Taniguchi, Rosalía Martínez Pérez, J. Anderson, Ronilda D’Cunha, Weihan Zhao, Nicholas DeVogel, Julie Parmentier, Romy Christmann, Dilek Arikan, Howard Amital
Abstract
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.