Inhibition of structural damage progression with the selective interleukin-23 inhibitor guselkumab in participants with active PsA: results through week 24 of the phase 3b, randomised, double-blind, placebo-controlled APEX study.

Abstract

Objectives: The APEX study evaluated the effects of guselkumab, a fully human, dual-acting monoclonal antibody able to bind CD64 and selectively inhibit the interleukin (IL)-23p19 subunit, on clinical and radiographic outcomes in active psoriatic arthritis (PsA).

Methods: APEX (ongoing, phase 3b, double-blind, placebo-controlled) randomised (5:7:7) biologic-naïve adults with active PsA (≥3 tender, ≥3 swollen joints; C-reactive protein ≥0.3 mg/dL; ≥2 erosive joints) to subcutaneous guselkumab 100 mg every 4 weeks (Q4W); guselkumab 100 mg at week 0, week 4, then every 8 weeks (Q8W); or placebo every 4 weeks. Primary (proportion of participants achieving ≥20% improvement in American College of Rheumatology response criteria [ACR20]) and major secondary (total PsA-modified van der Heijde-Sharp [vdH-S] score least squares mean [LSM] change from baseline) endpoints at week 24 were multiplicity-controlled for comparing each guselkumab group versus placebo.

Results: Among 1020 participants (Q4W: 273; Q8W: 371; placebo: 376), significantly greater proportions of participants receiving guselkumab Q4W (66.6%) and Q8W (68.3%) versus placebo (47.0%) achieved ACR20 at week 24 (both P < 0.001). Baseline mean total vdH-S scores were 26.7 to 27.7 across groups; guselkumab Q4W- and Q8W-treated participants exhibited significantly lower rates of radiographic progression versus placebo at week 24 (total vdH-S score LSM change: 0.55 and 0.54 vs 1.35; P = 0.002 and P < 0.001, respectively). Through week 24, 38.2%, 42.5%, and 37.3% of participants receiving guselkumab Q4W, Q8W, and placebo, respectively, had ≥1 adverse event, with no new safety signals.

Conclusions: Guselkumab, a fully human monoclonal antibody able to bind CD64 and simultaneously inhibit the IL-23p19 subunit, provided significantly higher rates of clinical improvement and significant inhibition of structural damage progression versus placebo, with no new safety signals, at week 24 in biologic-naïve participants with active and erosive PsA.