Efficacy and safety of tildrakizumab in patients with active psoriatic arthritis: results of a randomised, double-blind, placebo-controlled, multiple-dose, 52-week phase IIb study

Objectives To evaluate efficacy and safety of the anti-interleukin-23p19 monoclonal antibody tildrakizumab in patients with psoriatic arthritis (PsA). Methods In this randomised, double-blind, placebo-controlled, phase IIb study, patients with active PsA were randomised 1:1:1: 1:1 to tildrakizumab 200 mg every 4 weeks (Q4W); tildrakizumab 200, 100 or 20 mg Q12W; or placebo Q4W. Patients receiving tildrakizumab 20 mg or placebo switched to tildrakizumab 200 mg Q12W at W24; treatment continued to W52. The primary efficacy endpoint was proportion of patients with ACR20 response (>= 20% improvement by American College of Rheumatology criteria) at W24. Secondary efficacy endpoints were assessed without adjustment for multiplicity. Safety was evaluated from treatment-emergent adverse events (TEAEs). Results 391/500 patients screened were randomised and treated. At W24, 71.4%-79.5% of tildrakizumab-treated versus 50.6% of placebo-treated patients achieved ACR20 (all p<0.01). Patients receiving tildrakizumab versus placebo generally achieved higher rates of ACR50, Disease Activity Score in 28 joints with C reactive protein <3.2, minimal disease activity and 75%/90%/100% improvement from baseline Psoriasis Area and Severity Index responses at W24 and through W52. Improvement in dactylitis and enthesitis was not observed; results were mixed for other outcomes. Responses in patients switched to tildrakizumab 200 mg at W24 were consistent with treatment from baseline. TEAEs and serious TEAEs occurred in 64.5% and 3.3%, respectively, of all patients through W52 and were comparable among treatment arms. Conclusions Tildrakizumab treatment significantly improved joint and skin manifestations of PsA other than dactylitis and enthesitis. Treatment was generally well tolerated through W52.