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.

Abstract

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. Clinicaltrials.gov NCT02980692.

• Authors: Philip J Mease, Saima Chohan, Ferran J Garcia Fructuoso, Michael E Luggen, Proton Rahman, Siba P Raychaudhuri, Richard C Chou, Alan M Mendelsohn, Stephen J Rozzo, Alice Gottlieb
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 80 Issue 9 Pg. 1147-1157 (09 2021) ISSN: 1468-2060 [Electronic] England
• PMID: 33985942 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

• Antibodies, Monoclonal, Humanized
• Antirheumatic Agents
• Glucocorticoids
• Sulfasalazine
• tildrakizumab
• Leflunomide
• Methotrexate

Topics

• Adult
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Antirheumatic Agents (therapeutic use)
• Arthritis, Psoriatic (drug therapy, physiopathology)
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Glucocorticoids (therapeutic use)
• Humans
• Leflunomide (therapeutic use)
• Male
• Methotrexate (therapeutic use)
• Middle Aged
• Sulfasalazine (therapeutic use)