Article Text

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
  1. Philip J Mease1,2,
  2. Saima Chohan3,
  3. Ferran J Garcia Fructuoso4,
  4. Michael E Luggen5,6,
  5. Proton Rahman7,
  6. Siba P Raychaudhuri8,9,
  7. Richard C Chou10,
  8. Alan M Mendelsohn11,
  9. Stephen J Rozzo11,
  10. Alice Gottlieb12
  1. 1 Rheumatology Research, Swedish Medical Center, Seattle, Washington, USA
  2. 2 Providence St. Joseph Health and University of Washington, Seattle, Washington, USA
  3. 3 Arizona Arthritis and Rheumatology Research, PLLC, Phoenix, Arizona, USA
  4. 4 Hospital CIMA Sanitas, Barcelona, Spain
  5. 5 Cincinnati Rheumatic Disease Study Group, Cincinnati, Ohio, USA
  6. 6 Division of Immunology, Allergy, and Rheumatology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
  7. 7 Medicine, Eastern Health and Memorial University, St. Johns, Newfoundland, Canada
  8. 8 Division of Rheumatology, Allergy and Clinical Immunology, University of California School of Medicine, Davis, California, USA
  9. 9 Rheumatology, VA Medical Center Sacramento, Sacramento, California, USA
  10. 10 Division of Allergy, Immunology and Rheumatology, University at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York, USA
  11. 11 Sun Pharmaceutical Industries, Princeton, New Jersey, USA
  12. 12 Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
  1. Correspondence to Dr Philip J Mease, Rheumatology Research, Swedish Medical Center, Seattle, Washington, USA; pmease{at}philipmease.com

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.

  • arthritis
  • psoriatic
  • biological therapy
  • cytokines

Data availability statement

Data are available upon reasonable request. Data and other documents will be made available after publication, with no end date, to anyone who submits a reasonable request to the study sponsor.

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Data availability statement

Data are available upon reasonable request. Data and other documents will be made available after publication, with no end date, to anyone who submits a reasonable request to the study sponsor.

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Footnotes

  • Handling editor Josef S Smolen

  • Contributors All authors contributed to data interpretation and manuscript development, critically reviewed each draft for intellectual content and approved the final version for submission.

  • Funding The study was funded by Sun Pharma Global FZE. Analyses were funded by Sun Pharmaceutical Industries, Princeton, NJ, USA.

  • Competing interests PJM has received research grants from AbbVie; Amgen; Bristol Myers Squibb; Celgene; Janssen; Eli Lilly; Novartis; Pfizer; Sun Pharmaceutical Industries, Inc.; and UCB; consulting fees from AbbVie; Amgen; Bristol Myers Squibb; Boehringer Ingelheim; Galapagos; Gilead; GlaxoSmithKline; Janssen; Eli Lilly; Merck; Novartis; Pfizer; Sun Pharmaceutical Industries, Inc.; and UCB; and speaker fees from AbbVie, Amgen, Bristol Myers Squibb, Genentech, Janssen, Eli Lilly, Novartis, Pfizer and UCB. SC is a partner/physician at Arizona Arthritis and Rheumatology Associates. FJGF has received research grants, consulting fees and/or speaker fees from AbbVie, Eli Lilly, Gedeon Richter, MedImmune, Nichi-Iko, Pfizer, Sanofi-Aventis, Takeda and UCB. MEL has received research grants, consulting fees and/or speaker fees from AbbVie; Amgen; Eli Lilly; Genentech; Nichi-Iko; Novartis; Pfizer; R-Pharm; and Sun Pharmaceutical Industries, Inc. PR has received research grants from Janssen and Novartis, consulting fees from AbbVie, Amgen, Bristol Myers Squibb, Celgene, Janssen, Eli Lilly, Novartis, Pfizer, Roche and UCB; and speaker fees from AbbVie, Janssen, Eli Lilly, Novartis, Pfizer and UCB. SPR has received grants/research support from AbbVie; Janssen; Novartis; Pfizer; and Sun Pharmaceutical Industries, Inc.; and consulting fees from Amgen, Eli Lilly, Janssen, Novartis and Pfizer. RCC receives consultation fees from Sun Pharmaceutical Industries, Inc. AMM is a former employee of Sun Pharmaceutical Industries, Inc.; and has individual shares in Johnson and Johnson, and as part of retirement account/mutual funds. SJR is an employee of Sun Pharmaceutical Industries, Inc. ABG has received honoraria as an advisory board member and consultant for Avotres Therapeutics; Beiersdorf; Boehringer Ingelheim; Bristol-Myers Squibb Co.; Janssen; LEO Pharma; Eli Lilly; Novartis; Sun Pharmaceutical Industries, Inc.; UCB; and Xbiotech (stock options); and has received research/educational grants from Boehringer Ingelheim; Incyte; Janssen; Novartis; Sun Pharmaceutical Industries, Inc.; UCB; and Xbiotech (all paid to Mount Sinai School of Medicine).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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