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.

Keywords: arthritis; biological therapy; cytokines; psoriatic.

Conflict of interest statement

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).

© 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.

Figures

Figure 1

Patient status to week 52. PBO, placebo; Q4W, every 4 weeks; Q12W, every 12 weeks; W, week.

Figure 2

Response rates for (A) ACR20, (B) ACR50 and (C) ACR70 through week 52. Supporting values shown in online supplemental table S3. Missing responses were imputed as non-responses. Shown for randomised patients who received ≥1 dose of study drug. TIL 200 mg Q4W, n=78; TIL 200 mg Q12W, n=79; TIL 100 mg Q12W, n=77; TIL 20 mg Q12W→200 mg Q12W, n=78; PBO Q4W→TIL 200 mg Q12W, n=79. *p<0.05; †p<0.001; ‡p<0.0001 versus PBO; not adjusted for multiplicity, except ACR20 at week 24. P values were not analysed beyond week 24. ACR, American College of Rheumatology; PBO, placebo; Q4W, every 4 weeks; Q12W, every 12 weeks; TIL, tildrakizumab.

Figure 3

MDA responders (A) over time, (B) responders for each MDA subcomponent at week 24 and (C) VLDA responders by treatment and time point. Supporting values shown in online supplemental table S4. Shown for randomised patients who received ≥1 dose of study drug. Error bars represent 95% CI. Missing responses were imputed as non-responses. Proportion of responders shown as % in (B). TIL 200 mg Q4W, n=78; TIL 200 mg Q12W, n=79; TIL 100 mg Q12W, n=77; TIL 20 mg Q12W→200 mg Q12W, n=78; PBO Q4W→TIL 200 mg Q12W, n=79 except for tender entheseal points ≤1 in (B) (TIL 200 mg Q4W, n=76; TIL 100 mg Q12W, n=76; PBO Q4W→TIL 200 mg Q12W, n=78).*p<0.05; †p<0.001; ‡p<0.0001 versus PBO; not adjusted for multiplicity. P values were not analysed beyond week 24. BSA, body surface area; HAQ-DI, Health Assessment Questionnaire-Disability Index; MDA, Minimum Disease Activity; PASI, Psoriasis Area and Severity Index; PBO, placebo; PtGA, patients global assessment; Q4W, every 4 weeks; Q12W, every 12 weeks; TIL, tildrakizumab; VAS, visual analogue scale; VLDA, very low disease activity.

Figure 4

Response rates for (A) PASI 75, (B) PASI 90 and (C) PASI 100 through week 52 across treatment and time point. Supporting values shown in online supplemental table S6. Response rates were calculated in randomised patients who received ≥1 dose of study drug with BSA ≥3% at baseline. Error bars represent 95% CI. Missing responses were imputed as non-responses. TIL 200 mg Q4W, n=53; TIL 200 mg Q12W, n=44; TIL 100 mg Q12W, n=55; TIL 20 mg Q12W→200 mg Q12W, n=41; PBO Q4W→TIL 200 mg Q12W, n=42. P values are based on Cochran-Mantel-Haenszel test (with prior anti-TNF use and baseline weight as stratification factors). *p<0.05; †p<0.001; ‡p<0.0001 versus PBO; not adjusted for multiplicity. P values were not analysed beyond week 24. BSA, body surface area; PASI, Psoriasis Area and Severity Index; PBO, placebo; Q4W, every 4 weeks; Q12W, every 12 weeks; TIL, tildrakizumab; TNF, tumour necrosis factor.

Figure 5

Proportion of patients in remission based on (A) DAPSA, proportion of patients with PASDAS