Phase 2 Study Finds Tildrakizumab Effective for PsA Manifestations

Findings of a phase 2b study indicated that use of tildrakizumab was associated with significant improvements in joint and skin manifestations of patients with psoriatic arthritis (PsA), although improvement in symptoms of dactylitis and enthesitis were not observed.

Tildrakizumab may be safe and effective for the treatment of joint and skin manifestations in patients with psoriatic arthritis (PsA), according to study findings published in the Annals of Rheumatic Diseases.

As a chronic, progressive, and inflammatory form of arthritis, treatment to address all the clinical manifestations of PsA remains a significant challenge. Moreover, researchers highlight that chronic joint inflammation and potential joint damage from PsA can impose considerable economic burden.

In the current treatment of PsA, clinical recommendations include the use of conventional systemic disease-modifying antirheumatic drugs (csDMARDs) before other therapies, biological DMARDs targeting tumor necrosis factor alpha before csDMARDs, or either approach.

However, emerging research has shown the promise of targeted therapy against interleukin (IL)-23, a key regulatory cytokine in PsA pathogenesis. Guselkumab, an FDA-approved anti-IL-23p19 subunit antibody that targets IL-23 alone, has been shown to be effective in the treatment of signs and symptoms of PsA.

Seeking to investigate the efficacy of tildrakizumab, also an anti-IL-23p19 subunit antibody which is approved for the treatment of plaque psoriasis, researchers conducted a randomized, double-blind, placebo-controlled, multiple-dose, 52-week phase 2b study.

Patients with active PsA (N = 391) were randomized at 1:1:1:1:1 to receive either tildrakizumab 200 mg every 4 weeks (Q4W) (n = 78); tildrakizumab 200 mg (n = 79), 100 mg (n = 77), or 20 mg (n = 78) every 12 weeks (Q12W); or placebo (n = 79) Q4W.

At week 24, patients receiving tildrakizumab 20 mg or placebo switched to tildrakizumab 200 mg Q12W. The primary efficacy endpoint was the proportion of patients with ACR20 response at week 24.

“Secondary efficacy endpoints were assessed without adjustment for multiplicity,” added researchers. “Safety was evaluated from treatment-emergent adverse events (TEAEs).”

In their findings, 71.4%–79.5% of tildrakizumab-treated patients achieved ACR20 at week 24, compared with 50.6% of placebo-treated patients (all P < .01). Significant improvements in secondary outcomes of patients receiving tildrakizumab versus placebo were also observed:

  • ACR 50
  • Disease Activity Score in 28 joints with C reactive protein (DAS28-CRP) less than 3.2
  • Minimal disease activity (MDA)
  • 75%/90%/100% improvement from baseline Psoriasis Area and Severity Index (PASI) responses at week 24 and through week 52

Responses in patients switched to tildrakizumab 200 mg at week 24 were consistent with treatment from baseline.

Conversely, improvement in dactylitis and enthesitis was not observed, with results indicated by researchers to be mixed for other investigated secondary outcomes. TEAEs and serious TEAEs  of all patients through week 52 were comparable among all treatment arms, occurring in 64.5% and 3.3% of cases, respectively.

“These findings demonstrate that treatment with tildrakizumab 200 or 100 mg was more effective than placebo for rates of ACR20/50, DAS28-CRP, MDA, and PASI 75/90/100 responses, as well as improvement in physical function,” concluded researchers. “These results support tildrakizumab phase III clinical development in PsA.”

Reference

Mease PJ, Chohan S, Fructuoso FJG, et al. 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. Ann Rheum Dis. Published online May 13, 2021. doi:10.1136/annrheumdis-2020-219014