Tildrakizumab shows promise in psoriatic arthritis
The anti-interleukin (IL)-23p19 monoclonal antibody tildrakizumab showed better efficacy over placebo, along with a favourable safety profile, in patients with active psoriatic arthritis (PsA), according to a phase IIb study presented at EULAR 2019.
A total of 391 adults (median age 48.7 years, 55.0 percent female) with active PsA were randomized 1:1:1:1:1 to receive tildrakizumab (200 mg Q4W [T1], 200 mg, 100 mg, or 20 mg Q12W [T2, T3, and T4, respectively]) or placebo Q4W for 24 weeks. Stable concurrent leflunomide or methotrexate use was allowed but not mandated. [EULAR 2019, abstract LB0002]
At week 24, there were significantly greater proportions of ACR20/50/70* (p<0.001 for all) responders in the tildrakizumab groups regardless of dosing compared with placebo.
The T1–T3 dosing schedules also led to significantly higher PASI** 75 (64.2, 79.6, and 55.6 percent [T1, 2, and 3] vs 16.7 percent [placebo], respectively; p<0.0001 for all) and PASI 90 responses vs placebo (47.2, 50.0, and 38.9 percent vs 7.1 percent, respectively; p<0.0001 for all). Even the lowest tildrakizumab dose of 20 mg Q12W led to greater symptom reductions, as indicated by the higher PASI 75 and PASI 90 rates, compared with placebo (46.3 percent vs 16.7 percent [for PASI 75] and 36.6 percent vs 7.1 percent [for PASI 90]; p<0.05 for both).
The most frequent treatment-emergent adverse events (TEAEs) included nasopharyngitis (5.4 percent vs 6.3 percent for tildrakizumab [pooled] vs placebo, respectively) and diarrhoea (1.3 percent vs 0 percent, respectively). Serious TEAE rates in both arms were similar (2.2 percent vs 2.5 percent). There were no reports of TEAE-related discontinuations nor deaths.
There was a clear separation between tildrakizumab and placebo as early as week 8, noted Dr Philip Mease from the Swedish Medical Centre/Providence St Joseph Health and University of Washington in Seattle, Washington, US, thus highlighting the potential of tildrakizumab in treating the joint and skin manifestations of PsA.
Tildrakizumab is currently approved in Europe and the US for treating moderate-to-severe plaque psoriasis. Current recommendations indicate that biological DMARDs*** targeting the IL-12/23 or IL-17 pathways may be considered in PsA patients with peripheral arthritis (one or more tender and swollen joints) who have had an insufficient response to conventional synthetic DMARDs and are unsuitable for tumour necrosis factor inhibitor treatment. [Ann Rheum Dis 2016;75:499-510]
“We welcome these promising results for tildrakizumab in patients with PsA,” said EULAR President Professor Hans Bijlsma. “Extending research into different patient groups may bring benefits that address current unmet needs.”