Highlights from

EULAR 2019

European Congress of Rheumatology

Madrid 12-15 June 2019

Promising results of tildrakizumab in psoriatic arthritis

A phase 2B study (TIL trial) showed superior efficacy and comparable safety of tildrakizumab versus placebo in patients with psoriatic arthritis (PsA). Treatment-emergent adverse events (AEs) in the tildrakizumab-treated group were uncommon. These were the main conclusions presented by Dr P. Mease (University of Washington, USA) at EULAR 2019 [1].

PsA, a chronic inflammatory disease, affects the joints, causing pain and disability. Tildrakizumab is a high-affinity, human, monoclonal antibody targeting interleukin (IL)-23p19. Tildrakizumab, classified as a biological disease-modifying anti-rheumatic drug (bDMARD), is currently approved to treat moderate-to-severe plaque psoriasis [2,3]. According to current guidelines, bDMARDs, targeting IL-12/23 or IL-17 pathways may be considered in patients who have had an inadequate response to conventional synthetic DMARDs, and for whom TNF inhibitors are not appropriate.

The 24-week, randomised, double-blind, placebo-controlled, multiple-dose, TIL trial included 391 adult PsA patients, who had both ≥3 tender and swollen joints. There were 4 active treatment groups. Patients were randomised (1:1:1:1:1) to receive tildrakizumab 200 mg every 4 weeks; 200 mg, 100 mg, or 20 mg every 12 weeks; or placebo every 4 weeks. Stable concomitant methotrexate or leflunomide use was permitted but not mandated.

The primary efficacy endpoint was the proportion of patients who achieved a 20% reduction from baseline in ACR response criteria (ACR20) at week 24. Secondary outcome measurements included patients achieving ACR50/70 response, improved Psoriasis Area and Severity Index scores (PASI-75/90), and changes in swollen and tender joint count at week 24. Safety assessments included monitoring of treatment-emergent AEs.

By week 24, tildrakizumab was significantly more efficacious than placebo in

treatment of joint and skin manifestations of PsA. There were greater proportions of ACR20/50/70 and PASI-75/90 responders with tildrakizumab vs placebo at week 24. In some cases, differences in outcome measures between tildrakizumab and placebo were observed as early as week 8. The response rates improved with increasing dose. However, the shortening of the dosing interval of 200 mg from 12 to 4 weeks did not result in a measurable increase in skin or joint response scores. In patients receiving 200 mg tildrakizumab every 12 weeks, 79.6% achieved PASI-75 and 50% PASI-90, whereas, in the placebo group, 16.7% reached PASI-75 and 7.1% PASI-90 (P<0.0001).

Serious AEs occurred in 2.2% of tildrakizumab-treated patients vs 2.5% of placebo-treated patients. Treatment-related serious AEs occurred in 0.3% of patients. Frequently reported AEs included nasopharyngitis and diarrhoea with no reports of candidiasis, inflammatory bowel disease, major adverse cardiac events, or malignancy. No patients discontinued treatment due to AEs and no deaths were reported.

A promising role is suggested for tildrakizumab in the treatment of patients suffering from psoriatic arthritis.

  1. Maese P, et al. Abstract LB0002. EULAR 2019

  2. Beck KM, et al. Psoriasis (Auckl). 2018 Aug 29;8:49-58 doi:10.2147/PTT.S146640

  3. Frampton JE. Am J Clin Dermatol. 2019 Apr;20(2):295-306

The content and interpretation of these conference highlights are the views and comments of the speakers/authors.