Tildrakizumab Improves Joint, Skin Manifestations of Psoriatic Arthritis
By Denise Baez
NEW YORK -- November 5, 2020 -- Tildrakizumab improved joint and skin manifestations of psoriatic arthritis better than placebo through 52 weeks, and was well tolerated among patients, according to a study presented at the Virtual 29th Congress of the European Academy of Dermatology and Venereology (EADV).
“There is an unmet need for therapeutics that maximally address all of the manifestations of psoriatic arthritis and have an acceptable safety profile,” said Alan Mendelsohn, MD, Sun Pharmaceutical Industries, Princeton, New Jersey.
For the study, patients aged ≥18 years with psoriatic arthritis for ≥6 months and with ≥3 tender and ≥3 swollen joints were randomised to tildrakizumab 200 mg q4w (n = 78), tildrakizumab 200 mg q12w (n = 79), tildrakizumab 100 mg q12w (n = 77), tildrakizumab 20 mg q12w (n = 78), or placebo q4w (n = 79) for weeks 0 to 24. At week 24, patients in the placebo and tildrakizumab 20 mg q12w arms switched to tildrakizumab 200 mg q12w arm. All other treatments continued till week 52.
A total of 331 patients completed the first part of the study and 315 completed the second part. By week 52, 76 (19.4%) patients discontinued, mostly due to lack of efficacy (9.5%) or withdrawn consent (3.3%).
About 20% of patients in each group had prior therapy with anti-tumour necrosis factor inhibitors. Concomitant use of other antirheumatic medications in the total study population included leflunomide alone (3.8%), leflunomide plus prednisone/prednisolone (0.3%), methotrexate alone (51.5%), methotrexate plus prednisone/prednisolone (5.1%), sulfasalazine alone (0.3%), prednisolone alone (2.1%), and sulfasalazine plus leflunomide (0.3%).
At week 24, there was a significantly greater proportion of ACR20 responders -- the primary endpoint -- in the tildrakizumab groups (70% to 80%) compared with the placebo group (~50%). There was also a significantly greater proportion of ACR50 responders in the tildrakizumab groups (40% to 50%) compared with the placebo group (~25%).
“ACR20, ACR50, and ACR70 response rates continued to increase through week 52, including in the patients who switched from placebo or tildrakizumab 20 mg q12w to tildrakizumab 200 mg q12w,” said Dr. Mendelsohn.
There were more Psoriasis Area Severity Index (PASI) 75, PASI 90, and PASI 100 responders among patients receiving any dose of tildrakizumab compared with patients receiving placebo. These responses also continued to increase and were sustained through week 52.
The most frequent adverse events (AEs) associated with tildrakizumab were nasopharyngitis and upper respiratory tract infection. Most AEs were mild, including infections. Serious AEs occurred in 2.6% of patients in the 200 mg q4w group, in 2.5% of patients in the 200 mg q12w group, 2.6% of patients in the 100 mg q12w group, in 5.1% of patients in the 20 mg q12w group, and in 3.8% of patients in the placebo group.
One malignancy occurred (intraductal proliferative breast lesion) in a patient who switched from tildrakizumab 20 mg q12w to 200 mg q12w.
[Presentation title: Efficacy and Safety of Tildrakizumab, a High-Affinity Anti-Interleukin-23p19 Monoclonal Antibody, in Patients With Active Psoriatic Arthritis in a Randomized, Double-Blind, Placebo-Controlled, Multiple-Dose, Phase 2b Study. Abstract P0999-1853]