MADRID – Tildrakizumab, a high-affinity anti–interleukin-23p19 monoclonal antibody, significantly improved joint and skin manifestations in patients with psoriatic arthritis in an ongoing phase 2b study.
Sara Freeman/MDedge News
Dr. Philip J. Mease
“By week 24, all four doses of tildrakizumab were significantly more efficacious than placebo,” Philip J. Mease, MD, director of the division of rheumatology clinical research at Swedish Medical Center, Seattle, reported at the European Congress of Rheumatology. This included patient-rated pain, he observed.
Furthermore, “there was a clear separation between tildrakizumab and placebo as early as 8 weeks” for the trial’s primary endpoint, a 20% response rate on American College of Rheumatology criteria (ACR20) at 24 weeks.
The study (NCT02980692), which is projected to complete next year, was conducted to demonstrate the safety and efficacy of tildrakizumab in patients with active psoriatic arthritis. Tildrakizumab is already approved for the treatment of moderate to severe plaque psoriasis in multiple countries, Dr. Mease pointed out. Indeed, the drug – which is marketed as Ilumya in the United States and as Ilumetri in the Europe Union – was approved by the Food and Drug Administration in March last year based on the positive results of the phase 3 reSURFACE clinical trials program (Drugs. 2018;78[8]:845-9).
In presenting interim findings from the study, Dr. Mease observed that “it looked like shortening the dosing interval from Q12 to Q4 weeks for the 200-mg dose did not result in a measurable difference in skin or joint responses.”
The trial included 391 of 500 adult patients who were screened and then randomized to one of four tildrakizumab dosing groups or placebo; there were 78 patients treated with tildrakizumab 200 mg once every 4 weeks (Q4W) and 79 who were treated with tildrakizumab 200 mg once every 12 weeks (Q12W). A further 77 patients were treated with a 100 mg tildrakizumab dose Q12W, 78 patients with a 20 mg tildrakizumab dose Q12W, and 79 patients were treated with a placebo Q4W.
The mean age of patients included in the study was around 48 years. A total of 55% were female, and more than 96% were white. Across the groups, patients had a median of 7-8 tender joints and about 14-19 swollen joints, and 53%-70% had at least 3% psoriasis body surface area involvement.
The primary endpoint of ACR20 at 24 weeks was met by 79.5%, 77.2%, 71.4%, and 73.1% of patients in the tildrakizumab 200-mg Q4W, 200-mg Q12W, 100-mg Q12W, and 20-mg Q12W groups, and by 50.6% of the placebo-treated patients. “So even the very low dose had an effect,” Dr. Mease observed, also acknowledging the “very high placebo response.”
An ACR50 response was achieved by a respective 53.6%, 50.6%, 45.5%, 39.7%, 19.7%, and 24.1% of patients. ACR70 response rates were also “proportionately lower” than the ACR20 responses at around 25%-29% for the tildrakizumab groups and 16% for placebo.
“The skin scores were as expected quite high,” Dr. Mease said. The Psoriasis Area and Severity Index (PASI) 75 response rate was 79.6% in the tildrakizumab 200-mg Q12W group, 64.2% in the 200-mg Q4W group, 55.6% in the 100-mg Q12W group, 46.3% in the 20-mg Q12W group, and just 16.7% in the placebo group. The respective percentages of patients achieving a PASI 90 response rate were 50%, 47.2%, 38.9%, 36.6%, and 7.1%.
Patient pain assessment showed a clear reduction with tildrakizumab versus placebo treatment. “We see statistical separation between all of the tildrakizumab arms and placebo,” Dr. Mease said. “A greater than 50% response in pain is considered major clinical improvement, and that was achieved by all of the tildrakizumab arms.”
As for enthesitis, the mean change in Leeds Enthesitis Scores from baseline to week 24 were greater with all tildrakizumab doses than with placebo, although a high placebo response was again apparent.
“In general, the safety profile was very good for this agent,” Dr. Mease said. Any treatment-emergent adverse event (TEAE) occurred in 156 of 317 (49%) tildrakizumab-treated patients and in 34 of 70 (49%) placebo-treated patients. The rates of any severe TEAE were 2.2% for the tildrakizumab arms and 2.5% for placebo. Any TEAE related to treatment occurred in a respective 11.2% and 12.7%, but there were no discontinuations because of adverse events, nor were there any major cardiac adverse events, cases of malignancy, or deaths caused by TEAEs. There was a single serious infection, a case of tonsillitis, which occurred with tildrakizumab treatment.
In response to a question after his presentation, Dr. Measure noted: “In the psoriasis trials with this agent, even a single dose yielded a fairly meaningful PASI 75 responses out for extremely long periods of time, 6–12 months. So, it looks like the Q12 dosing is going to be reasonable and convenient for patients”. He also agreed with a comment that the more frequent dosing seemed to be linked to inferior responses in the skin.
The study was sponsored by Sun Pharmaceutical Industries. Dr. Mease has received research grants, consulting fees, and/or speaker fees from 15 pharmaceutical companies, including Sun Pharmaceutical Industries.