Tofacitinib effective in psoriatic arthritis patients with inadequate response to conventional synthetic DMARDs
Tofacitinib, a first-in-class Janus kinase (JAK) inhibitor, shows promise as an oral treatment with quick onset of action and sustained efficacy in patients with psoriatic arthritis (PsA) who do not respond adequately to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs).
In a phase III trial presented at the European League Against Rheumatism (EULAR) Annual Congress 2017 held recently in Madrid, Spain, ACR20 (20 percent improvement according to the American College of Rheumatology criteria) response rates at 3 months were 50 percent with tofacitinib 5 mg BID and 61 percent with tofacitinib 10 mg BID, compared with 33 percent with placebo (p≤0.05 and p<0.0001, respectively). ACR20 response rate at 3 months was 52 percent with adalimumab 40 mg Q2W. [EULAR 2017, abstract OP0216]
The 12-month trial included 422 patients with PsA for at least 6 months who were tumour necrosis factor (TNF)-inhibitor–naïve, had inadequate response to one or more csDMARDs, and were stabilized on ongoing treatment with one csDMARD. The patients were randomized in a 2:2:2:1:1 ratio to receive tofacitinib 5 mg or 10 mg BID, adalimumab 40 mg subcutaneous injection Q2W, or placebo advancing to tofacitinib 5 mg or 10 mg BID after 3 months.
“The study, however, was not designed for superiority or noninferiority testing between tofacitinib and adalimumab. Adalimumab was used as a comparator control,” highlighted lead author Professor Philip Mease of the University of Washington School of Medicine, Seattle, US.
“Our results showed significant improvement in ACR20 response rates with tofacitinib vs placebo as early as 2 weeks into treatment,” Mease reported. “At 2 weeks, ACR20 response rates were 22.4 and 31.7 percent with tofacitinib 5 mg and 10 mg, respectively, compared with 5.7 percent with placebo [p<0.001 and p<0.0001, respectively]. Greater efficacy was also seen with adalimumab vs placebo.”
In addition to significantly improved ACR20 response rates, significant decreases in Health Assessment Questionnaire Disability Index (HAQ-DI) scores were also observed with tofacitinib (5 mg, -0.35, p<0.01; 10 mg, -0.40, p<0.001) and adalimumab (-0.38, p<0.01) groups vs placebo at 3 months.
“At 12 months, ARC20 response rates were maintained at 68 percent for tofacitinib 5 mg, 70 percent for tofacitinib 10 mg, and 60 percent for adalimumab,” said Mease. “This is the first time we are seeing data up to 1 year for tofacitinib 5 mg BID. This was not studied before in the psoriasis programme for tofacitinib.”
“Patients who received the treatments also showed improvements in enthesitis, dactylitis and PASI 75 [75 reduction in Psoriasis Area and Severity Index score] over time, and more than 90 percent of all tofacitinib recipients were radiographic nonprogressors at month 12,” he added.
No new adverse events were reported compared with previous studies on rheumatoid arthritis. “A single death occurred in a patient originally in the placebo group who was re-randomized to receive tofacitinib 5 mg, but this was not attributed to the study medication,” noted Mease. “There were four malignancies among patients receiving tofacitinib, which were likely cancers that were missed when patients were enrolled, as one was noted on day 1 and the second on day 11.”