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MADRID -- The JAK inhibitor tofacitinib (Xeljanz) shows promise as a new oral treatment for psoriatic arthritis (PsA), a phase III trial suggested.

Among 422 patients with active PsA who had previously had an inadequate response to conventional disease-modifying anti-rheumatic drug treatment, 20% responses according to the criteria of the American College of Rheumatology (ACR20) were seen at 3 months in 33% of patients randomized to placebo, in 50% of patients receiving tofacitinib, 5 mg twice daily (P<0.05 versus placebo), in 61% of those given tofacitinib, 10 mg twice daily (P<0.0001), and in 52% of those receiving subcutaneous adalimumab (Humira), 40 mg every 2 weeks (P<0.05), according to Philip J. Mease, MD, of the University of Washington in Seattle.

"The efficacy of tofacitinib in PsA appears similar to what is seen with biologics such as adalimumab," he said in a press briefing at the at the annual European Congress of Rheumatology, organized by the European League Against Rheumatism.

"Many patients would like the option of having an oral option for treatment," he said.

The study was a 12-month trial that included patients who fulfilled the CASPAR criteria for PsA, had at least 3 tender and swollen joints, had active plaque psoriasis, and were tumor necrosis factor-naive. The first 3 months were placebo-controlled, and thereafter patients receiving placebo were re-randomized to 5 or 10 mg tofacitinib twice daily.

The study was not designed for superiority or non-inferiority; adalimumab was a comparator control. The analysis was done according to the nonresponder imputation method, which is the most strict way of looking at the data, Mease explained.

A total of 88% of patients completed the study, with most dropouts -- as expected -- being from the placebo arm.

Almost all patients were white, slightly more than half were women, and mean age was 48. Disease duration ranged from 5 to 7 years.

Already by week 2, ACR20 response rates were 22.4% and 31.7%, respectively, for the 5- and 10-mg groups compared with 5.7% in the placebo group (P<0.001 and P<0.0001, respectively).

On the Health Assessment Questionnaire Disability Index, changes at 3 months were -0.18 for the placebo group, -0.35 for the 5-mg tofacitinib group (P<0.05), -0.40 in the tofacitinib group (P<0.001), and -0.38 in the adalimumab group (P<0.05).

For enthesitis, a statistically significant change of -1.5 was seen at 3 months in the 10-mg group compared with -0.4 in the placebo group, while for dactylitis the changes were -5.5 versus -2 in those two groups.

The Psoriasis Area and Severity Index 75% (PASI 75) improvement at 3 months was seen in 43% of patients in the 5-mg group and 44% of those in the 10-mg group, which was similar to what was seen in the adalimumab group. By 12 months, the PASI 75 response was achieved by 56% of the 5-mg group and by 67% of the 10-mg group.

"This is the first time we've seen prolonged data out to the 1-year mark with the 5 mg twice daily dose. This was not studied in the psoriasis program for tofacitinib," Mease noted.

In addition, the vast majority (91%) of patients were considered radiographic non-progressors at 12 months, meaning that an increase in total Sharp score was 0.5 or less.

The most common adverse events were upper respiratory tract infections, seen in 7.5% to 10.6%, nasopharyngitis, in 7.5% to 11.5%, and headache, in 3.8% to 10.6%.

Serious adverse events were reported in eight patients in the 5-mg arm, in four patients in the 10-mg arm, and in nine patients in the adalimumab arm. A single death occurred, in a patient originally in the placebo group who was re-randomized to the 5-mg tofacitinib group. This was not attributed to the study medication.

Overall there were four malignancies among patients receiving tofacitinib. One of these was a urothelial bladder cancer noted at day 1, and a second was a squamous cell carcinoma found at day 11, "which likely were cancers that were missed as patients were enrolled," he said.

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