番茄社区

ORLANDO -- Patients with psoriatic arthritis (PsA) that did not respond to tumor necrosis factor (TNF) inhibitors had significant improvement with the Janus kinase (JAK) inhibitor (Xeljanz), a randomized trial showed.

As many as 60% of patients had at least 20% improvement in American College of Rheumatology (ACR20) criteria after 6 months of treatment. Treatment with 5 or 10 mg BID led to significantly higher rates of ACR 20 response as compared with placebo, according to of the Federal University of Parana in Curitiba, Brazil, and colleagues.

Treatment with the same two doses of tofacitinib led to significant reductions in physical limitation at 3 months, maintained out to 6 months. Significantly more patients had improvement in a psoriasis index and in the ACR50 response rate, they reported at the American Academy of Dermatology (AAD) annual meeting.

"This is the first report of a clinical trial of any drug for active psoriatic arthritis in a population restricted to patients with an inadequate response to TNF inhibitors," said Azevedo. "The primary endpoints were achieved, and onset of efficacy occurred as early as week 2. We observed significant improvement in ACR 50 response rates with tofacitinib. The efficacy observed at month 3 was maintained through month 6. Tofacitinib represents a potential future treatment option for psoriatic arthritis."

Anther study reported at AAD showed that treatment with tofacitinib led to improvement in psoriatic arthritis unresponsive to conventional disease-modifying agents (DMARDs) versus placebo and comparable to the efficacy attained with a TNF inhibitor control group.

Currently approved for treatment of rheumatoid arthritis, tofacitinib has ongoing evaluations in other inflammatory conditions, including PsA. Azevedo reported findings from a randomized trial that compared two tofacitinib dosages -- 5 and 10 mg BID -- against two placebo groups, who switched to one of the tofacitinib doses after 3 months. Eligible patients had a PsA diagnosis for at least 6 months, active plaque psoriasis, and attained inadequate disease control with one or more TNF inhibitors.

The primary endpoints were ACR20 response rate and improvement in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at 3 months. The trial had 263 patients in the upfront-tofacitinib groups and 131 in the two placebo groups combined.

At baseline the study population had a mean age of 50, median PsA duration of 9 years, mean HAQ-DI score of 1.3, mean swollen joint count of 11.8, and mean tender joint count of 22.0. A fourth of the patients were using concomitant oral corticosteroids and almost three-fourths were using methotrexate.

Twice as many patients had ACR20 responses at 3 months with tofacitinib: 50% with 5 mg BID, 47% with 10 mg BID, and 24% with placebo (P<0.0001). At 6 months, the response rates were 60% with tofacitinib 5 mg BID and 49% with 10 mg BID. Patients who started the 5-mg dose at 3 months had a 50% response rate at 6 months, and those who switched form placebo to 10 mg BID tofacitinib had a 54% response rate.

Patients who started tofacitinib upfront had significantly greater improvement in HAQ-DI at 3 months: -0.39 with 5 mg, -0.35 with 10 mg, and -0.14 with placebo (P<0.001, P=0.001). At 6 months, the mean change from baseline ranged from -0.34 to -0.48.

The tofacitinib groups had higher Psoriasis Area and Severity Index 75 (PASI 75) and ACR50 response rates at 3 months, and the rates were similar at 6 months. Enthesitis and dactylitis were reduced with both doses of tofacitinib versus placebo.

The frequency and type of adverse events were consistent with the established safety profile of tofacitinib, said Azevedo.

Investigators in another randomized trial compared the two doses of tofacitinib, the TNF inhibitor adalimumab (Humira), and placebo in 422 patients who had inadequate control of PsA with conventional disease-modifying anti-rheumatic drugs (DMARDs), including methotrexate. The trial had the same primary endpoints as in the trial of patients with TNF inhibitor-unresponsive disease.

After 3 months of randomized treatment, the ACR20 response rates were 61% with tofacitinib 10 mg BID, 50% with 5 mg BID, 52% with adalimumab, and 33% with placebo, reported , of Brigham and Women's Hospital in Boston. After patients in the placebo group switched to tofacitinib, ACR20 response rates at 12 months ranged between 58% and 70%.

Change in HAQ-DI and PASI 75 and ACR50 responses were significantly better with tofacitinib than with placebo at 3 months (P<0.001) and similar to those attained with adalimumab. Responses and improvement were maintained to 12 months in all groups, including the patients who switched to tofacitinib after the 3-month placebo evaluation.