Tofacitinib shows therapeutic potential in ankylosing spondylitis
Twice-daily tofacitinib 5 and 10 mg may produce greater improvements in signs, symptoms and objective endpoints of active ankylosing spondylitis (AS) in adults compared with placebo, according to data from a phase II study.
In addition, the drug has showed a 12-week safety profile that is similar to that reported in other indications.
A total of 207 patients were randomly assigned to one of the following treatment arms: tofacitinib 2 mg (n=52; mean age 41.8 years; 65.4 percent male), 5 mg (n=52; mean age 41.2 years; 75 percent male), 10 mg (n=52; mean age 41.6 years; 73.1 percent male) and placebo (n=51; mean age 41.9 years; 62.7 percent male). Treatment was given for 12 weeks, with a 4-week washout period.
The Assessment of SpondyloArthritis International Society 20 percent improvement (ASAS20) response rate at week 12 was used as the primary efficacy endpoint. Secondary endpoints were objective measures of disease activity, patient-reported outcomes and MRI of sacroiliac joints and spine. Safety was also assessed.
In an Emax model, ASAS20 response rate was 67.4 percent in the 10 mg arm, 63 percent in the 5 mg arm, 56 percent in the 2 mg arm, and 40.1 percent in the placebo arm.
Supportive normal approximation analysis found that the ASAS20 response rate with tofacitinib 5 mg was significantly higher than with placebo (80.8 vs 41.2 percent; p<0.001). Response rates were also greater with tofacitinib 2 and 10 mg, although the differences were not significant (51.9 and 55.8 percent, respectively).
There were general improvements observed in the secondary endpoints in the tofacitinib 5 and 10 mg arms vs placebo. Objective endpoints, including MRI, particularly showed clear dose response.
In terms of safety, adverse events showed no significant intergroup differences, without any unexpected safety findings.
Changes seen in dose-dependent laboratory outcomes returned close to baseline by week 16.