Tofacitinib may be a promising therapeutic option for AS
Tofacitinib demonstrated greater clinical and imaging efficacy vs placebo in reducing the signs and symptoms of AS, said lead investigator Professor Désirée van der Heijde from the Leiden University Medical Centre in Leiden, The Netherlands. “Our data are quite consistent if you look at objective measures of response. There was a clear dose-response [relationship] in all clinical imaging outcome measures at week 12.”
In the Bayesian Emax model analysis, patients taking tofacitinib 5 and 10 mg twice daily had a predicted 22.9 and 27.3 percent higher response in ASAS20 (improvement of at least 20 percent in the Assessment in Ankylosing Spondylitis Response Criteria at week 12) versus placebo. Those taking tofacitinib 2 mg twice daily had a 15.8 percent higher response in the ASAS20. [EULAR Congress 2016, abstract OP0002]
In addition, there was an improvement in MRI SPARCC (Spondyloarthritis Research Consortium of Canada) scores with tofacitinib, particularly in the 5 mg and 10 mg groups. There was almost no change in the SPARCC scores in the placebo group.
Patients in the study were randomized to tofacitinib 2mg, 5 mg, or 10 mg twice daily (n=52) or placebo (n=51) for 12 weeks and followed for an additional 4 weeks. Mean disease duration at baseline was 6.3 years. Over 85 percent of patients were HLA-B27 positive and a fairly large proportion of patients were taking disease-modifying antirheumatic drugs (DMARDs).
There were no new safety signals with tofacitinib beyond those observed in other rheumatic diseases. Dose-dependent changes in laboratory outcomes were observed in the tofacitinib groups but levels returned to baseline at study end. Also very few patients in the tofacitinib groups discontinued treatment.
Given these promising results, further investigation of JAK inhibitors for AS in large phase III trials is warranted.
Tofacitinib is FDA-approved for rheumatoid arthritis and has been explored in several phase III studies for the treatment of psoriasis.