The signs and symptoms of rheumatoid arthritis were improved at 3 months after various doses of the JAK 3 inhibitor decernotinib were administered.
The selective JAK 3 inhibitor decernotinib (VX 509; Vertex Pharmaceuticals) is effective in improving clinical signs and symptoms of rheumatoid arthritis (RA), according to the results of a phase 2a trial published in Arthritis & Rheumatology.
An international team of investigators assessed 204 adults with active RA who had been unsuccessfully treated with ≥ 1 DMARD in order to determine the safety and efficacy of oral decernotinib monotherapy. The patients were administered either a twice daily placebo or decernotinib at dosages of 25 mg, 50 mg, 100 mg, or 150 mg over the course of the 12 week study. The researchers examined the primary measures of efficacy at week 12 against the American College of Rheumatology 20 percent improvement criteria (ACR 20). Additionally, the researchers observed the mean change from baseline in the Disease Activity Score in 28 joints using the C reactive protein level (DAS28 CRP).
After 12 weeks of receiving decernotinib monotherapy, the patients ACR 20 response rates were 39.0 percent, 61.0 percent, 65.0 percent, and 65.9 percent in the 25 mg, 50 mg, 100 mg, and 150 mg groups, respectively. The researchers noted that the ACR 20 response rates were significantly higher in the 50 mg group and the 100 mg and 150 mg groups, when compared to the response rate of the placebo groups in those dosages.
The researchers commented that in the decernotinib groups, treatment resulted in higher ACR 50 and ACR 70 response rates. There were also more patients with DAS28 CRP scores < 2.6. Moreover, there were improvements in the Health Assessment Questionnaire disability index as compared to the placebo groups.
“The study showed that decernotinib is an effective oral medication with a safety profile comparable to what has been reported with other JAK inhibitors,” lead investigator Roy M. Fleischmann, MD, said in a report. “Although it is ‘more specific’ for JAK 3, the clinical and safety data reported here are not much different from JAK inhibitors that are approved or in reports published of several in development.”
The most common decernotinib adverse events in any dosage group were nausea (6.1 percent), headache (4.3 percent), an increase in levels of alanine aminotransferase (4.3 percent), and hypercholesterolemia (3.7 percent). For the decernotinib groups, there was an additional increased risk of infections and increased liver transaminase levels.