modifying antirheumatic drug (DMARD) and had not received any biologic DMARDs. Patients received either one or two doses of once-daily baricitinib or placebo in addition to their background therapy. The primary endpoint, ACR20 response, was met at Week 12 of treatment. There were no serious adverse events or treatment-emergent adverse events. There was one case of tuberculosis in a baricitinib-treated patient.
Results of an earlier Phase 3 study, RA-BEACON, also met the primary endpoint of ACR20 response, compared with placebo at Week 12 in patients with moderate to severe RA (n=527) who had previously failed at least one tumor necrosis factor inhibitor and were on stable doses of DMARDs.6 Adverse events, including serious events and infections, were similar to placebo-treated patients. Nasopharyngitis, headache and upper respiratory tract infection were the most common nonserious reactions. Discontinuation rates due to adverse events were similar between treatment groups.
Decernotinib, an oral selective JAK-3 inhibitor, recently showed significant symptom improvement in RA patients (n=204) in a multicenter Phase 2a, dose-ranging study.7 Patients enrolled in this trial had previously had an inadequate response to at least one DMARD and could have received one prior biologic agent. Stable doses of nonsteroidal antiinflammatory agents and low-dose prednisone were allowed. Twenty-five mg, 50 mg, 100 mg or 150 mg doses of decernotinib or placebo were evaluated. Mean disease duration was 7.7 years. Most patients were white women with a mean age of 56 years. Mean disease activity score in 28 joints (DAS28) was 6.1 at baseline. At Month 3, a 61% improvement in ACR20 was seen in patients who received 50 mg decernotinib compared with 29% of placebo-treated patients. At Month 3, a 65% improvement in ACR20 was obtained in patients who received 100 mg decernotinib daily and a 66% improvement in ACR20 was noted in patients who received 150 mg decernotinib daily. Mean DAS28 score changes from baseline and ACR50 responses were statistically significant for all doses except for 50 mg, compared with placebo.
Although the efficacy data were impressive, the safety data showed more serious infections and lipid and hepatic enzyme elevations in patients who received higher doses of decernotinib. Eight of nine patients who received decernotinib developed pneumonia compared with one placebo-treated patient. Three cases of herpes zoster occurred, as well as cases of erysipelas and osteomyelitis. One patient treated with 100 mg decernotinib died. Due to these serious adverse events, the manufacturer has decided not to continue developing decernotinib for RA.
