Safety and efficacy of baricitinib at 24 weeks in patients with rheumatoid arthritis who have had an inadequate response to methotrexate

Abstract

ObjectivesTo investigate baricitinib (LY3009104, formerly INCB028050), a novel, oral inhibitor of JAK1/JAK2 in patients with moderate to severe rheumatoid arthritis (RA) despite treatment with methotrexate.MethodsIn this phase IIb study, 301 patients were randomised 2:1:1:1:1 to receive once daily doses of placebo or 1, 2, 4 or 8 mg baricitinib for 12 weeks. Patients assigned to 2, 4 and 8 mg baricitinib continued blinded treatment for an additional 12 weeks. Patients assigned to placebo or 1 mg baricitinib were reassigned to 2 mg twice daily or 4 mg once daily baricitinib between weeks 12–24. The primary endpoint was the proportion of patients in the combined 4 and 8 mg groups achieving an American College of Rheumatology 20% (ACR20) response versus placebo at week 12.ResultsSignificantly more patients in the combined baricitinib 4 and 8 mg groups compared with placebo achieved an ACR20 response at week 12 (76% vs 41%, p<0.001). At week 12, significant differences versus placebo were also observed in patients achieving ACR50, ACR70 and remission as measured by Disease Activity Score for 28-joint counts, Clinical Disease Activity Index and Simplified Disease Activity Index. Patients receiving 2, 4, or 8 mg baricitinib maintained or improved in all measures through 24 weeks. Similar proportions of patients experienced at least one adverse event in the placebo and baricitinib groups. Serious infections developed in three patients receiving baricitinib. No cases of tuberculosis, herpes zoster, opportunistic infections or deaths were reported. Dose-dependent decreases in haemoglobin were observed with baricitinib.ConclusionsBaricitinib improved the signs and symptoms of RA in methotrexate inadequate responders with active disease. Baricitinib was well tolerated with no unexpected safety findings through week 24.Trial registration numberNCT01185353.

Efficacy and Safety of Baricitinib in Japanese Patients with Active Rheumatoid Arthritis Receiving Background Methotrexate Therapy: A 12-week, Double-blind, Randomized Placebo-controlled Study

“…Similar effects were observed for the 4-mg and 8-mg doses of baricitinib across most efficacy measures. These findings are consistent with previous studies of baricitinib in non-Japanese patients 9,21 .…”

“…The safety profile was consistent with previous studies of baricitinib in non-Japanese patients 9,21 . Baricitinib was generally well tolerated and few patients discontinued the study.…”

“…Changes in laboratory measures were observed with baricitinib treatment; the type and magnitude of the changes were similar to those seen with baricitinib in non-Japanese patients 9 and with other JAK inhibitors 22 JAK2/JAK2 homodimer 23 . Baricitinib at doses of 1 mg, 2 mg, and 4 mg did not affect hemoglobin concentrations or increase the percentage of patients experiencing a postbaseline increase in anemia based on CTCAE grade compared with placebo.…”

“…The result from the combined 4/8-mg baricitinib groups was assessed as the primary comparison for ACR20 response rate compared with placebo because previous studies have demonstrated that doses of 4 mg or greater achieved a similar and near-maximum efficacy response after 12 weeks of treatment 9,21 . The 1-mg and 2-mg doses were included to define the lower end of the dose range.…”

“…In a multinational, phase IIB randomized study, baricitinib was effective and well tolerated in patients (n = 301) who had active RA despite methotrexate (MTX) therapy 9 . After 12 weeks, significantly more patients in the combined 4/8-mg daily baricitinib dose group achieved an American College of Rheumatology (ACR) 20 response compared with placebo (76% vs 41%, p < 0.001).…”