A novel oral JAK inhibitor has shown promise in patients with rheumatoid arthritis who have failed to respond to other treatments, the results of a phase III trial show.
The 24-week double blind placebo-controlled trial involved 527 patients with an inadequate response to one or more TNF inhibitors who were randomised to receive 2mg or 4mg dose of the oral JAK I and 2 inhibitor baricitinib or placebo.
Results showed that significantly more patients receiving baricitinib than those receiving placebo had an ACR20 response at week 12 (55% vs. 27%, P<0.001), the primary endpoint of the study.
Differences between the higher-dose baricitinib group and the placebo group were also significant for the HAQ-DI score and the DAS28-CRP but not for an SDAI score of 3.3 or less, the researchers reported in the study published in the NEJM.
“This is the first drug to demonstrate meaningful clinical benefit in patients who’ve failed virtually every other commercial drug for rheumatoid arthritis,” said Mark Genovese, MD, professor of immunology and rheumatology and the study’s lead author.
“The drug worked well across all patient subgroups, independently of what they’d been taking before or how long they’d had the disease,” he said.
Adverse-event rates through 24 weeks were higher for patients receiving the 2-mg dose of baricitinib and those receiving the 4-mg dose than for patients receiving placebo (71% and 77%, respectively, vs. 64%), including infections (44% and 40%, vs. 31%).
The rates of serious adverse events were 4%, 10%, and 7% in the three groups, respectively. Two nonmelanoma skin cancers and two major adverse cardiovascular events, including a fatal stroke, occurred in the higher-dose group.
Baricitinib also appeared to raise both high-density and low-density lipoprotein levels, with unclear clinical implications, Professor Genovese said.
The trial was sponsored by Eli Lilly and Co., the manufacturer and licensee of baricitinib.