The oral Janus kinase (JAK) inhibitor baricitinib is more effective than placebo or adalimumab (Humira) among RA patients with an inadequate response to methotrexate, a phase III trial shows.
Results from the double-blind placebo and active controlled RA-BEAM study published in this week’s New England Journal of Medicine revealed that the trial’s primary efficacy end point – the proportion of patients at week 12 who showed an ACR20 response – was achieved by 70% of patients receiving baricitinib, compared with 40% of those randomised to placebo (P<0.001).
The international study involving 1305 patients with moderate to severe RA found baricitinib to be noninferior to adalimumab at week 12 for the ACR20 response, with a noninferiority margin of 12% (70% for baricitinib and 61% for adalimumab; (P=0.014).
“According to the statistical analysis plan, baricitinib was therefore considered to be significantly superior to adalimumab (P=0.01),” the study authors wrote.
In addition, baricitinib was superior to adalimumab according to the mean change in DAS28-CRP at week 12 (−2.24 for baricitinib vs. −1.95 for adalimumab (P<0.001).
However there was no difference in radiological assessment of joint damage between the two biologics at 24 weeks. Both inhibited progression of joint damage compared to placebo.
Commenting on the study rheumatologist and Associate Professor Peter Nash said the efficacy, safety and convenience of baricitinib will continue to drive increasing use of tablets over injectable medications for rheumatoid arthritis.
JAK inhibitors also offered other advantages including more flexibility with treatment, he told the limbic.
“Patients often stop and start all therapies for intercurrent illness especially infection or surgery, and overseas travel, which can lead to issues of immunogenicity with parenteral bDMARDs that is not seen with oral, small molecule JAK inhibitors,” he said.
“It’s early days but Australian experience of tofacitinib suggests patients and their rheumatologists prefer the convenience of oral versus parenteral administration.
Tofacitinib has already taken a significant proportion of the rheumatoid arthritis market including initiations of treatment.”
“The two JAK inhibitors will have to fight it out in the marketplace as will the three under development, but as a class of drugs, they add to our armamentarium and allow us to further fine tune treatment to individual patients.”
He said extra-articular features such as uveitis and IBD give parenteral bDMARDs the edge in the spondylarthropathies.
In response to a request for comment Abbvie, who manufacture adalimumab (Humira), said they were “awaiting the full, published results”.
The study was designed and sponsored by Eli Lilly and Incyte and several of the investigators were employees of the company.
Dr Peter Nash receives funding for research and clinical trials and honoraria for advice and lectures on behalf of all companies manufacturing biologic therapies and targeted synthetic DMARDs.