In Treating RA Pain, Could JAK Agents Beat Adalimumab?

For patients with rheumatoid arthritis (RA), controlling pain is a key treatment priority. However, even for patients who achieve inflammation control with therapy, pain may still be moderate or severe.

A recently published study used data from the RA-BEAM trial to assess what proportion of treated patients achieve pain relief and in what time frame, and found that baricitinib, an oral small-molecule Janus kinase (JAK) inhibitor recently approved as Olumiant by the FDA, may have some advantages over adalimumab (Humira) when it comes to reducing RA pain.

The trial, which has been reported on previously, enrolled 1305 patients with RA who were on background methotrexate. The patients were randomized to receive placebo, adalimumab, or baricitinib. Pain was measured using the visual analog scale, with 0 representing no pain and 100 representing the worst possible pain.

“Our initial observation of differential pain response between baricitinib and adalimumab was based on mean change from baseline. We wanted to understand if these differences persisted when pain relief was evaluated against various thresholds of success, as is typical for other patient-reported outcomes in RA,” write the authors, and they used the proportion of patients achieving 30%, 50%, or 70% improvements from baseline to week 24 of the study. They also assessed the relationship between inflammation and pain at week 24.

At baseline, the median pain score across all groups was 62. At week 24, the mean percentage reductions in pain from baseline for baricitinib, adalimumab, and placebo, respectively, were 51%, 39%, and 17% (P = .001 for baricitinib and adalimumab vs placebo; P = .030 for baricitinib vs adalimumab).

Compared with the adalimumab group, a greater proportion of patients in the baricitinib group achieved 30% and 50% pain relief as early as week 4, and 70% pain relief by week 8; differences between the adalimumab and baricitinib group were maintained through week 24.

The median time to achieve pain relief of 30% or greater was 2 weeks for baricitinib and adalimumab, but the median time to achieve 50% or greater pain relief was 4 weeks for baricitinib and 8 weeks for adalimumab. Baricitinib-treated patients were also more likely to achieve 50% or 70% pain relief than were adalimumab-treated patients.

While the total effect of baricitinib at week 24 was greater than that for adalimumab, inflammation changes, say the authors, accounted for approximately 40% of the pain improvement with baricitinib and 50% of the pain improvement with adalimumab.

“Our findings merit further investigation into the biological mechanisms underlying pain relief,” write the authors, adding that the relationship between inflammation and pain may be different for baricitinib versus adalimumab.

These findings could have implications for the treatment of RA even as biosimilars of adalimumab gain ground in Europe and draw closer in the United States. While biosimilar adalimumab offers the promise of substantial cost savings, newer agents could provide patients with important improvements in their RA-related pain.

Reference

Taylor PC, Lee YC, Fleischmann R, et al. Achieving pain control in rheumatoid arthritis with baricitinib or adalimumab plus methotrexate: results from the RA-BEAM trial. J Clin Med. 2019;8(6):831. doi: 10.3390/jcm8060831.