Baricitinib in early polymyalgia rheumatica (BACHELOR): a randomised, double-blind, placebo-controlled, parallel-group trial.

Abstract

Background: Moderate doses of glucocorticoids result in improvements in nearly all patients with polymyalgia rheumatica, but related adverse events are common in older individuals. We aimed to evaluate whether treatment with baricitinib (a Janus kinase 1/2 inhibitor) results in disease control without the use of oral glucocorticoids in people with recent-onset polymyalgia rheumatica.

Methods: We conducted a randomised, double-blind, placebo-controlled, parallel-group trial at six expert centres in France. Participants with recent (<6 months) polymyalgia rheumatica naive to glucocorticoids and a C-reactive protein polymyalgia rheumatica activity score (CRP PMR-AS) of more than 17 were randomly assigned (1:1), with stratification by hospital, to receive either 4 mg baricitinib orally or placebo (with oral glucocorticoids as rescue treatment in the event of high disease activity) for 12 weeks, followed by 2 mg baricitinib or placebo for another 12 weeks. Subdeltoid glucocorticoid injections at week 1 and week 4 were permitted. Participants, investigators, outcome assessors, and sponsor personnel were masked to group assignments. The primary outcome was a CRP PMR-AS of 10 or less at week 12 without oral glucocorticoid use from week 1 to week 12, analysed in all randomly assigned participants who did not withdraw before first treatment administration. Participants were followed up for 36 weeks. An individual with lived experience of polymyalgia rheumatica was involved in the study design. The trial was registered on ClinicalTrials.gov, NCT04027101, and is complete.

Findings: We assessed 39 individuals for eligibility between Dec 1, 2020, and Aug 30, 2023. 34 participants (22 women and 12 men) were randomly assigned; 18 participants were assigned to the baricitinib group and 16 participants were assigned to the placebo group. One person allocated to placebo withdrew before the first infusion and was not included in analyses. The primary endpoint was reached at week 12 by 14 (78%) of 18 participants in the baricitinib group and two (13%) of 15 participants in the placebo group (relative risk 5·8, 95% CI 3·2-10·6; crude p=0·0004; adjusted p<0·0001). The most common adverse events were musculoskeletal and connective tissue disorders (13 [72%] of 18 participants in the baricitinib group and four [25%] of 16 in the placebo group. There were no deaths and no major adverse cardiovascular events in either study group.

Interpretation: This study suggests that, compared with placebo, individuals with polymyalgia rheumatica receiving 4 mg baricitinib are less likely to need oral glucocorticoids to have low disease activity at week 12 of treatment without any new safety signals.

Funding: CHU Brest and Eli Lilly.