Baricitinib Shows Promise in Polymyalgia Rheumatica

Baricitinib can effectively treat polymyalgia rheumatica (PMR) without the use of oral glucocorticoids, according to results from a small, randomized, double-blind, placebo-controlled study.

Among the 18 patients randomly assigned to the oral Janus kinase (JAK) inhibitor baricitinib, 14 achieved a C-reactive protein PMR activity score (CRP PMR-AS) of 10 or less after 12 weeks of treatment. Two out of 15 participants in the placebo group reached the same benchmark.

The results of the trial, called BACHELOR, were published on January 13, 2025, in The Lancet Rheumatology.

“It’s a good proof-of-concept that you can potentially use no oral steroids in PMR,” said Anisha Dua, MD, MPH, professor of medicine and director of the Vasculitis Center at Feinberg School of Medicine, Northwestern University, in Chicago, commenting on the study for Medscape Medical News. (Optional subdeltoid injections of glucocorticoids were offered to both groups during the trial.)

“That’s a big deal in itself and should be looked at further,” she added.

An Unmeet Need

Glucocorticoids are the primary treatment for PMR, although relapses are common. One meta-analysis estimated that 43% of patients with PMR experience at least one relapse within 1 year of starting treatment. Long-term glucocorticoid use also remains a concern: 77% of patients with PMR remain on glucocorticoids for 1 year, and half are still taking the medication after 2 years. A quarter of patients remain on treatment after 5 years.

The 2015 ACR/EULAR treatment recommendations for PMR and recent 2024 treat-to-target recommendations for giant cell arteritis and PMR have called for more research on glucocorticoid-sparing interventions in these populations.

Sarilumab is the only biologic approved for treating PMR by the US Food and Drug Administration, specifically for those who have had an inadequate response to steroids or who cannot tolerate a steroid taper, both rituximab and tocilizumab have shown efficacy in treating new-onset and steroid-dependent disease. Another small, randomized trial of patients with PMR, the EAST PMR trial, also found that the JAK inhibitor tofacitinib was as effective as steroids. For all these studies of rituximab, tocilizumab, and tofacitinib, the comparator group remained on oral steroids, noted lead author Alain Saraux, MD, PhD, professor of rheumatology, Centre Hospitalier Universitaire Brest, Brest, France, and colleagues.

“This [BACHELOR] study shows for the first time that treating early polymyalgia rheumatica without oral glucocorticoids is feasible,” the authors wrote.

Baricitinib vs Placebo

The BACHELOR trial enrolled 34 patients with PMR with a disease duration of up to 6 months. All patients had CRP PMR-AS scores above 17, were not taking any additional immunosuppressive drugs, and did not take any glucocorticoids in the 2 weeks before the trial began. The researchers did not detail how many participants had taken glucocorticoids previously or were treatment naive.

Participants were randomly assigned to receive either 4 mg of baricitinib daily or placebo for 12 weeks. Patients could receive subdeltoid glucocorticoid injections (7 mg betamethasone or 3.75 mg cortivazol) at week 1 and 4 “according to investigator opinions,” the authors wrote. At week 12, the baricitinib dose was reduced to 2 mg through week 24. The treatment phase concluded at 24 weeks, followed by an additional 12-week follow-up.

The primary outcome was achieving a CRP PMR-AS of 10 or below at week 12 without oral glucocorticoids.

In the baricitinib group (n = 18), participants were with a median age of 70 years and 72% were women. In the placebo group (n = 16), patients were slightly younger, with a median age of 68 years and 56% were women. One participant in the placebo group withdrew from the study prior to initiating treatment.

At baseline, the median CRP PMR-AS score was 28.8 in the baricitinib group and 31.9 in the placebo group.

At week 12, 78% of participants taking baricitinib and 13% of those taking placebo had a CRP PMR-AS score of 10 or lower without taking oral glucocorticoids. Two participants receiving baricitinib and five participants receiving placebo underwent at least one subdeltoid glucocorticoid injection.

Secondary outcomes at week 12, such as erythrocyte sedimentation rate (ESR), ESR PMR-AS, and pain on the visual analog scale, were significantly lower in the placebo group than in the baricitinib group. These differences could be explained by the higher use of oral glucocorticoids in the placebo group, the authors noted.

“Participants in the placebo group received more oral glucocorticoids (nine participants received 19-23 mg in the placebo group compared with one patient who received 7 mg in the baricitinib group),” the authors wrote.

However, at 12 weeks, patients in the baricitinib group had higher mental component summary scores on the 36-item Short Form quality-of-life questionnaire and higher scores on the EuroQol five-dimensional questionnaire.

A reduced dose of baricitinib maintained efficacy through week 24, with most patients maintaining remission through week 36 despite completely tapering off the medication, the authors noted.

Twelve individuals assigned to baricitinib completed treatment. Of the six who discontinued treatment after week 12, three received rescue glucocorticoid treatment and three others stopped the study for other reasons. Eleven individuals in the placebo discontinued treatment after week 12, with six receiving rescue treatment, one lost to follow-up, and four discontinued for other reasons.

Safety Signals

Adverse events were “consistent with the known safety profile of baricitinib,” the authors said. The most common adverse events were musculoskeletal or connective tissue conditions, occurring in 72% of participants in the baricitinib group and 25% of those in the placebo group. The most common conditions were arthralgia and back pain.

There were no deaths or thromboembolic events reported in either group.

However, a larger trial would be necessary to tease out any safety concerns such as increased cardiovascular events, cancer, blood clots, and infections, Dua noted. These are of even greater concern given that PMR mainly affects individuals aged 70 years or older, who already have cardiovascular morbidities and a higher infection risk, noted Robert Spiera, MD, director of the Scleroderma, Vasculitis, and Myositis Center at Hospital for Special Surgery in New York City. He was not involved with the study. “These are not trivial medications,” he said.

Where Would JAK Inhibitors Fall on the Treatment Paradigm?

While the BACHELOR trial demonstrated that baricitinib has efficacy in PMR, it “doesn’t really tell us what [its] place is in treating patients,” Spiera added.

“There’s definitely a need for steroid-sparing strategies in many patients — and you can even say in the majority of patients with polymyalgia rheumatica — but that doesn’t mean every patient with polymyalgia rheumatica,” he said.

There are certain patients, for example, with brittle diabetes or neuropsychiatric issues previously exacerbated by steroids that could benefit from glucocorticoid-sparing medications. Refractory patients who cannot tolerate a steroid taper are also ideal candidates for these types of more targeted therapies, though the BACHELOR trial did not look at this patient population.

“What the optimal strategy is — be it [JAK inhibitors], IL-6 inhibitors, low-dose steroids, or some combination those therapies — requires further studies,” he said. “It should be looked at in the most important populations with this disease, who are patients refractory to steroid taper or those likely to be glucocorticoid intolerant because of comorbidities. That’s where the need is.”

The trial was funded by Eli Lilly, which manufactures baricitinib, and Centre Hospitalier Universitaire Brest. Saraux and some coauthors reported financial relationships with Eli Lilly and other pharmaceutical companies. Dua is a consultant for AbbVie, Amgen, AstraZeneca, GSK, Sanofi, and Novartis, and has received research grant support from Amgen, Novartis, and the Rheumatology Research Foundation. Spiera has been a consultant for Roche-Genentech, GSK, Sanofi, ChemoCentryx, Novartis, Galderma, Cytori, AstraZeneca, Amgen, and AbbVie, and received research grant support from GlaxoSmithKline, Roche-Genentech, AstraZeneca, Bristol Myers Squibb, Kadmon, Boehringer Ingelheim, Cytori, ChemoCentryx, Corbus, Novartis, Amgen, and AbbVie.