Patients on baricitinib had less disease activity, even without glucocorticoids, but more work is needed to translate these phase 2 findings.
Treating early-stage polymyalgia rheumatica without oral glucocorticoids may be feasible, according to new research showing baricitinib was safe and effective at reducing disease activity at three months and beyond.
The researchers randomly assigned 34 glucocorticoid-naïve patients with severe PMR to receive either 4mg of the JAK inhibitor or a placebo for 12 weeks, followed by either 2mg baricitinib or placebo for another 12 weeks.
All patients had the condition for under six months and a C-reactive protein activity score of more than 17. Glucocorticoid injections were allowed at weeks one and four.
The researchers found that 79% of the intervention group hit the primary endpoint of a CRP PMR-AS of 10 or less at week 12, compared to only 13% of the placebo group. There were no deaths or major cardiovascular events, but three in four patients taking the JAKi reported musculoskeletal and connective tissue disorders, compared to one in four patients taking the placebo.
“This study suggests that, compared with placebo, individuals with polymyalgia rheumatica receiving 4mg baricitinib are less likely to need oral glucocorticoids to have low disease activity at week 12 of treatment without any new safety signals,” the authors wrote.
“The results from this study could help alter the management of polymyalgia rheumatica and, by doing so, avoid the substantial morbidity that presently accompanies long-term use of low-dose prednisone,” they said.
The phase 2 BACHELOR study, which was funded by CHU Brest and Eli Lilly, also found there were no disease flares at week 36, even though patients had stopped taking the JAK inhibitor three months prior. A phase 3 trial is currently underway.
Dr Claire Owen, deputy director of rheumatology at Austin Health, called the study “exciting and highly novel”.
“The results, should they be replicated in a larger multi-centre phase 3 study, have real potential to revolutionalise the management of PMR by completely avoiding the significant morbidity that routinely accompanies long-term, low-dose prednisolone use in this common rheumatic disease,” she said.
“Importantly, no concerning safety signals were identified, however it should be noted that the study was not adequately powered for this.”
These sentiments were echoed in an accompanying editorial by rheumatologists Dr Milena Bond and Professor Christian Dejaco: “Although the recently published treat-to-target recommendations in giant cell arteritis and polymyalgia rheumatica suggest minimising the use of glucocorticoids, these drugs are still the standard treatment for these diseases”.
The editorial authors said that the results were “impressive”, but warned a glucocorticoid-free era for PMR was not quite here yet.
They noted that patients were allowed steroids at the beginning and week four of the study, adding that “although no glucocorticoid use was allowed in the two weeks before participants’ inclusion in the trial, participants could have had disease durations of up to six months, and information on cumulative glucocorticoid doses before randomisation was not provided”.
“Thus, although only one (6%) of 18 participants in the baricitinib group required rescue oral glucocorticoid treatment (mean cumulative dose 161mg) compared with 10 (3%) of 16 participants in the placebo group (mean cumulative dose 636·6mg), concluding that baricitinib can fully replace glucocorticoids in the management of polymyalgia rheumatica might be premature.”
Neither this study nor the EAST PMR trial into tofacitinib monotherapy were powered enough to detect major cardiovascular events, malignancies or serious injections, they added. These were known potential safety issues.
“On the other hand, long-term glucocorticoid use for polymyalgia rheumatica is prevalent, with usage rates of 77% at one year of treatment, 51% at two years, and 25% at five years, often resulting in substantial toxicity, including infections, cardiovascular disease and osteoporosis (in up to 85% of patients overall), and with a notable impact on patients’ quality of life.”
They said that another possible approach to reducing harms would be to reduce the dose of the JAK inhibitor when the treatment target had been met, pointing to this current BACHELOR study finding that most patients treated with baricitinib maintained their response after the dose dropped at three months, remaining in remission until the end of nine months – a full three months after baricitinib was stopped.
“The BACHELOR trial shows that baricitinib is effective in treating polymyalgia rheumatica and could substantially reduce cumulative glucocorticoid doses. Moving forward, strategic trials are essential to compare different agents in terms of efficacy and safety,” they wrote.
“Tailoring treatments to individual patient profiles—considering disease severity, giant cell arteritis overlap, comorbidities, and risk factors for glucocorticoid dependence or adverse events—will be key to developing a personalised, effective and safe treatment approach for patients with polymyalgia rheumatica.”
