Recent studies report successes with tocilizumab for PMR and baricitinib for GCA, paving the way for larger and longer trials.
Recent studies report successes with tocilizumab for polymyalgia rheumatica (PMR) and baricitinib for giant cell arteritis (GCA), paving the way for larger and longer trials.
People with PMR are usually treated with glucocorticoids, which are highly effective but often needed for several years. To avoid associated adverse events, effective steroid-sparing agents are still needed, and tocilizumab has shown promise in some small and uncontrolled trials.
In a double-blind multi-centre phase 2/3 study, 36 patients with new onset PMR were randomly assigned to receive tocilizumab or placebo as an adjunct to oral prednisone. The Austrian study was supported by a grant from Roche and published in Annals of the Rheumatic Diseases.
Prednisone was tapered from 20mg to 0mg over 11 weeks, and primary endpoint was prednisone-free remission at week 16. Tocilizumab was ceased at 16 weeks, with safety and efficacy monitored for a further eight weeks.
Around two-thirds (12/19) of the tocilizumab group achieved glucocorticoid remission at week 16, compared with only 2/17 from the placebo group (p=0.002). Eleven of the 12 who achieved remission in the tocilizumab group maintained it to week 24.
The authors pointed out that the study didn’t address the sustainability of tocilizumab treatment beyond the time limits of the study, making it difficult to conclude whether it had disease-modifying or curative properties, or it’s merely controlling symptoms.
Melbourne-based rheumatologist Dr Claire Owen said that the results are similar to those seen in GCA with the use of tocilizumab.
“However, the duration of follow-up is only 24 weeks here, the study is small and the application in newly diagnosed patients is probably not the clinical setting where we would expect to initiate a biologic,” she told Rheumatology Republic.
“So, it’s very promising, but there’s more work to be done in a larger phase 3 study, preferably also looking at patients with a relapsing disease course.”
And in another study investigating steroid-sparing options, this time in GCA, Mayo Clinic researchers conducted a prospective, open-label proof-of-concept study of baricitinib in relapsing GCA patients. Findings were published in Annals of the Rheumatic Diseases.
The 14 patients had physician-confirmed relapse within six weeks of study entry and evidence of active disease. Patients were given prednisone to achieve symptom control, whereafter they underwent accelerated glucocorticoid tapering over 15-22 weeks (depending on dosage) while taking 4mg baricitinib per day for the 52-week duration of the study.
Only one of the patients relapsed during the study period, with the other 13 patients able to taper then discontinue glucocorticoids and remain in remission for 52 weeks.
Just about all patients experienced at least one adverse event, including infections, gastrointestinal symptoms, leg swelling and fatigue.
“There were no major cardiovascular events or venous thromboembolism reported, but this will be a major concern among an elderly population following the recent black box warnings,” said Dr Owen.
“This very small pilot study shows preliminary safety and efficacy for baricitinib in GCA. Interestingly, patients are said to have relapsing GCA, but none had been treated with tocilizumab before – which is current standard of care.”
“There is definite need for other lines of therapy beyond tocilizumab in GCA, particularly those that don’t impact inflammatory markers. From a basic science standpoint, JAK inhibition makes sense,” she said.
Tocilizumab for PMR:
Ann Rheum Dis 2022, online 24 February
Baricitinib for GCA:
Ann Rheum Dis 2022, online 21 February
