The benefits of rituximab in polymyalgia rheumatica (PMR) extend out to one year, an extension to the previously reported proof-of-concept BRIDGE-PMR trial shows.
The latest findings published in Lancet Rheumatology [link here] warrant a larger trial to confirm the results and explore potential predictors of response as well as optimal dosing, the study authors say.
In the current trial, 47 patients with recently diagnosed or relapsing PMR who had previously taken part in the BRIDGE-PMR trial were randomised to rituximab 1000mg infusion or placebo.
The primary outcome was glucocorticoid-free remission at one year after infusion defined by a PMR-AS score of less than 10 without concurrent systemic glucocorticoids.
Because of the COVID pandemic, several patients were unable to attend follow-up appointments. PMR-AS values were therefore imputed for 6 of 47 patients who had a missing score component (4 in the rituximab group and 2 in the placebo group).
In this analysis, the between-group absolute difference reached statistical significance (12 [52%] of 23 in the rituximab group in glucocorticoid-free remission vs five [21%] of 24 participants in the placebo group [absolute difference 31% RR 2·5; p=0·04).
However, in an analysis of patients with complete data, 9 (47%) of 19 patients in the rituximab group and 5 (23%) of 22 patients in the placebo group were in glucocorticoid-free remission at 1 year (absolute difference 25%, relative risk (RR) 2·1; p=0·12).
In patients with newly diagnosed disease, the proportion of patients in glucocorticoid-free remission at one year was numerically higher in the rituximab group (11 [58%] of 19) vs 3 [16%] of 19 for placebo; RR 3·7; p=0·017). In patients with relapsing disease, this proportion numerically favoured the placebo group (1 [25%] of 4 for rituximab vs 2 [40%] of 5 for placebo; RR 0·63; p=1·00).
The authors speculated that these findings might indicate a limited window of opportunity during which the disease course could be modified with rituximab but noted that this would need confirming in larger trials as the numbers of patients in the current trial were small.
There were also between-group differences at 1 year in cumulative glucocorticoid dose (median dose: 1595 mg for rituximab vs 2302 mg for placebo; p=0·04) and PMR-AS (median score: 4·2 vs 7·2, p=0·046), favouring rituximab.
“As the effect of rituximab both on disease activity and glucocorticoid dose seems to persist beyond what is expected based on the drug’s pharmacodynamics, there might be a true disease-modifying effect of rituximab,” the study authors said.
“Larger trials, with optional rituximab retreatment, are necessary to confirm these results and explore predictors of response”, they concluded.
An accompanying editorial [link here] suggested that future trials use steroid-free remission as the primary endpoint and cumulative glucocorticoid dose and PMR-AS domains as secondary endpoints to explore which particular domains are responsive to treatment.
It was also important to adequately power newly diagnosed and relapsing subgroups in order to investigate the clinical efficacy and therapeutic window of opportunity.
“Hopefully, these efforts will eventually lead to the official licensing of systemic biological treatments for the indication of polymyalgia rheumatica, broadening treatment options in this disease,” they concluded.