medwireNews: Findings from two randomized controlled trials presented at the ACR Convergence 2021 virtual meeting suggest no significant benefits of treatment with the B-cell activating factor (BAFF) inhibitor belimumab or the heat shock response amplifier arimoclomol for patients with idiopathic inflammatory myopathy (IIM).
Presenting the belimumab study, Galina Marder (Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Great Neck, New York, USA) said that circulating BAFF levels are elevated in people with myositis and are associated with markers of disease severity.
This, along with evidence from other preclinical studies, “suggests that BAFF would be a useful therapeutic target in the development of treatment for inflammatory myositis,” she said.
For the phase 2/3 trial, 16 patients with treatment-refractory active IIM – defined as an inadequate response or intolerance to 3 months of glucocorticoids and one or more immunosuppressive agents – were randomly assigned to receive belimumab 10 mg/kg or placebo for 40 weeks in addition to standard care. Participants were aged a median of around 46 years; approximately two-thirds had polymyositis, while a third had dermatomyositis.
Marder reported that 37.5% of eight evaluable patients in the belimumab group achieved the coprimary endpoint of definition of improvement (DOI) at 40 weeks, compared with 16.7% of six evaluable patients in the placebo arm, a nonsignificant difference. Participants treated with belimumab also had comparable improvements in the second coprimary endpoint of average total improvement score (TIS) at week 40 compared with those given placebo, at 38.4 versus 34.6 points.
While the differences in DOI and TIS between the two treatment arms were not statistically significant, small patient numbers were “a major limitation of this study,” said Marder.
She reported that belimumab was well tolerated in the trial, with infections “evenly distributed between treatment arms.” The most frequently occurring infection was of the upper respiratory tract, affecting three belimumab-treated patients and five in the placebo arm.
The arimoclomol trial was an investigator-led phase 2 proof-of-concept study involving 150 patients with inclusion body myositis (IBM) with an average age of 67.2 years who were randomly assigned to receive arimoclomol citrate 400 mg or placebo three times daily for 20 months.
Pedro Machado (University College London, UK) reported that the average IBM Functional Rating Scale (IBMFRS) total score decreased by an average of 3.25 points from baseline to month 20 in the arimoclomol arm, compared with a reduction of 2.26 points in the placebo arm, giving a nonsignificant between-group difference of 0.99 points. Average baseline scores were 26.9 and 27.9, respectively.
There were also no significant differences between the two groups for a number of secondary endpoints, including hand grip strength, knee strength, and 6-minute walk test, noted Machado.
He said that there were “no major safety concerns” identified in the study, and the distribution of serious adverse events (SAEs) was comparable in the arimoclomol and placebo groups, with 15.1% and 23.1%, respectively experiencing SAEs. However, there were more AEs leading to treatment discontinuation among patients receiving arimoclomol versus placebo, at rates of 17.8% versus 5.1%.
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