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12-04-2022 | Vasculitis | News

ALEVIATE trial: Alemtuzumab may warrant further investigation for refractory vasculitis

Author: Claire Barnard


medwireNews: Findings from a phase 2b trial suggest that treatment with the anti-CD52 antibody alemtuzumab may be beneficial for some patients with primary systemic vasculitis (PSV) and an inadequate response to conventional therapies.

“There is an unmet need for alternative therapies, with an acceptable safety profile, that lead to remission in patients with relapsing or refractory PSV,” say Seerapani Gopaluni (University of Cambridge, UK) and co-investigators.

They explain that alemtuzumab, a licensed therapy for relapsing–remitting multiple sclerosis, “manipulates both innate and adaptive immune systems, transiently depleting monocytes and eosinophils, as well as causing long-term alterations in the number and proportion of T and B cell subsets.”

The ALEVIATE trial included 23 patients with antineutrophil cytoplasmic antibody-associated vasculitis (n=12) or Behçet’s disease (n=11), which Gopaluni and team say are “forms of PSV likely to benefit from alemtuzumab” because “T cell dysregulation is at the core of the pathogenesis for both diseases.”

These people were randomly assigned to receive intravenous alemtuzumab at a dose of 30 mg or 60 mg at baseline and at 6 months, with the treatment interval reduced to 3 months for those with uncontrolled or relapsing disease. Participants were aged a median of 41 years, 65% were women, and the median disease duration was 61 months.

As reported in Arthritis Research & Therapy, 70% of patients achieved a complete or partial vasculitis response at the 6-month follow-up, including a complete response (Birmingham Vasculitis Activity Score for Wegener’s granulomatosis [BVAS/WG] of 0) in 26% and a partial response (BVAS/WG ≤50% of baseline) in 44%. A total of 35% maintained remission without relapse throughout the 1-year study period.

There were no differences in efficacy or relapse rates between the two alemtuzumab doses tested, but Gopaluni et al note that “this may have reflected the small sample size, and it is not known whether higher doses, above 60 mg, may have had a more durable effect.”

The investigators say that the safety profile of alemtuzumab was “acceptable,” with serious adverse events (SAEs) reported in 30% of participants. These included six SAEs with a low probability of being related to alemtuzumab and four serious adverse reactions with a high probability of being related to the anti-CD52 antibody, namely infusion-related reaction (cytokine storm), viral gastroenteritis, cytomegalovirus colitis, and Clostridium difficile infection.

“[S]erious adverse event rates were no higher than seen with conventional therapies in this population,” write the researchers.

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group

Arthritis Res Ther 2022; 24: 81