Biologic DMARDs offer clinical benefits in adult-onset Still disease

Use of biologic disease-modifying antirheumatic drugs (bDMARDs), particularly tocilizumab (TCZ), anakinra (ANK), and canakinumab (CNK), appears safe and effective in the treatment of adult-onset Still disease (AOSD), results of a systematic review and meta-analysis have shown.

“Evidence supports TCZ, ANK, and CNK therapy for AOSD,” said lead author Dr Piero Ruscitti, Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy. “However, the magnitude of effect and comparative effectiveness of treatments is uncertain.”

Ruscitti and his team searched six databases, two trial registries, and conference abstracts from January 2012 to February 2023 for studies focusing on pharmacological interventions for AOSD. They assessed the following outcomes: remission and response rates, treatment discontinuation, complications, and treatment-related adverse events (AEs).

The authors assessed the risk of bias using the Cochrane risk of bias tool and the Joanna Briggs Institute tool for case series.

Forty-four studies met the eligibility criteria, evaluating the following treatments: nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, conventional synthetic (cs)DMARDs, and bDMARDs. The bDMARDs with the most available data were TCZ, ANK, and CNK. [J Rheumatol 2024;51:442-451]

Three randomized controlled trials (RCTs) found no significant benefits of bDMARDs for AOSD patients, but meta-analyses revealed high rates of complete remission and corticosteroid discontinuation.

Specifically, complete remission rates were 80 percent (95 percent confidence interval [CI], 59‒92; I², 36 percent) for TCZ, 73 percent (95 percent CI, 58‒84; I², 66 percent) for ANK, and 77 percent (95 percent CI, 29‒97; I², 82 percent) for CNK.

For corticosteroid discontinuation, the rates were 57 percent (95 percent CI, 29‒81; I², 66 percent), 47 percent (95 percent CI, 18‒78; I², 79 percent), and 34 percent (95 percent CI, 6‒81; I², 59 percent) for TCZ, ANK, and CNK, respectively. Notably, studies with a greater number of patients with prior bDMARD use found a trend toward lower corticosteroid discontinuation rates (p=0.05).

“The analyses had high clinical heterogeneity, largely because treatments were prescribed as different lines of therapy,” Ruscitti said.

Drug comparisons

These findings supported those of previous meta-analyses of bDMARDs for AOSD, but the current analysis included eight additional studies published more recently. [Ther Adv Musculoskelet Dis 2020;12:1759720X20933133; Expert Rev Clin Immunol 2017;13:1089-1097]

“Despite the absence of conclusive findings in the RCTs, there remains a large body of evidence suggesting that pharmacological treatments, particularly bDMARDs, can benefit patients with AOSD in both the short and long term,” Ruscitti said.

Only one RCT had a direct comparison of effectiveness between two drugs, namely ANK and csDMARD. The heterogeneity of the included studies made it difficult to conduct indirect comparisons, specifically for line of treatment in which various medications have been evaluated in different lines of therapy, according to the authors.

“Standardization of outcomes and outcome definitions should drive future research protocols, with studies of adequate duration,” Ruscitti said. “To reduce bias in studies comparing interventions, treatments should be given at similar stages in the treatment pathway.”