medwireNews: The first-line use of biologic disease-modifying antirheumatic drugs (DMARDs) over conventional synthetic DMARDS in adult-onset Still disease (AOSD) “is clearly advantageous,” say German researchers who conducted a multicenter study.
The proportion of participants who achieved the primary endpoint of sustained event-free remission was significantly higher among the 42 patients given first-line biologic DMARDs than among the 41 treated with conventional synthetic DMARDS, at both week 12 (64 vs 32%) and week 72 (50 vs 12%) of follow-up.
This gave a significant overall odds ratio (OR) for achieving the primary endpoint of 7.20 in favor of first-line biologic DMARD use.
Sustained event-free remission was defined in the study as a combination of sustained remission – denoted by a C-reactive protein level below 10 mg/L, and the absence of fever, arthritis, and rash – and no complications from medication use or flares of disease between weeks 12 and 72. The latter part of this combined endpoint included possible complications of glucocorticoid use, such as diabetes or dyslipidemia, that required intervention.
“This study helps to close an important knowledge gap, and supports the therapeutic approach of first-line biological DMARD therapy in AOSD,” write Stefan Vordenbäumen (St Elisabeth-Hospital Meerbusch-Lank) and fellow study authors in The Lancet Rheumatology.
They add: “We expect these findings to influence decision making in initial AOSD treatment.”
While recommended by recent EULAR–PReS guidelines, the evidence to support the first-line use of biologic rather than conventional DMARDs in AOSD has been lacking, the researchers point out. They note that prior studies were either too small or “unable to demonstrate statistically significant effects.”
Conversely, their study enrolled a relatively larger number (n=86) of participants who met Yamaguchi classification criteria for AODS and had active disease but were not receiving any current maintenance treatment.
The participants – of whom 58% were women, 98% were White, and the mean age was 39.4 years – were recruited from 16 secondary and tertiary rheumatology centers and data were obtained from medical chart review. For analysis, the two treatment arms were weighted according to the potential confounders of age at diagnosis, male sex, ferritin concentration, and baseline disease activity (Pouchot score) to give the final numbers of 42 in the biologic DMARD group and 41 in the conventional synthetic DMARD group.
The study was retrospective, so “[t]he effects we observed must be interpreted as associations, as causation cannot be determined,” says Vordenbäumen and team.
Other key findings were that glucocorticoid-related complications occurred more frequently in the conventional synthetic DMARD group, with two participants experiencing new-onset arterial hypertension, and three glucocorticoid-related skin diseases. Three participants also died in this group, the cause was macrophage activation syndrome in two cases and unknown in the other.
By contrast, there were no glucocorticoid-related complications associated with biologic DMARD use, and no patient died in this group.
Providing an expert commentary on the findings, Yi-Ming Chen (Taichung Veterans General Hospital, Taiwan) and Der-Yuan Chen (China Medical University, Taichung, Taiwan), say that the study “provides the compelling evidence that could fundamentally reshape” how AOSD is managed.
The study “brings several crucial insights to the field,” they observe, noting that the combined primary endpoint of sustained remission and absence of complications represents “a clinically meaningful outcome that is important to both physicians and patients.”
The commentators point out that a higher proportion of people in the biologic than conventional synthetic DMARD group were glucocorticoid-free at week 72 (73 vs 43%). This “is particularly important given the well-documented adverse effects of long-term glucocorticoid use,” they say.
Chen and Chen also note that here was a “predominance” of interleukin (IL)-1 inhibitor over IL-6 inhibitor use in the study. Anakinra was used by 84% of participants and canakinumab by 5%, compared with tocilizumab by 11% of patients. This “limits conclusions about the comparative efficacy of different biological DMARDs,” which is something that it “would be valuable” to look at in future prospective studies, they suggest.
While there could still be unmeasured confounding factors, the commentators conclude that, “combined with further insights into the molecular landscape of Still’s disease,” the study findings “support the feasibility of a more personalised, evidence-based approach to first-line biological DMARD therapy.”
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Lancet Rheumatol 2025; doi:10.1016/S2665-9913(25)00023-2
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