Still's disease is an unusual form of arthritis that, in children, is also called systemic juvenile idiopathic arthritis, but it can also develop in adults.Few rigorous studies have examined biologic drugs as first-line treatment in adult-onset Still's disease.Results from this cohort study showed that biologics were much more effective than conventional synthetic drugs as primary therapy.
Patients with adult-onset Still's disease were much more likely to achieve sustained remission when they were initially treated with biologic agents than corticosteroids or conventional disease-modifying anti-rheumatic drugs (DMARDs), a retrospective cohort study indicated.
Half of patients receiving biologics as first-line therapy were in sustained event-free remission after 72 weeks, compared with 12% of those treated with conventional medications in the 86-person study, according to Stefan Vordenbäumen, MD, PhD, of St Elisabeth-Hospital Meerbusch-Lank in Germany, and colleagues.
After statistical adjustments, odds of achieving sustained event-free remission -- the study's primary endpoint -- were more than seven times greater for those receiving biologics (OR 7.20, 95% CI 2.50-36.64), the researchers reported in Lancet Rheumatology.
"So far, the efficacy of first-line biological DMARD therapy versus conventional synthetic DMARD therapy for AOSD [adult-onset Still's disease] has largely been extrapolated from studies in children," Vordenbäumen and colleagues wrote. "Here, we provide evidence for more advantageous health benefits for first-line biological DMARD therapy versus conventional synthetic DMARD therapy in AOSD."
Still's disease is an unusual condition that includes arthritis but also other symptoms such as fever and skin rashes. Originally, the name referred to the disease when first seen in adulthood, while a very similar condition in children is known as systemic juvenile idiopathic arthritis (sJIA). Recently, however, many experts have come to believe that they are actually the same disease distinguished only by age at onset, and the term "Still's disease" is increasingly used for both.
Biologics are indeed often used in the adult form, most commonly drugs that target the interleukin-1 (IL-1) pathway including anakinra (Kineret) and canakinumab (Ilaris) -- unlike in other forms of inflammatory arthritis in which tumor necrosis factor inhibitors are usually the first biologic of choice. IL-1 blockers are recommended in a guideline published last year, mainly on the basis of their use in empirical reports and on trials in sJIA. Yet registration trials of biologics for adult-onset Still's disease have consistently missed their primary endpoints, Vordenbäumen's group observed, although some have been approved in certain countries anyway.
For the current study, Vordenbäumen and colleagues analyzed records from a cohort that began enrolling adult-onset Still's patients in 2007; a total of 86 were included in their analysis. Of these, 44 had started on biologics and 42 on conventional DMARDs and/or steroids.
Participants were about 40 years old on average at diagnosis and just under 60% were women. Of those with biologics as initial DMARD therapy, 85% started on anakinra, although injection site reactions eventually forced one-quarter to switch to canakinumab. Five patients started the IL-6 inhibitor tocilizumab (Actemra).
In the group initiating conventional DMARDs, 71% were on steroids alone and most of the rest were on methotrexate with steroids.
Statistical analyses included weighting to account for "important confounders," the researchers said, such as serum ferritin, levels of which were about doubled among patients starting biologic drugs relative to the conventional DMARD group. Adverse events counted in determining event-free status included medication change, as well as any of a long list of conditions known to occur in adult-onset Still's disease or those related to treatment, such as complications from chronic steroid use. As it happened, medication changes were the most common event recorded in the study; in a sensitivity analysis in which it was not considered an event, biologic drugs' advantage over conventional therapy shrank considerably and was no longer statistically significant (OR 1.54, P=0.26).
IL-1 inhibitors appeared more effective than tocilizumab. Among the five patients who started the anti-IL-6 product, only two met the primary endpoint of sustained event-free remission. Three continued on tocilizumab through week 72, while one switched to canakinumab and one of those in remission discontinued the drug altogether. Because there were so few patients starting tocilizumab, however, Vordenbäumen's group noted that "superiority of first-line IL-1 inhibition over IL-6 inhibition [cannot] be derived from our data."
One of the worst complications of adult-onset Still's disease is macrophage activation syndrome (MAS), which can be fatal. In fact, it was fatal for two patients in the conventional DMARD group. No one in the biologics group developed MAS nor did any die.
Limitations to the study included its retrospective, non-randomized design, which left room for unmeasured confounding despite adjusting for known covariates. The analysis was also underpowered to fully assess the utility of tocilizumab, and use of biologics with other targets was not assessed at all. The researchers acknowledged, too, that they were unable to stratify patients according to their specific clinical presentation (e.g., chronic articular versus systemic disease).
John Gever was Managing Editor from 2014 to 2021; he is now a regular contributor.
Disclosures
The study had no specific external funding.Authors reported extensive relationships with pharmaceutical companies and other commercial entities.
Primary Source
The Lancet Rheumatology
Source Reference: Kernder A, et al "First-line biological versus conventional synthetic disease-modifying antirheumatic drug therapy in adult-onset Still's disease: a multicentre, retrospective, propensity weighted cohort study" Lancet Rheumatol 2025; DOI: 10.1016/S2665-9913(25)00023-2.
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