medwireNews: The interleukin-6 inhibitor tocilizumab may improve systemic symptoms and reduce the need for glucocorticoids among patients with adult-onset Still’s disease refractory to glucocorticoid therapy, suggest findings from a small randomized trial.
However, Tsutomu Takeuchi (Keio University School of Medicine, Tokyo, Japan) and co-investigators stress that the primary outcome of their phase III study – the proportion of patients with an ACR50 response – was not significantly different among the 11 patients who were randomly assigned to receive intravenous tocilizumab at a dose of 8 mg/kg every 2 weeks and the 11 patients who were given placebo.
ACR50 response rates at week 4 were 61.5% in the tocilizumab group and 30.8% in the placebo group, and the same proportion of patients in each group achieved an ACR50 response at week 12.
“Although almost twice the number of patients who received tocilizumab achieved ACR50 through the double-blind phases, the primary endpoint […] was not statistically met,” write Takeuchi and team in the Annals of the Rheumatic Diseases.
They suggest that the study may not have met its primary endpoint due to the small number of participants, which made the study underpowered, or because a higher dose than that used in the trial may be necessary.
In their analysis of secondary endpoints, the investigators found that patients given tocilizumab experienced a significantly greater improvement in systemic feature score from baseline to week 12 than those in the placebo group, with reductions of 4.1 versus 2.3 points, as well as a significantly greater decrease in the dose of prednisolone over the same time period, at 46.2% versus 21.0%.
After week 12, participants in the placebo group were switched to open-label tocilizumab, while those in the tocilizumab group continued to receive the same treatment. Among those who switched from placebo to tocilizumab, the ACR50 response rate improved from 30.8% at week 12 to approximately 85.0% at week 16, and was maintained until the 1-year follow-up, at which time 84.6% of patients in both groups achieved an ACR50 response.
A total of 84.6% of patients in the tocilizumab group and 57.1% of those in the placebo group experienced adverse events (AEs) from baseline to week 12. Nasopharyngitis was the most commonly reported AE in the tocilizumab group (23.1% vs none in the placebo group), followed by constipation (15.4 vs 0.0%). No serious adverse events occurred during the double-blind period, but 11 were reported across both groups in the open-label part of the study.
Although the authors emphasize that solid conclusions cannot be drawn from their findings, they say that the study was the first randomized placebo-controlled trial of tocilizumab in this patient population and may “provide useful insights into the management of adult-onset Still’s disease.”
And the team concludes: “A well-designed, properly powered study will substantiate our preliminary findings.”
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