Canakinumab monotherapy tapering feasible in systemic JIA
medwireNews: Canakinumab monotherapy tapering, either through dose reduction or dose interval prolongation, is feasible in children with systemic juvenile idiopathic arthritis (sJIA) who achieve clinical remission, study findings indicate.
However, only a minority of the patients studied were able to completely discontinue treatment with the anti-interleukin (IL)-1β monoclonal antibody, suggesting that “a certain level of IL-1 inhibition may be important to maintain [clinical remission] in the majority of patients,” Pierre Quartier (Necker–Enfants Malades Hospital, Paris, France) and co-investigators remark.
In part I of the study, 75 (41.2%) of 182 patients with sJIA achieved clinical remission (inactive disease for at least 24 weeks) following treatment with subcutaneous canakinumab 4 mg/kg every 4 weeks.
These patients proceeded to part II where they were randomly assigned to undergo canakinumab tapering through dose reduction (n=38) or dose interval prolongation (n=37).
During the first step, 71% of participants who reduced their dose to 2 mg/kg every 4 weeks and 84% of those who extended the dose interval to 4 mg/kg every 8 weeks remained in clinical remission for a further 24 weeks and proceeded to step 2.
These proportions “significantly exceeded the predefined threshold of 40%,” meaning that the primary endpoint of the study was met, Quartier and team note.
At step 2, the proportions maintaining clinical remission for another 24 weeks were 68% and 81% with regimens of 1 mg/kg every 4 weeks and 4 mg/kg every 12 weeks, respectively.
These patients were then able to attempt discontinuation, but the researchers report in Arthritis & Rheumatology that just 45% in the dose reduction arm and 22% in the dose interval prolongation arm maintained clinical remission for 24 weeks post-discontinuation, giving an overall clinical remission rate of 33% after discontinuation.
This suggests that “consistent IL‐1 inhibition seems necessary to maintain [a clinical] response,” say Quartier et al.
The authors also note that the study was not designed to compare the two tapering strategies, “and as such, meaningful comparisons cannot be made.”
They conclude: “We believe that these results are relevant for clinical practice, particularly for designing personalized tapering strategies that can allow an adequate control of disease while minimizing the side effects of certain medications, notably glucocorticoids.”
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