Tapering canakinumab feasible in patients with juvenile arthritis who achieve remission
Tapering canakinumab in patients with systemic juvenile idiopathic arthritis who achieve remission may be feasible but holding this response may require consistent IL-1 inhibition, according to data published in Arthritis & Rheumatology.
“Canakinumab, a human anti-IL1-beta monoclonal antibody, has shown sustained efficacy in treating sJIA patients and allowing the tapering of glucocorticoids,” Pierre Quartier, MD, of Necker–Enfants Malades Hospital, in Paris, and colleagues wrote. “In the pivotal phase 3 study NCT00889863, the average glucocorticoid dose could be reduced from 0.34 to 0.05 mg/kg in patients treated with canakinumab, with 42/128 (33%) patients discontinuing glucocorticoids. However, limited information is available on the effects of reducing the exposure, or even discontinuation, of canakinumab in patients in [complete clinical remission (CR)].”
To analyze the efficacy and safety of two canakinumab (Ilaris, Novartis) tapering strategies aimed at maintaining complete clinical remission in children with sJIA, Quartier and colleagues conducted a two-part, open-label study. In the first part, 182 patients received 4 mg/kg doses of canakinumab subcutaneously every 4 weeks, and discontinued glucocorticoids or methotrexate as deemed appropriate. Participants who achieved remission — defined as inactive disease for at least 24 weeks — with canakinumab monotherapy went on to part two.
A total of 75 participants entered the second part of the study. These patients were randomized one of two groups — dose reduction from 4 mg/kg to 2, and then to 1 before discontinuation, or dose interval prolongation from every 4 weeks to every 8 weeks, and then to every 12 weeks prior to discontinuation. In both groups, canakinumab exposure could be reduced provided that patients remained in remission for 24 weeks with each step. The researchers then examined whether more than 40% of randomized patients in either group remained in remission for 24 weeks in the first step.
According to the researchers, among the 75 patients who entered part two, 71% of those in the dose reduction group, and 84% of those in the interval prolongation group, maintained clinical remission for 24 weeks in the first step (P .0001 for each group, compared with 40%). Overall, 33% of all part two participants discontinued canakinumab and remained in remission for at least 24 weeks. The researchers noted no new safety outcomes.
“Within this study we observed achievement of CR with canakinumab monotherapy in more than half of the patients in part 1, and maintenance of CR with reduced-exposure canakinumab monotherapy in a high proportion of patients in part 2,” Quartier and colleagues wrote. “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.”
“Our results also show that while CR was maintained in the majority of sJIA patients during canakinumab tapering, only a minority of patients could eventually discontinue canakinumab and maintain CR,” they added. “Therefore, a certain level of sustained inhibition of the IL-1 pathway seems important for the maintenance of CR in most sJIA patients.”
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