Efficacy and safety of canakinumab as a second line biologic after tocilizumab treatment failure in children with systemic juvenile idiopathic arthritis: A single-centre cohort study using routinely collected health data

Abstract

BackgroundA significant number of systemic juvenile idiopathic arthritis (sJIA) patients discontinue biologic disease-modifying antirheumatic drugs (bDMARDs) due to lack of efficacy or safety concerns. Studies of biologic therapy switch regimens in sJIA are required.MethodsPatients with sJIA who switched from tocilizumab (due to lack of efficacy or safety) to canakinumab (4 mg/kg every 4 weeks) and were hospitalized at the rheumatology department from August 2012 to July 2020 were included. Primary efficacy outcomes were 30% or greater improvement based on the paediatric criteria of the American College of Rheumatology (ACR30), achievement of inactive disease (JADAS-71 = 0) and clinical remission (ACR sJIA clinical inactive disease criteria). Follow-up from time first canakinumab dose administered was 12 months or the closest time point (not less than 6 and not more than 18 months). Data were extracted from electronic outpatient medical records.ResultsDuring the study period, 46 patients with sJIA switched from tocilizumab to canakinumab. Median age at baseline was 8.2 [interquartile range (IQR) 4.0–12.9] years, with the median sJIA duration being 1.8 (IQR 0.8–5.8) years; 37 (80%) patients received at least one conventional DMARD (cDMARD; oral corticosteroids, methotrexate and/or cyclosporine A). Study outcomes were followed up in 45 patients (one patient did not attend the follow-up for an unknown reason); median follow-up was 359 (IQR 282–404) days. During the follow-up, 1 patient discontinued canakinumab due to tuberculosis detection and the dose was reduced or the injection interval increased in 4 (9%) patients. In total, 27 (60%) patients continued to receive at least one cDMARD. Improvement according to the ACR30 criteria was achieved in 43 patients [96%; 95% confidence interval (CI) 85–99], inactive disease in 42 (93%; 95%CI 82–98), and remission in 37 (82%; 95% CI 69-91); after adjustment for actual time-at-risk, the rates were 83, 85 and 73 events per 100 person-years, respectively. During follow-up, 23 AEs (most frequently infections) were reported in 19/45 (42%) patients; 5/45 (11%) patients developed macrophage activation syndrome, with a favorable outcome in all cases.ConclusionsOne-year canakinumab therapy was found to be potentially effective as second-line biologic therapy after discontinuation of tocilizumab in patients with sJIA.

Efficacy of canakinumab in patients with Still’s disease across different lines of biologic therapy: real-life data from the International AIDA Network Registry for Still’s Disease

“…Of note, many patients required the introduction of cDMARDs in both groups; in this regard, concomitant use of conventional immunosuppressants could have a role in the final treatment outcome, and this has been the focus of other studies ( 20 ). The present study confirms the results recently proposed by Alexeeva et al ( 21 ) regarding the effective role of CAN in 46 patients with sJIA previously administered the IL-6 inhibitor tocilizumab, extending the concept to the whole spectrum of Still’s disease (both sJIA and AOSD) and confirming the results, regardless of the biologic agents previously used.…”

Biologics Versus JAK Inhibitors. Part I: Cancer Risk. A Narrative Review

“…We found five studies on anti-IL-1 agents and the risk of cancer: two analyzing various anti-IL-1 [ 89 , 90 ], two on canakinumab [ 91 , 92 ] and one on rilonacept [ 93 ]. All of the studies, including an SR with > 10,000 patients with cryopyrin-associated periodic syndromes (CAPS) treated with anti-IL-1 therapy, showed that these drugs did not increase the rate of neoplasms compared to the general population [ 90 ].…”

Canakinumab in the treatment of systemic juvenile idiopathic arthritis: a retrospective single center study in China

“…However, Horneff G et al found that tocilizumab was more frequently discontinued due to intolerance compared to IL-1 inhibitors ( 12 ). Alexeeva E et al had described that 82% of patients with sJIA achieved remission with one-year canakinumab therapy after tocilizumab treatment failure ( 13 ). Besides, He T et al had described tocilizumab-induced hypofibrinogenemia in patients with sJIA, which was not observed in patients with canakinumab therapy ( 14 ).…”