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. 2023 Feb 22:11:1114207.
doi: 10.3389/fped.2023.1114207. eCollection 2023.

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

Ekaterina Alexeeva  1   2   3 , Elizaveta Krekhova  2   3 , Tatyana Dvoryakovskaya  1   2   3 , Ksenia Isaeva  1 , Aleksandra Chomakhidze  1 , Evgeniya Chistyakova  2   3 , Olga Lomakina  1 , Rina Denisova  1 , Anna Mamutova  1 , Anna Fetisova  1 , Marina Gautier  1 , Dariya Vankova  1 , Ivan Kriulin  1   2   3 , Ruslan Saygitov  4
Affiliations

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

Ekaterina Alexeeva et al. Front Pediatr. .

Abstract

Background: A 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.

Methods: Patients 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.

Results: During 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.

Conclusions: One-year canakinumab therapy was found to be potentially effective as second-line biologic therapy after discontinuation of tocilizumab in patients with sJIA.

Keywords: canakinumab; second-line biologic; switching; systemic juvenile idiopathic arthritis; tocilizumab.

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Conflict of interest statement

Ekaterina Alexeeva has received grant/research support from Roche, Pfizer, Centocor, Eli Lilly, and Novartis, and has participated in Speakers bureau sessions for Roche, AbbVie, AbbVie, Bristol-Myers, Squibb, MSD, Novartis and Pfizer. Tatyana Dvoryakovskaya has received grant/research support from Roche, Pfizer, Centocor, Eli Lilly, and Novartis, and has participated in Speakers bureau sessions for Roche, AbbVie, Bristol-Myers, Squibb, MSD, Novartis and Pfizer. Ksenia Isaeva has received grant/research support from Roche, Novartis and Sanofi. Olga Lomakina has received grant/research support from Pfizer, Eli Lilly. Rina Denisova has received grant/research support from Roche, Pfizer, Centocor, Sanofi and Novartis, and has participated in Speakers bureau sessions for Roche, AbbVie, MSD, Novartis. Anna Mamutova has received grant/research support from Eli Lilly has participated in Speakers bureau sessions for Novartis. Anna Fetisova has received grant/research support from Amgen and AbbVie. Elizaveta Krekhova, Aleksandra Chomakhidze, Evgeniya Chistyakova, Marina Gautier, Dariya Vankova, Ivan Kriulin, and Ruslan Saygitov confirm that s(he) has no competing interests to declare.

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