Tapering Canakinumab Monotherapy in Patients With Systemic Juvenile Idiopathic Arthritis in Clinical Remission: Results From a Phase IIIb/IV Open‐Label, Randomized Study

Objective To evaluate the efficacy and safety of 2 canakinumab monotherapy tapering regimens in order to maintain complete clinical remission in children with systemic juvenile idiopathic arthritis (JIA). Methods The study was designed as a 2‐part phase IIIb/IV open‐label, randomized trial. In the f...

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Published in:	Arthritis & rheumatology (Hoboken, N.J.) Vol. 73; no. 2; pp. 336 - 346
Main Authors:	Chasnyk, Vyacheslav, Palmblad, Karin, I. Brunner, Hermine, Marzan, Katherine, Schneider, Rayfel, Horneff, Gerd, Martini, Alberto, Anton, Jordi, Wei, Xiaoling, Ruperto, Nicolino, Abrams, Ken, Ulbrich, A., Fodor, S., Lauwerys, B., Brichard, B., Knupp Feitosa, S., Felix Rodrigues, M., Mattei de, L., Kozu, K., Laxer, Ronald, Houghton, K., Mogenet, A., Bader Meunier, B., Meyzer, C., Semeraro, M., Ben‐Brahim, O., Kone‐Paut, I., Galeotti, C., Dusser, P., Duquesne, A., Desjonqueres, M., Foeldvari, I., Kienast, A., Geikowski, T., Schulz, A., Hirdes, M., Janda, A., Jacob, A., Emerich, C., Raab, A., Minden, K., Lieber, M., Haselbusch, D., Kolbeck, H., Kuemmerle Deschner, J., Hansmann, S., Schleich, T., Magunia, I., Anders, N., Helling‐Bakki, A., Garan, D., Orban, I., Butbul, Y., Helo, M., Uziel, Y., Haviv, R., Moshe, V., Rothschild, M., Harel, L., Amarilyo, G., Said, M., Gerstein, M., Ravelli, A., Schiappapietra, B., Varnier, G., Finetti, M., Caorsi, R., Pontikaki, I., Gerloni, V., Ubiali, T., Vastert, S., Szczygielska, I., Kwiatkowska, M., Snegireva, L., Kostik, M., Kalashnikova, O., Galindo Zavala, R., Iglesias, E., Calzada, J., Gamir, M. L., Merino, R., Alcobendas, R., Remesal, A., Calvo, I., Gonzalez, I., Barut, K., Adrovic, A., Sahin, S., Gozdenur Savci, R., Demir, S., Bilginer, Y., Batu, E. D., Reiff, Andreas, Brown, Diana, Shaham, Bracha, Higgins, G., Spencer, C., Jones, K., Farley, S., Akoghlanian, S.
Format:	Journal Article
Language:	English
Published:	United States Wiley Subscription Services, Inc 01-02-2021 John Wiley and Sons Inc
Subjects:	Adolescent Antibodies, Monoclonal, Humanized - administration & dosage Antirheumatic Agents - administration & dosage Antirheumatic Agents - therapeutic use Arthritis Arthritis, Juvenile - drug therapy Arthritis, Juvenile - physiopathology Child Child, Preschool Deprescriptions Drug Tapering - methods Exposure Female Full Length Glucocorticoids Glucocorticoids - therapeutic use Humans Interleukins Male Medicin och hälsovetenskap Methotrexate Methotrexate - therapeutic use Monoclonal antibodies Patients Pediatric Rheumatology Remission Remission (Medicine) Remission Induction Safety Tapering Toxicity
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Summary:	Objective To evaluate the efficacy and safety of 2 canakinumab monotherapy tapering regimens in order to maintain complete clinical remission in children with systemic juvenile idiopathic arthritis (JIA). Methods The study was designed as a 2‐part phase IIIb/IV open‐label, randomized trial. In the first part, patients received 4 mg/kg of canakinumab subcutaneously every 4 weeks and discontinued glucocorticoids and/or methotrexate as appropriate. Patients in whom clinical remission was achieved (inactive disease for at least 24 weeks) with canakinumab monotherapy were entered into the second part of the trial, in which they were randomized 1:1 into 1 of 2 treatment arms. In arm 1, the dose of canakinumab was reduced from 4 mg/kg to 2 mg/kg and then to 1 mg/kg, followed by discontinuation. In arm 2, the 4 mg/kg dose interval was prolonged from every 4 weeks, to every 8 weeks, and then to every 12 weeks, followed by discontinuation. In both arms, canakinumab exposure could be reduced provided systemic JIA remained in clinical remission for 24 weeks with each step. The primary objective was to assess whether >40% of randomized patients in either arm maintained clinical remission of systemic JIA for 24 weeks in the first part of the study. Results In part 1 of the study, 182 patients were enrolled, with 75 of those patients randomized before entering part 2 of the trial. Among the 75 randomized patients, clinical remission was maintained for 24 weeks in 27 (71%) of 38 patients in arm 1 (2 mg/kg every 4 weeks) and 31 (84%) of 37 patients in arm 2 (4 mg/kg every 8 weeks) (P ≤ 0.0001 for arm 1 versus arm 2 among those meeting the 40% threshold). Overall, 25 (33%) of 75 patients discontinued canakinumab, and clinical remission was maintained for at least 24 weeks in all 25 of these patients. No new safety signals were identified. Conclusion Reduction of canakinumab exposure may be feasible in patients who have achieved clinical remission of systemic JIA, but consistent interleukin‐1 inhibition appears necessary to maintain this response.
Bibliography:	Supported by Novartis Pharma AG. ClinicalTrials.gov identifier: NCT02296424. Dr. Quartier has received consulting fees, speaking fees, and/or honoraria from Novartis (less than $10,000). Dr. Brunner has received consulting fees, speaking fees, and/or honoraria from GlaxoSmithKline (less than $10,000) and from Roche and Novartis (more than $10,000 each). Dr. Schneider has received consulting fees from Novartis, NovImmune, Sobi, and Roche (less than $10,000 each). Dr. Horneff has received consulting fees, speaking fees, and/or honoraria from Eli Lilly, GSK, Novartis, Pfizer, and Sobi (less than $10,000 each). Dr. Martini has received consulting fees, speaking fees, and or honoraria from Eli Lilly, EMD Serono, Janssen, Novartis, Pfizer, and AbbVie (less than $10,000 each). Dr. Anton has received consulting fees, speaking fees, and/or honoraria from Novartis, Sobi, Roche, Sanofi, AbbVie, Pfizer, and NovImmune (less than $10,000 each). Dr. Wei owns stock or stock options in Novartis. Dr. Ruperto has received consulting fees from Ablynx, AbbVie, AstraZeneca‐Medimmune, Biogen, Boehringer, Bristol Myers Squibb, Eli Lilly, EMD Serono, GlaxoSmithKline, Hoffmann‐La Roche, Janssen, Merck, Novartis, Pfizer, R‐Pharma, Sanofi, Servier, Sinergie, Sobi, and Takeda (less than $10,000 each). No other disclosures relevant to this article were reported.
ISSN:	2326-5191 2326-5205 2326-5205
DOI:	10.1002/art.41488