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Pediatric rheumatology
Original research
Long-term outcomes in patients with polyarticular juvenile idiopathic arthritis receiving adalimumab with or without methotrexate
  1. Daniel J Lovell1,
  2. Hermine I Brunner1,
  3. Andreas O Reiff2,3,
  4. Lawrence Jung4,
  5. Katerina Jarosova5,6,
  6. Dana Němcová7,
  7. Richard Mouy8,
  8. Christy Sandborg9,
  9. John F Bohnsack10,
  10. Dirk Elewaut11,12,
  11. Christos Gabriel13,
  12. Gloria Higgins14,
  13. Isabelle Kone-Paut15,
  14. Olcay Y Jones16,
  15. Veronika Vargová17,
  16. Elizabeth Chalom18,
  17. Carine Wouters19,
  18. Ivan Lagunes20,
  19. Yanna Song20,
  20. Alberto Martini21,
  21. Nicolino Ruperto22,
  22. for the Pediatric Rheumatology Collaborative Study Group (PRCSG) and the Paediatric Rheumatology International Trials Organization (PRINTO)
  1. 1Department of Pediatrics, Division of Rheumatology, University of Cincinnati, Cincinnati Children’s Hospital Medical Center, PRCSG Coordinating Center, Cincinnati, Ohio, USA
  2. 2Department of Pediatrics, University of Southern California Keck School of Medicine, Los Angeles, California, USA
  3. 3Division of Rheumatology, Children’s Hospital of Los Angeles, Los Angeles, California, USA
  4. 4Department of Rheumatology, Children’s National Medical Center for Cancer and Immunology Research, Washington, District of Columbia, USA
  5. 5Institute of Rheumatology, Prague, Czech Republic
  6. 6Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic
  7. 7Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic
  8. 8Pediatric Rheumatology, Univeristé Paris-Descartes and Hôpital Necker-Enfants Malades, Paris, France
  9. 9Pediatric Rheumatology, Lucile Packard Children’s Hospital at Stanford, Palo Alto, California, USA
  10. 10Department of Pediatrics, Division of Allergy, Immunology and Pediatric Rheumatology, University of Utah, Salt Lake City, Utah, USA
  11. 11Rheumatology, University Hospital Gent, Gent, Belgium
  12. 12VIB Center for Inflammation Research, Gent University, Gent, Belgium
  13. 13Pediatric Rheumatology, Children’s Hospital of the King’s Daughters, Norfolk, Virginia, USA
  14. 14Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio, USA
  15. 15Department of Paediatric Rheumatology and CEREMAI, Hôpital De Bicêtre, National Reference Centre for Auto-inflammatory Diseases, Le Kremlin-Bicêtre, Paris, France
  16. 16Pediatric Rheumatology, Walter Reed National Military Medical Center, Bethesda, Maryland, USA
  17. 17Pediatric Rheumatology Unit, Faculty Hospital, Kosice, Slovakia
  18. 18Pediatric-Rheumatology, Saint Barnabas Medical Center, Livingston, New Jersey, USA
  19. 19Pediatric Immunology, University Hospital Gasthuisberg, Leuven, Belgium
  20. 20AbbVie Inc, North Chicago, Illinois, USA
  21. 21Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili (DiNOGMI),, Università degli Studi di Genova, Genoa, Italy
  22. 22Clinica Pediatrica e Reumatologia—PRINTO, IRCCS Istituto Giannina Gaslini, Genova, Italy
  1. Correspondence to Daniel J Lovell;Daniel.lovell{at}cchmc.org

Abstract

Objectives Long-term safety and efficacy of adalimumab among patients with juvenile idiopathic arthritis (JIA) was evaluated through 6 years of treatment.

Methods Children aged 4–17 years with polyarticular JIA were enrolled in a phase III, randomised-withdrawal, double-blind, placebo-controlled trial consisting of a 16-week open-label lead-in period, 32-week randomised double-blind period and 360-week long-term extension. Patients were stratified by baseline methotrexate use. Adverse events (AEs) were monitored, and efficacy assessments included JIA American College of Rheumatology (JIA ACR) 30%, 50%, 70% or 90% responses and the proportions of patients achieving 27-joint Juvenile Arthritis Disease Activity Score (JADAS27) low disease activity (LDA, ≤3.8) and inactive disease (ID, ≤1).

Results Of 171 patients enrolled, 62 (36%) completed the long-term extension. Twelve serious infections in 11 patients were reported through 592.8 patient-years of exposure. No cases of congestive heart failure-related AEs, demyelinating disease, lupus-like syndrome, malignancies, tuberculosis or deaths were reported. JIA ACR 30/50/70/90 responses and JADAS27 LDA were achieved in 66% to 96% of patients at week 104, and 63 (37%) patients achieved clinical remission (JADAS27 ID sustained for ≥6 continuous months) during the study. Attainment of JIA ACR 50 or higher and JADAS27 LDA or ID in the initial weeks were the best predictors of clinical remission. Mean JADAS27 decreased from baseline, 22.5 (n=170), to 2.5 (n=30) at week 312 (observed analysis).

Conclusions Through 6 years of exposure, adalimumab was well tolerated with significant clinical response (up to clinical remission) and a relatively low retention rate.

  • Juvenile Idiopathic Arthritis
  • Anti-TNF
  • Adult Onset Still’s Disease
  • Methotrexate
  • Arthritis
  • Dermatomyositis
  • Lupus Erythematosus
  • Systemic
  • Familial Mediterranean Fever
  • Autoimmune Diseases
https://creativecommons.org/licenses/by/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

https://doi.org/10.1136/rmdopen-2020-001208

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    Footnotes

    • Contributors The study was designed jointly by academic authors (DJL, HIB, AM and NR) and AbbVie, with data collected by PRINTO/PRCSG investigators. All authors had full access to study data, reviewed and revised the manuscript, and approved the final version to be published. All authors were involved in the decision to submit the manuscript for publication and had the right to accept or reject comments or suggestions.

    • Funding This study was funded by AbbVie.

    • Competing interests DJL has served on speakers’ bureaus for Genentech and Bristol-Myers Squibb and on data and safety monitoring boards for Forest Research and the National Institutes of Health-NIAMS. Cincinnati Children’s Hospital Medical Center has received consulting fees from AbbVie, AstraZeneca, Centocor, Bristol-Myers Squibb, Pfizer, Regeneron, Hoffman La-Roche, Novartis, UBC, Xoma and Genentech for the work of DJL.

      HIB has received speaker honoraria and consulting fees from AbbVie, AstraZeneca, Centocor, Bristol-Myers Squibb, Boehringer Ingelheim, Pfizer, Regeneron, Hoffman La-Roche, Novartis, Takeda, UCB, Genentech, Lilly, Janssen, EMD Serono and R-Pharm; and has served on speakers bureaus for Genentech and Novartis.

      AOR has received consulting fees and speaker fees from AbbVie and Novartis.

      LJ has served as a consultant for OncoImmune and Novartis; has received unrestricted education grants from AbbVie; has received clinical trial support from AbbVie, Bristol-Myers Squibb and UCB Biosciences; and has served on a data and safety monitoring board for Bristol-Myers Squibb.

      KJ has nothing to disclose.

      DN has nothing to disclose.

      RM has received honoraria from AbbVie as a co-investigator during this clinical trial.

      CS has nothing to disclose.

      JFB has nothing to disclose.

      DE has received research grants, consulting fees and/or speakers fees from AbbVie.

      CG has nothing to disclose.

      GH has nothing to declare.

      IK-P has received consulting fees from AbbVie, Pfizer, Roche, CHUGAI, Novartis, SOBI and Novimmune.

      OYJ has nothing to disclose.

      VV has received speaker fees from AbbVie and Pfizer.

      EC has received speaker fees from AbbVie.

      CW has received research grants to her institution from Roche, Pfizer and GSK.

      IL and YS are full-time employees of AbbVie and may hold stock or stock options.

      AM is a professor of pediatrics at the University of Genoa, Italy, and has consultancy agreements with Janssen, Novartis and Pfizer. Prior to January 2019, AM was a scientific director of the Giannina Gaslini Hospital and performed consultancy activities on behalf of the Gaslini Institute for the following companies: AbbVie, Biogen, Boehringer, Bristol-Myers Squibb, EMD Serono, Janssen, Novartis, Pfizer, and R-Pharm.

      NR is a full-time employee of the Gaslini Hospital, which has received contributions to support the research activities of the network of PRINTO from AbbVie, AstraZeneca, Bristol-Myers Squibb, Janssen Biologics B.V., Eli Lilly and Co., ‘Francesco Angelini’, GlaxoSmithKline, Italfarmaco, Novartis, Pfizer, Roche, Sanofi Aventis, Schwarz Biosciences GmbH, Xoma and Wyeth Pharmaceuticals. NR has served on speakers bureaus for Astellas, AstraZeneca, Bristol-Myers Squibb, Italfarmaco, Janssen Biologics B.V., MedImmune, Roche and Wyeth/Pfizer.

    • Patient consent for publication Not required.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymised, individual and trial-level data (analysis data sets), as well as other information (eg, protocols and Clinical Study Reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.

      This clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered. For more information on the process, or to submit a request, visit the following link: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html.