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. 2020 Jul;6(2):e001208.
doi: 10.1136/rmdopen-2020-001208.

Long-term outcomes in patients with polyarticular juvenile idiopathic arthritis receiving adalimumab with or without methotrexate

Daniel J Lovell  1 , Hermine I Brunner  2 , Andreas O Reiff  3   4 , Lawrence Jung  5 , Katerina Jarosova  6   7 , Dana Němcová  8 , Richard Mouy  9 , Christy Sandborg  10 , John F Bohnsack  11 , Dirk Elewaut  12   13 , Christos Gabriel  14 , Gloria Higgins  15 , Isabelle Kone-Paut  16 , Olcay Y Jones  17 , Veronika Vargová  18 , Elizabeth Chalom  19 , Carine Wouters  20 , Ivan Lagunes  21 , Yanna Song  21 , Alberto Martini  22 , Nicolino Ruperto  23
Affiliations

Long-term outcomes in patients with polyarticular juvenile idiopathic arthritis receiving adalimumab with or without methotrexate

Daniel J Lovell et al. RMD Open. 2020 Jul.

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.

Keywords: Adult Onset Still’s Disease; Anti-TNF; Arthritis; Autoimmune Diseases; Dermatomyositis; Familial Mediterranean Fever; Juvenile Idiopathic Arthritis; Lupus Erythematosus; Methotrexate; Systemic.

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Conflict of interest statement

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.

Figures

Figure 1
Figure 1
Patient disposition. *Not randomised at week 16 (n=12), sponsor decision (n=2), non-responder at week 16 (n=1). †Sponsor request/decision (n=2), randomised in error (n=1). ‡Site not participating in the extension (n=5), remission (n=1). §Not known (n=13). AE, adverse event; BSA, body surface area; DB, double-blind; FD, fixed- dose; MTX, methotrexate.
Figure 2
Figure 2
Percentage of patients achieving JIA ACR 30/50/70/90, JADAS27 LDA and JADAS27 inactive disease over time. (A) Observed and (B) NRI analyses. JADAS27 LDA, ≤3.8; JADAS27 inactive disease, ≤1. For observed analysis, n values are shown for weeks 0, 104, 200 and 312; for NRI analysis, N=171. JADAS27, 27-joint Juvenile Arthritis Disease Activity Score; JIA ACR 30/50/70/90, 30%, 50%, 70%, or 90% improvement in the Juvenile Idiopathic Arthritis American College of Rheumatology response; LDA, low disease activity; NRI, non-responder imputation.
Figure 3
Figure 3
Mean (A) JADAS27 and (B) CHAQ-DI over time, observed and LOCF analyses. N values for observed analysis are shown for weeks 0, 104, 200 and 312. Dotted lines represent JADAS27 LDA (≤3.8) and JADAS ID (≤1) cut-offs. CHAQ-DI, Childhood Health Assessment Questionnaire Disability Index; ID, inactive disease; JADAS27, 27-joint Juvenile Arthritis Disease Activity Score; LDA, low disease activity; LOCF, last observation carried forward; NRI, non-responder imputation.
Figure 4
Figure 4
Baseline and postbaseline (JIA ACR responses at weeks 4, 8, 12 and 16) predictors of JADAS27 clinical remission (JADAS27 ≤1 sustained for ≥6 continuous months). BL, baseline; ID, inactive disease; JADAS27, 27-joint Juvenile Arthritis Disease Activity Score; JIA ACR 30/50/70/90, 30%, 50%, 70% or 90% improvement in the Juvenile Idiopathic Arthritis American College of Rheumatology response; LDA, low disease activity; LOM, limitation of movement; wk, week.
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