Risk, Timing, and Predictors of Disease Flare After Discontinuation of Anti–Tumor Necrosis Factor Therapy in Children With Polyarticular Forms of Juvenile Idiopathic Arthritis With Clinically Inactive Disease

Lovell, Daniel J.; Johnson, Anne; Huang, Bin; Gottlieb, Beth S.; Morris, Paula; Kimura, Yukiko; Onel, Karen; Li, Suzanne C.; Grom, Alexei A.; Taylor, Janalee; Brunner, Hermine I.; Huggins, Jennifer; Nocton, James J.; Haines, Kathleen A.; Edelheit, Barbara; Shishov, Michael; Jung, Lawrence; Williams, Calvin B.; Tesher, Melissa; Costanzo, D.; Zemel, Lawrence; Dare, Jason; Passo, Murray H.; Ede, Kaleo; Olson, Judyann C.; Cassidy, Elaine; Griffin, Thomas A.; Wagner‐Weiner, Linda; Weiss, Jennifer E.; Vogler, Larry B.; Rouster‐Stevens, Kelly; Beukelman, Timothy; Cron, Randy Q.; Kietz, Daniel; Schikler, Kenneth N.; Schmidt, Kara; Mehta, Jay; Wahezi, Dawn M.; Ting, Tracy V.; Verbsky, James; Eberhard, B. Anne; Spalding, Steven; Chen, Chen; Giannini, Edward H.

doi:10.1002/art.40509

Cited by 29 publications

(37 citation statements)

References 41 publications

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“…Time-to-flare was similar across the arms. Overall flare rates (26%) were lower than 37%–60% mentioned in previous cohorts16 17 36 37 which may also depend on our limited total follow-up period of 24 months.…”

Section: Discussioncontrasting

confidence: 56%

Treat to target (drug-free) inactive disease in DMARD-naive juvenile idiopathic arthritis: 24-month clinical outcomes of a three-armed randomised trial

Müller

Brinkman²,

Schonenberg-Meinema

et al. 2018

Ann Rheum Dis

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QuestionWhich is the best strategy to achieve (drug-free) inactive disease in juvenile idiopathic arthritis (JIA)?MethodsIn a randomised, single-blinded, study in disease-modifying anti-rheumatic drug (DMARD)-naive patients with JIA, three treatment-strategies were compared: (1) sequential DMARD-monotherapy (sulfasalazine or methotrexate (MTX)), (2) combination therapy MTX + 6 weeks prednisolone and (3) combination therapy MTX +etanercept. Treatment-to-target entailed 3-monthly DMARD/biological adjustments in case of persistent disease activity, with drug tapering to nil in case of inactive disease.After 24 months, primary outcomes were time-to-inactive-disease and time-to-flare after DMARD discontinuation. Secondary outcomes were adapted ACRPedi30/50/70/90 scores, functional ability and adverse events.Results94 children (67 % girls) aged median (IQR) 9.1 (4.6–12.9) years were enrolled: 32 in arms 1 and 2, 30 in arm 3. At baseline visual analogue scale (VAS) physician was mean 49 (SD 16) mm, VAS patient 53 (22) mm, erythrocyte sedimentation rate 12.8 (14.7), active joints median 8 (5–12), limited joints 2.5 (1–4.8) and Childhood Health Assessment Questionnaire score mean 1.0 (0.6).After 24 months, 71% (arm 1), 70% (arm 2) and 72% (arm 3) of patients had inactive disease and 45% (arm 1), 31% (arm 2) and 41% (arm 3) had drug-free inactive disease. Time-to-inactive-disease was median 9.0 (5.3–15.0) months in arm 1, 9.0 (6.0–12.8) months in arm 2 and 9.0 (6.0–12.0) months in arm 3 (p=0.30). Time-to-flare was not significantly different (overall 3.0 (3.0–6.8) months, p=0.7). Adapted ACR pedi-scores were comparably high between arms. Adverse events were similar.ConclusionRegardless of initial specific treatments, after 24 months of treatment-to-target aimed at drug-free inactive disease, 71% of recent-onset patients with JIA had inactive disease (median onset 9 months) and 39% were drug free. Tightly controlled treatment-to-target is feasible.Trial registration number1574.

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Section: Discussioncontrasting

confidence: 56%

Treat to target (drug-free) inactive disease in DMARD-naive juvenile idiopathic arthritis: 24-month clinical outcomes of a three-armed randomised trial

Müller

Brinkman²,

Schonenberg-Meinema

et al. 2018

Ann Rheum Dis

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“…Details of the study design have been reported elsewhere . One hundred thirty‐seven patients with polyarticular‐course JIA, i.e., extended oligoarthritis, rheumatoid factor (RF)–positive polyarthritis, or RF‐negative polyarthritis, who were receiving anti‐TNF treatment, and whose disease was maintained in a state of clinical inactivity during anti‐TNF treatment, were enrolled in 16 tertiary pediatric centers in the US.…”

Section: Methodsmentioning

confidence: 99%

“…Study design. Details of the study design have been reported elsewhere (19). One hundred thirty-seven patients with polyarticular-course JIA, i.e., extended oligoarthritis, rheumatoid factor (RF)-ClinicalTrials.gov identifier: NCT00792233.…”

Section: Methodsmentioning

confidence: 99%

“…A previous report described the clinical characteristics of the patients with polyarticular‐course JIA in the current multicenter study cohort, and presented the clinical factors related to the maintenance of clinically inactive disease during anti‐TNF treatment in these patients and the occurrence of disease flare after anti‐TNF withdrawal. The objectives of the present prospective study were to determine the performance of the serum biomarkers S100A8/A9 and S100A12 at baseline and their relationship to maintenance of clinically inactive disease, their levels at the time of anti‐TNF therapy withdrawal, and their relationship to occurrence of disease flare after anti‐TNF treatment withdrawal in patients with polyarticular‐course JIA.…”

Section: Introductionmentioning

confidence: 99%

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Serum S100A8/A9 and S100A12 Levels in Children With Polyarticular Forms of Juvenile Idiopathic Arthritis: Relationship to Maintenance of Clinically Inactive Disease During Anti–Tumor Necrosis Factor Therapy and Occurrence of Disease Flare After Discontinuation of Therapy

Hinze

Foell

Johnson

et al. 2019

Arthritis & Rheumatology

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“…Of note, RF negativity was not a predictor of achieving remission in our analysis, although RF-positive polyarticular JIA has been associated with lower rates of remission than other JIA forms in the past. 37– 39…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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ObjectivesLong-term safety and efficacy of adalimumab among patients with juvenile idiopathic arthritis (JIA) was evaluated through 6 years of treatment.MethodsChildren 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).ResultsOf 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).ConclusionsThrough 6 years of exposure, adalimumab was well tolerated with significant clinical response (up to clinical remission) and a relatively low retention rate.

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Risk, Timing, and Predictors of Disease Flare After Discontinuation of Anti–Tumor Necrosis Factor Therapy in Children With Polyarticular Forms of Juvenile Idiopathic Arthritis With Clinically Inactive Disease

Abstract: Over one-third of patients with polyarticular JIA with sustained clinically inactive disease will experience a flare by 8 months after discontinuation of anti-TNF therapy. Several predictors of lower likelihood of flare were identified.

Cited by 29 publications

References 41 publications

Treat to target (drug-free) inactive disease in DMARD-naive juvenile idiopathic arthritis: 24-month clinical outcomes of a three-armed randomised trial

Treat to target (drug-free) inactive disease in DMARD-naive juvenile idiopathic arthritis: 24-month clinical outcomes of a three-armed randomised trial

Serum S100A8/A9 and S100A12 Levels in Children With Polyarticular Forms of Juvenile Idiopathic Arthritis: Relationship to Maintenance of Clinically Inactive Disease During Anti–Tumor Necrosis Factor Therapy and Occurrence of Disease Flare After Discontinuation of Therapy

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

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