title: Impact of medication withdrawal method on flare-free survival in patients with juvenile idiopathic arthritis on combination therapy.
abstract: OBJECTIVE
  To determine whether order of medication withdrawal in children with juvenile idiopathic arthritis (JIA) taking methotrexate (MTX) and tumor necrosis factor inhibitor (TNFi) combination therapy (CBT) affects flare-free survival (FFS).
  
  
  METHODS
  This retrospective observational study of 335 patients with polyarticular JIA or enthesitis-related arthritis analyzed FFS off medications in 4 withdrawal arms: 1) TNFi plus MTX, off MTX first, 2) TNFi plus MTX, off TNFi first, 3) MTX monotherapy, or 4) TNFi monotherapy. Outcomes were evaluated based on order of medication withdrawal, clinical presentation, serologic parameters, and duration of clinically inactive disease (CID) while taking medications.
  
  
  RESULTS
  Sixty-four percent of all patients achieved CID. However, 89% of patients on CBT who withdrew TNFi first flared within 12 months despite continuing MTX, compared to 12% of those who withdrew MTX and continued TNFi (P < 0.0005). Twenty-seven percent of patients discontinued all medications, but 63% flared within 12 months, and only 49% of these regained CID within 12 months of restarting therapy. Patients on MTX monotherapy had the best FFS after medication withdrawal. FFS was independent of disease subtype, rheumatoid factor status, initial erythrocyte sedimentation rate, initial joint count, corticosteroid exposure, time in CID, and method of medication discontinuation.
  
  
  CONCLUSIONS
  This study confirms that flare rates in JIA are high, and discontinuing medications is challenging. Withdrawal of TNFi from CBT first carries a significantly higher risk of disease flare than withdrawing MTX first. The high relapse rate after discontinuation of TNFi suggests that these medications may not modify the underlying disease process.
authors.affiliation: Children's Hospital Los Angeles, Los Angeles, California.
authors.forename: Caroline Y
authors.initials: CY
authors.lastname: Chang
authors.forename: Rika M L
authors.initials: RM
authors.lastname: Meyer
authors.forename: Andreas O
authors.initials: AO
authors.lastname: Reiff
mesh_terms: D000293:Adolescent; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001171:Arthritis, Juvenile / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D001688:Biological Products / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D015141:Los Angeles; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D012008:Recurrence; D012074:Remission Induction; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D018501:Antirheumatic Agents; D001688:Biological Products; D014409:Tumor Necrosis Factor-alpha; D008727:Methotrexate