title: Disease-modifying antirheumatic drug-free sustained remission in rheumatoid arthritis: an increasingly achievable outcome with subsidence of disease symptoms.
abstract: OBJECTIVE
  Disease-modifying antirheumatic drug (DMARD)-free sustained remission, the sustained absence of synovitis after cessation of DMARD therapy, is a relevant long-term outcome of rheumatoid arthritis (RA) if (1) its occurrence is promoted by treatment and (2) this status reflects resolution of symptoms and disability. This study investigated both items.
  
  
  METHODS
  1007 patients with RA diagnosed between 1993 and 2011, included in the Leiden Early Arthritis Clinic, were studied on achieving DMARD-free sustained remission. Patients included in 1993-1995 were initially treated with non-steroidal anti-inflammatory drugs, in 1996-1998 mild DMARDs were started early, from 1999 onwards methotrexate was initiated promptly and from 2005 onwards disease activity score (DAS)-steered treatment was common. Remission rates were compared using Kaplan-Meier curves and Cox proportional regression.
  
  
  RESULTS
  In total, 155 patients achieved DMARD-free sustained remission. Specific treatment strategies were significantly associated with achieving remission (p<0.001). Cox regression adjusted for anticitrullinated protein antibody/rheumatoid factor, swollen joint count, erythrocyte sedimentation rate, C-reactive protein revealed HRs for DMARD-free sustained remission of 1.13 (95% CI 0.48 to 2.64) in patients diagnosed in 1996-1998, 2.39 (1.07 to 5.32) in patients treated with early methotrexate (inclusion 1999-2004) and 3.72 (1.60 to 8.62) in those treated early with methotrexate and DAS-steered therapy (inclusion 2005-2011). At the time of remission, the Health Assessment Questionnaire was at the level of the general population (median 0.13, IQR 0-0.63). Also, patient-rated visual analogue scale (VAS) morning stiffness, fatigue, pain and disease activity were low (median (IQR) mm, 14 (2-27), 10 (0-47), 6 (0-20), 7 (0-20), respectively).
  
  
  CONCLUSIONS
  More intensive treatment strategies increased the chance for DMARD-free sustained remission, indicating that RA chronicity can be influenced. Patients with RA achieving DMARD-free sustained remission have a normalised functional status.
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands Rheumatology Unit, Department of Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Ajeganova
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: H W
authors.initials: HW
authors.lastname: van Steenbergen
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: J A B
authors.initials: JA
authors.lastname: van Nies
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: L E
authors.initials: LE
authors.lastname: Burgers
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: T W J
authors.initials: TW
authors.lastname: Huizinga
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: A H M
authors.initials: AH
authors.lastname: van der Helm-van Mil
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; D002097:C-Reactive Protein
keywords: Outcomes research; Patient perspective; Rheumatoid Arthritis