title: Two-year results of disease activity score (DAS)-remission-steered treatment strategies aiming at drug-free remission in early arthritis patients (the IMPROVED-study).
abstract: BACKGROUND
  Early suppression of disease activity in (rheumatoid) arthritis (RA) patients may result in drug-free remission and prevent damage. We assessed 2-year clinical and radiological outcomes of two disease activity score (DAS)-remission-steered treatment strategies in early arthritis patients.
  
  
  METHODS
  Patients (n = 610) with early RA or undifferentiated arthritis (UA) were treated with methotrexate (MTX) and tapered high dose of prednisone. Patients in early remission (44/53 joints DAS <1.6) after 4 months tapered and stopped medication. Patients who did not achieve early DAS-remission were randomized to either MTX plus hydroxychloroquine plus sulphasalazine plus low dose prednisone (arm 1) or to MTX + adalimumab (arm 2). At four-monthly intervals, medication was tapered and stopped if DAS was <1.6 but restarted, increased or switched if DAS was ≥1.6. Proportions of (drug-free) DAS-remission (DFR) after 2 years and Sharp-van der Heijde scores (SHS) were analyzed separately for the treatment strategies and patients with RA and UA.
  
  
  RESULTS
  After 2 years, 301/610 (49 %) patients were in DAS-remission and 131/610 (21 %) in DFR. In the early remission group 241/387 patients (62 %) were in DAS-remission and 111/387 (29 %) DFR. In arm 1 22/83 (27 %) and in arm 2 24/78 (31 %) were in DAS-remission, and 6/83 (7 %) and 7/78 (9 %), respectively, were in DFR. RA and UA patients achieved DAS-remission in comparable percentages (RA: 234/479 (49 %), UA: 64/122 (52 %), p = 0.25). More UA patients achieved DFR (41/122 (34 %)) compared to RA patients (89/479 (19 %), p<0.001). Mean (SD) DAS over time was 1.74 (0.58) across all patients, and median (IQR) SHS progression was 0 (0-0).
  
  
  CONCLUSIONS
  After 2 years remission-steered treatment in early RA and UA patients, DAS-remission and DFR percentages were relatively low. Patients who achieved early remission more often achieved (drug-free) remission after 2 years than patients who needed additional treatment steps in the randomization arms, and more UA than RA patients achieved DFR. Overall, disease activity and radiologic damage progression in all patients were well suppressed.
  
  
  BACKGROUND
  http://www.controlled-trials.com/ISRCTN11916566 Registered 07/11/2006 and EudraCT number 2006-06186-16 Registered 16/07/2007.
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, P.O. BOX 9600, Leiden, 2300 RC, The Netherlands. l.heimans@lumc.nl.
authors.forename: Lotte
authors.initials: L
authors.lastname: Heimans
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, P.O. BOX 9600, Leiden, 2300 RC, The Netherlands. g.akdemir@lumc.nl.
authors.forename: Gülşah
authors.initials: G
authors.lastname: Akdemir
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, P.O. BOX 9600, Leiden, 2300 RC, The Netherlands. kvcdeboer@hotmail.com.
authors.forename: Kirsten V C Wevers-de
authors.initials: KV
authors.lastname: Boer
authors.affiliation: Department of Rheumatology, Haga Hospital, The Hague, The Netherlands. y.ruiterman@hagaziekenhuis.nl.
authors.forename: Yvonne P
authors.initials: YP
authors.lastname: Goekoop-Ruiterman
authors.affiliation: Department of Rheumatology, Groene Hart Hospital, Gouda, The Netherlands. esmeralda.molenaar@ghz.nl.
authors.forename: Esmeralda T
authors.initials: ET
authors.lastname: Molenaar
authors.affiliation: Department of Rheumatology, Franciscus Hospital, Roosendaal, The Netherlands. whisperwoods@cs.com.
authors.forename: Johannes H L M
authors.initials: JH
authors.lastname: van Groenendael
authors.affiliation: Department of Rheumatology, Reinier de Graaf Gasthuis, Delft, The Netherlands. peeters@rdgg.nl.
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Peeters
authors.affiliation: Department of Rheumatology, Bronovo Hospital, The Hague, The Netherlands. gmsteup@bronovo.nl.
authors.forename: Gerda M
authors.initials: GM
authors.lastname: Steup-Beekman
authors.affiliation: Department of Rheumatology, MCH Antoniushove, Leidschendam, The Netherlands. l.lard@mchaaglanden.nl.
authors.forename: Leroy R
authors.initials: LR
authors.lastname: Lard
authors.affiliation: Department of Rheumatology, Admiraal de Ruyter Ziekenhuis, Goes, The Netherlands. PdSonnaville@reumazorgzwn.nl.
authors.forename: Peter B J
authors.initials: PB
authors.lastname: de Sonnaville
authors.affiliation: Department of Rheumatology, Zorgsaam, Terneuzen, The Netherlands. BGrillet@reumazorgzwn.nl.
authors.forename: Bernard A M
authors.initials: BA
authors.lastname: Grillet
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, P.O. BOX 9600, Leiden, 2300 RC, The Netherlands. t.w.j.huizinga@lumc.nl.
authors.forename: Tom W J
authors.initials: TW
authors.lastname: Huizinga
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, P.O. BOX 9600, Leiden, 2300 RC, The Netherlands. c.f.allaart@lumc.nl.
authors.forename: Cornelia F
authors.initials: CF
authors.lastname: Allaart
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis* / Q000628:therapy*; D018450:Disease Progression; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D006886:Hydroxychloroquine / Q000627:therapeutic use; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D012074:Remission Induction; D012720:Severity of Illness Index; D016037:Single-Blind Method; D012460:Sulfasalazine / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D012460:Sulfasalazine; D006886:Hydroxychloroquine; D008727:Methotrexate