title: A two-step treatment strategy trial in patients with early arthritis aimed at achieving remission: the IMPROVED study.
abstract: OBJECTIVE
  To assess which treatment strategy is most effective in inducing remission in early (rheumatoid) arthritis.
  
  
  METHODS
  610 patients with early rheumatoid arthritis (RA 2010 criteria) or undifferentiated arthritis (UA) started treatment with methotrexate (MTX) and a tapered high dose of prednisone. Patients in early remission (Disease Activity Score <1.6 after 4 months) tapered prednisone to zero and those with persistent remission after 8 months, tapered and stopped MTX. Patients not in early remission were randomised to receive either MTX plus hydroxychloroquine plus sulfasalazine plus low-dose prednisone (arm 1) or to MTX plus adalimumab (ADA) (arm 2). If remission was present after 8 months both arms tapered to MTX monotherapy; if not, arm 1 changed to MTX plus ADA and arm 2 increased the dose of ADA. Remission rates and functional and radiological outcomes were compared between arms and between patients with RA and those with UA.
  
  
  RESULTS
  375/610 (61%) patients achieved early remission. After 1 year 68% of those were in remission and 32% in drug-free remission. Of the randomised patients, 25% in arm 1 and 41% in arm 2 achieved remission at year 1 (p<0.01). Outcomes were comparable between patients with RA and those with UA.
  
  
  CONCLUSIONS
  Initial MTX and prednisone resulted in early remission in 61% of patients with early (rheumatoid) arthritis. Of those, 68% were in remission and 32% were in drug-free remission after 1 year. In patients not in early remission, earlier introduction of ADA resulted in more remission at year 1 than first treating with disease-modifying antirheumatic drug combination therapy plus prednisone.
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Heimans
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: K V C
authors.initials: KV
authors.lastname: Wevers-de Boer
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Visser
authors.affiliation: Department of Rheumatology, Haga Hospital, The Hague, the Netherlands.
authors.forename: R J
authors.initials: RJ
authors.lastname: Goekoop
authors.affiliation: Department of Rheumatology, Groene Hart Hospital, Gouda, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: van Oosterhout
authors.affiliation: Department of Rheumatology, Franciscus Hospital, Roosendaal, The Netherlands.
authors.forename: J B
authors.initials: JB
authors.lastname: Harbers
authors.affiliation: Department of Rheumatology, Reinier de Graaf Gasthuis, Delft, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Bijkerk
authors.affiliation: Department of Rheumatology, Bronovo Hospital, The Hague, The Netherlands.
authors.forename: I
authors.initials: I
authors.lastname: Speyer
authors.affiliation: Department of Rheumatology, Medical Center Haaglanden, The Hague, The Netherlands.
authors.forename: M P D M
authors.initials: MP
authors.lastname: de Buck
authors.affiliation: Department of Rheumatology, Admiraal de Ruyter Hospital, Goes, The Netherlands.
authors.forename: P B J
authors.initials: PB
authors.lastname: de Sonnaville
authors.affiliation: Department of Rheumatology, Zorgsaam, Terneuzen, The Netherlands.
authors.forename: B A M
authors.initials: BA
authors.lastname: Grillet
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: C F
authors.initials: CF
authors.lastname: Allaart
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001168:Arthritis / Q000000981:diagnostic imaging / Q000188:drug therapy; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000188:drug therapy*; D018450:Disease Progression; D004359:Drug Therapy, Combination / Q000379:methods; D061345:Early Medical Intervention / Q000379:methods; D005260:Female; D006801:Humans; D006886:Hydroxychloroquine / Q000627:therapeutic use*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use*; D011859:Radiography; D012074:Remission Induction / Q000379:methods; D016037:Single-Blind Method; D012460:Sulfasalazine / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D012460:Sulfasalazine; D006886:Hydroxychloroquine; D000068879:Adalimumab; D011241:Prednisone; D008727:Methotrexate
keywords: Anti-TNF; DMARDs (synthetic); Early Rheumatoid Arthritis