title: Aiming at low disease activity in rheumatoid arthritis with initial combination therapy or initial monotherapy strategies: the BeSt study.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of four different treatment strategies for patients with early rheumatoid arthritis (RA).
  
  
  METHODS
  In the BeSt study, 508 patients with newly diagnosed (< 2 years) active RA were randomised to be treated according to four treatment strategies: 1. sequential monotherapy, 2. step up to combination therapy (both starting with methotrexate), 3. initial combination therapy with methotrexate, sulphasalazine, and a tapered high dose of prednisone, and 4. initial combination therapy with methotrexate and infliximab. Three-monthly therapy adjustments were dictated by calculation of the Disease Activity Score (DAS), with the goal to achieve and maintain a DAS <or= 2.4. Functional ability was measured every 3 months with the Health Assessment Questionnaire. Radiographs of hands and feet were assessed yearly, blinded for patient identity and treatment, and in random order, to measure joint damage progression (Sharp/van der Heijde score).
  
  
  RESULTS
  After 2 years of treatment, 80% of all patients achieved the goal of DAS <or= 2.4, and 42% reached clinical remission (DAS < 1.6). Initial combination therapy, either with prednisone (group 3) or with infliximab (group 4), resulted in earlier improvement in functional ability, more continuous clinical remission (DAS < 1.6), and less joint damage progression than initial monotherapy (groups 1 and 2). Patients in groups 1 and 2 needed more therapy adjustments, including introduction of combination therapy with prednisone or infliximab, to achieve a DAS <or= 2.4, whereas many patients in groups 3 and 4 were able to taper their medication to sulphasalazine or methotrexate, respectively, monotherapy. The adverse events profile was comparable in all groups. The presence or absence of rheumatoid factor, HLA DR4, or anti-CCP was not associated with radiologic damage progression.
  
  
  CONCLUSIONS
  In patients with early, active RA, remarkable clinical improvement and suppression of joint damage progression can be achieved with frequent, objectively steered treatment adjustments. The best chance for an early clinical and radiologic response lies with initial combination therapy with either methotrexate, sulphasalazine and prednisone or with methotrexate and infliximab, which can be tapered to DMARD monotherapy once low disease activity is achieved.
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, RC Leiden, The Netherlands. C.F.Allaart@lumc.nl
authors.forename: C F
authors.initials: CF
authors.lastname: Allaart
authors.forename: Y P M
authors.initials: YP
authors.lastname: Goekoop-Ruiterman
authors.forename: J K
authors.initials: JK
authors.lastname: de Vries-Bouwstra
authors.forename: F C
authors.initials: FC
authors.lastname: Breedveld
authors.forename: B A C
authors.initials: BA
authors.lastname: Dijkmans
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D000069285:Infliximab; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage / Q000627:therapeutic use*; D012074:Remission Induction / Q000379:methods; D012720:Severity of Illness Index; D012460:Sulfasalazine / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D012460:Sulfasalazine; D000069285:Infliximab; D011241:Prednisone; D008727:Methotrexate