title: Step-down approach using either cyclosporin A or methotrexate as maintenance therapy in early rheumatoid arthritis.
abstract: OBJECTIVE
  To evaluate the feasibility and outcome of the step-down approach using either cyclosporin A (CSA) or methotrexate (MTX) as maintenance therapy following 6 months treatment with these 2 agents in combination in early, nonerosive rheumatoid arthritis (RA).
  
  
  METHODS
  Fifty-seven patients younger than 65 years with early, nonerosive RA were first treated with CSA and MTX in combination for 6 months. They were then randomly stepped down to single-agent maintenance treatment for another 18 months. Safety, clinical efficacy, survival on treatment, and radiographic progression were evaluated.
  
  
  RESULTS
  When being treated with combination therapy, 7 of the 57 patients (12.3%) withdrew because of adverse events. Of the remaining 50 patients, 42 (84.0%) were American College of Rheumatology (ACR) 20% responders, 30 (60.0%) were ACR 50% responders, and 23 (46.0%) were ACR 70% responders. At month 6, 22 patients were randomized to CSA and 27 to MTX. During this trial period, the treatment was discontinued by 16 patients taking CSA (mainly because of loss of efficacy) and by 4 taking MTX. At month 24, the probability (+/- SEM) of survival on treatment was 0.273 +/- 0.09 for CSA and 0.852 +/- 0.07 for MTX. Of the 6 CSA patients who completed the trial, 4 (66.7%) were ACR 20% responders, and 3 (50%) were both ACR 50% and ACR 70% responders. Of the 23 completers in the MTX arm, 21 (91.3%) were ACR 20% responders, 18 (78.3%) were ACR 50%, and 10 (43.5%) were ACR 70% responders. The treatment was not responsible for severe adverse events. Radiography showed a slow progression in the damage score and number of eroded joints in both treatment groups.
  
  
  CONCLUSIONS
  Stepping down to single agent maintenance therapy following 6 months of combination treatment with CSA and MTX in early RA was only successful with MTX. Because this treatment did not prevent some radiographic progression, other approaches (e.g., step-up approach) may be more appropriate in early RA.
authors.affiliation: G. Pini Orthopaedic Institute, Milan, Italy. marchesoni@g-pnin.unimi.it
authors.forename: Antonio
authors.initials: A
authors.lastname: Marchesoni
authors.forename: Norma
authors.initials: N
authors.lastname: Battafarano
authors.forename: Marco
authors.initials: M
authors.lastname: Arreghini
authors.forename: Raffaele
authors.initials: R
authors.lastname: Pellerito
authors.forename: Maria
authors.initials: M
authors.lastname: Cagnoli
authors.forename: Porziana
authors.initials: P
authors.lastname: Prudente
authors.forename: Alfonso
authors.initials: A
authors.lastname: Cerase
authors.forename: Francesco
authors.initials: F
authors.lastname: Priolo
authors.forename: Sergio
authors.initials: S
authors.lastname: Tosi
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001175:Arthrography; D016572:Cyclosporine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007596:Joints / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged
chemical_list: D018501:Antirheumatic Agents; D016572:Cyclosporine; D008727:Methotrexate