title: Combination treatment with methotrexate, cyclosporine, and intraarticular betamethasone compared with methotrexate and intraarticular betamethasone in early active rheumatoid arthritis: an investigator-initiated, multicenter, randomized, double-blind, parallel-group, placebo-controlled study.
abstract: OBJECTIVE
  To investigate whether disease control can be achieved in early active rheumatoid arthritis (RA) by treatment with methotrexate and intraarticular betamethasone, and whether the addition of cyclosporine to the regimen has any additional effect.
  
  
  METHODS
  Patients (n = 160) were randomized to receive methotrexate 7.5 mg/week plus cyclosporine 2.5 mg/kg of body weight/day (combination therapy) or methotrexate plus placebo-cyclosporine (monotherapy). At weeks 0, 2, 4, 6, and 8 and every 4 weeks thereafter, betamethasone was injected into swollen joints (maximum 4 joints or 4 ml per visit). Beginning at week 8, if synovitis was present, the methotrexate dosage was increased stepwise up to 20 mg/week, with a subsequent stepwise increase in the cyclosporine or placebo-cyclosporine dosage up to 4 mg/kg.
  
  
  RESULTS
  At 52 weeks, 20% improvement according to the American College of Rheumatology criteria (ACR20) was achieved in 85% of the combination therapy group versus 68% of the monotherapy group (P = 0.02). The median individual overall ACR response (ACR-N) in the 2 groups was 80.0% (interquartile range 40.1-91.8%) and 54.5% (interquartile range 2.4-87.8%), respectively (P = 0.025). At 48 and 52 weeks, ACR remission criteria were met in 35% of the combination therapy group and 28% of the monotherapy group. Progression in the Larsen score at 52 weeks was -0.2 +/- 6.5 and 0.4 +/- 6.9 (mean +/- SD) in the combination therapy and monotherapy groups, respectively. Serum creatinine levels increased by 7%, and hypertrichosis was more prevalent, in the combination therapy group.
  
  
  CONCLUSIONS
  Combined treatment with methotrexate and intraarticular glucocorticoid showed excellent disease control and stopped the progression of erosions in patients with early active RA, who had a poor prognosis. Addition of cyclosporine improved the ACR20 and ACR-N responses, whereas the ACR50 and ACR70 responses, remission rates, and radiographic changes did not differ between the 2 study groups.
authors.affiliation: Copenhagen University Hospital, Hvidovre, Denmark.
authors.forename: Merete Lund
authors.initials: ML
authors.lastname: Hetland
authors.forename: Kristian
authors.initials: K
authors.lastname: Stengaard-Pedersen
authors.forename: Peter
authors.initials: P
authors.lastname: Junker
authors.forename: Tine
authors.initials: T
authors.lastname: Lottenburger
authors.forename: Torkell
authors.initials: T
authors.lastname: Ellingsen
authors.forename: Lis Smedegaard
authors.initials: LS
authors.lastname: Andersen
authors.forename: Ib
authors.initials: I
authors.lastname: Hansen
authors.forename: Henrik
authors.initials: H
authors.lastname: Skjødt
authors.forename: Jens Kristian
authors.initials: JK
authors.lastname: Pedersen
authors.forename: Ulrik Birk
authors.initials: UB
authors.lastname: Lauridsen
authors.forename: Anders
authors.initials: A
authors.lastname: Svendsen
authors.forename: Ulrik
authors.initials: U
authors.lastname: Tarp
authors.forename: Jan
authors.initials: J
authors.lastname: Pødenphant
authors.forename: Gert
authors.initials: G
authors.lastname: Hansen
authors.forename: Hanne
authors.initials: H
authors.lastname: Lindegaard
authors.forename: Anselmo
authors.initials: A
authors.lastname: de Carvalho
authors.forename: Mikkel
authors.initials: M
authors.lastname: Østergaard
authors.forename: Kim
authors.initials: K
authors.lastname: Hørslev-Petersen
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001623:Betamethasone / Q000008:administration & dosage*; D016572:Cyclosporine / Q000008:administration & dosage*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D007270:Injections, Intra-Articular; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged
chemical_list: D018501:Antirheumatic Agents; D005938:Glucocorticoids; D016572:Cyclosporine; D001623:Betamethasone; D008727:Methotrexate