title: Response-driven combination therapy with conventional disease-modifying antirheumatic drugs can achieve high response rates in early rheumatoid arthritis with minimal glucocorticoid and nonsteroidal anti-inflammatory drug use.
abstract: OBJECTIVE
  To assess the safety and efficacy of combination therapy in recent-onset rheumatoid arthritis (RA), with dose adjustments determined by response, in a clinic setting over 3 years.
  
  
  METHODS
  Disease-modifying antirheumatic drug (DMARD)-naive patients with RA of median duration of 12 weeks (n = 61) attending an early arthritis clinic were treated with methotrexate, sulfasalazine, hydroxychloroquine, and fish oil. Dosage adjustments and additions of further DMARDs were contingent on response to therapy and tolerance. Outcome measures for efficacy were Disease Activity Score (DAS28), clinical remission, and modified Sharp radiographic score and for safety, adverse events, and DMARD withdrawal.
  
  
  RESULTS
  At baseline, subjects had at least moderately active disease (mean +/- SD DAS28 was 5.3 +/- 1.1), impaired function as measured by the modified Health Assessment Questionnaire (mHAQ) (0.9 +/- 0.5), and 37% had bone erosions. By 3 months, 29% were in remission; this increased to 54% at 3 years. The greatest fall in DAS28 and improvement in mHAQ scores occurred in the first 12 months. Erosions were detected in 62% at 3 years. The mean dose of parenteral glucocorticoid was equivalent to 0.1 mg/d of prednisolone. After 3 years, 48% remained on triple therapy; fish oil was consumed by 75% of patients, and 21% used nonsteroidal anti-inflammatory drugs. Gastrointestinal intolerance was the most frequent unwanted event (leading to DMARD withdrawal in 17 patients). Sulfasalazine was most frequently withdrawn (30%).
  
  
  CONCLUSIONS
  This implementation study demonstrates the feasibility, safety, and efficacy of combination therapy with inexpensive DMARDs, fish oil, and minimal glucocorticoid use, in routine clinical practice using predefined rules for dosage adjustment.
authors: Royal Adelaide Hospital, North Terrace, Adelaide, South Australia, Australia. sproudman@internode.on.net
authors: Susanna M
authors: SM
authors: Proudman
authors: Helen I
authors: HI
authors: Keen
authors: Lisa K
authors: LK
authors: Stamp
authors: Anita T Y
authors: AT
authors: Lee
authors: Fiona
authors: F
authors: Goldblatt
authors: Oliver C
authors: OC
authors: Ayres
authors: Maureen
authors: M
authors: Rischmueller
authors: Michael J
authors: MJ
authors: James
authors: Catherine L
authors: CL
authors: Hill
authors: Gillian E
authors: GE
authors: Caughey
authors: Leslie G
authors: LG
authors: Cleland
mesh_terms: D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005395:Fish Oils / Q000009:adverse effects / Q000627:therapeutic use; D005938:Glucocorticoids / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006886:Hydroxychloroquine / Q000009:adverse effects / Q000627:therapeutic use; D008137:Longitudinal Studies; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D017063:Outcome Assessment, Health Care / Q000379:methods; D012720:Severity of Illness Index; D012460:Sulfasalazine / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018501:Antirheumatic Agents; D005395:Fish Oils; D005938:Glucocorticoids; D012460:Sulfasalazine; D006886:Hydroxychloroquine; D008727:Methotrexate