title: Oral Methotrexate in split dose weekly versus oral or parenteral Methotrexate once weekly in Rheumatoid Arthritis: a short-term study.
abstract: OBJECTIVE
  To investigate whether methotrexate (MTX) administered orally to rheumatoid arthritis (RA) patients in split doses at 2-3 days' interval, would result in equal or better efficacy, tolerability and compliance, without increasing toxicity compared to single weekly dose given orally or parenterally.
  
  
  METHODS
  One hundred and thirty-five patients fulfilling the American College of Rheumatology (ACR) 2010 criteria for RA, on 7.5 mg of MTX weekly orally, with the Simplified Disease Activity Index (SDAI) > 11 were enrolled for a 24-week period. Patients were randomly divided into three groups and were given MTX: Group 1 7.5 mg twice or thrice weekly orally, Group 2 15 mg or 22.5 mg in a single dose weekly orally and Group 3 15 mg or 22.5 mg in a single dose weekly as an intramuscular injection. The primary outcomes were low disease activity (LDA) and mean change in SDAI at week 24, whereas secondary outcomes included remission, adverse events and compliance.
  
  
  RESULTS
  At week 24, adherence to treatment was maximum in Group 1, 69% (P = 0.09). In intention-to-treat analysis at 24 weeks, Group 1, 49%, Group 2, 36% and Group 3, 47% achieved LDA (P = 0.4). There was significant difference in mean change in SDAI at week 24 from baseline (P = 0.008) among the groups. Group 3 patients were more uncomfortable with the mode of administration of MTX (P = 0.003). There was no significant difference in adverse events.
  
  
  CONCLUSIONS
  Oral split doses of MTX are better than an oral single dose and similar to parenteral MTX in terms of efficacy.
authors.affiliation: Department of Rheumatology, King George Medical University, Lucknow, Uttar Pradesh, India.
authors.forename: Pooja
authors.initials: P
authors.lastname: Dhaon
authors.affiliation: Department of Rheumatology, King George Medical University, Lucknow, Uttar Pradesh, India.
authors.forename: Siddharth K
authors.initials: SK
authors.lastname: Das
authors.affiliation: Department of Rheumatology, King George Medical University, Lucknow, Uttar Pradesh, India.
authors.forename: Ragini
authors.initials: R
authors.lastname: Srivastava
authors.affiliation: Department of Statistics, Lucknow University, Lucknow, Uttar Pradesh, India.
authors.forename: Girdhar
authors.initials: G
authors.lastname: Agarwal
authors.affiliation: Department of Statistics, Lucknow University, Lucknow, Uttar Pradesh, India.
authors.forename: Akash
authors.initials: A
authors.lastname: Asthana
mesh_terms: D000284:Administration, Oral; D000328:Adult; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007194:India; D007273:Injections, Intramuscular; D057194:Intention to Treat Analysis; D008297:Male; D055118:Medication Adherence; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D012074:Remission Induction; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D008727:Methotrexate
keywords: methotrexate; oral; rheumatoid arthritis; split dose