title: Tolerability of methotrexate starting with 15 or 25 mg/week for rheumatoid arthritis.
abstract: The objective of the present study was to assess the rate of side-effects and dose-limiting toxicity in patients with rheumatoid arthritis (RA) receiving methotrexate (MTX) at an initial dose of 15 or 25 mg/week. One hundred and eighty-five patients with active RA were enrolled into a prospective non-blind trial over 12 months and randomized to start at a dose of 15 mg/week with subsequent increases if necessary (group A) or 25 mg/week with subsequent dose reductions according to effect (group B). With 168 patients eligible for evaluation 74% of patient in group A and 73% of patients in group B were on MTX after 12 months. Withdrawal due to side-effects amounted to 16% of patients in group A and 18% in group B, and decreases in dose due to side-effects amounted to 10% in group A and 9% in group B. The higher dose of MTX elicited a significantly higher rate of gastrointestinal side-effects (28% versus 17%, P < 0.05) and a tendency towards a higher rate of liver enzyme elevations (47% versus 39%). The frequencies of other side-effects did not differ significantly between the groups. We concluded that starting MTX treatment at a dose of 25 mg/week was associated with a higher rate of minor but not major toxicity as compared with 15 mg/week. With this profile of tolerability it is possible to examine the therapeutic potential of MTX doses exceeding 15 mg/week.
authors.affiliation: Department of Clinical Rheumatology, University of Lübeck, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Schnabel
authors.forename: E
authors.initials: E
authors.lastname: Reinhold-Keller
authors.forename: V
authors.initials: V
authors.lastname: Willmann
authors.forename: W L
authors.initials: WL
authors.lastname: Gross
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D016009:Chi-Square Distribution; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D008727:Methotrexate