Longterm methotrexate use in rheumatoid arthritis: 12 year followup of 460 patients treated in community practice.
OBJECTIVE
To extend our observations on the longterm tolerability of methotrexate (MTX) and reasons for discontinuation in a cohort of 460 patients with rheumatoid arthritis (RA).


METHODS
We studied all patients with RA who started MTX before June 1986 and attended the community based private practices of 6 rheumatologists in Melbourne. Information to at least April 1, 1995, or within one year of death was updated from the patient's medical records to include MTX discontinuation and reasons for discontinuation. Addition of disease modifying antirheumatic drugs (DMARD) concomitant with MTX was noted. Survival analyses based upon life table methods were used with MTX discontinuation as the observable endpoint. Three different definitions of MTX discontinuation were used (1) according to whether the patient was taking the drug at last followup irrespective of any periods of temporary discontinuation; (2) MTX discontinuation for > 3 months considered to be a treatment endpoint; and (3) addition of concomitant DMARD considered to be only partial success of MTX (as a need for additional therapy to meet treatment goals).


RESULTS
At 12 years, 53% of patients were continuing to take MTX (irrespective of any periods of temporary discontinuation). If discontinuation of the drug for 3 or more months was considered a treatment termination then 38% were still taking the drug at 12 years, and if addition of concomitant DMARD was regarded as a treatment endpoint only 17% of patients were continuing MTX at 12 years. Withdrawal for gastrointestinal toxicity declined over time but the risk of other adverse effects appeared to persist over time.


CONCLUSIONS
MTX in RA is well tolerated over the longer term, with > 50% of patients starting MTX in a community based rheumatology private practice continuing to take it 12 years later. However, a substantial number of patients had 2nd line therapies added over this time. Monitoring for toxicity should continue throughout the course of therapy.
Wluka
A
A
Department of Medicine, Alfred Hospital, Melbourne, Australia.
Buchbinder
R
R
Mylvaganam
A
A
Hall
S
S
Harkness
A
A
Lewis
D
D
Littlejohn
G O
GO
Miller
M H
MH
Ryan
P F
PF
D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000401:mortality; D015331:Cohort Studies; D003154:Community Medicine; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D016019:Survival Analysis; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
D018501:Antirheumatic Agents; D008727:Methotrexate