Abstract
ObjectiveTo examine restart of MTX treatment among patients with rheumatoid arthritis (RA) who discontinues treatment, and investigate predictors of restart.MethodsA cohort study was conducted based on data from medical databases. MTX drug discontinuation was defined as a gap ≥ 90 days from the expiration of one MTX prescription to the redemption of a new one. Kaplan Meier estimates were used to compute the cumulative probability of restarting MTX treatment and Cox proportional hazard to estimate the hazard of return to treatment. A case-crossover analysis compared the frequency of events that could potentially have a transient effect on MTX restart.ResultsAmong 788 patients, who started MTX, 299 patients experienced a gap ≥ 90 days. Within 1.4 years 50 % of these patients returned to treatment, and a total of 66 % restarted treatment during follow-up. Concurrent treatment with corticosteroid and disease-modifying antirheumatic drugs (DMARDs) tended to be negatively associated with MTX restart (OR: 0.7(95 % CI: 0.5-1.2) and (OR: 0.7 (95 % CI: 0.4-1.0)). Older patients were less inclined to restart treatment than middle-aged patients (Adjustet HR 0.7 (0.4-1.2)). Patients with a CRP > 300 nmol/L less often restarted MTX than patients with a CRP < 75 nmol/L (adjHR: 0.6 (95 % CI 0.3-1.2)), and men were more inclined to MTX restart than women (adjHR 1.30 (95 % CI 0.9-2.0)).ConclusionIt is important to support patients in remaining continuous users of MTX. A large proportion of RA patients who discontinued MTX later restarted treatment, but especially patients with high disease activity, old age or co-morbidity were less inclined to restart treatment.
Highlights
In rheumatoid arthritis (RA) methotrexate (MTX) is still considered the first drug of choice and early, aggressive and continuous treatment is recommended (Royal College of Physicians 2009; Lopez-Olivo et al 2014)
Sequencing of DMARD has recently been investigated in a systematic review among 503 RA patients in stable disease who were randomized to either continuous treatment or placebo
The database includes: 1) information on type of drug according to the Anatomical Therapeutical Chemical Classification System (ATC), 2) the date when the prescription was filled, 3) the patients civil registry number (CPR number), 4) packing size and the number of pills in each package, and 5) the amount of drug according to number of defined daily doses (DDD) (WHO 2015)
Summary
Study population The study was conducted in the County of Aarhus, Denmark, with a population of approximately 650,000 inhabitants, corresponding to 13 % of the Danish population. Defined MTX drug discontinuation as a gap ≥ 90 days from the expiration of one MTX prescription to the redemption of a new one. We defined return to treatment as redemption of an MTX prescription after a gap ≥ 90 days. As the PEPD does not contain data on the exact doses, but only the defined daily dose (DDD), we reviewed the medical records of all patients and retrieved the prescribed daily dose (PDD) defined as the dose the patients were receiving 6 months after stat of treatment (Steiner & Prochazka 1997). Case-crossover analysis was used to compare the frequency of factors with potential effect on MTX restart (CRP, hemoglobin, ALAT, Fig. 1 1-Kaplan Meier estimate of the cumulative probability of returning to Methotrexate treatment after a gap ≥ 90 days among 299 rheumatoid arthritis patients in the County of Aarhus, Denmark 1996–2006 concurrent use of conventional DMARDs and corticosteroids). The frequency was estimated within 60 days before MTX restart (the hazard period) and compared with the frequency 61–180 days before MTX restart (the control period) (Schneeweiss et al 1997)
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