A population model of early rheumatoid arthritis disease activity during treatment with methotrexate, sulfasalazine and hydroxychloroquine.

AIMS: To develop a population model describing the disease activity (DAS28) time course in patients with early rheumatoid arthritis (RA) treated with triple disease-modifying anti-rheumatic drug (DMARD) therapy (methotrexate, sulfasalazine and hydroxychloroquine).
METHODS: DAS28 was obtained in 263 patients with early RA from initiation of therapy until 60 weeks. Using NONMEM(®), base models (DAS28 vs. time) and covariate influences were investigated for the population.
RESULTS: The best model was an exponential model of DAS28 vs. time that was additive to baseline DAS28, with covariance between parameters, and a combined residual error model. Age and patient smoking history were covariates significantly affecting response to therapy. Population estimates were baseline DAS28 (5.7), extent of change in DAS28 (-2.8) and the half-life of disease activity (6.2 weeks; time to steady disease state achieved within approximately 30 weeks). Older individuals exhibited more severe baseline DAS28, described by a power function centred around 57 years (baseline DAS28 for 40- and 70-year-old patients were 5.4 vs. 5.8, respectively) and current smokers took longer to achieve a steady disease state (approximately 50 weeks). There was considerable within-patient random variability in DAS28 over time (empirical 90% CI for DAS28 in a population typical patient at 60 weeks: 1.8, 4.2 with median value of 2.8).
CONCLUSIONS: This is the first report of a disease activity model for early RA treated with triple DMARD therapy. Smoking and age were identified as covariates.