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A population model of early rheumatoid arthritis disease activity during treatment with methotrexate, sulfasalazine and hydroxychloroquine
Author(s) -
Wojciechowski Jessica,
Wiese Michael D.,
Proudman Susanna M.,
Foster David J. R.,
Upton Richard N.
Publication year - 2015
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.12553
Subject(s) - medicine , sulfasalazine , hydroxychloroquine , rheumatoid arthritis , nonmem , population , methotrexate , leflunomide , disease , pharmacokinetics , environmental health , covid-19 , ulcerative colitis , infectious disease (medical specialty)
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.