Clinical pharmacology of combination disease-controlling (DCART/DMARD) therapy in rheumatoid arthritis

Journal/Book: Z Rheumatol 1998; 57: 020 - 024. 1998;

Abstract: Prof. D. E. Furst; Clinical Professor of Medicine & Rheumatology University of Washington Introduction Rheumatoid arthritis (RA) results in work disability in a majority of patients within 10 years of disease onset (1). Rheumatoid arthritis is also associated with a decreased life span in those individuals with the most severe arthritis (1). Logic would suggest then that aggressive therapy be initiated to control disease activity in those patients who are destined to do poorly. A good justification for combination DCART therapy (Disease Controlling Anti-Rheumatic Therapy) would be as an attempt to prevent disability and early mortality in patients who are predicted to do poorly but who are early in their disease course. The term DCART rather than DMARD (Disease Modifying Anti-Rheumatic Drugs) will be utilized for convenience and because these drugs may well control rather than modify disease. Early predictors of poor prognosis are being developed. Thus the literature indicates the following predictors of poor prognosis: radiographic erosions early in rheumatoid arthritis high disease activity and severity (extra articular features such as nodules high numbers of swollen and tender joints low functional status) rheumatoid factor positivity and elevated acute phase reactants. In addition several studies indicate that patients homozygous for certain alleles of HLA-DR4 (also called HLADRB1) are susceptible to more severe disease (2 - 5). Believing that prognosis may be predictable rheumatologists are using combinations of DCARTs rather than the previous sequential approach. DCART combinations might also result in increased toxicity (Table 1). A rational approach to combination DCART therapy is both appropriate and necessary. If one could define the DCART's mechanism(s) of action pharmacokinetics efficacy and toxicity one could rationally combine the data to look for useful combinations. ... le

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