Rheumatology 1999; 38: 789
© 1999 British Society for Rheumatology
Letters to the Editor |
Combination therapy in rheumatoid arthritis
Rheumatology Unit, Western General Hospital NHS Trust, Crewe Road, Edinburgh EH4 2XU, UK
SIR, I read with interest the review of combination therapy in rheumatoid arthritis [1]. While I largely accept the authors' final conclusion, I would like to add a note of caution about the interpretation of data demonstrating enhanced efficacy from certain combinations, most notably cyclosporin (CyA) and methotrexate (MTX) [2]. It seems to have been assumed that improved efficacy is due to the additive effects of such drugs working at different immunological or inflammatory sites. There is an alternative, more prosaic explanation, namely that the effects observed are pharmacokinetic. For example, giving a nephrotoxic drug (CyA) to patients who are receiving oral MTX is likely to reduce the renal elimination of MTX. This would be expected to increase the effectiveness of MTX simply through increasing the `area under the curve' after dosing. The same effect could be achieved at substantially lower cost simply by switching from oral to parenteral MTX. Other plausible pharmacokinetic effects could also be postulated both for this and other combinations.
Before we move uncritically to using combinations such as CyA and MTX, we need to know whether the apparent benefit is simply due to altered pharmacokinetics. If it is, then there are certainly simpler, safer and cheaper ways of achieving the same result.
References
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Verhoeven AC, Boers M, Tugwell P Combination therapy in rheumatoid arthritis: updated systematic review. Br J Rheumatol 1998;37:612–9.
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Tugwell P, Pincus T, Yocum D et al. Combination with cyclosporin and methotrexate in severe rheumatoid arthritis. N Engl J Med 1995;333:137–41.
[Abstract/Free Full Text]
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