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Sulfasalazine in the treatment of rheumatoid arthritis

Michael H Weisman, MD
Renee Z Rinaldi, MD
Section Editor
Ravinder N Maini, BA, MB BChir, FRCP, FMedSci, FRS
Deputy Editor
Paul L Romain, MD


Salicylazosulfapyridine (sulfasalazine, SSZ) was originally proposed as a treatment for rheumatoid arthritis (RA) because of its antiinflammatory and antimicrobial activities [1,2]. Although early studies suggested a beneficial effect, the drug’s efficacy was challenged by the findings of a negative 1948 report, which was influential despite a severely flawed study design [3,4]. The introduction of cortisone during this period, an event hailed as a modern medical miracle, further dampened enthusiasm for the use of SSZ in RA.

SSZ was resurrected as a therapeutic agent for rheumatic disorders after beneficial results were reported in a trial performed in the late 1970s and in the first placebo-controlled trial in 1983, and it is widely available [5,6].

The use of SSZ for the treatment of RA is discussed here and in the individual treatment topics on RA. The management of RA and the use of SSZ in inflammatory bowel disease are presented separately. (See "General principles of management of rheumatoid arthritis in adults" and "Alternatives to methotrexate for the initial treatment of rheumatoid arthritis in adults" and "Treatment of rheumatoid arthritis in adults resistant to initial nonbiologic DMARD therapy" and "Sulfasalazine and 5-aminosalicylates in the treatment of inflammatory bowel disease".)


Approximately 30 percent of sulfasalazine (SSZ) is rapidly absorbed by the small bowel and is then returned, largely unaltered, via the enterohepatic circulation into the bile. Thus, approximately 90 percent of the ingested drug reaches the large intestine as an intact molecule [3,7]. In the colon, SSZ is reduced by the bacterial enzyme azoreductase to sulfapyridine and 5-aminosalicylic acid (5-ASA). Coliform bacteria are, therefore, necessary to reduce the relatively inactive parent drug to its active moieties. Nearly all of the sulfapyridine is absorbed, while 5-ASA is largely excreted in the feces, thereby explaining its utility in inflammatory bowel disease.

Sulfapyridine is subsequently metabolized in the liver via hydroxylation and acetylation. The half-life of these components is prolonged in slow acetylators, a property which may affect toxicity but not efficacy [3,7]. No major drug-drug interactions have been reported [3].


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Literature review current through: Sep 2016. | This topic last updated: Sep 12, 2016.
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