SULFASALAZINE - A REVIEW OF ITS PHARMACOLOGICAL PROPERTIES AND THERAPEUTIC EFFICACY IN THE TREATMENT OF RHEUMATOID-ARTHRITIS

Sulfasalazine was first used for rheumatic polyarthritis in the 1940s and in the past 2 decades has become firmly established as a disease-m odifying antirheumatic drug (DMARD). The drug is split by the action o f bacterial azoreductases in the large intestine into sulfapyridine an d mesalazine (mesalamine, 5-aminosalicylic acid), although whether the parent molecule or the sulfapyridine moiety, or both, is the active p rinciple remains uncertain. Sulfasalazine is an effective treatment fo r rheumatoid arthritis (RA), producing improvements in disease paramet ers similar to those seen with penicillamine, hydroxychloroquine or or al or parenteral gold in comparative clinical trials. However, there a re no direct comparisons of the drug with methotrexate. Most adverse e vents associated with sulfasalazine are minor and tend to occur within 3 months of starting therapy. A meta-analysis of studies investigatin g DMARD therapy, which included almost 5000 evaluable patients, conclu ded that sulfasalazine was close to methotrexate in terms of efficacy but was slightly less well tolerated. However, unlike sulfasalazine, m any DMARDs may be unsuitable for women who are, or may become, pregnan t because of their potential to cause teratogenic effects. Sulfasalazi ne may also offer a more rapid onset of action than other DMARDs and m ay slow down the radiological progression ofRA. Combination therapy wi th other DMARDs, particularly methotrexate, appears more effective tha n single DMARD therapy. If the safety of these regimens is shown in la rge numbers of patients they are likely to become more widely used in the future. Sulfasalazine is a therapy of first choice in patients wit h RA and may be the DMARD of choice in women who are, or may become, p regnant.