How Sulfasalazine Works

Sulfasalazine and 5-aminosalicylates in the treatment of inflammatory bowel disease

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Salicylazosulfapyridine () was originally proposed as a treatment for rheumatoid arthritis. It was…
uptodate.com

Salicylazosulfapyridine (, SSZ) was originally proposed as a treatment for rheumatoid arthritis (RA) because of its antiinflammatory and antimicrobial activities. Although early studies suggested a beneficial effect, the drug’s efficacy was challenge
uptodate.com

Sulfasalazine is metabolized in the body to 2 major components: Sulfapyridine and 5-aminosalicylic acid (5-ASA). While 5-ASA is believed to be the main immunomodulator in Ulcerative Colitis, acting locally in the colon, Sulfapyridine is thought to be the active moiety in patients with Rheumatoid Arthritis.


Women With Autoimmune Diseases: Medications During Pregnancy and Lactation

Many more classes of immunosuppressive therapies are available to treat inflammatory and autoimmune diseases in pregnant women. Knowledge of…
medscape.org

Sulfasalazine is a useful DMARD especially for women planning pregnancy. Special cautions to bear in mind:
1) Increase folic acid supplement dose in pregnancy;
2) Avoid in early lactation.


Sulfasalazine and MTX in RA

Sulfasalazine is a powerful inhibitor of the reduced folate carrier, which in turn reduces cellular uptake of methotrexate. This explains why giving the drugs together is no better than giving MTX alone and significantly increases the risk of…
medscape.com

Sulfasalazine and Methotrexate are not infrequently combined in the treatment of Rheumatoid Arthritis, especially in the famed “triple therapy” regimen that is recently shown to be more cost-effective and sustainable than MTX in combination with a biologic anti-TNF. Yet, it is often mentioned that it is mechanistically illogical to combine SSZ with MTX, since they act in similar fashion.

Yes and No. They both interfere with folate metabolism (and DNA synthesis, in turn), but they individually have many other differing actions, some of which have not been thoroughly elucidated. MTX, for example, is recently reported to modulate JAK-STAT intracellular signaling. SSZ, on the other hand, is known to interact with the microbiome. While mechanistically they may even conflict with each other’s metabolism in vitro, there is clinical evidence that combination therapy is synergistic.