Sulfasalazine
| Evidence Level: L5 | Predicted Indications: 8 |
Table of Contents
- Sulfasalazine
- Pharmacist Assessment Report
- Sulfasalazine: From Rheumatoid Arthritis and Inflammatory Bowel Disease to Brachydactyly-Syndactyly Syndrome
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- Australia Market Information
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Sulfasalazine: From Rheumatoid Arthritis and Inflammatory Bowel Disease to Brachydactyly-Syndactyly Syndrome
One-Sentence Summary
Sulfasalazine is an anti-inflammatory drug originally used for rheumatoid arthritis, ulcerative colitis and other inflammatory bowel and joint diseases. The TxGNN model gives its highest-ranked prediction as brachydactyly-syndactyly syndrome, a rare congenital limb malformation, but there are no clinical trials and no publications supporting this prediction. It is a purely computational result, and the most biologically plausible candidate in the top 10 is osteoarthritis, supported only by preclinical data.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Rheumatoid arthritis, ulcerative colitis, inflammatory bowel disease, juvenile idiopathic arthritis, spondyloarthropathy (the ARTG entry lists no approved indication text) |
| Predicted New Indication | Brachydactyly-syndactyly syndrome |
| TxGNN Prediction Score | 0.9994 |
| Evidence Level | L5 |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data are not available in the data compiled for this report. Sulfasalazine is known to have anti-inflammatory activity, and the compiled preclinical literature points to inhibition of NF-kB signalling and of the cystine/glutamate antiporter (xCT).
For brachydactyly-syndactyly syndrome, no mechanistic link could be identified. It is a rare congenital limb malformation of genetic origin, and sulfasalazine’s anti-inflammatory actions have no evident relevance to its pathophysiology. The high score reflects a computational pattern only, and the same applies to the other rare genetic conditions in the top 10 (for example colobomatous microphthalmia-rhizomelic dysplasia syndrome, WHIM syndrome and acromesomelic dysplasia, Hunter-Thompson type).
Two other top-10 predictions are more meaningful:
- Osteoarthritis (rank 5): Preclinical studies suggest sulfasalazine reduces cytokine-stimulated cartilage proteoglycan and collagen release, lowers prostaglandin and leukotriene production, and attenuates cartilage destruction in an animal model. A sulfasalazine-hyaluronic acid formulation also reduced inflammation and cartilage degradation in a rat model. This is in vitro and animal data only, with no human efficacy data.
- Spondyloarthropathy, susceptibility to (rank 8): This is already among sulfasalazine’s original indications, so it reflects existing use rather than true repurposing.
Clinical Trial Evidence
Currently no related clinical trials registered for brachydactyly-syndactyly syndrome, or for osteoarthritis and spondyloarthropathy in the data compiled for this report.
Literature Evidence
Currently no related literature available for brachydactyly-syndactyly syndrome.
For the most plausible candidate, osteoarthritis, the most relevant publications are preclinical:
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 29548914 | 2018 | Preclinical (rat model) | Int J Biol Macromol | Sulfasalazine-containing hyaluronic acid released drug for up to 60 days and reduced inflammation and cartilage degradation in a rat osteoarthritis model |
| 26466556 | 2016 | Preclinical (animal model) | J Orthop Res | Sulfasalazine attenuated cartilage destruction after ACL transection and meniscectomy, via inhibition of the cystine/glutamate antiporter |
| 19690126 | 2009 | Preclinical (in vitro) | Rheumatology (Oxford) | Sulfasalazine blocked proteoglycan and collagen release from cytokine-stimulated cartilage and down-regulated metalloproteinases |
| 24329131 | 2014 | Preclinical (chondrocyte proteomics) | Mod Rheumatol | Examined the effects of sulfasalazine and tofacitinib on the protein profile of articular chondrocytes |
| 1673814 | 1991 | Preclinical (in vitro) | Wien Klin Wochenschr | Sulfasalazine and its metabolites altered prostaglandin and leukotriene release from human synovial tissue |
| 35958605 | 2022 | Review | Front Immunol | Review of ferroptosis in inflammatory arthritis, including osteoarthritis (indirect evidence) |
For spondyloarthropathy, the retrieved literature is mainly reviews, plus one pharmacogenetic study:
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 25413361 | 2014 | Pharmacogenetic case-control | BMC Pharmacol Toxicol | NAT polymorphisms in Han Chinese patients with ankylosing spondylitis and their link to sulfasalazine adverse reactions |
| 19938189 | 2009 | Review | World J Gastroenterol | Rheumatic manifestations of inflammatory bowel disease |
| 15922688 | 2005 | Review | Am J Med | Update on spondyloarthritis pathogenesis and management |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 13433B | Pyralin EN | Tablet 500 mg (enteric coated) | Not stated in the data compiled for this report |
Safety Considerations
Contraindications and cautions (from the knowledge graph, not label text): Sulfasalazine is associated with caution or contraindication in the following conditions:
- Porphyria (including inherited porphyria and porphyrin metabolism disease)
- Kidney disease, liver disease, gallbladder disease, urinary tract obstruction and pyoureter
- Asthma (including intrinsic and allergic asthma)
- Blood disorders: neutropenia, agranulocytosis, aplastic anaemia (including idiopathic)
- G6PD deficiency and slow acetylator status
- Metabolic disorders: glycogen storage disease, cystinuria, galactosemia
Drug Interactions: The interaction screen returned 100 interactions in total. The first 20 shown include:
- Major: prilocaine (topical), human immunoglobulin G (intravenous), methenamine
- Moderate: ketorolac, ibuprofen, celecoxib, acyclovir, ethinylestradiol, estradiol, alpelisib, amphotericin B, amikacin, apalutamide, azathioprine, asparaginase, bacitracin, aminolevulinic acid (topical)
- Minor: folic acid
Please refer to the TGA-approved Product Information (PI) for the official warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The top-ranked prediction (brachydactyly-syndactyly syndrome) has no clinical trials, no literature and no plausible mechanism, so it is a model output only (Evidence Level L5). Osteoarthritis has a plausible rationale (Evidence Level L4), but support is limited to in vitro and animal studies. It would be better treated as a research question than as a candidate for clinical use. Spondyloarthropathy is an existing indication, not a new one.
To proceed, the following is needed:
- Detailed mechanism of action data for sulfasalazine
- Human efficacy data for osteoarthritis, such as a pilot clinical trial, before any clinical decision
- Approved indication text and safety information from the TGA Product Information, which were not available in the data compiled for this report
- Confirmation of the route and formulation needed (the only Australian product is an oral enteric-coated tablet, whereas the preclinical osteoarthritis work used a sulfasalazine-hyaluronic acid formulation)
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.