Mesalazine
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
- Mesalazine
- Mesalazine: From Ulcerative Colitis to Congenital Hypotrichosis with Juvenile Macular Dystrophy
Mesalazine: From Ulcerative Colitis to Congenital Hypotrichosis with Juvenile Macular Dystrophy
One-Sentence Summary
Mesalazine (5-aminosalicylic acid) was originally used to treat ulcerative colitis, inflammatory bowel disease and ulcerative proctosigmoiditis. The TxGNN model's top-ranked prediction is congenital hypotrichosis with juvenile macular dystrophy, but no clinical trials and no publications support it. The prediction appears to be a graph-based artifact. Among the top 10 predictions, only rheumatoid arthritis (indirect literature) and osteoarthritis (one computational study) have any supporting material, and neither includes direct efficacy data for mesalazine.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Ulcerative colitis, inflammatory bowel disease, ulcerative proctosigmoiditis (from the knowledge-graph indication list; the Singapore licence records contain no indication text) |
| Predicted New Indication | Congenital hypotrichosis with juvenile macular dystrophy |
| TxGNN Prediction Score | 99.65% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 14 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data is not available in the data compiled for this report. Based on known information, mesalazine is a 5-aminosalicylic acid anti-inflammatory agent. Its efficacy in ulcerative colitis is well established. Its proposed actions include PPAR-gamma activation, COX/lipoxygenase inhibition and NF-kB modulation.
For the top-ranked prediction, no plausible mechanistic link was identified. Congenital hypotrichosis with juvenile macular dystrophy is a rare genetic disorder of hair and retinal development caused by CDH3 (cadherin) mutations. Mesalazine's anti-inflammatory action does not address this defect. The high score most likely reflects network proximity in the knowledge graph rather than true pharmacological relevance.
Other top-10 predictions fall into two groups:
- Weak or indirect rationale: Osteoarthritis has a low-grade inflammatory component, so a theoretical anti-inflammatory link exists. Rheumatoid arthritis is linked through sulfasalazine, which is split into sulfapyridine and mesalazine. However, sulfasalazine's antirheumatic effect is generally attributed to the sulfapyridine moiety, not mesalazine.
- No rationale: Seborrheic keratosis, osteoarthritis susceptibility, vulvar inverted follicular keratosis, pseudoachondroplasia, acromesomelic dysplasia (Hunter-Thompson type), colobomatous microphthalmia-rhizomelic dysplasia syndrome and brachydactyly-syndactyly syndrome are mostly rare genetic or benign conditions. They have no plausible connection to mesalazine.
Clinical Trial Evidence
Currently no related clinical trials registered for the top-ranked prediction, or for any of the top 10 predicted indications.
Literature Evidence
Currently no related literature available for the top-ranked prediction. The table below lists the most relevant publications found for the next-ranked predictions. None is an efficacy trial of mesalazine.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 7588084 | 1995 | Review | Drugs | Sulfasalazine is an established DMARD for rheumatoid arthritis. It splits into sulfapyridine and mesalazine, and which part is the active principle remains uncertain. (Rheumatoid arthritis) |
| 7781502 | 1995 | Review | Dtsch Med Wochenschr | General review of mesalazine (no abstract available). (Rheumatoid arthritis) |
| 7904547 | 1993 | Review | Clin Pharmacokinet | Pharmacokinetics of slow-acting antirheumatic drugs, including sulphasalazine. Months-long delays to full effect are reported. (Rheumatoid arthritis) |
| 38491514 | 2024 | Computational | J Transl Med | Transcriptomic and drug-target analysis to identify therapeutic targets. This is computational prediction, not clinical evidence. (Osteoarthritis) |
| 12235076 | 2002 | Pharmacovigilance | Gut | Re-evaluation of serious adverse reactions to sulphasalazine and mesalazine from spontaneous reports. (Safety signal) |
| 42565551 | 2026 | Cohort | Rheumatology (Oxford) | Medication use and pregnancy outcomes in women with immune-mediated inflammatory diseases. (Rheumatoid arthritis) |
| 41443863 | 2026 | Case report | Intern Med | 5-ASA-induced colitis in a rheumatoid arthritis patient without IBD. (Safety signal) |
| 31830393 | 2019 | Case report | G Ital Nefrol | DRESS syndrome with acute renal failure after sulfasalazine and then mesalazine in a rheumatoid arthritis patient. (Safety signal) |
| 36855206 | 2023 | Case report | J Med Case Rep | Tofacitinib in IBD-associated arthritis (two cases). This does not involve mesalazine. |
Singapore Market Information
All 14 licences are valid single-ingredient products. Indication text is not recorded for any of them. The five main authorisations are listed below.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN09340P | Salofalk 500 Tablet 500 mg | Enteric coated tablet | Not recorded |
| SIN07883P | Pentasa Prolonged Release Tablets 500 mg | Tablet | Not recorded |
| SIN15137P | Pentasa Rectal Suspension 1 g | Suspension | Not recorded |
| SIN14999P | Mezavant XL Gastro-resistant Prolonged Release Tablet 1200 mg | Tablet, delayed release | Not recorded |
| SIN14275P | Asacol Tablet 800 mg | Tablet, enteric coated | Not recorded |
The remaining nine licences cover Pentasa (suppositories, granules and 1 g tablets) and Salofalk (granules, enema and suppositories). Available forms include oral, rectal (suppository, enema, suspension) and granule presentations.
Safety Considerations
- Disease-level contraindication signals (knowledge graph, not label text): kidney disease, interstitial nephritis, lipoid nephrosis, pyoureter, liver disease, gallbladder disease, neutropenia, agranulocytosis, anaemia (including macrocytic anaemia) and pyloric stenosis.
- Drug interactions: 100 interactions were identified. The two Major ones in the retrieved subset are cidofovir and human botulinum neurotoxin A/B immune globulin. Moderate interactions include NSAIDs (ketorolac, ibuprofen, celecoxib, bromfenac), nephrotoxic agents (acyclovir, amphotericin B formulations, amikacin, bacitracin, capreomycin, cisplatin), azathioprine, and sulfonylureas (acetohexamide, chlorpropamide). Anisindione, an anticoagulant, is also listed as Moderate.
- Safety signals in the retrieved literature: Case reports describe 5-ASA-induced colitis and DRESS syndrome with acute renal failure. A pharmacovigilance analysis also covers serious adverse reactions to 5-aminosalicylates.
Please refer to the package insert for full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The top-ranked prediction has no trials, no literature and no plausible mechanism, so its high TxGNN score is best read as a graph artifact. The evidence level is L5. Even the more credible candidates, rheumatoid arthritis (L4) and osteoarthritis (L5), rest only on indirect or computational evidence. Mesalazine's own antirheumatic efficacy is unproven, since the benefit of sulfasalazine is attributed mainly to sulfapyridine.
To proceed, the following is needed:
- Detailed mechanism of action data (MOA)
- Singapore package insert warnings and contraindications from the HSA
- Re-prioritisation of the predictions, with focus on indications that have a plausible inflammatory mechanism
- Direct preclinical or clinical evidence of mesalazine efficacy in any chosen new indication
- A safety plan covering renal and haematological monitoring and the identified drug interactions
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.