Chloroquine
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
- Chloroquine
- Chloroquine: From Rheumatoid Arthritis and Malaria to Rheumatoid Factor-Positive Polyarticular Juvenile Idiopathic Arthritis
Chloroquine: From Rheumatoid Arthritis and Malaria to Rheumatoid Factor-Positive Polyarticular Juvenile Idiopathic Arthritis
One-Sentence Summary
Chloroquine is an established antimalarial and antirheumatic drug, originally used for malaria, rheumatoid arthritis and lupus. The TxGNN model predicts it may be effective for rheumatoid factor-positive polyarticular juvenile idiopathic arthritis, but no clinical trials and only 1 publication (about a different drug, leflunomide) support this direction, so the prediction currently rests on the model alone.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Rheumatoid arthritis, systemic lupus erythematosus, malaria (the Singapore licence has no indication text recorded; indications come from the knowledge graph) |
| Predicted New Indication | Rheumatoid factor-positive polyarticular juvenile idiopathic arthritis |
| TxGNN Prediction Score | 99.41% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 1 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data for chloroquine is not available in the data compiled for this report. Based on known information, chloroquine is an antimalarial that is also used as an antirheumatic agent. Its immunomodulatory effects include raising lysosomal pH, reducing antigen processing and presentation, lowering pro-inflammatory cytokine signalling and inhibiting Toll-like receptors.
Rheumatoid factor-positive polyarticular JIA resembles adult rheumatoid arthritis in its disease process. Chloroquine's proven use in adult RA therefore makes a mechanistic extrapolation plausible.
There is an important caveat. The only paper retrieved for this exact prediction concerns leflunomide, not chloroquine, so it does not test the hypothesis. Modern JIA care has also moved to conventional synthetic DMARDs and biologics.
Among the other predictions, only osteoarthritis has a registered trial involving chloroquine. This is a completed Phase 4 add-on study (NCT00805519, n=230). It is not a chloroquine-alone design, and no results were available.
Clinical Trial Evidence
Currently no related clinical trials registered for the top prediction.
For reference, the closest trial found for a lower-ranked prediction (osteoarthritis, rank 5):
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00805519 | Phase 4 | Completed | 230 | Prednisolone and chloroquine add-on to glucosamine plus chondroitin in knee osteoarthritis. Results not available, and the combination design makes chloroquine's own effect hard to isolate. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 24334641 | 2014 | Cohort | The Journal of Rheumatology | Long-term real-life experience with leflunomide in JIA. It does not evaluate chloroquine, so it is only indirectly relevant. |
Related JIA literature from the broader JIA prediction (juvenile idiopathic arthritis, rank 4) includes:
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 18021335 | 2007 | Cohort | J Clin Pharm Ther | Methotrexate pharmacokinetics in JIA patients on methotrexate alone versus methotrexate plus chloroquine. |
| 4608161 | 1974 | Clinical study | Scand J Rheumatol | Dosing of chloroquine and hydroxychloroquine in children with JIA and lupus, guided by serum concentrations. |
| 2047820 | 1991 | Review | Schweiz Med Wochenschr | Therapeutic strategy in 119 juvenile chronic arthritis patients, discussing chloroquine among disease-modifying drugs. |
| 7409700 | 1980 | Review | Fortschr Med | Benefits and adverse effects of gold, D-penicillamine, chloroquine and azathioprine in juvenile arthritis. |
| 9523387 | 1998 | Case report | Rev Rhum (Engl Ed) | Third-degree atrioventricular block in a patient on long-term chloroquine, who had juvenile-onset arthritis. |
| 1450810 | 1992 | Case report | Br J Rheumatol | Chloroquine-induced vitiligo in juvenile-onset rheumatoid arthritis. |
Most of this literature is old (1962–1991), narrative or descriptive, and does not provide controlled evidence of efficacy.
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN01559P | Chloroquine Tablets 250 mg (Beacons Pharmaceuticals Pte. Ltd.) | Tablet, film coated | Not recorded in the data compiled |
Safety Considerations
Contraindications (from knowledge graph associations, not label text): epilepsy; porphyria and porphyrin metabolism disorders; liver disease; gallbladder disease; eye, retinal and vision disorders (including retinitis, scotoma and blindness); hearing disorders; psoriasis and parapsoriasis; neutropenia, agranulocytosis and leukopenia; anaemia (including macrocytic anaemia); G6PD deficiency; glycogen storage disease; cystinuria; galactosemia; substance abuse/dependence.
Drug Interactions: 100 interactions were found in the interaction database. Major-level examples include:
- Agalsidase beta
- Bupropion
- Cisapride
- Clarithromycin
- Dolasetron
- Granisetron
Moderate-level examples include antacids (aluminium hydroxide, calcium carbonate), H2 blockers (famotidine, cimetidine), sulfonylureas and insulin (glimepiride, glipizide, glyburide, insulin human), metronidazole, loperamide and aprepitant. Many of the major interactions involve QT-prolonging drugs, and antidiabetic drugs may need glucose monitoring.
Other signals from the literature: reports of chloroquine-associated cardiac toxicity (atrioventricular block), a QTc interval study, and vitiligo. These matter particularly in a paediatric population.
Please refer to the package insert for the full warnings, as label warnings were not available for this report.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction score is high (99.41%), and the mechanism is plausible given chloroquine's use in adult RA. However, there are no clinical trials, the only supporting paper concerns another drug, and the evidence level is L4. Cardiac, retinal and other safety concerns are significant in children. JIA also already has established, better-evidenced treatments.
To proceed, the following is needed:
- Mechanism of action data for chloroquine from a drug database
- The HSA package insert, including warnings, contraindications and approved indications
- Direct clinical evidence of chloroquine in JIA, such as a systematic review of antimalarials in JIA or a controlled study
- A paediatric safety assessment covering retinal and cardiac (QT/AV block) risk and dosing
- A comparison against current standard JIA therapies (methotrexate, biologics) to define any unmet need
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.