Guselkumab
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
- Guselkumab
- Guselkumab: From Plaque Psoriasis to Drug-Induced Osteoporosis (and Other Predicted Uses)
Guselkumab: From Plaque Psoriasis to Drug-Induced Osteoporosis (and Other Predicted Uses)
One-Sentence Summary
Guselkumab is an IL-23 p19 inhibitor sold in Singapore as TREMFYA, and the data compiled for this report do not list its approved indication. The TxGNN model's top-ranked prediction is drug-induced osteoporosis, which has no clinical trials and no publications behind it. Two lower-ranked predictions are better supported: psoriasis (30 clinical trials, 20 publications) and ulcerative colitis (10 clinical trials, 20 publications).
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the Singapore licence data (approved indication text is empty) |
| Predicted New Indication | Drug-induced osteoporosis (rank 1) |
| TxGNN Prediction Score | 99.84% |
| Evidence Level | L5 (model prediction only) |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 2 |
| Recommended Decision | Hold |
Other predictions in context
| Predicted Indication | TxGNN Score | Evidence Level | Decision |
|---|---|---|---|
| Psoriasis | 99.75% | L1 | Proceed with Guardrails |
| Ulcerative colitis | 99.70% | L1 | Proceed with Guardrails |
| Severe nonproliferative diabetic retinopathy, diabetic retinopathy, renal osteodystrophy, congenital hypotrichosis with juvenile macular dystrophy, primary release disorder of platelets, Glanzmann thrombasthenia, non-renal secondary hyperparathyroidism | 99.55%–99.80% | L5 | Hold |
Psoriasis and ulcerative colitis are the only predictions with actionable evidence, so the sections below cover them in detail.
Why is This Prediction Reasonable?
Detailed mechanism-of-action data is not available in the compiled data. Based on known information, guselkumab is a monoclonal antibody that selectively blocks the p19 subunit of IL-23. This cytokine drives the Th17 pathway, which underlies several chronic inflammatory diseases.
Drug-induced osteoporosis (top-ranked prediction). IL-23/IL-17 signalling has been linked to inflammatory bone loss. However, there is no direct connection to drug-induced osteoporosis, such as glucocorticoid-induced bone loss. No trials or literature were found, so this prediction rests on the model score alone.
Psoriasis. Blocking IL-23 interrupts the Th17 axis that drives keratinocyte overgrowth and skin inflammation. This is guselkumab's established use, so the evidence confirms the prediction and is not a new repurposing finding. The label should still be checked, because the licence data do not state the approved indications.
Ulcerative colitis. IL-23 drives mucosal Th17 inflammation in inflammatory bowel disease, and guselkumab's p19 blockade targets this pathway directly. The Phase 3 QUASAR programme provides direct efficacy and safety evidence.
Clinical Trial Evidence
No clinical trials are registered for drug-induced osteoporosis, and none for the other seven low-evidence predictions. The tables below cover the two predictions that have trials.
Psoriasis (selected from 30 trials)
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT03090100 | Phase 3 | Completed | 1048 | Guselkumab vs secukinumab in moderate-to-severe plaque psoriasis |
| NCT03573323 | Phase 4 | Completed | 1027 | Ixekizumab vs guselkumab over 24 weeks in moderate-to-severe plaque psoriasis |
| NCT02207244 | Phase 3 | Completed | 992 | Placebo- and active-comparator-controlled study with randomised withdrawal and retreatment |
| NCT02203032 | Phase 3 | Completed | 872 | Guselkumab in patients with inadequate response to ustekinumab |
| NCT02207231 | Phase 3 | Completed | 837 | Efficacy and safety vs placebo and active comparator |
| NCT06039189 | Phase 3 | Completed | 338 | Placebo-controlled study in low-body-surface-area plaque psoriasis with special-site involvement |
| NCT04914429 | Phase 4 | Completed | 327 | Placebo-controlled study in Chinese participants |
| NCT02951533 | Phase 3 | Completed | 119 | Guselkumab vs fumaric acid esters in patients naive to systemic treatment |
| NCT04882098 | Phase 3 | Active, not recruiting | 1054 | Psoriatic arthritis: signs, symptoms and radiographic progression |
| NCT02343744 | Phase 3 | Completed | 21 | Generalised pustular or erythrodermic psoriasis |
Ulcerative colitis (selected from 10 trials)
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT04033445 | Phase 2b/3 | Active, not recruiting | 1064 | QUASAR: placebo-controlled induction and maintenance in moderately to severely active UC |
| NCT05528510 | Phase 3 | Active, not recruiting | 418 | Subcutaneous induction vs placebo (clinical remission) |
| NCT05242484 | Phase 2b | Active, not recruiting | 577 | Guselkumab plus golimumab combination vs each alone |
| NCT03662542 | Phase 2a | Completed | 214 | Proof-of-concept of guselkumab plus golimumab combination |
| NCT06260163 | Phase 3 | Active, not recruiting | 112 | Paediatric UC: open-label induction, double-blind maintenance |
| NCT06663332 | Phase 3 | Recruiting | 196 | Long-term safety in paediatric Crohn's disease, UC or juvenile psoriatic arthritis |
| NCT07577856 | Phase 3 | Recruiting | 644 | JNJ-78934804 vs guselkumab at Week 48 |
| NCT07245394 | N/A | Recruiting | 200 | Switching to guselkumab in ustekinumab-exposed IBD patients |
| NCT07726888 | N/A | Recruiting | 97 | Real-world prospective cohort in UC |
Literature Evidence
No publications were found for drug-induced osteoporosis. The tables below cover psoriasis and ulcerative colitis.
Psoriasis
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 28057360 | 2017 | RCT | J Am Acad Dermatol | VOYAGE 1: guselkumab vs adalimumab and placebo in moderate-to-severe psoriasis |
| 28057361 | 2017 | RCT | J Am Acad Dermatol | VOYAGE 2: randomised withdrawal and retreatment |
| 28635018 | 2018 | RCT | Br J Dermatol | NAVIGATE: efficacy after inadequate response to ustekinumab |
| 31583255 | 2019 | Meta-analysis | J Immunol Res | Network meta-analysis of IL-17, IL-12/23 and IL-23 inhibitors |
| 38503473 | 2024 | Systematic review | Ann Rheum Dis | Pharmacological treatment of psoriatic arthritis (2023 EULAR update) |
| 35791876 | 2022 | Cohort | JAMA Dermatol | Drug survival of guselkumab and other biologics |
| 32427307 | 2020 | Review | JAMA | Pathophysiology, presentation and treatment of psoriasis |
| 38796266 | 2024 | Review | Dermatol Clin | Overview of biologics for psoriasis |
Ulcerative colitis
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 39706209 | 2025 | RCT | Lancet | QUASAR phase 3 induction and maintenance in moderately to severely active UC |
| 37659673 | 2023 | RCT | Gastroenterology | QUASAR phase 2b induction study |
| 41544637 | 2026 | RCT | Lancet Gastroenterol Hepatol | ASTRO: subcutaneous induction in UC |
| 39425738 | 2024 | Network meta-analysis | Gastroenterology | AGA evidence synthesis on advanced therapies in UC |
| 39572132 | 2024 | Guideline | Gastroenterology | AGA living guideline for moderate-to-severe UC |
| 40407729 | 2025 | Network meta-analysis | Aliment Pharmacol Ther | Biologics and small molecules as maintenance therapy in UC |
| 37069321 | 2023 | Review | Nat Rev Gastroenterol Hepatol | IL-12 and IL-23 pathway inhibition in IBD |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN15876P | TREMFYA Solution for Injection in Pre-filled Pen 100mg/ml | Injection, solution | Not stated in the licence data |
| SIN15508P | TREMFYA Solution for Injection in Pre-filled Syringe 100mg/1ml | Injection, solution | Not stated in the licence data |
Both licences are valid single-ingredient products from Cilag AG.
Safety Considerations
- Drug Interactions: 100 interactions were found. The only Major interaction in the listed results is with adalimumab. Moderate interactions include simvastatin, apixaban, warfarin, rivaroxaban, dicoumarol, tacrolimus, theophylline, roflumilast, lidocaine, nifedipine, fentanyl, hydrocodone and a tetanus toxoid vaccine. Several zinc salts have Minor interactions.
- Trial-based signals: Safety findings come from long-term integrated analyses (PMID 37906417) and the QUASAR programme. The ulcerative colitis evidence notes that infection and liver safety should be monitored.
For warnings and contraindications, please refer to the package insert.
Conclusion and Next Steps
Decision: Hold (for the top-ranked prediction, drug-induced osteoporosis)
Rationale: The top prediction is supported only by a model score of 99.84%. It has no trials, no literature and no clear mechanistic link to IL-23 blockade. Psoriasis and ulcerative colitis are L1 and could proceed with guardrails, but psoriasis is already established use, and ulcerative colitis is supported by Phase 3 programmes that have not all completed.
To proceed, the following is needed:
- Singapore package insert, to confirm approved indications, warnings and contraindications
- Mechanism-of-action data
- For drug-induced osteoporosis: preclinical or mechanistic evidence on IL-23 and bone loss, and then a pilot study if that evidence supports one
- For ulcerative colitis: confirmation of Singapore regulatory status for this indication, and a monitoring plan for infection and liver safety
- A review of co-medications, especially concomitant adalimumab use (Major interaction)
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.