Guselkumab

證據等級: L5

預測適應症: 10 個

Guselkumab: From Plaque Psoriasis to Ulcerative Colitis

One-Sentence Summary

Guselkumab (Tremfya®) is a fully human anti-IL-23p19 monoclonal antibody, globally established as a first-line biologic for moderate-to-severe plaque psoriasis, but currently without Health Canada authorization. The TxGNN model’s top-scored predictions — drug-induced osteoporosis (#1, 99.84%) and severe nonproliferative diabetic retinopathy (#2, 99.80%) — lack mechanistic support and clinical data (L5, Hold); however, psoriasis (rank #3, 99.74%) and ulcerative colitis (rank #6, 99.70%) each reach L1 evidence level, backed by completed Phase 3 RCTs and recent FDA approvals. With 40+ clinical trials and 20 publications for psoriasis, and 17 clinical trials and 20 publications for UC, both represent high-priority repurposing candidates for the Canadian market.

Quick Overview

Item	Content
Original Indication	Not approved in Canada; globally established for moderate-to-severe plaque psoriasis (FDA approved 2017)
Primary Predicted New Indication	Psoriasis — TxGNN rank #3, score 99.74% (L1)
Secondary Predicted New Indication	Ulcerative Colitis — TxGNN rank #6, score 99.70% (L1)
TxGNN Top Score	99.84% (drug-induced osteoporosis, rank #1 — L5, Hold)
Evidence Level	L1 (psoriasis & ulcerative colitis) / L5 (all other predictions)
Canada Market Status	✗ Not marketed
Number of DINs	0
Recommended Decision	Proceed with Guardrails (psoriasis & UC) · Hold (all other predictions)

Why is This Prediction Reasonable?

Detailed mechanism of action data is not available in the current evidence pack (Data Gap: DG002). Based on global clinical and scientific literature, guselkumab is a fully human IgG1λ monoclonal antibody that selectively binds to the p19 subunit of interleukin-23 (IL-23), preventing its binding to the IL-23 receptor. This blocks downstream Th17 cell differentiation and the downstream production of IL-17A, IL-17F, and IL-22 — key effectors of chronic immune-mediated inflammation — while leaving IL-12/Th1 immunity (important for infection defence) largely intact.

For psoriasis, the IL-23/Th17 axis is the core pathogenic driver. IL-23 secreted by dermal dendritic cells and macrophages expands Th17 populations that produce IL-17, driving keratinocyte hyperproliferation, epidermal thickening, and plaque formation. Guselkumab’s selective p19 blockade directly interrupts this loop without broad immunosuppression. The VOYAGE 1 and VOYAGE 2 pivotal Phase 3 trials (vs adalimumab and placebo) established guselkumab as superior to an anti-TNF biologic for sustained skin clearance, and the ECLIPSE trial further confirmed superiority over secukinumab (IL-17A inhibitor) for durable PASI 90 at week 48.

For ulcerative colitis, the intestinal lamina propria in active UC shows marked IL-23-driven Th17 expansion. IL-23 promotes secretion of IL-17A, IL-22, and IFN-γ that compromise mucosal barrier integrity and sustain colonic inflammation. Guselkumab’s IL-23p19 blockade interrupts this mucosal inflammatory circuit through the same molecular mechanism validated in psoriasis. The large Phase 2b/3 QUASAR programme (n = 1,064) demonstrated significant clinical remission and endoscopic response versus placebo for both induction and maintenance, leading to FDA approval for moderately-to-severely active UC in late 2024/2025.

Both indications are classic IL-23-driven immune-mediated inflammatory diseases (IMIDs) sharing susceptibility loci (IL23R, CARD9) — the mechanistic bridge from psoriasis to UC is biologically robust and now clinically validated across multiple jurisdictions.

Clinical Trial Evidence — Psoriasis (TxGNN Rank #3)

Trial Number	Phase	Status	Enrollment	Key Findings
NCT02325219	Phase 3	Completed	192	VOYAGE 1: guselkumab vs adalimumab vs placebo; PASI 90 at week 24 significantly superior to adalimumab; foundational for FDA 2017 approval
NCT02207244	Phase 3	Completed	992	VOYAGE 2: randomized withdrawal and retreatment; disease control maintained; retreatment successfully re-establishes response
NCT03090100	Phase 3	Completed	1,048	ECLIPSE: head-to-head vs secukinumab; guselkumab superior for sustained PASI 90 at week 48
NCT02207231	Phase 3	Completed	837	Confirmatory Phase 3 for moderate-to-severe plaque psoriasis; consistent long-term efficacy through week 100
NCT05272150	Phase 3b	Completed	213	Efficacy in skin-of-color participants; supports generalizability across diverse populations
NCT03818035	Phase 3b	Completed	880	Extended dosing interval (q16w) non-inferior in super-responders (PASI = 0 at weeks 20 & 28)
NCT06039189	Phase 3b	Completed	338	Low BSA moderate psoriasis with special site involvement (facial, genital, scalp, nail); efficacy vs placebo confirmed
NCT04340076	Phase 4	Completed	244	BeNeBio: controlled dose reduction of IL-17/IL-23 inhibitors non-inferior to standard care; informs dosing strategy
NCT04914429	Phase 4	Completed	327	Chinese population Phase 4 study confirming efficacy and safety consistency across ethnicities
NCT03451851	Phase 3	Active, not recruiting	120	Pediatric (age 6–18) safety and efficacy study; ongoing through December 2026

Literature Evidence — Psoriasis

PMID	Year	Type	Journal	Key Findings
28057360	2017	RCT (Phase 3)	J Am Acad Dermatol	VOYAGE 1: PASI 90 at week 24: guselkumab 73.3% vs adalimumab 49.7% vs placebo 2.9%; primary endpoint met with high statistical significance
28057361	2017	RCT (Phase 3)	J Am Acad Dermatol	VOYAGE 2: confirmed durable efficacy; patients re-randomized to placebo at week 28 who relapsed were successfully retreated
28635018	2018	RCT (Phase 3)	Br J Dermatol	NAVIGATE: guselkumab superior to continued ustekinumab in inadequate responders; PASI 90 significantly higher at weeks 28 and 52
31402114	2019	RCT (Phase 3)	Lancet	ECLIPSE: guselkumab vs secukinumab; 84.5% vs 70.0% sustained PASI 90 at week 48 (p < 0.001); first head-to-head IL-23 vs IL-17 superiority
34105767	2021	Long-term Follow-up	Br J Dermatol	VOYAGE 1&2: 5-year sustained PASI 90/100 and HRQoL improvement; no new safety signals at 5 years
31583255	2019	Network Meta-Analysis	J Immunol Res	NMA of IL-17/IL-12/23/IL-23 inhibitors: guselkumab ranks among highest for PASI 90 response with favourable safety
32022825	2020	Meta-Analysis	JAMA Dermatol	Comprehensive meta-analysis of biologics and oral treatments; guselkumab demonstrates top-tier PASI 90/100 rates
37906417	2024	Integrated Safety Analysis	Drug Safety	Pooled safety from 11 Phase 2/3 studies in psoriasis and PsA; guselkumab well-tolerated; no increased malignancy or MACE signal
30772098	2019	Clinical Guidelines	J Am Acad Dermatol	AAD-NPF joint guidelines: guselkumab recommended as a first-line biologic for moderate-to-severe psoriasis
32427307	2020	Review	JAMA	Psoriasis pathophysiology and treatment overview; IL-23p19 inhibitors highlighted as paradigm-shifting therapeutic class

Clinical Trial Evidence — Ulcerative Colitis (TxGNN Rank #6)

Trial Number	Phase	Status	Enrollment	Key Findings
NCT04033445	Phase 2b/3	Active, not recruiting	1,064	QUASAR core trial: IV induction (200 mg q8w × 3 doses) followed by SC maintenance; primary basis for FDA approval of UC indication
NCT05528510	Phase 3	Active, not recruiting	418	ASTRO: all-SC induction regimen; aims to simplify treatment without IV administration
NCT05242484	Phase 2b	Active, not recruiting	577	Guselkumab + golimumab dual-biologic combination vs monotherapy in bio-experienced moderate-to-severe UC
NCT06260163	Phase 3	Active, not recruiting	112	Pediatric UC Phase 3: induction and maintenance in children with moderately-to-severely active UC
NCT03662542	Phase 2a	Completed	214	Proof-of-concept combination (guselkumab + golimumab) in UC; combination arm showed numerical superiority over monotherapy
NCT06408935	Phase 3b	Recruiting	112	Transmural healing endpoint (MaRIA score) as disease modification marker at week 48 in CD
NCT07102368	Observational	Recruiting	400	Real-world effectiveness in IBD (UC and CD) post-approval; multiple European centres
NCT07245394	Observational	Recruiting	200	SHIFT-IBD (Canada-based): switching from ustekinumab to guselkumab in active IBD; provides Canadian real-world data
NCT07302360	Observational	Recruiting	200	Real-world bio-naïve UC patients in China receiving guselkumab; supplements ethnic diversity data
NCT07242248	Observational	Recruiting	220	UK real-world effectiveness in UC and CD by lines of therapy and subpopulations

Literature Evidence — Ulcerative Colitis

PMID	Year	Type	Journal	Key Findings
39706209	2025	RCT (Phase 3)	Lancet	QUASAR induction & maintenance: clinical remission and endoscopic response significantly superior to placebo; FDA approval basis for UC (2024/2025)
41544637	2026	RCT (Phase 3)	Lancet Gastroenterol Hepatol	ASTRO: SC induction achieves clinical remission and endoscopic improvement vs placebo; enables fully SC treatment pathway
37659673	2023	RCT (Phase 2b)	Gastroenterology	QUASAR Phase 2b: dose-ranging induction (200 mg and 1,200 mg IV) both superior to placebo for clinical remission; dose selection confirmed
40113101	2025	RCT (Phase 3)	Gastroenterology	GRAVITI: SC induction/maintenance in Crohn’s disease; confirms IL-23p19 class effect across IBD spectrum
39572132	2024	Clinical Guidelines	Gastroenterology	AGA Living Guideline: guselkumab included as a recommended advanced therapy for moderate-to-severe UC
39425738	2024	Network Meta-Analysis	Gastroenterology	AGA evidence synthesis: guselkumab ranks among top-tier agents for clinical remission and endoscopic improvement in UC
37069321	2023	Review	Nat Rev Gastroenterol Hepatol	Comprehensive mechanistic and clinical review of IL-12/IL-23 pathway inhibition in IBD; guselkumab as selective IL-23 option
41324615	2025	Expert Review	Expert Opin Biol Ther	Expert evaluation of guselkumab for UC: positioning, clinical data review, and place in current treatment algorithm
35553666	2022	Review	J Crohns Colitis	IL-23 blockade pipeline in IBD: selective vs non-selective inhibition; mechanistic rationale for guselkumab in UC and CD
39994836	2025	Review	Chin Med J	IBD epidemiology, pathogenesis, diagnosis, and treatment update; IL-23 inhibitors including guselkumab highlighted as key advance

Canada Market Information

Guselkumab currently has no Health Canada authorization and no DINs on file.

DIN	Product Name	Dosage Form	Approved Indication
—	Not applicable	—	No Canadian approval

Note: Guselkumab (Tremfya®) holds regulatory approvals in the United States (FDA, 2017 — plaque psoriasis; 2022 — psoriatic arthritis; 2024/2025 — ulcerative colitis), the European Union (EMA), Japan, and multiple other jurisdictions. The absence of Canadian authorization represents a regulatory filing gap, not a gap in global evidence.

Safety Considerations

Health Canada-specific safety data (product monograph, warnings, contraindications) is not available (Data Gap: DG001). No drug-drug interactions were identified in the DDI database. Based on global regulatory documents and integrated clinical trial safety analyses:

Key Warnings: Risk of serious infections (bacterial, mycobacterial, fungal, viral); tuberculosis screening required before initiation; do not administer during clinically significant active infections; interrupt treatment if serious infection develops
Contraindications: Clinically important active infections; known hypersensitivity to guselkumab or to any excipient
Immunization: Avoid live vaccines during treatment; bring vaccinations up to date before initiating therapy

For complete safety information, refer to the FDA Prescribing Information (Tremfya® US label) or EMA Summary of Product Characteristics, as Health Canada-specific guidance is not yet available.

Conclusion and Next Steps

TxGNN Prediction Summary

Rank	Indication	TxGNN Score	Evidence Level	Decision
1	Drug-induced osteoporosis	99.84%	L5	Hold
2	Severe nonproliferative diabetic retinopathy	99.80%	L5	Hold
3	Psoriasis	99.74%	L1	Proceed with Guardrails
4	Diabetic retinopathy	99.74%	L5	Hold
5	Renal osteodystrophy	99.73%	L5	Hold
6	Ulcerative colitis	99.70%	L1	Proceed with Guardrails
7–10	Genetic/hematologic disorders	99.67–99.55%	L5	Hold

Decision: Proceed with Guardrails (Psoriasis & Ulcerative Colitis)

Rationale: Guselkumab has completed multiple Phase 3 RCTs for both psoriasis and UC with consistent, statistically significant superiority over placebo and active comparators; the IL-23p19 mechanistic basis is directly validated by FDA and EMA approvals. The absence of Health Canada authorization is a regulatory filing gap — the Canadian clinical evidence base already exists. TxGNN’s top-ranked predictions (ranks #1 and #2) score highly due to shared inflammatory network neighbours in the knowledge graph but lack direct mechanistic rationale or clinical data and should remain on Hold.

To proceed, the following is needed:

Regulatory filing: Prepare or expedite a Health Canada New Drug Submission (NDS) leveraging existing FDA/EMA dossier; consider Priority Review or Standard Review pathway
Safety documentation: Obtain full Health Canada Product Monograph equivalent; complete Data Gap DG001 (TFDA-equivalent warnings and contraindications)
MOA documentation: Complete DrugBank lookup (DB11834) to fill Data Gap DG002 for formal mechanistic risk assessment
Pharmacoeconomic review: Commission CADTH (Canadian Drug Review) health technology assessment for public payer reimbursement of both psoriasis and UC indications
Canadian real-world evidence: Monitor SHIFT-IBD (NCT07245394, recruiting in Canada) for domestic UC effectiveness data
Hold indications: For drug-induced osteoporosis, diabetic retinopathy, and other L5 predictions — initiate targeted mechanistic and preclinical studies before any clinical investment
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.