Infliximab
| Evidence Level: L1 | Predicted Indications: 10 |
Table of Contents
- Infliximab
- Infliximab: From TNF-α-Driven Autoimmune Disease to Expanded Immune-Mediated Indications
- Summary
- Quick Overview (Highest-Evidence Candidate)
- All Predicted Indications — Ranked Overview
- Why Are These Predictions Reasonable?
- Clinical Trial & Literature Evidence by Indication
- 7. Inflammatory Spondylopathy (L1, Proceed with Guardrails)
- 8. Polyarticular Juvenile Rheumatoid Arthritis (L1, Proceed with Guardrails)
- 5. Anus Disease / Perianal Crohn’s (L2, Proceed with Guardrails)
- 3. Rheumatoid Vasculitis (L3, Research Question — mixed signal)
- 10. Crohn Disease of the Esophagus (L3, Research Question)
- 9. Bronchitis (L4, Hold)
- EU/Taiwan Market Information
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Infliximab: From TNF-α-Driven Autoimmune Disease to Expanded Immune-Mediated Indications
Summary
Infliximab (DB00065) is a chimeric anti-TNF-α monoclonal antibody long used across the autoimmune/inflammatory disease spectrum (rheumatoid arthritis, Crohn’s disease, ulcerative colitis, psoriatic arthritis, psoriasis, ankylosing spondylitis), though its formal original-indication and MOA text are missing from this evidence pack ([Data Gap], DG001/DG002). This is a multi-candidate TxGNN run against 10 predicted indications; evidence quality varies enormously — from L1 (Phase 3 RCT-backed) extensions of well-established anti-TNF biology (inflammatory spondylopathy, polyarticular juvenile RA) down to L5 model-only hits for rare skeletal/ocular dysplasia syndromes that even the model’s own rationale flags as mechanistically implausible. This report focuses evaluation effort on the 6 indications with actual trial/literature support and flags the 4 unsupported ones for immediate Hold.
Quick Overview (Highest-Evidence Candidate)
| Item | Content |
|---|---|
| Original Indication | Not available in this pack ([Data Gap]) — publicly known anti-TNF indications: RA, Crohn’s disease, UC, PsA, psoriasis, ankylosing spondylitis |
| Predicted New Indication (top actionable) | Inflammatory spondylopathy |
| TxGNN Prediction Score | 80.92% (rank 130,860) |
| Evidence Level | L1 |
| Taiwan Market Status | Not marketed (Not currently marketed per this dataset) |
| Number of Authorizations | 0 |
| Recommended Decision | Proceed with Guardrails |
All Predicted Indications — Ranked Overview
| Rank | Disease | TxGNN Score | Evidence Level | Decision Stage | Recommendation |
|---|---|---|---|---|---|
| 1 | Colobomatous microphthalmia-rhizomelic dysplasia syndrome | 90.22% | L5 | S0 | Hold — no mechanistic link, model artifact |
| 2 | Brachydactyly-syndactyly syndrome | 89.88% | L5 | S0 | Hold — model artifact |
| 3 | Rheumatoid vasculitis | 85.32% | L3 | S1 | Research Question — conflicting signal (treats vs. induces) |
| 4 | Hypermobility of coccyx | 82.49% | L5 | S0 | Hold — model artifact |
| 5 | Anus disease (perianal Crohn’s) | 81.21% | L2 | S3 | Proceed with Guardrails |
| 6 | Kummell disease | 81.15% | L5 | S0 | Hold — model artifact |
| 7 | Inflammatory spondylopathy | 80.92% | L1 | S3 | Proceed with Guardrails |
| 8 | Polyarticular juvenile rheumatoid arthritis | 80.14% | L1 | S3 | Proceed with Guardrails |
| 9 | Bronchitis | 77.87% | L4 | S0 | Hold — evidence shows adverse pulmonary events, not efficacy |
| 10 | Crohn disease of the esophagus | 77.58% | L3 | S2 | Research Question |
Ranks 1, 2, 4, 6 are rare structural/developmental or degenerative-bone conditions with zero clinical trial or literature hits and mechanism rationales that explicitly state “no reasonable connection to TNF-α” — these are excluded from further evaluation below.
Why Are These Predictions Reasonable?
Detailed mechanism-of-action data for infliximab is currently unavailable in this pack ([Data Gap], DG002). Based on known public information, infliximab is a chimeric IgG1 monoclonal antibody that neutralizes soluble and membrane-bound TNF-α, a cytokine central to synovial, enteric, entheseal, and vascular inflammation. Its established efficacy in RA, Crohn’s disease, and ankylosing spondylitis-type diseases stems from interrupting this pathway.
The credible candidates in this pack are essentially mechanistic line-extensions of already-approved anti-TNF biology: inflammatory spondylopathy and polyarticular juvenile RA share the same TNF-α-driven synovitis/enthesitis pathway as adult RA and AS; anus disease (perianal fistulizing Crohn’s) and esophageal Crohn’s disease are anatomic sub-phenotypes of Crohn’s disease itself. Rheumatoid vasculitis is mechanistically plausible (TNF-α contributes to vasculitic endothelial injury) but the literature is genuinely bidirectional — several case reports describe infliximab inducing vasculitis via anti-drug antibody/immune-complex mechanisms, which is an unusual and important caveat.
Clinical Trial & Literature Evidence by Indication
7. Inflammatory Spondylopathy (L1, Proceed with Guardrails)
Clinical Trials
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00051623 | Phase 3 | Completed | 70 | Multicenter double-blind RCT of infliximab in psoriatic/spondyloarthritic disease |
| NCT00439283 | Phase 3 | Completed | 240 | Continuous vs. on-demand infliximab maintenance in ankylosing spondylitis; ± methotrexate |
| NCT00207701 | Phase 3 | Completed | 279 | RCT of infliximab vs. placebo in ankylosing spondylitis on background NSAIDs |
| NCT00367237 | Phase 3 | Completed | 115 | Infliximab + MTX vs. MTX alone in MTX-naïve active psoriatic arthritis |
| NCT00591201 | Phase 2/3 | Completed | 26 | RCT + 52-week open extension of infliximab in juvenile spondyloarthropathies |
Literature
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 27650650 | 2016 | Review | BioDrugs | Infliximab biosimilar CT-P13 review; PLANETAS pivotal trial data in AS |
| 24832835 | 2014 | Meta-analysis | Eur J Health Econ | Systematic review/meta-analysis of infliximab-biosimilar efficacy/safety in AS |
| 17651658 | 2007 | Systematic Review | Health Technol Assess | Comparative effectiveness/cost-effectiveness of anti-TNFs in AS |
| 17644552 | 2008 | Cohort | Ann Rheum Dis | Inflammatory biomarkers correlate with infliximab response and MRI spinal inflammation in AS |
| 12379627 | 2002 | Review | Ann Rheum Dis | Infliximab clinical/radiological efficacy in rheumatic disease |
8. Polyarticular Juvenile Rheumatoid Arthritis (L1, Proceed with Guardrails)
Clinical Trials
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00036374 | Phase 3 | Completed | 123 | Randomized double-blind trial of infliximab + MTX in polyarticular JRA |
| NCT01015547 | Phase 3 | Completed | 60 | Anti-TNF+MTX vs. combination DMARDs vs. MTX alone in very early polyarticular JIA |
Literature
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 17763439 | 2007 | RCT | Arthritis Rheum | Placebo-controlled RCT of infliximab + MTX in polyarticular-course JRA |
| 20237125 | 2010 | Cohort | Ann Rheum Dis | Long-term open-label extension confirming sustained efficacy/safety |
| 31612428 | 2020 | Cohort | World J Pediatr | Single-center China study of infliximab outcomes in pJIA |
| 33626206 | 2021 | Cohort | Clin Pharmacol Ther | Response-exposure similarity between pJIA and adult RA supports extrapolation |
| 23337074 | 2013 | Systematic Review | Semin Arthritis Rheum | Systematic review of biologic response modifiers in polyarticular JIA |
5. Anus Disease / Perianal Crohn’s (L2, Proceed with Guardrails)
Clinical Trials
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02883296 | N/A | Completed | 15 | Long-term MRI follow-up of anal fistulae in Crohn’s on infliximab/adalimumab |
| NCT02177071 | Phase 4 | Completed | 211 | Infliximab maintenance ± antimetabolites to sustain steroid-free remission |
| NCT03801928 | N/A | Completed | 118 | Real-world observational study of Infliximab (Inflectra) in IBD, US/Canada |
| NCT02925338 | N/A | Completed | 1,431 | National real-world registry of Inflectra (infliximab biosimilar) use |
| NCT02539368 | N/A | Completed | 2,565 | Post-marketing cohort of CT-P13 (infliximab) in IBD (CONNECT-IBD) |
Literature
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 20623697 | 2011 | Cohort | Inflamm Bowel Dis | Combined infliximab + MTX + sphincter-sparing surgery in severe fistulizing anoperineal CD |
| 12641520 | 2003 | Cohort | Aliment Pharmacol Ther | Mucosal immune regulation and relapse after infliximab in fistulating CD |
| 29126509 | 2017 | Review | Semin Pediatr Surg | Treatment of perianal Crohn’s disease |
| 17402327 | 2007 | Review | Isr Med Assoc J | Overview of perianal Crohn’s disease management |
| 39882221 | 2025 | Review | J Anus Rectum Colon | Contemporary management of anal fistula with Crohn’s disease |
3. Rheumatoid Vasculitis (L3, Research Question — mixed signal)
Clinical Trials: No trials directly target rheumatoid vasculitis; the 4 identified trials (NCT07138898, NCT05696106, NCT02590562, NCT01579006) are indirect RA/biologic-management studies graded C relevance — not included as supporting evidence.
Literature
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 33058033 | 2021 | Systematic Review | Clin Rheumatol | Systematic review of biological drugs (incl. infliximab) in rheumatoid vasculitis treatment |
| 16078342 | 2005 | Case Report | J Rheumatol | Rheumatoid vasculitis treated successfully with infliximab |
| 40385904 | 2025 | Case Report | Cureus | Infliximab-induced leukocytoclastic vasculitis in an RA patient (paradoxical) |
| 35650123 | 2023 | Case Report | Intern Med | IgA vasculitis nephritis after 11 years of infliximab in RA |
| 28123776 | 2017 | Cohort | RMD Open | BSRBR-RA cohort: risk of vasculitis-like events with TNF inhibitors |
⚠️ Evidence is directionally mixed — infliximab has case-report support for treating RV but also multiple case reports/cohort data showing it can induce vasculitis. This safety signal should be weighted heavily before pursuing this indication.
10. Crohn Disease of the Esophagus (L3, Research Question)
Clinical Trials: Currently no related clinical trials registered.
Literature
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 41622053 | 2026 | Cohort | Dig Liver Dis | Nationwide GETECCU cohort of esophageal/gastric/duodenal CD in the biologic era |
| 16954965 | 2006 | Cohort | J Pediatr Gastroenterol Nutr | Infliximab as first-line therapy in severe pediatric Crohn’s disease |
| 11907371 | 2002 | Case Report | J Clin Gastroenterol | Infliximab treatment of esophagobronchial fistula in esophageal CD |
| 17298766 | 2007 | Review | Curr Treat Options Gastroenterol | Overview of Crohn’s disease of the esophagus |
| 40386539 | 2025 | Case Report | ACG Case Rep J | Anti-TNF-refractory esophageal CD lesions requiring switch to upadacitinib — signals possible treatment failure in this niche |
9. Bronchitis (L4, Hold)
Literature is dominated by case reports of infliximab causing or coinciding with bronchial/pulmonary complications (tracheobronchitis, organizing pneumonia, granulomatous bronchiolitis) rather than treating bronchitis itself — the directional evidence does not support pursuing this candidate.
EU/Taiwan Market Information
No authorization records are present in this dataset (total_licenses: 0, market_status: Not marketed). This does not reflect infliximab’s actual global regulatory status (it is a long-marketed biologic, e.g., Remicade/CT-P13 biosimilars), but rather a data gap in this specific regulatory extract — TFDA label/license retrieval (DG001) is required before any safety or dosing claims can be finalized.
Safety Considerations
Formal safety data (key warnings, contraindications, DDI) is entirely absent from this pack ([Data Gap], DG001). Please refer to the SmPC/label for authoritative safety information.
Literature-derived signal (not formal label data): Across the rheumatoid vasculitis literature review, infliximab appears repeatedly both as a treatment for and a trigger of vasculitis (via anti-drug antibodies/immune complexes) and other paradoxical autoimmune events (drug-induced lupus, cutaneous vasculitis). This pattern should be explicitly flagged in any downstream clinical evaluation, particularly for the rheumatoid vasculitis indication.
Conclusion and Next Steps
Decision: Proceed with Guardrails (for inflammatory spondylopathy, polyarticular JRA, and perianal Crohn’s/anus disease) · Research Question (rheumatoid vasculitis, esophageal Crohn’s) · Hold (bronchitis and the 4 mechanistically implausible L5 predictions)
Rationale:
- Three candidates (inflammatory spondylopathy, polyarticular JRA, anus disease) are backed by multiple completed Phase 2–4 RCTs and are essentially phenotype extensions of infliximab’s already-established anti-TNF mechanism.
- Rheumatoid vasculitis and esophageal Crohn’s have plausible mechanisms but evidence limited to case reports/reviews, and rheumatoid vasculitis carries a documented paradoxical-induction risk.
- The four L5 predictions (colobomatous microphthalmia-rhizomelic dysplasia, brachydactyly-syndactyly, coccyx hypermobility, Kummell disease) have zero supporting evidence and explicit mechanistic rationale against them — do not advance.
To proceed, the following is needed:
- TFDA label/SmPC retrieval to resolve DG001 (warnings, contraindications) before any S1+ safety evaluation
- DrugBank MOA confirmation to resolve DG002
- Route-compatibility and dosing data (currently “pending” for all candidates)
- For rheumatoid vasculitis: a dedicated benefit-risk review given the induction-vs-treatment paradox before further scoring
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.