Ixekizumab
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Ixekizumab: From Ankylosing Spondylitis to Inflammatory Spondylopathy
One-Sentence Summary
Ixekizumab is an IL-17A–blocking antibody, originally used for ankylosing spondylitis and related spondyloarthropathy. The TxGNN model's top-ranked prediction is rheumatoid vasculitis, but this is supported by no direct evidence. The best-supported prediction is inflammatory spondylopathy (rank 6), which has 18 listed clinical trials and 20 publications, and which largely overlaps with the drug's existing indications.
Note: The top-ranked prediction (rheumatoid vasculitis, score 97.5%) has only one incidental trial and no literature. This report therefore presents the rank 1 prediction in the overview, and discusses the best-evidenced prediction, inflammatory spondylopathy, in the evidence sections.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Ankylosing spondylitis; spondyloarthropathy (from the knowledge graph; the Singapore licence has no indication text recorded) |
| Predicted New Indication | Rheumatoid vasculitis (rank 1). Best-evidenced: inflammatory spondylopathy (rank 6) |
| TxGNN Prediction Score | 97.53% (rheumatoid vasculitis); 96.77% (inflammatory spondylopathy) |
| Evidence Level | L5 (rheumatoid vasculitis); L1 (inflammatory spondylopathy) |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 1 |
| Recommended Decision | Hold (rheumatoid vasculitis); Proceed with Guardrails (inflammatory spondylopathy) |
Other Predictions at a Glance
| Rank | Predicted Indication | Score | Evidence Level | Decision |
|---|---|---|---|---|
| 1 | Rheumatoid vasculitis | 97.53% | L5 | Hold |
| 2 | Acute lymphoblastic leukaemia | 97.35% | L5 | Hold |
| 3 | CLL/SLL (IGHV-mutated) | 97.07% | L5 | Hold |
| 4 | Pregerminal centre CLL/SLL | 97.07% | L5 | Hold |
| 5 | Hypermobility of coccyx | 96.87% | L5 | Hold |
| 6 | Inflammatory spondylopathy | 96.77% | L1 | Proceed with Guardrails |
| 7 | Kümmell disease | 96.70% | L5 | Hold |
| 8 | Polyarticular juvenile rheumatoid arthritis | 96.42% | L5 | Hold |
| 9 | Vertebral disease | 95.13% | L3 | Research Question |
| 10 | Gingival fibromatosis | 92.21% | L5 | 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, ixekizumab is a monoclonal antibody that neutralises IL-17A, a cytokine that drives inflammation and new bone formation in axial spondyloarthritis. Its efficacy in ankylosing spondylitis is the basis of its original indication.
Inflammatory spondylopathy (rank 6): this is the most credible prediction, but it is closer to an on-label or label-adjacent use than to true repurposing. Multiple Phase 3 randomised trials show benefit in radiographic and non-radiographic axial spondyloarthritis. The main step needed is to confirm which disease subtype is meant.
Rheumatoid vasculitis (rank 1): IL-17A is implicated in autoimmune inflammation, so a theoretical link to vasculitis exists. However, there is no direct evidence that ixekizumab works here, and the high score is a computational prediction only.
Other predictions (leukaemias, coccyx hypermobility, Kümmell disease, gingival fibromatosis): no clear IL-17A mechanism links these conditions to the drug. Several likely reflect proximity in the knowledge graph (for example, spinal conditions near spondylitis), and the two CLL/SLL entries share an identical score, suggesting one shared graph signal rather than independent evidence. Polyarticular juvenile arthritis is plausible, since IL-17 inhibitors have been studied in related juvenile subtypes, but no supporting trials or literature were compiled.
Clinical Trial Evidence
Rheumatoid vasculitis (rank 1)
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT07138898 | Phase 2 | Recruiting | 80 | Perioperative immunosuppressant management in rheumatology patients having shoulder arthroplasty; does not test ixekizumab for vasculitis |
Inflammatory spondylopathy (rank 6): top relevant trials
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02696785 | Phase 3 | Completed | 341 | Double-blind, active- and placebo-controlled study in biologic-naive radiographic axSpA |
| NCT02696798 | Phase 3 | Completed | 316 | Placebo-controlled study in TNF-inhibitor-experienced radiographic axSpA |
| NCT02757352 | Phase 3 | Completed | 303 | 52-week placebo-controlled study in non-radiographic axSpA |
| NCT04285229 | Phase 3 | Completed | 147 | Placebo-controlled study in Chinese patients with radiographic axSpA |
| NCT03129100 | Phase 3 | Completed | 773 | 104-week extension with randomised withdrawal and retreatment in axSpA |
| NCT02349295 | Phase 3 | Completed | 363 | Placebo-controlled study in biologic-experienced active psoriatic arthritis |
| NCT02584855 | Phase 3 | Completed | 394 | Open-label lead-in then randomised withdrawal in psoriatic arthritis |
| NCT03151551 | Phase 4 | Completed | 566 | Open-label ixekizumab vs adalimumab in biologic-naive psoriatic arthritis |
| NCT04527380 | Phase 3 | Active, not recruiting | 101 | Open-label study in juvenile enthesitis-related arthritis (including juvenile-onset AS) and juvenile PsA |
| NCT01870284 | Phase 3 | Withdrawn | 0 | Planned study in active AS; withdrawn, no participants enrolled |
Literature Evidence
Inflammatory spondylopathy (rank 6): selected publications
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 27553214 | 2017 | Phase 3 RCT | Ann Rheum Dis | SPIRIT-P1: ixekizumab in biologic-naive active psoriatic arthritis |
| 31563894 | 2020 | Randomised open-label trial | Ann Rheum Dis | Head-to-head ixekizumab vs adalimumab in psoriatic arthritis |
| 41903163 | 2026 | RCT | Arthritis Rheumatol | Ixekizumab plus tirzepatide gave greater disease control than ixekizumab alone in PsA with overweight/obesity |
| 38503473 | 2024 | Systematic review | Ann Rheum Dis | Efficacy and safety of PsA drugs, informing the 2023 EULAR recommendations |
| 36847624 | 2023 | Review | Drugs Today | Secukinumab, ixekizumab, bimekizumab and brodalumab in psoriasis and PsA |
| 32719044 | 2020 | Review | Ann Rheum Dis | Paradoxical gastrointestinal effects (disease exacerbation) of IL-17 blockers |
Vertebral disease (rank 9): selected publications
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 31813637 | 2020 | RCT | Lancet | COAST-X: ixekizumab in non-radiographic axSpA |
| 30343531 | 2019 | RCT | Arthritis Rheumatol | 16-week results in radiographic axSpA after TNF-inhibitor failure |
| 36270657 | 2023 | Systematic review | Ann Rheum Dis | bDMARD efficacy and safety informing the 2022 ASAS-EULAR axSpA recommendations |
| 31436026 | 2019 | Guideline | Arthritis Care Res | 2019 ACR/SAA/SPARTAN recommendations for AS and nr-axSpA |
| 40701624 | 2025 | Cohort study | RMD Open | Real-world effectiveness of ixekizumab in 709 Danish axSpA and PsA patients |
| 34407705 | 2021 | Review | Expert Rev Clin Immunol | Ixekizumab as an IL-17A inhibitor in axial spondyloarthritis |
No literature was found for rheumatoid vasculitis or for the other predictions.
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN15501P | TALTZ Solution for Injection in Pre-filled Pen 80 mg/ml | Injection, solution | Indication text not recorded |
The product is supplied by Eli Lilly and Company as an injectable.
Safety Considerations
- Drug Interactions: 100 interactions were identified. The only one rated Major among those listed is adalimumab (combining two biologic immunomodulators). Many listed interactions are rated Moderate, including warfarin, apixaban, rivaroxaban, dicoumarol, simvastatin, tacrolimus, theophylline, aminophylline, roflumilast, nifedipine, lidocaine, fentanyl and hydrocodone, and a tetanus toxoid vaccine. Zinc salts are rated Minor.
- Class-related risks to monitor: exacerbation of inflammatory bowel disease and candida infections, as noted in the evidence for IL-17 blockers.
Please refer to the package insert for the full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold for rheumatoid vasculitis (rank 1); Proceed with Guardrails for inflammatory spondylopathy (rank 6)
Rationale:
- Rheumatoid vasculitis has a high model score but no direct trials or literature, so it remains a prediction only (L5).
- Inflammatory spondylopathy is supported by multiple completed Phase 3 randomised trials in axial spondyloarthritis (L1), but it largely overlaps with the drug's original indication, so it is not a true new use.
To proceed, the following is needed:
- Mechanism of action data to support the mechanistic-link analysis
- Package insert warnings and contraindications from the HSA, to complete safety screening (currently blocking)
- Confirmation of the specific disease subtype for inflammatory spondylopathy and vertebral disease
- Any mechanistic or exploratory data for rheumatoid vasculitis before further consideration
- A monitoring plan for inflammatory bowel disease flares and candida infections, and for combination use with other biologics
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.