Anakinra

證據等級: L5

預測適應症: 10 個

Anakinra: From Autoinflammatory Disorders to Extracutaneous Mastocytoma

One-Sentence Summary

Anakinra is a recombinant human interleukin-1 receptor antagonist (IL-1Ra), internationally approved for rheumatoid arthritis and autoinflammatory conditions, but currently not registered in Taiwan. The TxGNN model ranks extracutaneous mastocytoma as the top predicted new indication (score 99.93%), though this carries only AI-prediction-level evidence (L5) with no supporting clinical data. Across all 10 predicted indications in this multi-indication pack, the strongest clinical evidence lies in autosomal recessive familial Mediterranean fever (20 publications, L3) and pyogenic autoinflammatory syndrome (19 publications, L3), both of which share a direct IL-1β overactivation pathomechanism that Anakinra is mechanistically designed to block.

Quick Overview

Item	Content
Original Indication	Not registered in Taiwan; internationally used for rheumatoid arthritis and autoinflammatory conditions
Top TxGNN Prediction	Extracutaneous Mastocytoma
TxGNN Prediction Score	99.93%
Evidence Level (Top Prediction)	L5
Taiwan Market Status	Not marketed
Number of Taiwan Authorizations	0
Recommended Decision (Top Prediction)	Hold

All Predicted Indications Overview

Rank	Disease	TxGNN Score	Evidence Level	Publications	Recommendation
1	Extracutaneous mastocytoma	99.93%	L5	0	Hold
2	Hepatic infarction	99.89%	L5	0	Hold
3	Autosomal recessive familial Mediterranean fever	99.89%	L3	20	Research Question
4	Aggressive systemic mastocytosis	99.88%	L4	2	Research Question
5	Hepatic veno-occlusive disease	99.88%	L5	0	Hold
6	Peliosis hepatis	99.85%	L5	0	Hold
7	Oligoarticular JIA with ANA	99.85%	L4	1	Research Question
8	Oligoarticular JIA without ANA	99.85%	L4	1	Research Question
9	Pyogenic autoinflammatory syndrome	99.83%	L3	19	Proceed with Guardrails
10	Unclassified autoinflammatory syndrome	99.81%	L3	2	Research Question

Why is This Prediction Reasonable?

Top Prediction: Extracutaneous Mastocytoma (Rank 1)

Currently, detailed mechanism of action data is not available from the Evidence Pack. Based on known pharmacology, Anakinra is a recombinant form of the naturally occurring human IL-1 receptor antagonist that competitively inhibits the binding of both IL-1α and IL-1β to the IL-1 type I receptor (IL-1RI), thereby blocking IL-1-driven inflammatory signalling.

For extracutaneous mastocytoma specifically, the TxGNN rationale notes that IL-1 signalling may participate in mast cell activation. Mast cells are known to produce IL-1β, and systemic mast cell diseases can be accompanied by inflammatory cytokine release. However, extracutaneous mastocytoma is an extremely rare neoplastic disease, and no direct or indirect clinical evidence currently supports the efficacy of IL-1 blockade in this condition.

The high TxGNN score (99.93%) most likely reflects the global network connectivity of mast cell disease nodes in the knowledge graph rather than disease-specific mechanistic evidence. Until preclinical or clinical data emerge, this prediction should be treated as hypothesis-generating only.

Best-Evidenced Predictions

Autosomal Recessive Familial Mediterranean Fever (Rank 3, L3)

FMF is caused by mutations in the MEFV gene encoding pyrin (marenostrin). Mutant pyrin undergoes abnormal hypophosphorylation in response to RhoA GTPase signalling, leading to constitutive activation of the pyrin inflammasome, excessive caspase-1 cleavage, and uncontrolled IL-1β and IL-18 secretion. This IL-1β overproduction is the central driver of recurrent febrile serositis attacks and, over time, systemic AA amyloidosis.

Anakinra, as a direct IL-1 receptor antagonist, is mechanistically the most rational intervention in this pathway. Multiple published case series report successful use of Anakinra in colchicine-resistant or colchicine-intolerant FMF patients, including suppression of attacks and partial reversal of amyloid-related proteinuria. Genetic association data (PMID 26861613) further demonstrate that IL-1Ra polymorphisms influence FMF susceptibility, directly linking the drug target to disease biology.

Pyogenic Autoinflammatory Syndrome (Rank 9, L3)

Pyogenic autoinflammatory syndromes — including PAPA (pyogenic arthritis, pyoderma gangrenosum, acne), PAPASH, and PASH — are caused by gain-of-function mutations in PSTPIP1, which encodes a scaffolding protein regulating NLRP3 inflammasome assembly. Hyperphosphorylated PSTPIP1 binds pyrin, dysregulates caspase-1 activation, and drives massive IL-1β overproduction. This makes IL-1Ra the most direct targeted therapy.

A 2023 systematic scoping review (PMID 38259483) and a 2024 case report (PMID 39006661) directly document Anakinra’s efficacy and safety in PSTPIP1-associated inflammatory diseases, supporting an evidence-backed rationale for further investigation.

Clinical Trial Evidence (Top Prediction: Extracutaneous Mastocytoma)

Currently no related clinical trials registered.

Literature Evidence: Autosomal Recessive Familial Mediterranean Fever (Rank 3, L3)

PMID	Year	Type	Journal	Key Findings
19033248	2009	Case Series	Nephrol Dial Transplant	Anakinra successfully treated colchicine-resistant FMF with AA amyloidosis; stable graft function maintained post-renal transplant
20386914	2012	Case Report	Rheumatol Int	Anakinra effective in a 52-year-old colchicine-resistant FMF patient with secondary amyloidosis and end-stage renal disease
21931121	2012	Case Series	Nephrol Dial Transplant	IL-1 inhibitor (including Anakinra) showed dramatic benefit in FMF patients complicated with amyloidosis and renal failure
23928237	2013	Case Report	Joint Bone Spine	FMF-associated myositis and spondyloarthritis successfully treated with Anakinra after colchicine failure
21277619	2011	Case Series + Review	Semin Arthritis Rheum	Multi-patient series demonstrating IL-1 targeting (Anakinra/canakinumab) as a rational new approach for FMF; mechanistic link via pyrin-IL-1 axis
23322405	2013	Review	Clin Rev Allergy Immunol	IL-1β biological treatment of FMF; summarises evidence base for Anakinra and canakinumab in colchicine-resistant disease
26861613	2016	Genetic Association	Gene	IL-1Ra (rs2234663) polymorphisms associated with FMF susceptibility in Turkish population, directly linking drug target to disease biology
34550430	2022	Cohort	Rheumatol Int	Real-world data: canakinumab effective in FMF patients resistant/intolerant to colchicine and/or Anakinra, confirming Anakinra as prior standard of care
26572612	2016	Review	Curr Med Chem	Comprehensive review of colchicine and biologics (including Anakinra) for FMF; positions IL-1 blockade as second-line for non-responders
31205631	2019	Review	Mediterr J Hematol Infect Dis	FMF treatment planning review; RhoA/pyrin axis described as mechanistic basis for IL-1β overactivation and IL-1Ra relevance

Literature Evidence: Pyogenic Autoinflammatory Syndrome (Rank 9, L3)

PMID	Year	Type	Journal	Key Findings
38259483	2023	Systematic Review / Case Series	Front Immunol	Comprehensive scoping review of Anakinra and canakinumab efficacy/safety in PSTPIP1-associated inflammatory diseases (PAPA, PAMI spectrum)
39006661	2024	Case Report	Cureus	Anakinra successfully used in PAPASH spectrum disorder; case report with literature review confirming IL-1 pathway as the therapeutic target
27448064	2016	Review	Hautarzt	Anakinra used in PASH and PAPASH autoinflammatory diseases based on IL-1β involvement
24275598	2013	Review	Semin Immunol	Landmark review on IL-1 blocking therapies; documents expanding list of diseases responsive to IL-1Ra, including pyogenic syndromes
22161697	2012	Case Series	Arthritis Rheum	Genotype-phenotype correlation in 5 PAPA syndrome patients; IL-1β overproduction identified as molecular hallmark
21532836	2010	Review	Curr Genomics	PAPA syndrome: PSTPIP1 mutations cause hyper-phosphorylated protein, dysregulated inflammasome, and IL-1β overproduction — rationale for IL-1Ra
28251506	2017	Case Report + Review	Infection	PAPA syndrome diagnosis and clinical management challenges; includes discussion of IL-1 targeting
21745697	2012	Case Report	J Am Acad Dermatol	PASH syndrome described as distinct from PAPA; PSTPIP1 promoter involvement and IL-1 pathway dysregulation documented
29742056	2018	Review	Clin Exp Rheumatol	Dermatologic perspective on autoinflammatory diseases; IL-1 blockade positioned as key therapeutic strategy in PSTPIP1-related syndromes
27464597	2016	Review	Curr Opin Rheumatol	Expanding spectrum of PSTPIP1 autoinflammatory diseases and pathogenesis insights; supports mechanistic rationale for Anakinra

Literature Evidence: Unclassified Autoinflammatory Syndrome (Rank 10, L3)

PMID	Year	Type	Journal	Key Findings
36589607	2022	Retrospective Cohort	Arch Rheumatol	Single-centre experience of Anakinra in paediatric rheumatic diseases including unclassified autoinflammatory conditions; documents real-world efficacy
37747561	2024	Multicentre Cohort	Rheumatol Int	German GARROD registry: 152 patients with autoinflammatory diseases receiving anti-IL-1 therapy (including Anakinra); includes FMF, CAPS, TRAPS, and unclassified AIDs

Literature Evidence: Aggressive Systemic Mastocytosis (Rank 4, L4)

Note: Retrieved literature relates to Schnitzler syndrome (an IL-1-driven urticarial disorder with mast cell overlap), not aggressive systemic mastocytosis directly. This constitutes indirect mechanistic evidence only.

PMID	Year	Type	Journal	Key Findings
40718535	2025	Case Report	Oxford Med Case Reports	Anakinra effective in Schnitzler syndrome (IL-1-driven chronic urticaria with mast cell involvement); 14 months of good tolerance without steroids
25840575	2015	Case Report	Hellenic J Nucl Med	Schnitzler syndrome with bone remodelling abnormalities responds well to IL-1 inhibitor Anakinra; bone imaging characterised

Taiwan Market Information

Anakinra is not registered in Taiwan (market status: 未上市). No marketing authorizations are on file with the Taiwan FDA. Prescribers wishing to use Anakinra in Taiwan would need to apply for special import approval on a compassionate use or named-patient basis.

For reference: Anakinra (Kineret®, Swedish Orphan Biovitrum) holds EMA marketing authorization in the EU for rheumatoid arthritis and selected autoinflammatory conditions including NOMID/CINCA syndrome. No Taiwan-specific regulatory data is available in this Evidence Pack.

Safety Considerations

No Taiwan FDA prescribing information, key warnings, or contraindication data were available for this analysis. Drug-drug interaction data query returned no results.

Please refer to the current Kineret® Summary of Product Characteristics (SmPC) for full safety information, including:

Risk of serious infections (immunosuppression)
Contraindication in patients with active infection
Neutropenia monitoring requirements
Injection site reactions (most common adverse effect)
Use in renal impairment (dose adjustment required for eGFR < 30 mL/min)

Conclusion and Next Steps

For the Top TxGNN Prediction (Extracutaneous Mastocytoma)

Decision: Hold

Rationale: Extracutaneous mastocytoma is an extremely rare neoplastic disease with no clinical or preclinical evidence supporting IL-1 blockade. The high TxGNN score likely reflects non-specific knowledge graph topology rather than disease-specific biology.

To proceed, the following is needed:

Preclinical data (in vitro or murine model) demonstrating IL-1β involvement in extracutaneous mastocytoma pathogenesis
Case reports or registry data from international mastocytosis centres

For Autosomal Recessive Familial Mediterranean Fever (Rank 3)

Decision: Research Question — Proceed to Investigator-Initiated Study

Rationale: Multiple published case series and reviews document Anakinra efficacy in colchicine-resistant FMF with a direct IL-1Ra mechanistic rationale. Evidence is L3 (observational); formal prospective data is lacking but biological plausibility is high.

To proceed, the following is needed:

Systematic review or meta-analysis of existing case series
Prospective registry study in colchicine-resistant FMF patients
Taiwan-specific assessment: identify FMF patient population via rheumatology centres (rare in Taiwan but cases reported in Japanese/Korean populations)
Obtain Anakinra SmPC and establish named-patient import pathway

For Pyogenic Autoinflammatory Syndrome (Rank 9)

Decision: Proceed with Guardrails

Rationale: A 2023 systematic scoping review and 2024 case report directly document Anakinra efficacy in PSTPIP1-associated inflammatory diseases. The mechanistic link (IL-1β overproduction via mutant PSTPIP1 → inflammasome dysregulation) is well-established, and Anakinra is a rational first-line biologic for patients refractory to conventional therapy.

To proceed, the following is needed:

Genetic testing capability for PSTPIP1 mutation confirmation in target patients
Establish compassionate use / special import approval pathway for Anakinra in Taiwan
Define monitoring protocol: CBC, CRP/SAA, injection site assessment, infection surveillance
Prospective documentation of cases to build local evidence registry
Full MOA data retrieval from DrugBank and TFDA SmPC equivalent to complete safety assessment (current DG001 and DG002 data gaps must be resolved before clinical implementation)

Disclaimer: This report is for research reference only and does not constitute medical advice. All drug repurposing candidates require clinical validation before application.

Disclaimer

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

Anakinra

目錄

Anakinra: From Autoinflammatory Disorders to Extracutaneous Mastocytoma

One-Sentence Summary

Quick Overview

All Predicted Indications Overview

Why is This Prediction Reasonable?

Top Prediction: Extracutaneous Mastocytoma (Rank 1)

Best-Evidenced Predictions

Autosomal Recessive Familial Mediterranean Fever (Rank 3, L3)

Pyogenic Autoinflammatory Syndrome (Rank 9, L3)

Clinical Trial Evidence (Top Prediction: Extracutaneous Mastocytoma)

Literature Evidence: Autosomal Recessive Familial Mediterranean Fever (Rank 3, L3)

Literature Evidence: Pyogenic Autoinflammatory Syndrome (Rank 9, L3)

Literature Evidence: Unclassified Autoinflammatory Syndrome (Rank 10, L3)

Literature Evidence: Aggressive Systemic Mastocytosis (Rank 4, L4)

Taiwan Market Information

Safety Considerations

Conclusion and Next Steps

For the Top TxGNN Prediction (Extracutaneous Mastocytoma)

For Autosomal Recessive Familial Mediterranean Fever (Rank 3)

For Pyogenic Autoinflammatory Syndrome (Rank 9)

Disclaimer