Abatacept

證據等級: L5

預測適應症: 10 個

Drug Repurposing Evidence Report: Abatacept (DB01281)

Candidate ID: TW-DB01281-multi Report Version: v4 Date Generated: 2026-04-03 Data Cutoff: 2026-04-03 Prepared for: Lægemiddelstyrelsen (Danish Medicines Agency) Context

1. Executive Summary

Field	Detail
Drug (INN)	Abatacept
DrugBank ID	DB01281
Brand Name	Orencia (Bristol-Myers Squibb)
Number of Predicted Indications	5 (unique diseases)
Highest Evidence Level Achieved	L1 — Inflammatory spondylopathy (psoriatic arthritis subtype)
Top Recommendation	Proceed with Guardrails (inflammatory spondylopathy / PsA)

Key Findings Summary:

Abatacept, a selective T-cell co-stimulation modulator (CTLA-4-Ig fusion protein), was evaluated by the TxGNN knowledge graph model across five predicted disease indications. The analysis reveals a spectrum of evidence maturity:

Inflammatory spondylopathy (specifically the psoriatic arthritis [PsA] subtype): L1 evidence — supported by a completed Phase 3 RCT (NCT01860976, n=489), ACR/NPF 2018 guideline inclusion, and large-scale post-marketing safety data including a Denmark-specific DANBIO registry study (NCT05421442, n=38,396). Abatacept is already EMA/FDA-approved for PsA. Recommendation: Proceed with Guardrails.
Ankylosing spondylitis (AS): L2 evidence — a Phase 2 open-label pilot (NCT00558506, n=30; PMID 21415053) demonstrated limited efficacy, consistent with a mechanistic mismatch (AS driven primarily by IL-17/IL-23 axis rather than T-cell co-stimulation). Recommendation: Hold.
Rheumatoid vasculitis: L4 evidence — case reports show contradictory signals (both therapeutic benefit and new-onset vasculitis during abatacept therapy). No clinical trials. Recommendation: Research Question.
Hypermobility of coccyx: L5 evidence — AI prediction only. No biological plausibility. Recommendation: Hold.
Kümmell disease: L5 evidence — AI prediction only. No biological plausibility. Recommendation: Hold.

Data Gaps Identified: Lægemiddelstyrelsen product label warnings/contraindications and detailed mechanism of action data require supplementation from DrugBank API and the Danish product resume (produktresumé).

2. Drug Overview

2.1 Approved Indications

Denmark (Lægemiddelstyrelsen / EMA Centralised Authorisation)

Abatacept (Orencia) holds a centralised EMA marketing authorisation valid in Denmark for:

Indication	Population	Route
Rheumatoid arthritis (RA)	Adults with moderate-to-severe active RA with inadequate response to DMARDs including methotrexate or a TNF inhibitor	IV infusion / SC injection
Polyarticular juvenile idiopathic arthritis (pJIA)	Paediatric patients ≥2 years	IV / SC
Psoriatic arthritis (PsA)	Adults with active PsA with inadequate response to DMARDs	SC injection

Note: The evidence pack indicates Taiwan regulatory status as “未上市” (not marketed). In contrast, abatacept is authorised and marketed in Denmark under the EMA centralised procedure.

FDA (United States)

FDA-approved indications mirror EMA approvals: RA (adult), pJIA (≥2 years), PsA (adult), and additionally the prevention of acute graft-versus-host disease (aGVHD) in combination with a calcineurin inhibitor and methotrexate.

2.2 Mechanism of Action

Abatacept is a soluble fusion protein comprising the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) linked to the modified Fc portion of human immunoglobulin G1 (IgG1). It acts as a selective co-stimulation modulator by:

Binding CD80/CD86 on antigen-presenting cells (APCs), thereby blocking interaction with CD28 on T cells
Inhibiting the “Signal 2” co-stimulatory pathway required for full T-cell activation
Preferentially suppressing naïve T-cell activation while having a lesser effect on memory T cells
Downstream reduction of pro-inflammatory cytokines (TNF-α, IL-6, IL-2) and autoantibody production

⚠️ Data Gap (DG002): Full MOA characterisation from DrugBank API was flagged as incomplete in the evidence pack. The above is reconstructed from published literature.

2.3 Pharmacokinetic Profile

Parameter	IV Formulation	SC Formulation
Bioavailability	100% (reference)	~78.6% (SC vs IV)
T_max	End of infusion	~7 days (SC)
Half-life (t½)	~13 days (range 8–25 days)	~14.3 days
Steady-state	By week 8 (with loading)	By week 12–13
Clearance	~0.22 mL/h/kg	Similar
Volume of distribution (Vss)	~0.07 L/kg	—
Dosing (IV)	Weight-based: <60 kg: 500 mg; 60–100 kg: 750 mg; >100 kg: 1000 mg; Day 1, 15, 29, then q4w	—
Dosing (SC)	—	125 mg weekly (with or without IV loading dose)
Metabolism	Proteolytic degradation (not CYP-mediated)	Same
Immunogenicity	Low anti-drug antibody formation (~2–3%)	Similar

3. Evidence Analysis

Overview: Predicted Indications Summary

Rank	Disease	TxGNN Score	Evidence Level	Decision Stage	Recommendation
1	Rheumatoid vasculitis	0.999	L4	S1	Research Question
2	Ankylosing spondylitis	0.999	L2	S1	Hold
3	Hypermobility of coccyx	0.999	L5	S0	Hold
4	Inflammatory spondylopathy	0.998	L1	S3	Proceed with Guardrails
5	Kümmell disease	0.998	L5	S0	Hold

3.1 Inflammatory Spondylopathy (Psoriatic Arthritis Subtype)

**Evidence Level: L1

Decision Stage: S3

Recommendation: Proceed with Guardrails**

This is the strongest candidate identified. Inflammatory spondylopathy encompasses psoriatic arthritis (PsA), for which abatacept is already approved globally. The evidence base is robust.

3.1.1 Clinical Trials

NCT ID	Title	Phase	Status	N	Key Finding
NCT01860976	Phase 3 RCT: Abatacept SC in Active PsA	Phase 3	Completed	489	Pivotal trial: abatacept SC vs placebo in PsA; primary endpoint met. Led to regulatory approval.
NCT00534313	Phase 2b RCT: Abatacept vs Placebo in PsA	Phase 2b	Terminated	191	Dose-finding study; established optimal dosing for PsA.
NCT05421442	Post-marketing safety: DANBIO Register (Denmark)	Post-marketing	Completed	38,396	Denmark-specific: nationwide post-marketing monitoring of abatacept in RA and PsA patients via DANBIO.
NCT05413044	Post-marketing safety: SRQ Register (Sweden)	Post-marketing	Completed	140,706	Swedish nationwide safety monitoring; malignancy incidence data.
NCT03419143	ALTEA: Real-world PsA (Germany)	Observational	Completed	190	Long-term real-world efficacy and safety in PsA.
NCT04106804	ABEPSA: Bone Biomarkers in PsA	Phase 4	Unknown	20	Abatacept bone effects in PsA via MRI and biomarkers.
NCT00558506	Pilot: Abatacept in AS	Phase 2	Unknown	30	Relevant to AS subtype only; limited efficacy reported.
NCT05080218	COVER: COVID-19 Vaccine Response	Phase 4	Completed	841	Safety data on vaccine response in patients on abatacept.

3.1.2 Published Literature

Tier 1 (Guidelines / Meta-analyses):

PMID 30499246 — ACR/NPF 2018 Guideline for the Treatment of PsA (Arthritis & Rheumatology, 2019): Abatacept is included as a recommended biologic DMARD option for PsA patients with inadequate response to csDMARDs. This is a clinical practice guideline from the two leading professional bodies.
PMID 39992258 — Abatacept and the risk of malignancy: a meta-analysis across disease indications (Rheumatology, 2025): Cross-indication meta-analysis assessing malignancy risk; provides critical safety data relevant to long-term use in spondyloarthritis.

Tier 2 (Systematic Reviews / Key Reviews):

PMID 28612180 — Systematic review on immunogenicity of biologics across inflammatory diseases.
PMID 38331098 — Vaccination guidelines for patients on biologics including abatacept.
PMID 38499181 — Perioperative management guidelines for abatacept in PsA patients.
PMID 29737909 — Review of biological and clinical profiles of PsA responders to abatacept; notes differential efficacy across PsA domains (effective for peripheral arthritis, less so for axial disease and skin).
PMID 31171316 — Emerging treatment options for SpA; positions abatacept within the therapeutic landscape.
PMID 38639758 — Drug therapy in juvenile spondyloarthritis; reviews abatacept evidence in paediatric JSpA.

3.1.3 Mechanistic Rationale

Inflammatory spondylopathy encompasses conditions driven by adaptive immune dysregulation, particularly PsA. Abatacept’s inhibition of T-cell co-stimulation effectively modulates the adaptive immune response in PsA, particularly for peripheral joint manifestations. The ACR/NPF 2018 guidelines conditionally recommend abatacept for treatment-naïve PsA patients and those with inadequate response to TNF inhibitors.

Important caveat: Abatacept shows limited efficacy for axial disease within the spondyloarthritis spectrum. Its approval and guideline recommendations are restricted to peripheral PsA manifestations, not axial spondyloarthritis (including AS).

3.1.4 Denmark-Specific Evidence

The DANBIO registry study (NCT05421442) is of particular relevance:

Design: Nationwide post-marketing surveillance using the Danish DANBIO biologics register
Sample: 38,396 participants with RA or PsA treated with abatacept
Status: Completed (2019–2025)
Objective: Expanded post-marketing monitoring of abatacept safety
This study provides real-world Danish population-level safety data, directly applicable to Lægemiddelstyrelsen decision-making.

3.2 Ankylosing Spondylitis

**Evidence Level: L2

Decision Stage: S1

Recommendation: Hold**

3.2.1 Clinical Trials

NCT ID	Title	Phase	Status	N	Key Finding
NCT00558506	Pilot Open-Label: Abatacept in AS	Phase 2	Unknown	30	Core evidence: 24-week open-label pilot demonstrated limited efficacy (PMID 21415053).
NCT04610476	Phase 3 PsA Tapering RCT	Phase 3	Unknown	270	PsA-focused; tangential to AS.

3.2.2 Published Literature

Key Publication:

PMID 21415053 — Treatment of active ankylosing spondylitis with abatacept: an open-label, 24-week pilot study (Song et al., Ann Rheum Dis, 2011): This is the only direct clinical study of abatacept in AS. Results showed limited clinical efficacy, with the majority of patients not achieving ASAS20 response. The study was not progressed to Phase 3.

Supporting Reviews:

PMID 27856659 — Sieper (Rheumatology, 2016): Explicitly states that “conventional DMARDs and also non-TNF-blocker biologics targeting IL-1, IL-6 and T cells (abatacept) are not effective” in axSpA.
PMID 22450391 — Kiltz et al. (Curr Opin Rheumatol, 2012): Reviews alternatives for TNF-refractory AS; abatacept assessed but found insufficiently effective.
PMID 19822066 — Braun & Kalden (Clin Exp Rheumatol, 2009): Discusses pathogenic differences between RA and AS that explain differential biologic responses.

3.2.3 Mechanistic Rationale

AS is primarily driven by the HLA-B27/IL-17/IL-23 axis, with innate immunity playing a predominant role. T-cell co-stimulation blockade via abatacept does not effectively target this pathway. The clinical data (PMID 21415053) confirm this mechanistic mismatch. This indication should not be pursued further.

3.3 Rheumatoid Vasculitis

**Evidence Level: L4

Decision Stage: S1

Recommendation: Research Question**

3.3.1 Clinical Trials

No clinical trials directly studying abatacept for rheumatoid vasculitis were identified. One tangentially related trial (NCT07138898, immunosuppressant management in shoulder arthroplasty) received relevance grade C.

3.3.2 Published Literature

The evidence consists entirely of case reports with contradictory signals:

PMID	Type	Year	Key Finding	Signal Direction
22124545	Case Report	2012	38-year-old woman with refractory RV: abatacept produced rapid clinical improvement after failure of steroids, plasmapheresis, and tocilizumab.	Positive ✅
29930884	Case Report/Series	2018	Patient with RA + common variable immunodeficiency: abatacept used as alternative to rituximab for cutaneous RV.	Positive ✅
27052429	Case Report	2016	New onset of rheumatoid vasculitis developed during abatacept therapy; subsequently improved with rituximab.	Negative ⚠️
30119075	Case Report	2018	RA-associated orbital vasculitis presented while on abatacept.	Negative ⚠️
36418100	Case Report	2023	ANCA-associated nephritis developed during abatacept + adalimumab therapy.	Negative ⚠️

3.3.3 Mechanistic Rationale

Rheumatoid vasculitis (RV) is a severe extra-articular manifestation of RA involving T-cell-mediated vascular wall inflammation. Theoretically, abatacept’s inhibition of T-cell co-stimulation could suppress the upstream autoimmune vascular inflammation. However, the published case reports present contradictory evidence:

In favour: Cases of refractory RV responding to abatacept (PMID 22124545, 29930884)
Against: Cases of new-onset vasculitis developing during abatacept therapy (PMID 27052429, 30119075)

This discordance suggests that the relationship between CTLA-4 pathway modulation and vasculitis is complex and possibly patient-subtype dependent.

3.4 Hypermobility of Coccyx

**Evidence Level: L5

Decision Stage: S0

Recommendation: Hold**

No clinical trials, no literature, no mechanistic plausibility. Coccygeal hypermobility is a mechanical/structural condition involving ligamentous laxity or joint instability. There is no immune-mediated component that would respond to T-cell co-stimulation blockade. The high TxGNN score (0.999) likely reflects graph proximity artefact within the musculoskeletal disease node neighbourhood. This is considered a false positive.

3.5 Kümmell Disease

**Evidence Level: L5

Decision Stage: S0

Recommendation: Hold**

No clinical trials, no literature, no mechanistic plausibility. Kümmell disease (delayed post-traumatic vertebral body collapse / avascular necrosis of the vertebral body) is a mechanical/vascular condition. There is no rational basis for immunomodulatory therapy. This is considered a false positive.

4. Safety Considerations

⚠️ Data Gap (DG001): Product label warnings and contraindications from the Danish/EMA produktresumé were not available in the evidence pack. The following is based on the EMA Summary of Product Characteristics (SmPC) for Orencia and published literature.

4.1 Known Adverse Effects

Common (≥1/100 to <1/10):

Upper respiratory tract infections (nasopharyngitis, sinusitis)
Urinary tract infections
Headache
Nausea, diarrhoea
Injection site reactions (SC formulation)
Infusion-related reactions (IV formulation)

Uncommon (≥1/1,000 to <1/100):

Herpes zoster
Pneumonia
Elevated transaminases

Rare but Serious:

Serious infections (including sepsis, tuberculosis, opportunistic infections)
Malignancy (meta-analysis PMID 39992258 found no significantly increased risk of malignancy excluding NMSC)
Hypersensitivity/anaphylaxis
Autoimmune phenomena (paradoxical vasculitis — see Section 3.3)

4.2 Drug Interactions

Interaction	Severity	Detail
Other biologics (TNF inhibitors, IL-6 inhibitors, rituximab)	Contraindicated	Concurrent use increases serious infection risk without added efficacy
Live vaccines	Contraindicated	Live vaccines should not be administered concurrently or within 3 months of discontinuation
Methotrexate	Permitted	Commonly used in combination; no significant PK interaction
Corticosteroids	Permitted	No significant interaction; standard concomitant use
Non-live vaccines	Caution	Immune response may be attenuated; timing considerations apply (see PMID 38331098)

Note: DDI query returned 0 results from the evidence pack database (query status: not_found). The above is compiled from SmPC data and published guidelines.

4.3 Contraindications

Based on EMA SmPC:

Hypersensitivity to abatacept or any excipient
Severe and uncontrolled active infections (e.g., sepsis, opportunistic infections, active tuberculosis)
Concurrent use with other biological DMARDs

4.4 Special Populations

Population	Recommendation
Pregnancy	Limited data; use only if clearly needed (PMID 40256995 — scoping review of DMARDs in pregnancy)
Breastfeeding	Abatacept detected in breast milk; risk-benefit assessment needed
Tuberculosis screening	Mandatory before initiation (PMID 39963138)
Hepatitis B/C	Screen before initiation
Elderly	No dose adjustment; increased infection vigilance

4.5 Post-Marketing Safety Data (Denmark-Specific)

The DANBIO registry study (NCT05421442) provides large-scale Danish safety data:

38,396 participants with RA or PsA in Denmark
Monitoring period: 2019–2025 (completed)
Focus: expanded post-marketing safety including malignancy, infections, and cardiovascular events

The complementary Swedish SRQ registry study (NCT05413044) enrolled 140,706 participants, providing additional Nordic real-world safety benchmarking.

5. Regulatory Status

5.1 Denmark (Lægemiddelstyrelsen)

Parameter	Status
Product Name	Orencia
Marketing Authorisation	Authorised (EMA centralised procedure, valid in Denmark)
Approved Indications	RA (adult), PsA (adult), pJIA (≥2 years)
Formulations	IV infusion (lyophilised powder 250 mg); SC injection (125 mg/mL prefilled syringe/pen)
DANBIO Registry	Active; abatacept included in national biologics monitoring
Post-marketing study	NCT05421442 completed (n=38,396)

5.2 EMA Status

Parameter	Detail
First Authorisation	2007 (RA)
PsA Extension	2017
Current SmPC Version	Regularly updated
PASS Requirements	Ongoing post-authorisation safety studies (including NCT05421442, NCT05413044)

5.3 FDA Status

Parameter	Detail
First Approval	2005 (RA)
PsA Approval	2017
aGVHD Prevention	2021 (unique to FDA, not EMA-approved for this)
Formulations	IV and SC (same as EMA)

5.4 Regulatory Status Summary for Predicted Indications

Predicted Indication	Denmark/EMA	FDA	Status
Inflammatory spondylopathy (PsA subtype)	Approved	Approved	Already authorised
Ankylosing spondylitis	Not approved	Not approved	Phase 2 failed; unlikely to progress
Rheumatoid vasculitis	Not approved	Not approved	Case reports only
Hypermobility of coccyx	Not approved	Not approved	No evidence
Kümmell disease	Not approved	Not approved	No evidence

6. Conclusion and Recommendations

6.1 Overall Assessment

Indication	Evidence Level	Verdict	Actionability
Inflammatory spondylopathy (PsA)	L1	✅ Already approved	No repurposing needed; ensure full utilisation in Danish clinical practice
Ankylosing spondylitis	L2	❌ Negative evidence	Do not pursue; mechanistic mismatch confirmed clinically
Rheumatoid vasculitis	L4	⚠️ Contradictory signals	Academic research interest only; no clinical pathway justified
Hypermobility of coccyx	L5	❌ False positive	Discard; no biological plausibility
Kümmell disease	L5	❌ False positive	Discard; no biological plausibility

6.2 Evidence Gaps

Gap ID	Item	Severity	Recommended Remediation
DG001	Lægemiddelstyrelsen produktresumé warnings/contraindications	Blocking	Download and parse the Danish-language SmPC from Lægemiddelstyrelsen/EMA product database
DG002	Detailed MOA data from DrugBank	High	Query DrugBank API for complete target/enzyme/transporter profiles
—	Route compatibility assessment	Medium	Cross-reference available Danish formulations with required administration routes for each indication
—	Disease mapping completeness	Low	Several literature items have “pending” classification; complete relevance grading
—	Duplicate entries in evidence pack	Low	Ranks 1/2, 3/4, 5/6, 7/8, 9/10 appear duplicated; deduplicate in future pipeline runs

6.3 Suggested Next Steps

For Inflammatory Spondylopathy (PsA):

No repurposing action required — abatacept is already EMA-authorised for PsA and available in Denmark
Leverage DANBIO data (NCT05421442) to inform Lægemiddelstyrelsen post-marketing surveillance reporting
Consider a utilisation study via DANBIO to assess real-world uptake and treatment sequencing of abatacept in Danish PsA patients

For Rheumatoid Vasculitis:

Formulate as research question for academic investigation
Conduct a systematic review of all published cases of abatacept use in RV (both therapeutic and paradoxical)
Consider a national case series via Danish rheumatology centres to identify any off-label use patterns
Do not recommend clinical use outside of a formal research protocol given contradictory safety signals

For Ankylosing Spondylitis:

No further action — negative Phase 2 data and mechanistic mismatch
Archive evidence for reference

For Hypermobility of Coccyx and Kümmell Disease:

Flag as TxGNN false positives for model calibration
These likely represent knowledge graph node proximity artefacts in the musculoskeletal disease cluster

6.4 Pipeline Quality Notes

The evidence pack contained duplicate entries (ranks 1/2, 3/4, 5/6, 7/8, 9/10 are identical disease pairs). This should be addressed in the data pipeline to prevent inflated candidate counts. After deduplication, there are 5 unique predicted indications rather than 10.

Appendix A: Data Sources Queried

Source	Queries Run	Results Found
DrugBank	1	1 (drug profile)
ClinicalTrials.gov	10	32 trials (across all indications)
ICTRP	10	0
PubMed	10	97 publications (across all indications)
DDI Database	1	0 (not found)

Appendix B: Key References

Song I-H et al. Treatment of active ankylosing spondylitis with abatacept: an open-label, 24-week pilot study. Ann Rheum Dis. 2011;70(6):1108-1110. PMID: 21415053
Singh JA et al. 2018 ACR/NPF Guideline for the Treatment of Psoriatic Arthritis. Arthritis Rheumatol. 2019;71(1):5-32. PMID: 30499246
Zuckerman BP et al. Abatacept and the risk of malignancy: a meta-analysis across disease indications. Rheumatology. 2025. PMID: 39992258
Fujii W et al. The rapid efficacy of abatacept in a patient with rheumatoid vasculitis. Mod Rheumatol. 2012;22(3):440-443. PMID: 22124545
Carvajal Alegria G et al. New onset of rheumatoid vasculitis during abatacept therapy. Joint Bone Spine. 2016;83(5):589-590. PMID: 27052429
Al Attar L, Shaver T. Abatacept as a Therapeutic Option for Rheumatoid Vasculitis. Cureus. 2018;10(6):e2793. PMID: 29930884
Zizzo G et al. Abatacept in the treatment of psoriatic arthritis: biological and clinical profiles of the responders. Immunotherapy. 2018;10(6):465-478. PMID: 29737909
Sieper J. New treatment targets for axial spondyloarthritis. Rheumatology. 2016;55(suppl_2):ii38-ii42. PMID: 27856659

Disclaimer: This report is generated for research purposes only and does not constitute medical advice. All drug repurposing candidates require clinical validation before therapeutic application. Drug repurposing predictions are based on computational models (TxGNN knowledge graph) and require independent verification. Always consult healthcare professionals and the current Lægemiddelstyrelsen-approved produktresumé before making treatment decisions.

Report generated: 2026-04-03 | Data cutoff: 2026-04-03 | Pipeline version: v4

Disclaimer

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

Abatacept

目錄

Drug Repurposing Evidence Report: Abatacept (DB01281)

1. Executive Summary

2. Drug Overview

2.1 Approved Indications

Denmark (Lægemiddelstyrelsen / EMA Centralised Authorisation)

FDA (United States)

2.2 Mechanism of Action

2.3 Pharmacokinetic Profile

3. Evidence Analysis

Overview: Predicted Indications Summary

3.1 Inflammatory Spondylopathy (Psoriatic Arthritis Subtype)

3.1.1 Clinical Trials

3.1.2 Published Literature

3.1.3 Mechanistic Rationale

3.1.4 Denmark-Specific Evidence

3.2 Ankylosing Spondylitis

3.2.1 Clinical Trials

3.2.2 Published Literature

3.2.3 Mechanistic Rationale

3.3 Rheumatoid Vasculitis

3.3.1 Clinical Trials

3.3.2 Published Literature

3.3.3 Mechanistic Rationale

3.4 Hypermobility of Coccyx

3.5 Kümmell Disease

4. Safety Considerations

4.1 Known Adverse Effects

4.2 Drug Interactions

4.3 Contraindications

4.4 Special Populations

4.5 Post-Marketing Safety Data (Denmark-Specific)

5. Regulatory Status

5.1 Denmark (Lægemiddelstyrelsen)

5.2 EMA Status

5.3 FDA Status

5.4 Regulatory Status Summary for Predicted Indications

6. Conclusion and Recommendations

6.1 Overall Assessment

6.2 Evidence Gaps

6.3 Suggested Next Steps

For Inflammatory Spondylopathy (PsA):

For Rheumatoid Vasculitis:

For Ankylosing Spondylitis:

For Hypermobility of Coccyx and Kümmell Disease:

6.4 Pipeline Quality Notes

Appendix A: Data Sources Queried

Appendix B: Key References

Disclaimer