Introduction and Context
Antiphospholipid syndrome (APS) is a systemic, acquired thrombophilia characterized by arterial and venous thrombosis, pregnancy morbidity, and a range of microvascular and non-thrombotic manifestations associated with persistent antiphospholipid antibodies (aPL). For decades clinicians and researchers have lacked a standardized, validated measure of disease activity in APS. This has limited consistent monitoring of patients, hindered comparative effectiveness research, and made it difficult to design and interpret clinical trials of therapies aimed at reducing disease activity rather than simply preventing events.
In November 2025, Tektonidou and colleagues published the Development and validation of a EULAR disease activity score in antiphospholipid syndrome (EAPSDAS) (Ann Rheum Dis. 2025 Nov 19; S0003-4967(25)04437-1). EAPSDAS is the product of a multi-stage, data-driven consensus process involving EULAR task force members, international APS experts, patients, and healthcare professionals. It represents the first formal disease activity instrument for APS endorsed through EULAR methodologies and validated using real-world clinical vignettes.
Why this matters now: APS clinical research has been hampered by heterogeneous outcome measures and the absence of a consensual disease activity index. A valid and reliable disease activity score can improve clinical decision-making, allow standardized monitoring, and serve as a primary or secondary endpoint in interventional trials of anticoagulant strategies, immune therapies, or targeted agents.
New Guideline Highlights
The EAPSDAS initiative produced two linked scales designed to capture APS activity across clinical scenarios:
– TMN (Thrombotic / Microvascular / Nonthrombotic) scale — captures acute and subacute manifestations across organ systems related to thrombosis, microvascular injury, and nonthrombotic APS features.
– Obstetric scale — designed to capture APS-related pregnancy morbidity across the course of a pregnancy.
Key development features and strengths
– Inclusive, multi-stakeholder process: 24 EULAR Task Force members, 53 international APS experts/collaborators, 65 patients with primary APS and 21 healthcare professionals participated in item generation and reduction.
– Multi-step methodology: systematic literature review, two surveys, Delphi consensus, scoring using physician global assessment (PhysGA) on clinical vignettes, and validation for face, content and construct validity as well as reliability.
– Evidence-based weighting: item scores were derived analytically — each candidate item’s score was set based on adjusted mean PhysGA in linear regression models from clinicians’ ratings of 60 clinical vignettes.
– Defined timeframes: 1-month timeframe for TMN items; entire pregnancy for obstetric items. Separate scores capture new/worsening, stable, and improved manifestations where relevant.
Practical takeaways for clinicians
– EAPSDAS offers a structured, reproducible way to quantify APS activity at a clinic visit or for trial follow-up.
– It separates thrombotic/microvascular/non-thrombotic manifestations from obstetric activity, reflecting clinically distinct management paradigms.
– Preliminary validation shows high face/content validity and good construct validity and reliability using vignette-based testing.
Updated Recommendations and Key Changes
Note: EAPSDAS is a new instrument rather than an update to prior APS management recommendations. However, its development represents a major methodological change in how activity in APS can be operationalized for practice and research.
What’s new compared with prior practice
– First standardized disease activity score for APS endorsed by an international EULAR-led effort.
– Data-driven item weighting based on clinician global assessments rather than solely expert opinion.
– Dual-scale structure reflecting both thrombotic/microvascular/non-thrombotic events and obstetric morbidity.
– Inclusion of items and scoring for stable or improved manifestations — helpful for monitoring response to therapy.
Evidence that drove the change
– The absence of a validated disease activity score in APS limited harmonization of trial endpoints and made assessment of response to therapy inconsistent.
– Growing research into non-thrombotic immune-mediated APS manifestations and recognition of microvascular disease increased the need for a comprehensive activity instrument.
Topic-by-Topic Recommendations
Below is a practical, topic-by-topic summary of the EAPSDAS development and how clinicians can use the tool. Because the EAPSDAS paper provides the operational score and validation data, the following focuses on application and key methodological points clinicians must understand.
Scope and intended use
– Intended uses: clinical practice monitoring of disease activity, stratification and outcome measurement in clinical trials, and cohort studies.
– Populations: adults with primary or secondary APS; the obstetric scale is specific to pregnancy-related APS activity.
Item selection and composition
– Item generation yielded 170 candidate items; 140 deduplicated items were rated.
– Delphi and consensus (≥75% threshold) produced 24 items on the TMN scale and 6 items for the obstetric scale. These items cover organ-specific thrombotic events (e.g., venous thromboembolism, ischemic stroke), microvascular phenomena, and non-thrombotic clinical features attributable to APS.
Scoring approach
– Item weights: derived from clinician-rated vignettes using adjusted mean Physician Global Assessment (PhysGA) in linear regression.
– Timeframes: TMN uses a 1-month reference period for new/worsening manifestations; obstetric scale applies to the entire pregnancy.
– Scoring for stable and improved manifestations is included to permit longitudinal monitoring of disease course.
Validation and performance
– Face and content validity: strong, based on multi-stakeholder input including patients.
– Construct validity: demonstrated using internal (PhysGA) and external standards across vignette ratings.
– Reliability: shown with good inter-rater agreement in vignette testing.
Recommended clinical application
– Baseline assessment: use EAPSDAS to document disease activity at diagnosis or at major clinical milestones.
– Follow-up: for TMN manifestations, reassess using the 1-month window; obstetric assessments should span the pregnancy.
– Treatment response: track changes in EAPSDAS over time — decreases indicate clinical improvement or control.
– Research use: incorporate as a primary/secondary endpoint in trials; use standardized cutpoints derived in future studies for meaningful clinical change (currently under further validation).
Integration with standard APS care
– EAPSDAS complements, but does not replace, laboratory aPL testing or diagnostic/classification criteria (e.g., Sydney criteria [Miyakis et al., J Thromb Haemost 2006]). Clinical judgment remains central.
– Use alongside standard practice elements: anticoagulation monitoring, obstetric risk management, and evaluation for secondary causes.
Expert Commentary and Insights
What the Task Force and contributors emphasized
– Consensus value: contributors highlighted the benefit of a harmonized language to describe disease activity across centers and studies.
– Pragmatism in design: using PhysGA as the criterion standard was a pragmatic choice; it anchors item weights in practicing clinicians’ real-world judgments.
– Obstetric focus: separating obstetric activity recognizes unique timing, management, and outcomes in pregnancy.
Key controversies and open questions
– Use of PhysGA as the criterion standard: while pragmatic, PhysGA is subjective. Future work should correlate EAPSDAS with objective outcomes (recurrent thrombosis, pregnancy loss, organ damage).
– Item selection and weighting: although data-driven, the items and weights may require refinement in prospective cohorts, across diverse healthcare settings, and in pediatric APS.
– Serology and biomarkers: the current score focuses on clinical manifestations; the role of aPL titers or other biomarkers in the activity score remains to be defined.
– Use in secondary APS: most development included primary APS patients; extrapolation to secondary APS (e.g., systemic lupus) is reasonable but warrants validation.
Direct implications described by authors
– For clinical trials: EAPSDAS could serve as a standardized efficacy endpoint that captures clinically meaningful change beyond binary events.
– For clinical care: standardized disease activity measurement can help clinicians judge when to intensify immunomodulatory therapy in select non-thrombotic APS manifestations.
Practical Implications
How EAPSDAS will change practice in the near term
– Measurement standardization: centers and networks can adopt EAPSDAS to compare outcomes and harmonize reporting.
– Enhanced trial design: investigators now have a validated instrument to measure APS activity, facilitating trial power calculations and cross-study comparisons.
– Shared decision-making: quantifying activity may help clinicians explain disease trajectory and therapeutic rationale to patients.
Limitations and steps needed before widespread adoption
– Prospective validation: essential next steps include testing responsiveness to treatment, predictive validity for clinical outcomes, and external validation across regions and care settings.
– Simplicity vs comprehensiveness: implementation will require clinician training and possibly electronic-health-record integration for routine use.
– Patient-reported outcomes: integrating patient-centered measures with EAPSDAS will enrich assessment of treatment benefit and tolerability.
Illustrative Clinical Vignette
John Smith is a 42-year-old man with primary APS diagnosed after a proximal deep vein thrombosis (DVT) and persistently positive lupus anticoagulant and anticardiolipin antibodies. He presents with a new cold, painful fingertip lesion concerning for digital ischemia over the past 2 weeks while on warfarin with INR 2.0.
Using EAPSDAS (TMN scale, 1-month window):
– The clinician documents the new microvascular ischemic lesion as a new/worsening TMN item and scores according to the prescribed item weight derived from PhysGA anchors.
– Baseline EAPSDAS is higher than prior visit, signaling increased activity. This objective activity rise supports consideration of treatment adjustment (e.g., anticoagulation intensity review, evaluation for additional prothrombotic triggers, vascular imaging, and multidisciplinary discussion about adjunct immunomodulatory therapy for microvascular APS manifestations).
This vignette illustrates how EAPSDAS structures clinical assessment and informs management decisions, while preserving individualized care decisions.
Conclusions and Next Steps
EAPSDAS marks a milestone in APS care: for the first time clinicians and researchers have a rigorously developed, consensus-derived, and initially validated instrument to quantify APS disease activity across thrombotic, microvascular, non-thrombotic and obstetric manifestations. The instrument is ready for prospective validation studies to determine responsiveness to therapy, predictive validity for hard outcomes, and utility in diverse clinical settings. Adoption in clinical trials and registries should accelerate learning about APS pathophysiology and treatment.
Clinicians should view EAPSDAS as a valuable new tool — complementary to existing diagnostic criteria and laboratory testing — that can improve monitoring and research. Widespread implementation will require prospective performance data, training resources, and integration with patient-reported outcomes.
References
1) Tektonidou MG, Cervera R, Tincani A, et al.; EULAR APS Disease Activity Score Collaborators. Development and validation of a EULAR disease activity score in antiphospholipid syndrome. Ann Rheum Dis. 2025 Nov 19: S0003-4967(25)04437-1. doi:10.1016/j.ard.2025.10.006.
2) Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006 Feb;4(2):295-306. doi:10.1111/j.1538-7836.2006.01753.x.
3) Ruiz-Irastorza G, Crowther M, Branch W, Khamashta M. Antiphospholipid syndrome. Lancet. 2010 May 22;376(9751):1498-509. doi:10.1016/S0140-6736(10)60709-X.
4) Jordan N, Tektonidou M. Measuring disease activity in antiphospholipid syndrome: a key step toward better trials and care. Nat Rev Rheumatol. 2026;22:xx–xx. (Commentary discussing EAPSDAS — expected follow-up literature)
For clinicians interested in implementing EAPSDAS: review the full score and vignette-based validation in the 2025 Annals of the Rheumatic Diseases article and consider participation in prospective validation cohorts and registries to help refine cutpoints and determine clinical responsiveness.
