Investigators supported by the ACR and EULAR presented a draft of new classification criteria for antiphospholipid syndrome (APS) at ACR Convergence 2022. The previous criteria were developed in 1999 and revised in 2006.
The classification criteria are under review by ACR/EULAR for endorsement and pending final approval. Detailed results and consensus discussions will be presented in future manuscripts.
“Today we present our international, multidisciplinary effort to develop new, rigorous, consensus- and evidence-based, highly specific classification criteria to identify patients with high likelihood of APS for clinical research,” said Medha Barbhaiya, MD, MPH, Assistant Professor of Medicine and Population Health Sciences, Weill Cornell Medicine.
Dr. Barbhaiya, along with Stéphane Zuily, MD, PhD, and Doruk Erkan, MD, MPH, presented the methodology, novel aspects, and application of the draft criteria during Draft ACR/EULAR Antiphospholipid Syndrome Classification Criteria on Sunday, November 13. The session is available for on-demand viewing for registered ACR Convergence participants through October 31, 2023, on the virtual meeting website.
“The goal for classification is to identify a well-defined study sample representative of the majority,” Dr. Barbhaiya said. “We tried to achieve high specificity, sometimes at the cost of sensitivity.”
The methodology involved four phases—item generation, item reduction, weighting of items and threshold identification, and validation—each balancing expert-based and data-driven processes.
Dr. Barbhaiya listed several strengths of the methodology, such as rigorous clinical and laboratory criteria definitions and international cases, and the inclusion of international cases that captured the APS spectrum, reducing the risk of selection bias and increasing generalizability.
Dr. Zuily, Professor of Medicine, Lorraine University, France, presented novel aspects of the new APS criteria such as clinical domain features, including risk stratification of macrovascular events by traditional thrombosis risk factors, well-defined microvascular domain items, re-defined pregnancy morbidity definitions, and the addition of cardiac valve disease and thrombocytopenia.
“These novel clinical features will help us better stratify patients according to their risk factor profile, which will be very important,” Dr. Zuily said.
New APS criteria in the laboratory domain quantify single-, double-, and triple-antiphospholipid (aPL) positivity based on different domains and weights; separate anticardiolipin (aCL) and anti-beta-2 glycoprotein I (aB2GPI) IgG and IgM isotypes; and define two levels of aCL/aB2GPI positivity that will be interpreted as clinically relevant by most investigators, he noted.
Dr. Erkan, Professor of Medicine and Attending Physician, Hospital for Special Surgery, Weill Cornell Medicine, demonstrated the draft criteria in action, starting with the entry criteria of at least one documented clinical criterion plus a positive aPL test within three years of the clinical criterion.
But he offered an important reminder: “Do not count a criterion if there is an equally or more likely explanation than APS. Within each domain, only count the highest weighted criterion toward the total score.”
Dr. Erkan also highlighted the point system for domains presented by Dr. Zuily, noting that the final classification criteria manuscript includes specific definitions and instructions.
Among the strengths of the draft classification system are absolute point requirements and the capability to modify individual domains when new information becomes available, he noted. Limitations include the fact that the cohorts do not represent all subpopulations, and there is no definite gold standard for APS, a disease for which rheumatology professionals’ understanding is evolving rapidly.
If a case does not meet the APS classification criteria, the case may still be uncertain or equivocal rather than “not APS,” Dr. Erkan said. Uncertain or controversial cases should be studied separately to guide future updates of the new criteria.
“We believe our criteria reflect the current thinking about APS, providing high specificity and a stronger foundation for APS research,” he concluded.