Antiphospholipid Syndrome Clinical Research at HSS: 2023 Update – Top 10 Series

1. What is antiphospholipid syndrome?
2. What is research, and what are different types of research studies?
3. What is a clinical trial, and how does it differ from the standard care/treatment?
4. What are the ongoing major clinical APS research studies at HSS?
5. What is APS ACTION – Network?
6. What is APS ACTION – Registry?
7. What is 2023 ACR/EULAR APS Classification Criteria?
8. What is DARE-APS?
9. What is IMPACT Study?
10. What should I do to learn more about the ongoing APS research at HSS?

1. What is antiphospholipid syndrome?

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder associated with abnormal blood clotting. Patients with APS make antibodies called antiphospholipid antibodies (aPL), which increase the risk of blood clots and pregnancy-related problems such as miscarriages. For the diagnosis of APS, there are three tests used to detect aPL:

• Lupus anticoagulant (LA) test
• Anticardiolipin antibody (aCL) test
• Anti-Beta-2-glycoprotein-I (aβ2GPI) antibody test

For more information on APS, please visit our main Antiphospholipid Syndrome page, where you may also read additional Top 10 series articles on APS.

2. What is research, and what are different types of research studies?

“Research” is defined as a systematic inquiry to discover and/or advance knowledge through hypothesis, data collection, and analysis, with the help of appropriate research methods. The goal of any research study is to better understand what is already known, or to investigate what is still unknown or what ideas can be further developed.

Research can be carried out in many fields. Medical research aims to understand the causes and natural progress of diseases as well as to develop new drugs or medical instruments/techniques. Medical research extends from “basic medical research” to “clinical medical research”:

• Basic Medical Research, also referred to as "experimental research," comprises studies on cells, animals, biochemical, genetic, and physiological processes, as well as investigations into the properties of medications and materials. The goal of basic medical research is to understand the cellular, molecular, and physiological mechanisms underlying human health and diseases, and to provide new insights that can be advanced further.
• When basic research directly examines human subjects and has the potential to directly impact disease diagnosis and treatment, it is referred to as “translational research.”
• Clinical Medical Research, is the study of the effect and safety of the most innovative developments in humans. Clinical research is important to help us diagnose, treat, and prevent diseases. There are two main types of clinical research: a) observational research focuses on identifying and analyzing patterns in medical data without any treatment given to individuals; and b) interventional research, which is also referred as ‘Clinical Trials’ that test the effect and the safety of the treatment in human participants.

3. What is a clinical trial, and how does it differ from the standard care/treatment?

Clinical trials study the effect and safety of a treatment or intervention, which is different from standard care treatment. While the standard of care treatment addresses the needs of an individual patient, the clinical trial involves volunteers to answer specific questions by strictly following the “study protocol.” The change of the treatment, follow-up period, and assessment methods can be personalized in standard care based on patient’s needs; however, in clinical trials the systematic and periodic assessment of the patients depend on the research protocol and cannot be individualized. Also, the clinical trials are generally funded either by pharmaceutical companies or government agencies, whereas standard care is covered by the patient or the health insurances.

Clinical trials are conducted in four phases:

1. Phase I trials’ main goal is to determine the safety, side effects, and the dosage range of the medication in a smaller group of healthy volunteers. Throughout Phase I, researchers understand how this medication is absorbed, distributed, metabolized, and excreted, which are the steps of Pharmacokinetics.
2. Phase II trials’ goal is to determine if the medication is working efficiently on a certain illness/disease, and most effective dose. In addition to that, Phase II trials help researchers to understand which dosage works better for the patient by sometimes performing double-blind study, which means neither physician/investigator nor the patient is not informed about the dosage of the medication.
3. Phase III is another investigational phase, where hundreds or thousands of patients are involved. The extensive testing helps researchers to have more detailed information about the medications’ effectiveness and safety, generally comparing different medications, or comparing a medication to a placebo (substance which has no therapeutic effect but appears to patients to be a medication).
4. Phase IV trials are conducted after a new treatment is approved. The goal is to understand the long-term effects of medications, or any rare side effects that can develop over time.

4. What are the ongoing major clinical APS research studies at HSS?

Hospital for Special Surgery has been one of the major centers in the world for APS patient care and research. In addition to multiple completed clinical studies and trials over the years, HSS is the founding and lead coordinating center for Antiphospholipid Syndrome Alliance for Clinical Trials & International Networking (APS ACTION). Currently active major APS studies include:

• APS ACTION – the network and the non-interventional clinical registry
• 2023 ACR/EULAR APS Classification Criteria Development
• DARE-APS – interventional clinical trial
• IMPACT – interventional clinical trial

5. What is APS ACTION – Network?

Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) is the first international research network, which was established specifically to plan and carry out large-scale, multicenter clinical trials and studies in patients with positive antiphospholipid antibodies (aPL). The network consists of multidisciplinary groups of physicians and investigators whose primary aim is to prevent, treat and cure aPL-associated clinical manifestations. Since the creation in 2010, there are 80 members participating in the network worldwide; Dr Doruk Erkan is the founding member and current co-chair of APS ACTION. Please visit the APS ACTION website to learn more about the network.

6. What is APS ACTION – Registry?

A research registry is a collection of data from patients who have a particular disease and/or who receive a specific treatment. APS ACTION clinical database and repository (“Registry”), first started in 2012, is an international, multicenter registry aiming to look at the long-term, natural course of patients with persistent antiphospholipid antibody positivity. With the help of this Registry, large-scale, multicenter and prospective studies are conducted that help us better understand the clinical characteristics and the natural course of APS. Participating in the APS ACTION Registry is voluntary, with no cost to the participant. Patients are followed annually with clinical data and blood collection for at least 10 years. The patient’s medical history, physical exam findings, and laboratory tests are collected and stored through a secure web-based application. To date, there are approximately 1,200 international patients included in the APS ACTION Registry.

7. What is 2023 ACR/EULAR APS Classification Criteria?

Classification criteria are used to establish a uniform pool for patients who participate in the same clinical research. The first APS classification criteria were developed in 1999 and revised in 2006. Please visit this page for more information regarding classification versus diagnostic criteria.

New Antiphospholipid Syndrome Classification Criteria, jointly supported by American College of Rheumatology (ACR) and European Alliance of Associations of Rheumatology (EULAR), have been under development by an international team co-led by Dr Doruk Erkan (co-principal investigator). Now referred to as 2023 ACR/EULAR APS classification criteria, which are clustered, additive, weighted, and risk-stratified, they were published in August 2023, and reflect the current thinking about APS, providing high specificity, and a stronger foundation for APS research.

8. What is DARE-APS?

DARE-APS, a clinical trial jointly designed by APS ACTION and Immune Tolerance Network (ITN). Dr Doruk Erkan, as the protocol co-chair, has been working with the ITN team for the development of this clinical trial; the goal of the study is to investigate if a medication (daratumumab), approved by FDA for multiple myeloma, is safe in APS and if it can eliminate antiphospholipid antibodies. In this multicenter trial, HSS is currently one of the active centers recruiting patients.

Patients who participate in DARE-APS receive eight weekly intravenous doses during the treatment period. When treatment period is completed, patients are expected to be followed up for six clinical visits over a 10-month period.

If you are between the ages of 18 and 65, and have APS with no other systemic autoimmune diseases, you may be eligible for DARE-APS. Learn more at, including study locations at dare-aps.org.

9. What is IMPACT Study?

Patients with APS are at increased risk for pregnancy complications, and inflammation contributes to injury of the placenta. Studies in APS animal models demonstrated that blockade to Tumor Necrosis Factor (TNF), a cytokine of inflammation, prevents pregnancy complications.

IMPACT stands for IMProve Pregnancy in APS with Certolizumab Therapy (a TNF blocking medication that does not cross the placenta). The goal of this study is to understand if the treatment with Certolizumab, in addition to heparin and aspirin, would improve the pregnancy outcomes, i.e., that it would decrease the frequency of severe pregnancy complications, such as preeclampsia, in pregnant women with APS. Learn more about the IMPACT study.

10. What should I do to learn more about the ongoing APS research at HSS?

If you would like to learn more information about APS research and the current clinical trials going on at HSS, please contact JoAnn Vega:

Hospital for Special Surgery Research Coordinator
APS ACTION Lead Coordinator
Telephone: 212.774.2795.
Fax: 212.774.7298
Email: vegaj@hss.edu

Posted: 9/15/2023

Authors

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