Lupus is a complex and multifaceted disease that can target any part of the body, including skin, joints and organs, with varying levels of severity. Despite its prevalence, lupus remains one of the most enigmatic and challenging diseases to manage due to its unpredictable flare-ups and the wide range of symptoms it can manifest.
In the US, lupus not only carries a significant health burden but also a substantial economic one, with increased healthcare costs and a higher rate of disability among patients. Women are disproportionately affected, particularly African American women who are three times more likely to be diagnosed with lupus than Caucasian women. This disparity extends to Hispanic, Asian and Native American women, who also exhibit higher risks compared to their Caucasian counterparts.
These statistics underscore the urgent need for innovative treatments and inclusive clinical trials that can address the diverse needs of the lupus population. The complexity of lupus, combined with its significant impact on individuals and communities, makes it a critical area of focus for rheumatology research.
In our exclusive interview with Dr. Anca Askanase, a leading rheumatologist and lupus expert at Columbia University and member of the Lupus Foundation of America’s Medical-Scientific Advisory Council, we delve into the latest developments in lupus clinical trials.
Dr. Askanase shares her insights on the crucial role of patient voices in shaping research, offering hope for new, more effective lupus treatments.
XTALKS CLINICAL EDGE: Issue 2 — Lupus Foundation of America Interview
Xtalks Clinical Edge is a magazine for clinical research professionals and all who want to be informed about the latest trends and happenings in clinical trials. This magazine immerses you in a world where industry leaders, patient advocates and top researchers converge to provide the most insightful perspectives on clinical trials.
Transformative Clinical Trials in Lupus
Dr. Anca Askanase and her team at Columbia University are at the forefront of pioneering research. Their current focus is on systemic lupus erythematosus (SLE), a form of lupus that poses significant challenges due to its ability to affect virtually any organ system, leading to a wide array of clinical manifestations.
“I am working on systemic lupus clinical trials. That’s my main area of expertise. There’s a lot of interest in new therapeutic development for systemic lupus because it’s a disease with a large unmet need in terms of improving health and outcomes for people with lupus.”
Dr. Anca Askanase
One of the most promising areas of research involves CAR T-cell therapy, traditionally used in cancer treatment. This innovative approach is being adapted for lupus, with the hope of developing a cure that goes beyond symptom management to address the root causes of the autoimmune responses in lupus patients.
In lupus, B cells — part of the immune system — mistakenly attack the body’s own tissues, producing antibodies that lead to inflammation and damage. By using CAR-T cells targeted at CD19, a protein on the surface of these B cells, researchers hope to eliminate the cells responsible for the harmful antibodies.
“There’s a lot of excitement about using CD19-targeted CAR T cells that attack the B cells that produce antibodies for people with lupus,” Dr. Askanase says. Those studies are more like Phase I, but because they have the potential or hope of being curative and also allowing for a drug-free cure, they’ve gathered a lot of interest from both lupus physicians and patients.”
Dr. Askanase explains that the mechanism of action of CAR T-cell therapies studied in lupus clinical trials are also applicable to other autoimmune and rheumatic diseases, such as rheumatoid arthritis and scleroderma. This research could pave the way for novel therapies that benefit a wider range of patients suffering from similar autoimmune conditions.
Amplifying Patient Voices in Clinical Trials for Lupus
Patient involvement in clinical trials is transforming from a novel idea to a standard practice, thanks in large part to advocacy. Recognizing that patients are not just subjects but partners in research, Dr. Askanase emphasizes the vital role they play in every phase of clinical trial design and implementation.
Dr. Askanase explains, “More and more patients are included at all stages of thinking about a clinical trial, designing the clinical trial, figuring out the patient-reported outcomes and understanding how to use the medication.” This holistic engagement aims to create trials that are not only scientifically rigorous but also deeply attuned to the practical and personal aspects of patient experiences.
Patients sit on steering committees, where their insights into living with lupus help shape the objectives and methods of upcoming studies. This engagement ensures that trials address real-world issues and measure outcomes that matter most to those affected.
A standout example of patient involvement was when the Lupus Foundation of America collaborated with the Lupus and Allied Diseases Association and the Lupus Research Alliance to organize a patient-focused drug development (PFDD) meeting in 2017. During this gathering, individuals from the lupus community expressed to the US Food and Drug Administration (FDA) their experiences and the impact of living with the disease. This direct dialogue with regulators not only impacted the course of lupus research but also highlighted the critical importance of patient experiences in shaping policy and therapeutic approaches.
Dr. Askanase notes significant progress in the use of patient-reported outcomes (PROs) in trials. “I think that we used to have one patient-reported outcome for all clinical trials. Now, there are five to seven patient-reported outcomes that we’re looking at in every therapeutic trial development,” she mentions. This increase in PROs signifies a deeper understanding of the multifaceted nature of lupus and a greater commitment to assessing treatment impacts from the patient’s perspective.
The inclusion of multiple PROs, however, brings its challenges. Dr. Askanase acknowledges that while this can lead to a more comprehensive understanding, it may also risk overburdening participants. The goal moving forward is to refine these instruments to capture the most relevant data without overwhelming the patients involved.
Looking ahead, Dr. Askanase is optimistic about the evolving role of patient voices in clinical research. With ongoing efforts to enhance patient engagement and feedback mechanisms, the future of lupus clinical trials appears poised for even greater inclusivity and responsiveness to patient needs. “It’s been rewarding to see that patients are partners at the decision-making table,” she reflects.
Addressing Enrollment Barriers
Enrollment in clinical trials is a critical step in the development of new treatments, yet it is fraught with challenges, particularly for conditions as complex as lupus. Dr. Askanase acknowledges a trio of barriers — patient, provider and system — that often deter participation in lupus research. Understanding and addressing these barriers is essential for advancing treatment options and ensuring that clinical trials reflect the diversity of the lupus community.
Patient-Specific Barriers
One of the primary challenges in lupus clinical trials is the inclusion criteria, which often select patients with moderate to severe disease who are not critically ill. This selective process can unintentionally exclude a significant portion of the lupus population. “Clinical trials don’t include all lupus patients,” Dr. Askanase explains. “They’re looking for people that have moderate to severe disease, that are sick, but not that sick to allow to measure improvement.” Additionally, certain trials may exclude patients who have specific autoantibodies or other disease characteristics, further narrowing the eligible pool.
Provider Challenges
Providers also play a crucial role in patient enrollment. Often, there is a cultural and informational gap where doctors may not consider clinical trials as a viable option for their patients, or they might lack the resources to support patient participation. “Sometimes doctors don’t think about clinical trials,” Dr. Askanase notes, stressing the need for cultural changes within the medical community to make clinical trials a more integral part of lupus treatment planning.
Systemic Challenges
From a systemic perspective, the lack of awareness and understanding among both patients and healthcare providers can lead to underrepresentation in trials. This is particularly heightened among minority populations, who face additional socioeconomic and systemic barriers that reduce their access to and participation in clinical research.
Efforts to Increase Minority Participation
Recognizing the underrepresentation of minority groups in lupus clinical trials, Dr. Askanase highlights significant efforts aimed at increasing diversity in research studies. The Lupus Foundation of America worked with Congress to fund initiatives at the Department of Health and Human Services (HHS) that are supporting collaborations with organizations like the Lupus Foundation of America and the American College of Rheumatology and designed to outreach and educate minority communities about the benefits of participating in clinical trials.
“We are already seeing some of the people that have been through the program and that we try to reach out to impart knowledge about lupus clinical trials, about what it means to be part of the research effort,” Dr. Askanase remarks. These efforts not only aim to bridge the knowledge gap but also to foster a more inclusive research environment that can lead to better, more universally applicable treatment outcomes.
In addition, initiatives like the PALS (Patient Advocates for Lupus Studies) program by Lupus Therapeutics, an affiliate of the Lupus Research Alliance, aim to educate and engage a more diverse patient population, addressing disparities in clinical trial participation.
The Lupus Research Action Network, launched by the Lupus Foundation of America and supported by the HHS Office of Minority Health, is an innovative approach to help increase participation in lupus clinical trials, particularly among women and diverse populations. The program educates people with lupus about clinical trials and provides tools and resources they can use to engage their peers about the importance of participating in lupus research, whether that’s focus groups, advisory committees or clinical trials. The program also helps to break down barriers to participation, including mistrust of the health system, and provides opportunities for people with lupus to participate in efforts such as Research Accelerated by You (RAY), a patient registry platform that not only shares research opportunities with patients, but also collects information about patient experiences and preferences that can inform clinical trial design and regulatory decision making.
As these initiatives take root, there is optimism about their potential to break down barriers and enhance patient engagement in lupus research. This not only improves the quality of the research but also ensures that the advancements in lupus treatment can benefit the broadest possible spectrum of patients.
RELATED: Enhancing Lupus Clinical Trials with Real-World Data Sources
The Future of Decentralized Clinical Trials for Lupus
The evolution of decentralized clinical trials (DCTs) represents a paradigm shift in how clinical research is conducted. The integration of DCTs is seen not just as a response to temporary challenges, such as those posed by the COVID-19 pandemic, but as a sustainable and transformative approach to clinical research.
The pandemic accelerated the adoption of telemedicine, revealing its potential for broader application in clinical trials. “Early on in the pandemic, it became clear that telemedicine and tele-rheumatology are part of care delivery and that we’re going to be using them for both clinical care but also for clinical research,” Dr. Askanase points out. With funding from the Department of Defense, her team has been evaluating how outcome measures in lupus, obtained via video visits, correlate with those obtained in traditional face-to-face evaluations. This research is crucial as it helps evaluate the validity and reliability of remote assessments, which are integral to the success of DCTs.
Decentralized trials offer numerous advantages, particularly for diseases like lupus where patients may experience mobility issues or live far from clinical centers. DCTs can reduce the burden of travel and increase the feasibility of participation, making clinical trials accessible to a wider audience. “Decentralization will play a huge role in allowing more people to be part of drug development and clinical research,” Dr. Askanase emphasizes.
Moreover, DCTs can lead to higher retention rates and more diverse participant pools. By removing geographical and logistical barriers, researchers can gather data that is more representative of the general population, enhancing the generalizability of the study findings.
While the benefits are significant, decentralized trials also pose unique challenges. Ensuring data integrity, managing technology distribution and support and maintaining patient engagement remotely are critical issues that researchers must address. Additionally, while remote assessments are promising, certain aspects of clinical evaluations, such as detailed physical examinations or laboratory tests, may still require in-person visits or innovative solutions to be fully decentralized.
As the tools and technologies for DCTs continue to evolve, so too will the methods for integrating them into lupus research and beyond. Dr. Askanase remains optimistic about the future, seeing decentralized trials as not just an alternative but as an enhancement to traditional clinical research models. “I think that we’ve kind of learned that tele-rheumatology is here to stay and I think that we’re developing the tools to make sure that our evaluations are accurate,” she concludes.
Dr. Askanase’s insights reveal a dynamic shift towards more innovative, inclusive, and patient-focused approaches in rheumatology research. The ongoing trials and initiatives promise to enhance treatment options for lupus and other rheumatic diseases and reshape the landscape of clinical research through enhanced patient engagement and cutting-edge technologies. As these efforts unfold, they hold the potential to significantly improve the lives of those battling these complex conditions.
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