Anca Askanase | Chair, Department of Medicine; Chief, Division of Rheumatology, Hospital for Special Surgery, New York City, New York, USA
Citation: AMJ Rheumatol. 2026; https://doi.org/10.33590/rheumatolamj/ABU5F432
After over 15 years on the faculty at New York University, you transitioned to Columbia University (New York City, New York, USA) to found and build their dedicated Lupus Center from the ground up. What did that project teach you about the clinical infrastructure needed to support complex patients with lupus, and how did your public health background guide its design?
Building the Lupus Center meant focusing on the three pillars essential to both patient care and research. Patients are the first and most important pillar, making sure that they are both aware of the possibilities and engaged; we need patients that want to come in, see us, and participate in their own care. Clinicians are the second: having a dedicated team of clinicians to care for patients that develop both the connection and the engagement is essential for excellent clinical care. The third pillar is considering interesting clinical research questions and providing patients with a simple, effortless path to transition from clinical care to clinical research. This needed time, effort, and commitment, and it took a village of committed researchers, family members who could put up with complicated schedules, and patients who were interested in what we were offering because it would make their lives or the lives of their loved ones better. These were the guiding principles we considered as we built the infrastructure to create the Lupus Center.
When it came to thinking about all the pieces of the project and how they work together, my public health background was incredibly useful. The connections that I’ve created with epidemiologists, biostatisticians, and bioinformaticians both in my training at the Mailman School of Public Health, New York City, New York, USA, and those I rekindled when I returned to Columbia University solidified all those collaborative networks I needed to support both the clinical and the research work. Columbia University supported this effort, with resources, space, and staff, and we are grateful for that.
You are running clinical trials for both autologous CAR-T cell and “off-the-shelf,” healthy-donor chimeric antigen receptor natural killer therapies. From a practical and economic standpoint, do you believe “off-the-shelf” products are the true future of cellular therapy for lupus?
Everybody’s really excited about the possibility of cures offered by cell therapy in lupus. Cure is a very powerful word; a word that we never dared to think about until very recently. It is the power of the cure that has galvanized the world of patients with lupus, lupus investigators, and clinicians to embark on this extraordinary journey. If we’re thinking about a cure for patients, in terms of health economics, autologous CAR-Ts are not prohibitively expensive. Although the initial cost is very high,, the hope is that this treatment will ultimately save a decade or two of extensive healthcare costs that are needed to manage lupus. At this time, all of this is hypothetical, but worth a try. As the numbers accumulate, we will become more confident in these economic decisions. It is easier and cheaper to deliver “off-the-shelf” treatments and a smaller ask of patients. Over the past 2 years, we’ve organized systematic reviews of the published literature on cell therapy products, and we are working on evaluating the comparisons between available data to understand differences between autologous and allogeneic therapies. We hope to be able to present our findings on chimeric antigen receptors at the American College of Rheumatology (ACR). Allogeneic therapy may be cheaper and it may be easier, but will it deliver efficacy at the same level as we’re expecting from autologous therapy? I . If efficacy is found to be equal, and the duration of remission or cure is about the same, then allogeneic therapy makes a lot more sense. There’s a lot more work to do, and a lot of sweat and tears that need to go into answering this question, but we’re getting there.
Our collaborations with hematologists and oncologists have taught us that dreaming of a cure is possible. I’m very grateful to our colleagues who paved the way for these therapies to be borrowed in our field. I feel privileged and grateful to be a part of this journey. The Erlangen group, Georg Schett, and his collaborator, Andreas Mackensen, both from Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, Germany, really deserve a powerful shout-out because they pioneered these treatments for autoimmune diseases and showed us the power of those therapies through the phenomenal efficacy they had on their . We all owe them a debt of gratitude for opening these possibilities.
You recently co-authored a major study on an experimental drug called dapirolizumab that acts like a shield to block the key CD40 ligand (CD40L) protein that signals the immune system to attack itself. This pathway was historically too dangerous to target, because it caused blood clots. How does this new drug’s design bypass those safety risks, and what do the results mean for patients?
The drug is an anti-CD40L developed by Biogen Inc. (Cambridge, Massachusetts, USA) and Union Chimique Belge (UCB; Brussels, Belgium). Compared with early anti-CD40L monoclonal antibodies, this drug is only a fragment of the whole antibody: the antigen-binding domain. It lacks the Fc portion, which is responsible for adverse reactions such as platelet activation and thrombotic events. It was designed to get around these potential risks, and target both the B and T cells. Cell therapy provides a profound depletion of B cells and the possibility of an immune reset by also targeting the T cells. Dapirolizumab pegol brings in the same balance between T and B cells to target disease activity in lupus. It both reduces B cell activity and dampens T cell activation, both of which are central to the pathogenesis of lupus. Because it acts in this path of the , the hope is that this drug, once it’s available, could allow for better control of disease activity in patients with systemic lupus erythematosus.
Because of its place in this crosstalk between T and B cells, the drug also lowers interferon α (IFN-α), which is a major player in systemic lupus erythematosus pathogenesis. There’s always a concern that when B cells are depleted, there may be a slight surge of B cell activating factor and interferons, and some worsening of cutaneous activity. Accordingly, this drug could get around that; it works on the cellular level, but also on the downstream cytokines. Systemic lupus erythematosus pathogenesis is complex: in some people, it’s the lymphocytes that drive the process, in others, it’s more myeloid cell driven, and, in some others, it’s more influenced by interferons or cytokines. This is why a drug that could address multiple levels is appealing as a mechanism of action.
Your work includes developing virtual lupus disease activity measures to train and standardize investigations around the world. What has this digital standardization effort taught you about how we can best train the next generation of doctors to utilize digital, standardized metrics in treating their patients?
The world of medicine is evolving very rapidly. COVID-19 was a dark time for humanity, but, for medicine, it provided the reassurance that we can face a major crisis and learn from it. One of the major teachings from the crisis involved the use of telemedicine and a better understanding of its place in the care of people with a variety of conditions and symptoms. As part of that, we have embarked on developing and validating outcome measures for lupus in a virtual environment using a video visit conferencing platform. First, we put together a standardized virtual physical exam, starting by directing patients through a self-examination, while showing us their findings. In a way, the patient is our assistant. We walk them through how to do the physical exam, and then we ask them to demonstrate it to us. Just like we teach medical students how to do a physical exam, we can teach the patients. However, it needs the same rigor that a physical exam would need, otherwise it is incomplete and doesn’t provide all the information. Therefore, a standardized virtual physical exam followed by the evaluation of disease activity instruments is the only way to do excellent evaluations of systemic lupus erythematosus in telemedicine.
We started this study early in 2021 and have just finished it, and we hope to have a manuscript ready for publication in the next couple of weeks. It is very exciting. We had 163 patients from all over the nation participating in the study that were evaluated using both the traditional face-to-face physical exam and virtual assessments. The findings on disease activity from the video encounters correlated very highly with those from the face-to-face exams. We hope that this will increase the confidence of both patients and providers in the quality of these assessments and allow for broader use of telemedicine in clinical care and clinical research. For people in remote areas, being able to access specialized centers and clinicians is a critical need. We are providing the tools physicians need to deliver this care.
Lupus disproportionately affects women of color, who also frequently face the steepest hurdles to receiving timely, quality care. Through a major project funded by the Office of Minority Health (OMH), you launched a dedicated clinical outreach and education program in New York City, New York, USA, specifically tailored for uninsured and minority patients. From your experience, what do you think are the most critical, unseen barriers these patients face when trying to navigate their care, and how can the medical community help overcome them?
It’s very clear that there are inequalities in healthcare, some of which are rooted in socioeconomic differences. We’re not going to be able to fix the world as physicians, but we can do what is within our power to address some of these problems. A patient is not going to be able to take good care of themselves if they don’t have food on the table. They’re not going to be able to take care of their families if their lights are turned off, because they haven’t been able to pay for electricity. So, part of our work is to connect people with the resources that are available to start to address some of these issues. We may not be able to offer an apartment, but we’re able to connect people with community health workers and social workers to try to identify available options. We’re not going to be able to provide food, but we can put them in touch with community resources where they can access sources of sustenance. It is our job to understand that patients are more than their lupus or rheumatic disease. We need to take care of the whole person. By implementing this, we’re giving these ideas a much bigger place in our daily interactions with people with chronic conditions. A big piece of this is awareness and education in both lupus and general health. Health literacy is how we empower people to be better advocates for their health, take better care of themselves, and make bigger changes in their lives and the lives of their communities and families.
You helped develop the Lupus Optical Tomography Imaging System, which is a wearable, near-infrared device that maps joint inflammation in real time. How could a patient-friendly tool like this transform the clinical experience, especially by giving patients a visible, objective way to validate their joint pain when standard blood tests show no active inflammation?
A big problem in taking care of lupus arthritis is that, sometimes, we’re unable to identify swelling in the affected joints. We embarked on looking at ultrasound or MRI, but those are complicated, operator-dependent, and time-consuming. Optical tomography offers the option of having a quick, operator-independent, low-cost device to allow for objective quantification of lupus arthritis. It validates symptoms that present without objective evidence of arthritis, as well as allowing for a clear measure of arthritis’ response to treatment.
You have dedicated over 20 years to caring for patients with complex lupus, and a core pillar of your clinical philosophy is “front-loading” treatment, which means using aggressive therapies early on so you can quickly taper patients off toxic drugs like steroids. How do you navigate the delicate personal challenge of explaining this intensive strategy to a newly diagnosed patient who might currently be feeling relatively well?
It’s hard, especially if patients are not feeling sick. It comes down to building bridges, creating relationships, allowing time for questions and creating space for dialogue, providing data and support around decisions, and creating an environment where there’s trust and connection, so that these decisions are shared and guided and don’t feel like a burden on only one side. I think that there’s a point of no return in lupus due to the accrual of damage. So, if we’re able to intervene early to stop the disease, we prevent damage and improve long-term outcomes; making these changes early on is the only way to modify the disease until we reach the cure. Nevertheless, even with a cure, once there’s damage, it cannot be reversed. That’s why it is important to stop progression before the point of chronicity. There are no formulas here, but people are designing ways to become more methodical about creating connections, such as creating decision aids and apps. It all comes down to spending the time to create connection and trust.
