Addressing Barriers in SLE Diagnosis, Care, and Access to Treatment

needle on paper that says lupus
needle on paper that says lupus
Dr Costenbader talks about the contributions made by the Lupus Foundation of America, the barriers affecting outcomes in lupus, and the current state of diagnostic tools and treatments for the disease.

Systemic lupus erythematosus (SLE) predominantly occurs among younger women of color and individuals from low socioeconomic backgrounds. From prior research, it has been seen that some of the obstacles that have resulted in poor outcomes for patients with lupus include a lack of a large number of targeted therapies, unsuccessful clinical trials, and reduced access to care.1,2

Rheumatology Advisor spoke with Karen H. Costenbader, MD, MPH, a notable rheumatologist, lupus advocate, and Chair of the Lupus Foundation of America (LFA)’s Medical-Scientific Advisory Committee.

Rheumatology Advisor: Let’s talk about the LFA in more detail. What is the significance of the organization?

Karen Costenbader, MD: Everything the LFA does is driven by its mission to improve the quality of life for people with lupus through research, education, and advocacy programs. Helping people who are experiencing the effect of this disease is at the center of everything LFA does.

The LFA works hard to address the key challenges in lupus research, diagnosis, treatment, and disease management, also focusing on the areas of greatest need and with the potential of having the greatest effect in the shortest amount of time. This includes working to identify the causes of lupus, controlling its symptoms, and creating a clear path toward developing better treatments and a cure. Layered within the organization’s efforts to advance and fund research is its work with the Centers for Disease Control and Prevention (CDC) and the Office of Minority Health to conduct studies regarding clinical trial enrollment in lupus. In addition, the LFA’s advocacy program plays a big role in driving its mission forward and giving a voice to people experiencing the effect of lupus. The LFA is truly leading the field of lupus nationwide.

Rheumatology Advisor: Have there been any changes regarding lupus since the initiation of these efforts?

Dr Costenbader: The LFA has been involved with campaigns for lupus awareness for many years now, and I think there has been a growing awareness of the disease in [the United States]. In fact, the LFA conducted a seminal study about the delay in diagnosing lupus and the heterogeneous nature of the disease. They surveyed a large population and found that the average time between a patient’s first lupus symptoms and its diagnosis was 6 years, which is far too long. The team conducted a large awareness campaign about how early diagnosis can reduce organ damage and that people with lupus who are closely monitored do much better.

Rheumatology Advisor: With respect to the diagnosis of lupus, what is the sensitivity of current-day diagnostic tools? Can any improvements be made to better detect and diagnose the disease?

Dr Costenbader: Lupus can be difficult to diagnose, and both acumen and experience are needed to diagnose the disease. Lupus is an autoimmune, autoantibody-driven disease. Often patients tell me they had a positive “lupus test,” and I presume they mean an antinuclear antibody test. But this antibody is not very specific for lupus, so it is not a good diagnostic test.

There are also other autoantibodies that we see in lupus. There could be pathologic findings in the kidneys, on the skin, or in other organs, but the entire picture has to be put together to rule out other possible conditions. It would be great if physicians were considering lupus at first presentation, but they also have to make sure that they are thinking about many other possible diagnoses. It is indeed challenging.

There is a lot of effort and ongoing research regarding biomarkers for lupus. Our Holy Grail will be to find 1 or more biomarker(s) that says, “It’s lupus!” But there are so many related types of lupus that [finding biomarkers] may not be possible; however, having different biomarkers for the various types of lupus will be helpful because it would not only reveal that a patient could be developing lupus, but it could also indicate whether the development is of the kidney vs of the blood type of lupus. Gene expression profiling, genetics, and cytokine-based tests are being developed to aid in the detection of lupus and its forms.

Rheumatology Advisor: Regarding your recent paper on achieving the “first-ever consensus on barriers to research, drug development, care and access” in lupus: what was your experience on this project, and what can the findings from this study mean to other rheumatologists?

Dr Costenbader: The Addressing Lupus Pillars for Health Advancement (ALPHA) project is the first time that a global advisory committee has come together to discuss and think about the barriers for lupus in general. In the past, there has only been consensus around other topics, including lupus classification criteria and treatment guidelines.

This time we took a step back and thought about where we are, where we want to be, and what the barriers are for patients with lupus. There is a lot of excitement related to autoimmune diseases, including rheumatoid arthritis and psoriasis, for which a recent flood of new medications has come onto the market. This is where we want to be with lupus. There has only been one US Food and Drug Administration (FDA)-approved medication in the United States and in Europe, in the last 60 years. There may be many reasons for this and why drug development has been slow; that’s why we put our heads together to resolve these issues.

The research studies that led to belimumab’s FDA approval were huge trials of more than 500 patients with lupus in 2 global trials. Such enormous trials can be difficult, and conducting smaller, smarter trials and enrolling the right populations of people most affected by the disease may make lupus clinical trials more effective. In addition, not having the right outcome measures may be why some clinical trials for lupus have been unsuccessful. We tend to use composite lupus end points that measure organ damage or activity in many different organ systems simultaneously, but this could be the wrong way to go about it.

Young people, mostly women, and often individuals of lower socioeconomic status and nonwhites, are affected by lupus. The prevalence of lupus is higher in people of African, Hispanic, Native American, and Asian descent. Therefore, enrolling the right representative populations in clinical trials has been challenging. 

Several barriers were identified as part of the ALPHA project, and coming to a consensus on which were the most important was challenging. However, it was very encouraging and energizing for the global community to come together on these issues. Lupus heterogeneity was identified as the primary barrier to the development of clinically meaningful treatments, the advancement of clinical care, and improvements to access and value. The study validated known challenges in lupus, identifying the 5 top barriers to improving outcomes in lupus: clinical trials, biomarkers, diagnosis of lupus, differentiation of its subtypes, and outcome measures for the disease.

Another question that the global council tried to address was how we can get better access to care for patients with lupus. In the United States, people have Medicaid, no health insurance, no access in rural populations, or a combination of all factors. These populations face huge barriers in getting timely and high-quality medical care for lupus.

Rheumatology Advisor: Is there a correlation between mental health and lupus, as there is with many other autoimmune diseases? How can physicians better screen such patients?

Dr Costenbader: There is definitely a complicated connection between lupus and mental health, including anxiety and depression, and other mental and neurologic conditions.

In the past 1½ years, we have been looking at lupus and prediagnosis depression. The prevalence of depression was found to be much higher in women who later developed lupus, although there may be many reasons for this. There is a prediagnostic period in which people are not feeling well, but have not yet been diagnosed with lupus, and during this time they may be developing or be diagnosed with depression. Also, it would be important to know whether depression is somehow triggering the development of lupus.

In another study, we followed a cohort of women who had answered questions about posttraumatic stress disorder (PTSD), and we observed that women who had PTSD were at a much higher risk for developing lupus.

In addition, we have seen strong links with childhood violence, which is related to PTSD and depression, in both the Nurses’ Health Study and the Black Women’s Lupus Study. Experiencing childhood violence was seen to be related to the development of lupus. The mechanisms are unknown but could be because of the influence of the hypothalamic pituitary adrenal axis or stress hormones.

On the other hand, patients diagnosed with lupus often have fever, fatigue, joint pain, and/or muscle pain, and they may not be able to work. They may develop adverse effects from their medications as well, so it is not surprising that [lupus] is associated with mental health effects. We need to work on this aspect and treat patients with lupus with care and awareness of the effect of the disease on mental health.

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Rheumatology Advisor: How can physicians play a part in bridging these gaps and addressing the barriers? Are there any interventions already in progress?

Dr Costenbader: Physicians need to come together and talk about these barriers. Unfortunately, we have finite resources, but if we put our heads together, we will hopefully be able to enumerate how rheumatologists can better manage lupus, how they can take care of their patients, how stakeholders can get involved, and which barriers to address first. Some of these challenges are structural, especially in the United States, and we need to go after those. Healthcare access in [the United States] and in many other countries is under threat. How do we deal with this and advocate for more funding for lupus treatment and lupus research? The National Institutes of Health (NIH), for example, typically develops a strategic plan for issues that need to be addressed, and lupus should be on that list. If we reach a consensus and apply our efforts to the barriers surrounding lupus, it will help us tackle issues including lupus biomarkers, access, and advocacy. I think that is where we are going next.

Rheumatology Advisor: Lastly, how would you summarize where lupus stands today, and how can other rheumatologists contribute to the cause?

Dr Costenbader: The global consensus on the ALPHA project, the results of which we just published, provides an outline of where the lupus field is right now and shows us the areas we need to address in order to improve the lives of people with lupus. There is a lot of hope for better awareness, treatment, and access to care, and there is recognition that today’s patients with lupus are receiving better care and have improved outcomes. We want newer, smarter medications so that patients don’t have to be exposed to steroids for long periods of time.

We are also realizing that we have been studying the basic mechanisms, genes, and environmental factors for a while and still don’t fully understand lupus. We realize that the disease is complicated and has many subforms; in lupus, no 2 patients are the same. Lupus also often affects medically disadvantaged patients who do not have access to care, making it incredibly challenging for them and us. We need to improve, and reaching this first-ever global consensus is an important step forward. I encourage others to visit the LFA’s website to learn more about the ALPHA project and its next steps.

Disclosure: Dr Costenbader declared affiliations with the pharmaceutical industry.


1. Manzi S, Raymond S, Tse K, et al. Global consensus building and prioritisation of fundamental lupus challenges: the ALPHA project. Lupus Sci Med. 2019;6:e000342.

2. Lupus Foundation of America. International lupus community reaches first-ever agreement on barriers to research, drug development, care and access. Published July 19, 2019. Accessed August 6, 2019.