Lupus Research, Medication, and Treatment: Past, Present, and Future

Summary of a Presentation to the SLE Workshop at HSS

Stephen Paget, MD, FACP, FACR

Physician-in-Chief, Chairman of the Division of Rheumatology, Hospital for Special Surgery
Joseph P. Routh Professor of Medicine, Weill Cornell Medical College


  1. Introduction
  2. Historical Milestones in Lupus Treatment
  3. The Importance of Therapeutic Balance
  4. Multidisciplinary Care at HSS
  5. Current Lupus Research at HSS
  6. The Future of Lupus Research
  7. Conclusion

Introduction

We are at the threshold of a number of new treatment modalities being researched and offered to people with lupus. Through many innovative initiatives, such as HSS’s Mary Kirkland Center for Lupus Research and the multi-site Lupus Clinical Trials Consortium, Inc., the way is being paved for more effective and safer medicines to treat this challenging illness.

Since lupus is chronic, with systemic inflammatory reactions flaring up unpredictably over the years, a course of treatment must balance short-term, as well as long-term, goals for optimal disease control and the best overall outcome. Historically, treatments for lupus have not always been successful in maintaining this balance.

“It’s the inflammation we’re trying to suppress with the medications we use,” Dr. Paget explains. “It’s an autoimmune process, and these medications are aimed at ‘bringing down the noise’ of the immune system without causing significant, secondary effects.”

In this presentation, Dr. Paget describes the importance of multidisciplinary treatments and the complex interactions lupus medications have with the disease, as well as the promise of medications and treatments on the horizon.

Historical Milestones in Lupus Treatment

Several milestones have occurred over the years in our modern understanding of lupus.

In the early 1900s, the first clinical description of lupus was presented, but many years would pass before any major discoveries would take place. Simply put, lupus wasn’t yet on the “radar screen,” and so it garnered little attention from medical professionals.

There was, however, a mid-20th century discovery that determined that the presence of the LE (lupus erythematosus) cell in the body was a positive indication of lupus at that time. It became a diagnostic test (eventually replaced with the more sensitive ANA [anti-nuclear antibody] test) that added important knowledge of the inner immune workings of the disease.

In 1951, a Nobel Prize was awarded for the use of anti-inflammatory steroids in lupus, rheumatoid arthritis, and rheumatic fever. Physicians and patients were extremely impressed with the amazing effect of steroids on these diseases. Within a short time, however, steroids would prove to be the classic “double-edged sword.”

On the one hand, they made patients feel better. On the other, patients paid a price for their comfort, often experiencing side effects that ranged from mild to severe. Nonetheless, the availability of anti-inflammatory steroids was a tremendous advance. Today, scientists, researchers, and clinicians are working toward modern, more focused treatments with fewer side effects.

In the 1960s, the medical community began to understand the concept of autoimmunity, or the ways in which the body’s immune system attacks itself, and great strides in our knowledge of how autoimmunity works continue to be made, almost on a daily basis. In the 1970s, the natural history of lupus, both in individuals and populations of patients, became more clearly understood.

It was also around this time that researchers began to appreciate the genetic aspects of the disease. Genes are clearly necessary but not sufficient to cause the illness - that significant point is one that turned out to be increasingly important over time. It means that if an individual happens to have the genes for lupus, a trigger in the environment is apparently necessary for the disease to become active.

In the 1980s, the effects of drugs, both positive and negative, became evident. Medical professionals also came to appreciate the sensitive issue of pregnancy with lupus; HSS now maintains a very large registry regarding pregnancy loss and other manifestations of lupus. Over the last twenty years, effective treatments have become customized for pregnant women with lupus. This has lead to improved outcomes. Additionally, the use of aspirin and anticoagulants, has transformed lupus treatment during pregnancy in the last two to three decades.

Certainly, from the 1990s through the present day, the emphasis on more focused medications and treatments has allowed patients to suffer a significantly reduced set of side effects.

“And there’s really hope,” adds Dr. Paget. “Help is not on the way; it’s already here.”

Dr. Paget stresses the importance for those with lupus to realize the following point: In the last century, scourges that had made our lives horrible, including tuberculosis, syphilis, polio, and rheumatic fever – are either easily controlled or almost entirely gone. These remarkable, and swift, advances have resulted from the discovery of the fact that infectious organisms caused in these diseases. Bacteria, viruses, and other organisms cause those infections, and researchers have discovered and developed medications such as antibiotics that control them.

“Please rest assured,” Dr. Paget states, “that just as those are gone, this will be. It’s just a matter of doing the research, finding the reasons why autoimmunity occurs. We’re working on that, as are others.”

The Importance of Therapeutic Balance

When considering how to care for patients, Dr. Paget stresses the importance of considering “therapeutic balance.” As a patient, it is necessary to become an informed consumer in order to ensure that all medication options are presented. Similarly, attaining substantial knowledge of the disease will enable a patient to know the positive and negative effects of the medications and what to do about potential side effects. Those with lupus should not accept any treatment until sufficient information is available to allow them to make an appropriate decision.

“If I give you a certain medicine, it may make you feel better, but what will it do in the short and long run?” he explains. “You have to feel very comfortable in a unique partnership with your doctor in which you discuss all the options.”

Dr. Paget also notes that the need to focus on women’s issues cannot be understated, primarily because there is a nine-to-one ratio of lupus effecting women over men. Osteoporosis (particularly if you have been on steroids), atherosclerosis, and pregnancy are the most important factors to consider for women with lupus. A steady supplement of calcium and vitamin D are critical, and medications such as Fosamax, Actonel and Boniva may help those who are experiencing bone loss as a result of a steroid regimen.

Multidisciplinary Care at HSS

Perhaps the most important facet of modern lupus treatment is the focus on multidisciplinary care. This refers to numerous professionals with different skills providing a total treatment approach for each patient by focusing on the varying aspects of the physical and psychological effects of the disease. The complexity of lupus requires such a complex and multi-faceted approach.

With 44 adult and pediatric rheumatologists, the rheumatology program at HSS is the largest in the world. These physicians are tightly integrated with the rest of the staff of HSS nurses, social workers, and radiologists. Many of the new treatments for lupus are in IV form and have to be infused, requiring an infusion therapy program such as the HSS Infusion Therapy Unit, which is located on the 7th floor within the Hospital.

Although the treatment program begins with medication and pain relief, critical work by each of the HSS lupus support programs, including LupusLine, Charla de Lupus, LANtern, and the SLE Workshop, has aided patients with some of their emotional questions and concerns. Patients may not always feel comfortable speaking about these concerns with their doctor, yet may feel the need to pass them through someone else - perhaps someone who either has the disease or has a personal understanding of it. Many psychosocial issues can be relieved through these support groups, which are open to the public.

“They work with your medical team to support you, and they’re quite a unique resource,” adds Dr. Paget.

There is also managed care support in the form of the VOICES and VOICES 60+ programs. These patient management programs help HSS patients get through the extraordinarily complex maze of today’s governmental insurance systems. In addition, HSS provides other patient support services such as case management, pastoral care, and patient advocacy.

“One thing’s for sure,” says Dr. Paget, “you need to know the facts - not only about your illness and medicines, but also about the support available within your societal structure that’s there to make your life better.”

Current Lupus Research at HSS

There is vast, ongoing clinical research being done with lupus patients all over the world. Clinical trials have been set up with the intention of learning more about the disease by monitoring patients who are undergoing various treatments.

On a more scientific level, there is what is called “basic” research, which involves work done in the lab. The Mary Kirkland Center for Lupus Research was generously founded and supported at HSS by Katherine and Arnold Snider through their foundation called Rheuminations, Inc. and was created to define the immunological essence of lupus, and no less than its causes and cures. The goal of this type of research is to find out what the basic problem is, where it originates and, more importantly, how to make it better. Funding for basic, translational and clinical research initiatives, as well as other research programs focusing on “quality of life,” is provided by foundations like Rheuminations, Inc., private institutions, individuals, and the government.

Translational research is a recent concept that refers to the idea of bringing new discoveries in basic research directly to the patient. It has become known as “bench to bedside” research.

“That’s what science is all about today,” explains Dr. Paget, “transferring laboratory research findings to the patient, sometimes within a few years.”

Also, HSS has recently formed an SLE clinic, which meets on Friday mornings and brings together the different aspects of lupus patient care. There are social workers, medical doctors, rheumatologists, kidney and skin doctors, nurses, and other people present to support lupus patients.

“We hope to form a family environment in which our patients feel comfortable,” says Dr. Paget. “In order to broaden our care of people with lupus, we aim to bring the best and brightest to them with the most cutting-edge therapy. That way, they can receive the most comprehensive treatment in one place.”

The Future of Lupus Research

Another unique component of lupus research at HSS and around North America is the Lupus Clinical Trials Consortium, Inc. (LCTC), which is also generously supported by Katherine and Arnold Snider, the same donors who founded and partner in the administration of the Kirkland Center. Formed because the last four decades have been quite slow in producing FDA-approved lupus medications, the LCTC is comprised of over twenty of the best lupus centers in North America whose shared mission is to support the process of getting promising new therapies to market for people with lupus.

FDA-approved drugs for lupus over the last 40 years have included only four medications: antimalarial drugs, azathioprine, cyclophosphamide, and prednisone. In contrast, there are now 20 to 30 clinical trials for new lupus drugs currently underway. An important stimulus for this has been the formation of LCTC because its mission is to assure an optimal drug trials infrastructure and capability in the world-class institutions that are acknowledged to be the leaders in lupus research and care. Because being an LCTC center has allowed for the transformation of these centers into effective and efficient drug trial units, this has been extraordinarily successful; a large proportion of patients entered into lupus studies today come from these centers.

The immune system is commonly known as the “armed forces” of the body. It has several ways of attacking what it perceives as “threats,” and there are specific parts of the immune system that are very important in the onset of lupus and the related inflammation. These include T lymphocytes, which are specific immune cells in the body known as the “master regulators” of the immune system, and B lymphocytes, which are cells that lead to the production of the autoantibodies that cause lupus inflammation and damage. It is these antibodies that are called antinuclear antibodies or ANAs.

Currently, there are many drugs that are focused on these areas of immune dysfunction, and within the next few years, newer and more focused medicines should be available that are safer and more effective in controlling lupus.

Conclusion

Although lupus research has had its fits and starts, the 21st century looks to be an extremely promising one in terms of new medications and advanced methods of care.

The stages of research - all the way from the bench to the bedside - are being streamlined and improved, and major lupus centers have banded together to make these new lupus medications safer, more effective, and more focused.

At the same time, the benefits of multidisciplinary care, both physical and psychological, have become known and are being practiced like never before. Because lupus is such a personal disease with many emotional effects, HSS has developed many different patient support programs to help patients cope with this illness; these programs are available to the public lupus community at no charge.

Those with lupus should believe in the progress researchers have made in the past, and should be assured that help – and hope – is on the way.

Learn more about the HSS SLE Workshop, a free support and education group held monthly for people with lupus and their families and friends.

Summary by Mike Elvin

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