From the Archives: Spring 2007 Issue of Lupus Now Magazine
Meeting Highlights from 70TH Annual Scientific Meeting of The American College of Rheumatology (ACR)
Reported by Evelyn V. Hess, M.D., MACR, MACP
The 2006 meeting of the ACR was held in Washington, D.C., November 10-15, in conjunction with the 41st Annual Scientific Meeting of the Association of Rheumatology Health Professionals (ARHP). The meeting was attended by more than 13,500 physicians, scientists, and others interested in the rheumatic diseases. Throughout the meeting's five days, there were more than 60 sessions related to every aspect of lupus. Many of these were plenary sessions, which were attended by a large number of participants. It should be noted that physicians and scientists from every continent were in attendance.
It was gratifying to see that many physicians and researchers who have contributed a great deal to our understanding of lupus were honored with various awards.
Because of the incredible progress in our understanding of immunology and the immune system, this area is now the focus for much of the research on systemic lupus and other aspects of lupus management. This report will focus on some of the highlights of what is known to date.
Lupus and Cardiovascular Disease (CVD)
Cardiovascular disease is occurring in an increasing number of lupus patients, in part because most people with lupus are now living much longer and are reaching the age where atherosclerosis can be detected. There were a number of presentations on this topic that focused on how to recognize CVD in people with lupus.
There was less agreement on how best to treat it. Statin therapy has been evaluated but needs to be studied much more. Other studies have involved percutaneous coronary intervention (PCT); however, the outcome in lupus patients one year later was quite poor. Other research highlighted the fact that, while there should be very aggressive control of lupus, physicians also need to lower homocysteine levels. These are important observations for all physicians treating lupus patients.
Clinical Aspects and Potential New Treatments
There were a number of sessions on these important aspects of lupus. Results of a large study of belimumab, a fully human monoclonal antibody to the B lymphocyte simulator, or BLyS, showed an improvement in some patients, while stabilizing lupus activity in others. This large study was unusual in that it combined multiple disease activity measurements and the disease assessment was improved by all these methods.
There were numerous reports of rituximab treatment for lupus kidney disease. In one study, a very beneficial clinical effect was noted at six months' follow-up. The study was a little unusual in that, as well as the ordinary reviews of kidney tissue, electron microscopy was used and showed some very clear-cut improvements. Another study using rituximab with cyclophosphamide showed a significant reduction in various types of antibodies, particularly in the anti-DNA titers. A third study showed a definite recovery of the B cells that the drug depletes, although not so much change in the T cells.
Research from Austria on the use of infliximab, which blocks the tumor necrosis factor (TNF), showed that the drug helped a majority of the lupus patients with active kidney disease who took part in the clinical trial.
There were preliminary results presented in a study of sirolimus (Rapamycin), a kind of antibiotic that can regulate the membrane of the mitochondria. The compound appeared to be safe and effective in a small number of lupus patients who did not respond to the usual immunosuppressant medicines. These results will be followed with interest.
Other Aspects of Lupus
In one study, a large number of lupus patients were evaluated with the special damage index (SDI) in order to compare the characteristics of disabled and never-disabled individuals. Formal work disability in ambulatory lupus patients occurred in 42.7 percent of the subjects. The SDI performed very well in identifying disabled patients, and should be helpful when people with lupus are being evaluated for work disability. In a study that evaluated more than 140 lupus patients for obesity (a common problem in the U.S.), obesity didn't appear to be associated with high blood pressure, diabetes, or with severe or active lupus disease. One study determined frequency and severity of lung involvement in lupus. It turned out that this is relatively uncommon, a finding which supports the observations of physicians with lupus patients.
An important question addressed was whether or not vaccination, particularly with the hepatitis B vaccine, is safe for people with lupus. A group of lupus patients with no sign of disease activity at the time were studied. They tolerated the vaccine and their bodies made an excellent immune response to the hepatitis B vaccine. Many papers were presented on work with mice to determine the cause(s) of lupus. These observations increase our knowledge of lupus in humans, and we should all respect this research and say "thank you" to the mice. Numerous studies were presented on illnesses in family members and the presence or absence of the autoantibodies in family members. One such study showed an increased frequency of autoantibodies associated with lupus that appeared in family members of lupus patients. In many cases, this also is associated with the reduced number of the NK (natural killer) T cells, suggesting that they could play a role in the regulation of antinuclear autoantibodies. German researchers showed an association between smoking and anticardiolipin antibodies.
Lastly, we must not leave out the men. One study showed that men who have lupus have low levels of testosterone and high levels of estradiol. Some of these men also have anti-testes antibodies. These are new areas of observation and we will wait with interest for more information.
In conclusion, we must reassure patients, their families, and their physicians that a tremendous amount of research is under way into the cause(s), treatments, and we hope, cure of lupus.
Lupus-Related Abstracts Presented at the Meeting
Evidence for Premature Atherosclerosis in Antiphospholipid Syndrome Without Traditional Risk Factors Using Non-Invasive Methods – Danieli C.O. Andrade et al, Rheumatology Division and INCOR, University of São Paulo, São Paulo, Brazil
Conclusions: Two sensitive measures were studied in lupus patients to look for evidence of atherosclerosis (hardening of the arteries, which is associated with risk for heart attacks and strokes). These measures were a non-invasive Pulse Wave Velocity (PWV) and Echo-Tracking (ET) device. The study suggests that atherosclerosis can be detected in patients with the antiphospholipid syndrome (autoimmune blood clotting syndrome) who do not have traditional risk factors for heart disease, especially those who have had blood clots in their arteries. Antimalarial treatment may have a beneficial effect on this risk in this preliminary study.
The Association Between Pregnancy Complications and Subsequent Risk of Cardiovascular Disease (CVD) in Women with SLE – Pin Lin, Northwestern University, Chicago, Ill., et al
Conclusions: This study suggests that women with SLE who develop complications in pregnancy might have more risk factors for heart disease or strokes.
Antibodies to Two Regulators of Coagulation and Complement are Prevalent in SLE Even in the Absence of Conventional Antiphospholipid Antibody Tests – Kathleen O'Brien, Oklahoma Medical Research Foundation, Oklahoma City, Okla., et al
Conclusions: Antibodies to two proteins which regulate blood clotting and inflammation are found in lupus patients. These are not routinely tested for but this study suggests they might add useful diagnostic information.
Accelerated Damage Accrual Among Male SLE Patients: Results From a Multiethnic U.S. Cohort – Rosa M. Andrade, University of Alabama at Birmingham, et al
Conclusions: Men with lupus are thought to have relatively aggressive disease overall, and this is reflected by this study which suggests that men are at higher risk to develop organ damage early in the course of the disease.
Striking Differences in the Clinical Expression of SLE in Hispanic Patients Residing in Mexico and the U.S. – América G. Uribe, BC Children's Hospital, Vancouver, B.C., Canada, et al
Conclusions: This study found differences between Hispanic lupus patients from Mexico and Houston. Mexican patients had more types of disease manifestations but less disease activity and less organ damage, and more aggressive treatments. They also tended to be younger and better educated than the patients in the U.S.
Clinical Features Associated with Cardiac Abnormalities in SLE – CA Pineau et al, McGill University Health Centre, Montreal, Quebec, Canada
Conclusions: Abnormalities of a heart valve (the mitral valve) are found in 36.7 percent of SLE patients, therefore routine screening may be needed in patients with SLE, especially in those patients with risk factors for this heart problem (steroid treatment or antiphospholipid antibodies).
Cognitive Functioning in SLE: Impact of Disease Severity, Manifestations, and Medication Effects – Laura J. Julian et al, University of California, San Francisco
Conclusions: The level of disease activity (including new kidney involvement and high blood pressure) seemed to have an impact on learning ability in lupus patients. Anticoagulation treatment seemed to benefit learning functions in patients over time.
Racial/Ethnic Differences in the Prevalence and Treatment of Major Depressive Disorder in a Large Observational Cohort of Persons with SLE – Jinoos Yazdany et al, University of California, San Francisco
Conclusions: Depression is common in people with SLE, and this study found that African American and Asian patients were far less likely to receive treatment for depression, suggesting that doctors need to be more aware of this potential problem in various racial/ethnic groups.
Neuropsychiatric Events in SLE: Mortality Related to Cerebrovascular Disease – S. Bernatsky, McGill University, Montreal, Quebec, Canada, et al
Conclusions: This study found that brain complications increased the risk for death from lupus. More deaths from lupus seem to be attributed to brain hemorrhage than to strokes, suggesting that low platelet counts or complications from anticoagulant treatments or other treatments may be important risk factors for doctors to keep in mind.
Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort Registry to Study Risk Factors for Atherosclerosis: Report on the First 852 Patients – M. B. Urowitz, University of Toronto Lupus Clinic, Toronto Western Hospital, Toronto, ON, Canada, et al
Conclusion: A large international study of risk factors for heart disease and strokes (atherosclerosis) in lupus reports preliminary findings which suggest that many patients have risk factors within an average of 5.4 months from their diagnosis. This study will enroll up to 1,500 patients with new onset lupus who will be followed yearly for 10 years. This will provide a unique opportunity to evaluate risk factors for accelerated atherosclerosis in SLE.
Corticosteroid Dose Correlates Inversely with Vitamin D Levels in Patients with Lupus – L. Manuela Marinescu, Albert Einstein College of Medicine, Bronx, N.Y., et al
Conclusions: Vitamin D is important for strong bones. This study suggests that severe vitamin D deficiency is common among lupus patients, especially African Americans, and this may be linked to treatment with steroids such as prednisone. It may be that regular vitamin D supplements are inadequate for patients with lupus, especially for individuals being treated with corticosteroids.
Comparison of Outcomes Between Patients with Childhood and Adult-Onset Disease in a Large Observational Cohort with SLE – Aimee O. Hersh et al, University of California, San Francisco
Conclusion: This study compared the long-term outcomes of patients who developed SLE in childhood with those who develop SLE later, and found that the childhood-onset patients had a higher risk for severe kidney disease and heart attacks. These findings underscore the importance of aggressive treatment to prevent severe organ disease in young SLE patients.
IV Cyclophosphamide in Pediatric Lupus Nephritis: An Extended 9 Month Protocol – Ankur A. Kamdar et al, Baylor College of Medicine, Houston, Texas
Conclusions: This study gave the chemotherapy cyclophosphamide for a longer time than has traditionally been used (9 monthly doses) for children with active lupus kidney disease. This treatment seemed to be reasonably safe and effective in this study, with improved results seen in kidney biopsies, blood tests, kidney function, and the ability to decrease the doses of steroids used for these children. Further studies will be needed to determine the long-term safety and effectiveness of this treatment.
Quality of Life and Disease Status in Patients with SLE: The Importance of Healthcare Access, Health Literacy and Disease Knowledge – Shaiba Z. Ansari-Ali, Loyola University Medical Center, Maywood, Ill., et al
Conclusions: This study suggests that access to healthcare is associated with a better quality of life for lupus patients, but knowledge about lupus does not have the same impact. Fatigue and body pain also seem to have an impact on quality of life, and these are not always picked up strongly on measurements that are used in clinical studies of lupus patients.
Osteoporosis in Men and Women with SLE from a Large Single Centre Lupus Cohort: Prevalence and Predictive Factors – Sergio M.A. Toloza et al, University of Toronto Lupus Clinic, Toronto Western Hospital, Toronto, ON, Canada
Conclusions: Osteoporosis (OP) or thinning of the bones, putting people at risk for fractures, was found in 13 to 15 percent of men and women with SLE. Steroid treatment contributes significantly to OP in both men and women. In women, menopause is another important risk factor for OP whereas hormone replacement therapy is protective.
Osteoporosis in Pre- and Postmenopausal Women with SLE From a Large Single Centre Lupus Cohort: Prevalence and Predictive Factors – Sergio M.A. Toloza et al, University of Toronto Lupus Clinic, Toronto Western Hospital, Toronto, ON, Canada
Conclusions: In premenopausal women, osteoporosis is associated with younger age at diagnosis of SLE and higher cumulative dose of steroids. In post-menopausal women, osteoporosis is associated with more damage to organs.
Extra-renal Manifestations of SLE After Renal Transplantation – Arielle S. Silver et al, SUNY-Downstate Medical Center, Brooklyn, N.Y.
Conclusions: SLE appears to affect patients after they receive a kidney transplant. Although patients reported more symptoms before they lost their kidney function, there was a trend towards more lupus symptoms (not related to kidney diseases) after a transplant than during dialysis. Lack of follow-up by a rheumatologist after a transplant may delay the recognition and treatment of lupus flares.]
Anti-Prothrombin Antibodies Predict Thrombosis in Patients with SLE – Anna Ghirardello, University of Padova, Padova, Italy, et al
Conclusions: Antiphospholipid antibodies are increasingly recognized to be a spectrum of antibodies against different blood clotting regulators. This study confirms that antibodies against a blood clotting regulator called prothrombin are associated with a risk for blood clots in lupus patients and may be important to test.
Anti-doublestranded DNA and Antiphospholipid Antibodies are Associated with Abnormal Brain MRI in Newly Diagnosed SLE Patients – Mohammad Naqibuddin, Johns Hopkins University, Baltimore, Md., et al
Conclusions: This study performed serial brain MRI procedures in newly diagnosed SLE patients and found that two kinds of antibodies (anti-dsDNA and antiphospholipid antibodies) were associated with abnormal MRI findings. Further study of these patients may help to determine whether these findings have any clinical consequences.