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  1. Benlysta Formulation for Lupus Gets FDA Nod August 01, 2017 | Lupus By Rheumatology Network Staff A new subcutaneous formulation of Benlysta (belimumab) has received FDA approval for the treatment of adult patients with active, autoantibody-positive systemic lupus erythematosus (SLE) who are receiving standard therapy, GSK announced. This is the first subcutaneous self-injection treatment option for patients with SLE, according to GSK. Patients will be able to administer the medicine as a once-weekly injection of 200 mg, from a single-dose prefilled syringe or a single-dose autoinjector, after receiving training from their health care provider. This is the second formulation of Benlysta to be granted FDA approval for SLE, GSK noted. The intravenous formulation, approved in 2011, is administered to patients as a weight-based dose of 10 mg/kg, via a 1-hour infusion in a hospital or clinic setting every 4 weeks (after an initial loading phase given on days 0, 14, and 28). “Lupus can impact the lives of patients in many different ways with varied and often unpredictable symptoms,” said Vlad Hogenhuis, GSK’s Senior Vice President, Head of Specialty Care. “Since it launched in its IV form, thousands of patients worldwide have received treatment with Benlysta. The approval of the new injectable formulation will now provide an additional choice for patients, allowing them to self-administer their medicine at home rather than going to hospitals or clinics for their infusions.” The approval is based on data from the BLISS-SC phase III pivotal study of more than 800 patients with active SLE. The study measured reduction in disease activity at Week 52 in patients receiving belimumab plus standard of care versus those receiving placebo plus standard of care (assessed by the SLE Responder Index). The Benlysta subcutaneous formulation will be available in specialty pharmacies in the United States in late August. Further regulatory submissions for the subcutaneous formulation of Benlysta are under review or planned in other countries during the course of 2017.
  2. GSK receives FDA approval for a new self-injectable formulation of Benlysta (belimumab) for systemic lupus erythematosus Issued: London, UK GSK receives FDA approval for a new self-injectable formulation of Benlysta (belimumab) for systemic lupus erythematosus GSK announced today that the US Food and Drug Administration (FDA) has approved a new subcutaneous formulation of Benlysta (belimumab) for the treatment of adult patients with active, autoantibody‑positive SLE who are receiving standard therapy. Systemic Lupus Erythematosus (SLE) is the most common form of lupus, a chronic, incurable autoimmune disease producing autoantibodies that can attack almost any system in the body. The approval marks the first subcutaneous self-injection treatment option for patients with SLE. After training from their health care provider, patients will be able to administer the medicine as a once weekly injection of 200mg, from either a single-dose prefilled syringe or from a single-dose autoinjector. This is the second formulation of Benlysta to be granted approval for SLE, adding to the existing intravenous (IV) formulation, approved in 2011, which is administered by healthcare professionals to patients as a weight-based dose of 10mg/kg, via a one-hour infusion in a hospital or clinic setting every four weeks (following an initial loading phase given on days 0, 14 and 28). Vlad Hogenhuis, Senior Vice President, Head of Specialty Care, GSK said, “We are delighted with today’s decision. Lupus can impact the lives of patients in many different ways with varied and often unpredictable symptoms. Since it launched in its IV form, thousands of patients worldwide have received treatment with Benlysta. The approval of the new injectable formulation will now provide an additional choice for patients, allowing them to self-administer their medicine at home rather than going to hospitals or clinics for their infusions.” The approval is based on data from the BLISS-SC phase III pivotal study of more than 800 patients with active SLE, which measured reduction in disease activity at Week 52 in patients receiving belimumab plus standard of care, versus those receiving placebo plus standard of care (assessed by SRI, a composite measure of efficacy in lupus). Benlysta subcutaneous formulation will be available in specialty pharmacies in the US in late August. Further regulatory submissions for the subcutaneous formulation of Benlysta are under review or planned in other countries during the course of 2017. About Benlysta (belimumab) Benlysta is currently the only medicine specifically developed and approved for SLE. Benlysta, a BLyS-specific inhibitor, is a human monoclonal antibody that binds to soluble BLyS. Benlysta does not bind B cells directly. By binding BLyS, Benlysta inhibits the survival of B cells, including autoreactive B cells, and reduces the differentiation of B cells into immunoglobulin-producing plasma cells. Benlysta is indicated in the US for the treatment of adult patients with active, autoantibody‑positive, systemic lupus erythematosus (SLE) who are receiving standard therapy: Limitations of Use: The efficacy of Benlysta has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus. Benlysta has not been studied in combination with other biologics or intravenous cyclophosphamide. Use of Benlysta is not recommended in these situations. Full US prescribing information including Medication Guide will be available in the near future at: gsksource.com. In the meantime, you may request a copy through GSK Communications. Benlysta is licensed in the European Union as an add-on therapy in adult patients with active autoantibody-positive SLE, with a high degree of disease activity (e.g. positive anti-dsDNA and low complement), despite standard therapy. Benlysta subcutaneous formulation is currently not approved in the European Union. For the EU Summary of Product Characteristics for Benlysta, please visit www.ema.europa.eu About systemic lupus erythematosus (SLE) Systemic lupus erythematosus (SLE) is the most common form of lupus, affecting approximately 70 percent of an estimated 5 million people with lupus worldwide. Approximately 170,000-200,000 Americans live with SLE. It is a chronic, incurable autoimmune disease producing autoantibodies that can attack almost any system in the body. Important Safety Information for belimumab Please consult the full Prescribing Information for all the labelled safety information for Benlysta (belimumab). BENLYSTA (belimumab): CONTRAINDICATION BENLYSTA is contraindicated in patients who have had anaphylaxis with belimumab. WARNINGS AND PRECAUTIONS MORTALITY There were more deaths reported with BENLYSTA than with placebo during the controlled period of the intravenous clinical trials. Out of 2,133 patients in 3 clinical trials, a total of 14 deaths occurred during the placebo-controlled, double-blind treatment periods: 3/675 (0.4%), 5/673 (0.7%), 0/111 (0%), and 6/674 (0.9%) deaths in the groups receiving placebo, BENLYSTA 1 mg/kg, BENLYSTA 4 mg/kg, and BENLYSTA 10 mg/kg, respectively. Etiologies included infection, cardiovascular disease, and suicide. In the controlled clinical trial of BENLYSTA administered subcutaneously (N = 836), a total of 5 deaths occurred during the placebo-controlled, double-blind treatment period (0.7% [2/280] of patients receiving placebo and 0.5% [3/556] of patients receiving BENLYSTA). Infection was the most common cause of death. SERIOUS INFECTIONS Serious and sometimes fatal infections have been reported in patients receiving immunosuppressive agents, including BENLYSTA. Caution should be exercised when considering use in patients with severe or chronic infections. Consider interrupting therapy with BENLYSTA in patients who develop a new infection while receiving BENLYSTA and monitor these patients closely. In controlled clinical trials of BENLYSTA administered intravenously, serious infections occurred in 6.0% and 5.2% of patients receiving BENLYSTA and placebo, respectively. The most frequent serious infections included pneumonia, urinary tract infection, cellulitis, and bronchitis. Infections leading to discontinuation of treatment occurred in 0.7% and 1.0% of patients receiving BENLYSTA and placebo, respectively. Infections resulting in death occurred in 0.3% (4/1,458) and 0.1% (1/675) of patients receiving BENLYSTA and placebo, respectively. In the controlled trials of BENLYSTA administered subcutaneously (N = 836), serious infections occurred in 4.1% and 5.4% of patients receiving BENLYSTA and placebo, respectively. Progressive Multifocal Leukoencephalopathy (PML): Cases of JC virus-associated PML resulting in neurological deficits, including fatal cases, have been reported in patients with SLE receiving immunosuppressants, including BENLYSTA. Risk factors for PML include treatment with immunosuppressant therapies and impairment of immune function. Consider the diagnosis of PML in any patient presenting with new-onset or deteriorating neurological signs and symptoms and consult with a neurologist or other appropriate specialist as clinically indicated. In patients with confirmed PML, consider stopping immunosuppressant therapy, including BENLYSTA. HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS) Acute hypersensitivity reactions, including anaphylaxis and death, have been reported in association with BENLYSTA. These events generally occurred within hours of the infusion; however, they may occur later. Non-acute hypersensitivity reactions including rash, nausea, fatigue, myalgia, headache, and facial edema have been reported and typically occurred up to a week following the most recent infusion. Hypersensitivity, including serious reactions, has occurred in patients who have previously tolerated infusions of BENLYSTA. Limited data suggest that patients with a history of multiple drug allergies or significant hypersensitivity may be at increased risk. In the controlled clinical trials of BENLYSTA administered intravenously, hypersensitivity reactions occurring on the day of the infusion were reported in 13% (191/1,458) and 11% (76/675) of patients receiving BENLYSTA and placebo, respectively. Anaphylaxis was observed in 0.6% (9/1,458) and 0.4% (3/675) of patients receiving BENLYSTA and placebo, respectively. Manifestations included hypotension, angioedema, urticaria or other rash, pruritus, and dyspnea. Some patients (13%) received premedication, which may have mitigated or masked a hypersensitivity response. There is insufficient evidence to determine whether premedication diminishes the frequency or severity of these reactions. Healthcare providers should be aware of the risk of hypersensitivity reactions and be prepared to manage anaphylaxis. In the event of a serious hypersensitivity reaction, discontinue BENLYSTA immediately and administer appropriate medical therapy. Patients should be monitored during and for an appropriate period of time after the intravenous administration of BENLYSTA. Patients receiving BENLYSTA should be informed of the signs and symptoms of an acute hypersensitivity reaction, and be instructed to seek immediate medical care should a reaction occur. In the controlled trial of BENLYSTA administered subcutaneously (N = 836), the incidence and severity of systemic hypersensitivity reactions were similar to those observed in the intravenous clinical trials. INFUSION REACTIONS In the controlled clinical trials, infusion reactions occurring on the day of the infusion were reported in 17% (251/1,458) and 15% (99/675) of patients receiving BENLYSTA and placebo, respectively. Serious infusion reactions (excluding hypersensitivity reactions) were reported in 0.5% and 0.4% of patients receiving BENLYSTA and placebo, respectively. Serious infusion reactions included bradycardia, myalgia, headache, rash, urticaria, and hypotension. The most common infusion reactions occurring in ≥3% of patients receiving BENLYSTA were headache, nausea, and skin reactions. Some patients (13%) received premedication, which may have mitigated or masked an infusion reaction; however, there is insufficient evidence to determine whether premedication diminishes the frequency or severity of these reactions. BENLYSTA should be administered by healthcare providers prepared to manage infusion reactions. The infusion rate may be slowed or interrupted if the patient develops an infusion reaction. Healthcare providers should be aware of the risk of hypersensitivity reactions, which may present as infusion reactions, and monitor patients closely. DEPRESSION In controlled clinical trials of BENLYSTA administered intravenously, serious psychiatric events were reported in 0.8% and 0.4% of patients receiving BENLYSTA and placebo, respectively. Serious depression was reported in 0.4% and 0.1% of patients receiving BENLYSTA and placebo, respectively. Two suicides were reported in patients receiving BENLYSTA. In the controlled trial of BENLYSTA administered subcutaneously, serious psychiatric events were reported in 0.2% of patients receiving BENLYSTA and in no patients receiving placebo. It is unknown if treatment with BENLYSTA is associated with increased risk for these events. Instruct patients to contact their healthcare provider if they experience new or worsening depression, suicidal thoughts, or other mood changes. MALIGNANCY The impact of treatment with BENLYSTA on the development of malignancies is not known. The mechanism of action of BENLYSTA could increase the risk for the development of malignancies. IMMUNIZATION Live vaccines should not be given for 30 days before or concurrently with BENLYSTA. BENLYSTA may interfere with the response to immunizations. USE WITH BIOLOGIC THERAPIES OR IV CYCLOPHOSPHAMIDE BENLYSTA has not been studied in combination with other biologic therapies, including B-cell targeted therapies, or IV cyclophosphamide. Therefore, use of BENLYSTA is not recommended in combination with these therapies. ADVERSE REACTIONS Intravenous administration Adverse reactions, regardless of causality, occurring in at least 3% of patients with SLE who received BENLYSTA 10 mg/kg and placebo respectively and, at an incidence at least 1% greater than that observed with placebo in the 3 controlled studies, were: nausea 15% and 12%; diarrhea 12% and 9%; pyrexia 10% and 8%; nasopharyngitis 9% and 7%; bronchitis 9% and 5%; insomnia 7% and 5%; pain in extremity 6% and 4%; depression 5% and 4%; migraine 5% and 4%; pharyngitis 5% and 3%; cystitis 4% and 3%; leukopenia 4% and 2%; viral gastroenteritis 3% and 1%. Subcutaneous administration The safety profile observed for BENLYSTA administered subcutaneously was consistent with the known safety profile of BENLYSTA administered intravenously, with the exception of local injection site reactions, which occurred in 6.1% and 2.5% of patients receiving BENLYSTA and placebo, respectively. OTHER IMPORTANT INFORMATION FOR BENLYSTA USE IN SPECIFIC POPULATIONS Pregnancy: There are insufficient data on use of BENLYSTA in pregnant women to establish whether there is drug-associated risk for major birth defects or miscarriage. Following an assessment of benefit versus risk, if prevention is warranted, women of childbearing potential should use effective contraception during treatment and for at least 4 months after the final treatment. Lactation: There is no information available on the presence of belimumab in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for BENLYSTA and any potential adverse effects on the breastfed child from BENLYSTA or from the underlying maternal condition. Black/African American Patients: In controlled clinical trials of BENLYSTA administered intravenously, SLE Responder Index-4 (SRI-4) response rates were lower for black/African American patients receiving BENLYSTA relative to black/African American patients receiving placebo. In the controlled trial of BENLYSTA administered subcutaneously, SRI-4 response was slightly higher for black/African American patients receiving BENLYSTA relative to black/African American patients receiving placebo, but the treatment difference was not as great as that observed in the overall population. Use with caution in black/African American patients. Populations not studied Benlysta has not been studied in the following patient groups, and is not recommended in patients with: ∙ severe active central nervous system lupus ∙ severe active lupus nephritis ∙ HIV ∙ a history of, or current, hepatitis B or C ∙ hypogammaglobulinaemia (IgG <400 mg/dl) or IgA deficiency (IgA <10 mg/dl) ∙ a history of major organ transplant or hematopoietic stem /cell /marrow transplant or renal transplant.
  3. Researchers identify new genetic markers in patients with lupus Langefeld CD, et al. Nat Commun. 2017;doi:10.1038/ncomms16021. July 21, 2017 Among patients with lupus, researchers have identified new genetic markers that predispose patients to the disease, according to a recently published study. “This study is the largest multi-ethnic lupus genetics study to date and allowed us to identify many new genetic markers, some of which are specific to individual ethnic groups and others that are shared across ethnicities,” Carl Langefeld, PhD, lead author of the study and professor of biostatistical sciences at Wake Forest School of Medicine, said in a press release. “With this information, we can begin to better understand the differences in the rates and severity of disease across ethnic groups.” Researchers assessed 27,574 participants. They identified 58 distinct non-human leukocyte antigen regions in the Europeans, nine in the Africans and 16 in the Hispanic Americans. All of these included 24 new lupus regions. “In addition, we observed that many of the genetic markers associated with lupus are shared across numerous autoimmune diseases, and those that are not shared may allow us to understand why a person develops lupus instead of another autoimmune disease,” Langefeld said. “These results will help us identify the biological pathways that pharmaceutical companies may target, and ultimately, develop personalized medicine for the treatment of lupus.” Reference: www.wakehealth.edu/News-Releases/2017/Large_Multiethnic_Study_Identifies_Many_New_Genetic_Markers_for_Lupus.htm Large Multi-ethnic Study Identifies Many New Genetic Markers for Lupus WINSTON-SALEM, N.C. – July 17, 2017 – Scientists from an international consortium have identified a large number of new genetic markers that predispose individuals to lupus. The study is published in the July 17 issue of the journal Nature Communications and was led by researchers at Wake Forest Baptist Medical Center, Oklahoma Medical Research Foundation, King’s College of London and Genentech Inc. Autoimmune diseases strike one in 15 Americans, are among the top 10 causes of death in women and cost an estimated $100 billion a year in medical care. In autoimmune diseases, the body attacks itself. Systemic lupus erythematosus, the form of lupus studied here, is the most common type of lupus and is a prototypical autoimmune disease. Lupus strikes women nine times more often than men and its onset is most common during childbearing age. Also, African-American and Hispanic women are two to three times more likely to develop lupus and tend to have more severe cases than Caucasian women. At present, there is no cure for lupus, which can affect many parts of the body, including joints, skin, kidney, heart, lungs, blood vessels and brain, according to the Lupus Research Alliance. “This study is the largest multi-ethnic lupus genetics study to date and allowed us to identify many new genetic markers, some of which are specific to individual ethnic groups and others that are shared across ethnicities,” said Carl Langefeld, Ph.D., lead author of the study and professor of biostatistical sciences at Wake Forest School of Medicine, a part of Wake Forest Baptist. “With this information, we can begin to better understand the differences in the rates and severity of disease across ethnic groups. “In addition, we observed that many of the genetic markers associated with lupus are shared across numerous autoimmune diseases, and those that are not shared may allow us to understand why a person develops lupus instead of another autoimmune disease. These results will help us identify the biological pathways that pharmaceutical companies may target, and ultimately, develop personalized medicine for the treatment of lupus.” This study analyzed genetic data from 27,574 individuals of European, African American and Hispanic ancestry using the Immunochip, a genotyping technology designed specifically for autoimmune diseases. The researchers identified 58 regions of the genome in Caucasians, nine in African Americans and 16 in Hispanics. These regions appear independent of the well-known Human Leukocyte Antigen (HLA) associations, also studied in depth here. An important observation was that nearly 50 percent of these regions had multiple genetic variants that predispose someone to lupus, Langefeld said. Another key finding was that as the number of genetic risk variants (alleles) a person has increases, the risk for lupus increases more than expected if the variants were working independently. These observations led the authors to propose a “cumulative hits hypothesis for autoimmune disease”. In future research, the team hopes to better understand how these genetic variants influence the risk of lupus, identify any possible drug targets and determine if any environmental factors, such as infections, can trigger the development of the disease in someone who has a genetic susceptibility. They emphasize that it is important to increase the number of understudied populations, such as African-American and Hispanic, to better understand the genetic causes of health disparities in lupus and the unique risks in all ethnic groups. “We are delighted to see the work we funded on the ImmunoChip come to fruition and congratulate Dr. Langefeld along with his colleagues on this tremendous success," said Kenneth M. Farber, CEO and President, Lupus Research Alliance. "This study is among the few to concentrate heavily on non-Caucasian populations for a significantly broader evaluation, while utilizing the most current and comprehensive information about human DNA.” Key support for the study was provided by the Lupus Research Alliance and the National Institutes of Health. Additional corresponding authors are: Patrick M. Gaffney, M.D., Oklahoma Medical Research Foundation; Robert R. Graham, Ph.D., Genentech, Inc.; and Timothy J. Vyse, M.D., Ph.D., King’s College London. Media Relations Contacts: Marguerite Beck: marbeck@wakehealth.edu,336-716-2415
  4. Large Multi-ethnic Study Identifies Many New Genetic Markers for Lupus http://www.wakehealth.edu/News-Releases/2017/Large_Multiethnic_Study_Identifies_Many_New_Genetic_Markers_for_Lupus.htm WINSTON-SALEM, N.C. – July 17, 2017 – Scientists from an international consortium have identified a large number of new genetic markers that predispose individuals to lupus. The study is published in the July 17 issue of the journal Nature Communications and was led by researchers at Wake Forest Baptist Medical Center, Oklahoma Medical Research Foundation, King’s College of London and Genentech Inc. Autoimmune diseases strike one in 15 Americans, are among the top 10 causes of death in women and cost an estimated $100 billion a year in medical care. In autoimmune diseases, the body attacks itself. Systemic lupus erythematosus, the form of lupus studied here, is the most common type of lupus and is a prototypical autoimmune disease. Lupus strikes women nine times more often than men and its onset is most common during childbearing age. Also, African-American and Hispanic women are two to three times more likely to develop lupus and tend to have more severe cases than Caucasian women. At present, there is no cure for lupus, which can affect many parts of the body, including joints, skin, kidney, heart, lungs, blood vessels and brain, according to the Lupus Research Alliance. “This study is the largest multi-ethnic lupus genetics study to date and allowed us to identify many new genetic markers, some of which are specific to individual ethnic groups and others that are shared across ethnicities,” said Carl Langefeld, Ph.D., lead author of the study and professor of biostatistical sciences at Wake Forest School of Medicine, a part of Wake Forest Baptist. “With this information, we can begin to better understand the differences in the rates and severity of disease across ethnic groups. “In addition, we observed that many of the genetic markers associated with lupus are shared across numerous autoimmune diseases, and those that are not shared may allow us to understand why a person develops lupus instead of another autoimmune disease. These results will help us identify the biological pathways that pharmaceutical companies may target, and ultimately, develop personalized medicine for the treatment of lupus.” This study analyzed genetic data from 27,574 individuals of European, African American and Hispanic ancestry using the Immunochip, a genotyping technology designed specifically for autoimmune diseases. The researchers identified 58 regions of the genome in Caucasians, nine in African Americans and 16 in Hispanics. These regions appear independent of the well-known Human Leukocyte Antigen (HLA) associations, also studied in depth here. An important observation was that nearly 50 percent of these regions had multiple genetic variants that predispose someone to lupus, Langefeld said. Another key finding was that as the number of genetic risk variants (alleles) a person has increases, the risk for lupus increases more than expected if the variants were working independently. These observations led the authors to propose a “cumulative hits hypothesis for autoimmune disease”. In future research, the team hopes to better understand how these genetic variants influence the risk of lupus, identify any possible drug targets and determine if any environmental factors, such as infections, can trigger the development of the disease in someone who has a genetic susceptibility. They emphasize that it is important to increase the number of understudied populations, such as African-American and Hispanic, to better understand the genetic causes of health disparities in lupus and the unique risks in all ethnic groups. “We are delighted to see the work we funded on the ImmunoChip come to fruition and congratulate Dr. Langefeld along with his colleagues on this tremendous success," said Kenneth M. Farber, CEO and President, Lupus Research Alliance. "This study is among the few to concentrate heavily on non-Caucasian populations for a significantly broader evaluation, while utilizing the most current and comprehensive information about human DNA.” Key support for the study was provided by the Lupus Research Alliance and the National Institutes of Health. Additional corresponding authors are: Patrick M. Gaffney, M.D., Oklahoma Medical Research Foundation; Robert R. Graham, Ph.D., Genentech, Inc.; and Timothy J. Vyse, M.D., Ph.D., King’s College London. Media Relations Contacts: Marguerite Beck: marbeck@wakehealth.edu,336-716-2415
  5. Cumulative hydroxychloroquine and aspirin may prevent cardiovascular events in patients with SLE https://www.healio.com/rheumatology/lupus/news/online/{f8a80a3a-3122-457d-ae5e-b2f34606cc5d}/cumulative-hydroxychloroquine-and-aspirin-may-prevent-cardiovascular-events-in-patients-with-sle?utm_source=selligent&utm_medium=email&utm_campaign=rheumatology news&m_bt=1879111151405 Fasano S. Et al. J Rheumatol. 2017;doi:https://doi.org/10.3899/jrheum.161351. July 14, 2017 In patients with lupus, ongoing use of hydroxychloroquine plus low-dose aspirin may be associated with increased effectiveness in the primary prevention of cardiovascular events, according to recently published findings. Researchers identified 189 patients from a database of the Rheumatology Unit of the Second University of Naples. The study group included 175 women and the overall mean age at baseline was 31 years. Patients had a diagnosis of systemic lupus erythematosus (SLE) upon admission, and had never experienced a cardiovascular event (CVE). Patients were seen for follow-up every 3 months to 6 months, depending upon their clinical condition. Investigators documented any CVE that occurred during the intervening time and information about the use of aspirin (ASA) and cumulative dosages of hydroxychloroquine (c-HCQ). Researchers used Kaplan-Meier analysis to determine the cumulative dosage that yielded a lower rate of CVE. Cox regression analysis was used to determine factors linked to an initial CVE. They found 10 patients experienced the following non-lethal thrombotic events: stroke, one patient; transient ischemic attack, five patients; and acute myocardial infarction, four patients. The mean time to the first CVE was 5 years. Four (2.1%) patients died during the course of the study; none of these deaths were related to CV complications. Kaplan-Meier analysis demonstrated a significant disparity in CVE-free rates among the four patient subgroups. There was no difference in CVE-free rate between the 135 patients treated with ASA plus HCA and the 28 patients treated with aspirin monotherapy. A lower rate of CVEs was reported in the c-HCQ patients. A higher CVE-free rate was documented in the 85 patients on an ASA-HCA regimen who had arrived at a cHCQ dosage greater than 600 g than in the 28 patients who were treated with ASA monotherapy or the 51 patients treated with ASA/cHCQ at a dosage less than 600g. There were no differences in traditional CV risk factors and those specific to SLE among the patient groups, nor were there differences between medications (statins, high-dose steroids). Multivariate analysis revealed that cumulative treatment with hydroxychloroquine, when added to ASA, was thromboprotective. High blood pressure and antiphospholipid antibody positivity were identified as predictive of an initial CVE. Serena Fasano “Systemic lupus erythematosus is associated with an increased risk of cardiovascular disease. This study was performed to investigate the role of aspirin and distinct hydroxychloroquine cumulative dosages and treatment durations,” researcher Serena Fasano told Healio/Rheumatology. “We found that aspirin and antimalarials, when administered for more than 5 years at a cumulative dosage greater than 600 g, may reduce the CVE risk in SLE patients.” – by Jennifer Byrne Disclosure: The researchers report no relevant disclosures.
  6. Speakers: Lupus remains challenging disease July 6, 2017 Healio Rheumatology recently interviewed Richard Furie, MD, from Hofstra Northwell School of Medicine, Lars Rönnblom, MD, from Uppsala University in Sweden, and Peggy K. Crow, MD, from Hospital for Special Surgery, about the future of lupus during the Interferon Summit. “We need better drugs,” Furie said. “There is a major need for safer and more efficacious therapies. The typical patient who gets this disease is a young woman and it can be devastating.” SEE ALSO Furie discusses advances in SLE treatment Through the Cracks: Niche Patient Population Battles... Elusive Target: A Rundown of the Drug Pipeline for Systemic... Richard Furie To illustrate the need for better therapies, Furie discussed the progression of treatments for the disease. “We have come a long way with treatments,” he said. “If you go back before steroids were developed, the mortality was high. It was probably 50% at 7 years, but steroids were introduced and they have been a major advance. Then, after that, it was the immunosuppressives; but, until we get rid of all mortality and morbidity, we need new drugs.” To derive better therapies for a disease, there needs to be better disease classification. Rönnblom talked about the current classification of lupus patients and how to treat the underlying cause vs. a cluster of symptoms. “We classify patients with an auto[body] or antibody profile,” Rönnblom said. “In lupus, we classify them according to organ manifestation, but also when they have this interferon signature. My guess is that we will see more pathways coming up. Much of this data will be generated by the clinical trials, of course, who responds and who does not respond.” Lars Rönnblom Crow said better understanding about the molecular pathway and underlying mechanisms of the disease can lead to better therapy. “My own speculation is that we will probably end up with combination therapies and maybe combinations will allow us to use lower doses, each of one or two or three therapies to avoid toxicity. For example, we might want to target this type 1 interferon pathway that I believe is active in a sustained way throughout the disease, but may be more important in some stages than others,” she said. Peggy K. Crow “To have a more effective therapeutic activity, we might also want to target activated T cells or B cell differentiation. My guess is that we, as a community, will end up trying different combinations and some of the selection of those might be informed by the molecular pathways that an individual shows to be activated or abnormal.” – by Will A. Offit Disclosures: The researchers report no relevant financial disclosures. https://www.healio.com/rheumatology/lupus/news/online/{0b28f725-2f50-4168-b619-abd1de8a4266}/speakers-lupus-remains-challenging-disease?utm_source=selligent&utm_medium=email&utm_campaign=rheumatology news&m_bt=1879111151405
  7. Glucocorticoids Use and Organ Damage in Lupus http://www.rheumatologynetwork.com/lupus/glucocorticoids-use-and-organ-damage-lupus Glucocorticoids exposure is strongly associated with the accrual of irreversible organ damage in systemic lupus erythematosus patients, independent of disease activity, researchers report. “Our findings suggest that only extremely low doses of glucocorticoid can be considered free of association with damage accrual in patients with SLE,” write researchers in the Nov. 22 issue of Lupus Science and Medicine Glucocorticoids are a mainstay treatment in both acute and chronic systemic lupus erythematosus. Previous studies have demonstrated that damage accrual is associated with cumulative disease activity. However, more recent studies suggest that damage accrual may also be associated with systemic lupus erythematosus treatment. Approximately 60 percent of systemic lupus erythematosus patients experience permanent organ damage within seven years of being diagnosed with the disease. Given that glucocorticoids are often used in the context of high disease activity, it has been challenging for researchers to tease out the independent effect of systemic lupus erythematosus treatment on damage accrual. This was an observational study of 162 systemic lupus erythematosus patients — 75 percent of whom received glucocorticoids. The patients were observed for two to 4.7 years by Diane Apostolopoulos, M.D., of Monash University in Australia, and colleagues. They measured damage accrual finding that glucocorticoid patients were 42 percent more likely to have significantly more damage as compared to patients who were not prescribed glucocorticoids (42% vs 15%, p<0.01). The observational nature of the study was one of the limitations of the study, yet, it is noteworthy, the researchers wrote. “Given the limitations of observational studies in the face of confounding by indication, our findings suggest the urgent need for a randomized study comparing the effect on damage accrual of usual care with that of a strategy that stringently limits glucocorticoid dosing,” Dr. Apostolopoulos and colleagues wrote. In an editorial that was published online April 7 in Lupus Science and Medicine, Maarten Boers, M.D., of VU University Medical Center in the Netherlands, conveys concerns of the medical community misinterpreting observational studies by limiting applications of a potentially life-saving treatment. “The truth of the matter is that trials on glucocorticoid beneficial and adverse effects are not being done, and that observational studies (invariably only focusing on glucocorticoid adverse effects, both related and unrelated to the disease) are hopelessly and irretrievably confounded by indication,” wrote Boers. “In brief, patients with the most severe disease are preferentially treated with glucocorticoids, and this leads to the associations found in observational studies, regardless of the beneficial effects of glucocorticoids.” The study Glucocorticoid use is associated with harm in both domains of the (Systemic Lupus International Collaborating Clinics Damage Index (SDI) traditionally associated with glucocorticoid-induced harm (cataracts, osteoporotic fracture, avascular necrosis, diabetes mellitus) and the residual SDI domains not previously associated with glucocorticoid-induced harm. Even lower doses of glucocorticoid are associated with damage accrual in SLE. The threshold identified was a time-adjusted mean prednisolone of 4.4 mg per day. Cumulative prednisolone exposure was associated with overall damage accrual after controlling for ethnicity and disease activity and was significant at time-adjusted mean doses above 4.42 mg prednisolone per day. A dose-response relationship between cumulative prednisolone use and irreversible organ damage accrual was observed, with increasing odds ratios with each ascending quartile. Compared to patients in the lowest quartile, patients in the highest quartile of cumulative prednisolone had adjusted odds ratio of 13.46, 95 percent CI (3.59 to 50.4), p<0.01 for damage accrual. Of the demographic factors evaluated, only ethnicity was associated with damage accrual. Asian patients had reduced odds of damage accrual compared with Caucasians (adjusted OR=0.22, 95% CI (0.09 to 0.53), p<0.01). “Our findings further emphasize the need for new, more effective treatments for SLE that minimize or eliminate the need for glucocorticoids,” wrote Apostolopoulos and team. DISCLOSURES This research was supported by a grant from Eli Lilly. REFERENCES Apostolopoulos D, Kandane-Rathnayake R, Raghunath S, et al. “Independent association of glucocorticoids with damage accrual in SLE,” Lupus Science and Medicine. Published online November 22, 2016. DOI: 10.1136/lupus-2016-000157. Boers M. “Observational studies on glucocorticoids are harmful!” Lupus Science and Medicine. Published online April 7, 2017. DOI: 10.1136/lupus-2017-000219
  8. Neonatal Lupus May Not Require Steroid Treatment News | June 30, 2017 | Lupus By Whitney L. Jackson One in 50 pregnant women with systemic lupus erythematosus (SLE) are at risk for having a child with neonatal lupus erythematosus (NLE), according to Dr. Jill Buyon, a rheumatologist with New York University School of Medicine. Although neonatal lupus is rare and is most often benign, when it is not, it can be life-threatening for at-risk newborns. Awareness is important, she said. “Though we think of it as being rare, the recurrence rate is about 18 percent. This is a significant portion of people,” Dr. Buyon said. The first signs of disease often occur during the first few weeks of birth as nonscarring and non-atrophic skin lesions that resemble subacute cutaneous lupus erythematosus. More serious abnormalities effect the cardiovascular system, but can also effect the hematological, hepatobiliary, central nervous and pulmonary systems (1). One of the most controversial issues associated with neonatal lupus is whether the use of fluorinated steroids during pregnancy can protect the fetus from worsening heart block, which is associated with NLE. Dr. Buyon’s research shows that it does not. Neonatal lupus Neonatal lupus occurs when a mother with active or asymptomatic lupus or other autoimmune disease passes autoantibodies against Ro/SSA, La/SSB and U1-ribonucleoprotein (U1-RNP), through the placenta to the fetus. It is rare and one estimate shows only a 1-2 percent risk of having a child with NLE, regardless of whether the mother is symptomatic (1). Dexamethasone or fluorinated steroids have been standard treatments to prevent heart block in NLE. “The idea behind this is that maybe heart block is caused by inflammation and maybe we could stop the inflammation in the beginning, during or even after the initial insult. The question is whether this would change the ultimate prognosis for the fetus,” she said. A 2015 retrospective chart review by Dr. Buyon and colleagues published in the Annals of Rheumatic Diseases addressed whether daily doses of fluorinated steroids effectively treated isolated heart block in utero to prevent the progression of disease beyond the atrioventricular (AV) node. They found that fluorinated steroids did not significantly prevent the development of disease beyond the AV node, reduce mortality or delay or prevent the need for a pacemaker (2). It is believed inflammation plays a significant role in the development and worsening of heart block, making steroids an attractive treatment option. However, evidence doesn't support the use of these steroids to prevent worsening disease or death from this condition. The results, she said, should alleviate worries from providers and expectant mothers who have concerns about using steroids, such as dexamethasone, during pregnancy. There has been a concern about the effect of steroids crossing the placenta into the fetal circulation system. Additionally, steroid use can cause complications in the mother, such as increased risk of infection, as well as other problems in the fetus, including low-birth weight and the loss of amniotic fluids. The 20-year retrospective study analyzed treatment and outcomes for enrollees in the Research Registry for Neonatal Lupus. Only women with diagnosed cases of anti-SSA/Ro-associated cardiac neonatal lupus, meaning their fetus had second- or third-degree heart block, were included. Heart block scars the atrioventricular node, the structure responsible for heart rate. Children born with permanent heart block require pacemaker implantation, and approximately 20 percent die. Although there is some disagreement with Canadian research that supports the use of fluorinated steroids when second- or third-degree heart block is present, recently published French investigations verify her team's findings, she said. Previous studies over the last 20 years have shown that the most challenging aspect in heart block is that once it’s reached a third-degree level, it is generally immutable and by then, steroids cannot reverse the course of disease. “There is a vulnerable period to the development of heart block which is usually about 16 – 26 weeks, with the most heightened time around 19-20 weeks. Once the heart block has happened it’s not common to develop worsening injury because the vulnerable period begins to pass. Admittedly, our colleagues in Canada don’t agree and they almost always subject the mother to steroids for the rest of the pregnancy. And because that carries risk, we felt this study was important,” she said. Now, with this study, Dr. Buyon hopes that physicians will reconsider steroid therapy in these cases. “I appreciate that a mother wants to do all she can to save her baby, but there are also health considerations for her part and on part of the fetus. The idea of taking a steroid that will cross into the fetal circulation can be very anxiety provoking both for the patient and physician. This is the study that was needed to help in pregnancy counseling,” she said. Dr. Buyon discusses the structure, findings and importance of this work with Rheumatology Network in this video. http://www.rheumatologynetwork.com/lupus/neonatal-lupus-may-not-require-steroid-treatment REFERENCES 1. Kam Lun Hon and Alexander K. C. Leung. "Neonatal Lupus Erythematosus." Autoimmune Dis. 2012; 2012: 301274. Published online 2012 Sep 2. DOI: 10.1155/2012/301274 2. Izmirly PM, Saxena A, Sahl SK, et al. “Assessment of fluorinated steroids to avert progression and mortality in anti-SSA/Ro-associated cardiac injury limited to the fetal conduction system.” the Annals of Rheumatic Diseases. Published Online First: 01 December 2015. DOI: 10.1136/annrheumdis-2015-208311
  9. Women with Lupus Overwhelmingly Have Healthy Pregnancies News | June 30, 2017 | Lupus By Whitney L. Jackson In contradiction to long-standing beliefs, a healthy pregnancy is possible for women who have lupus, says Jill Buyon, M.D., a rheumatologist and lupus specialist from New York University School of Medicine. “Patients with lupus have been under the impression that pregnancy would be a very dangerous thing for them. From the mother’s perspective, the concerns are: Will the mother sustain a lupus flare? For mothers who have once had kidney involvement: How safe is it to get pregnant? Will there be adverse pregnancy outcomes? Will the baby be very small? Will the baby be born so early that it needs to be in the hospital for a long time. And, of course, the scary question is: Will my baby die? These are the outcomes we look at from the perspective of counseling and what we wanted to learn from this study,” she said. Dr. Buyon recently published research in the Annals of Internal Medicine showing that women with relatively inactive lupus without serious flares experienced a normal pregnancy with a positive outcome. Study participants were women, ages 18-to-45, enrolled in the Predictors of Pregnancy Outcome: Biomarker in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus (PROMISSE) Trial. The investigation was multi-center, multi-racial and multi-ethnic. Out of the 385 women followed during the study, 81 percent experienced no adverse events. Overall, 9 percent of pregnancies resulted in premature birth, 4 percent experienced pregnancy loss during the second or third trimester, 1 percent encountered infant death due to pregnancy complications, and 10 percent had very low birth weight. Throughout the study, investigators identified four factors that appeared to increase a woman's likelihood for a negative outcome — high blood pressure during pregnancy, more active lupus during gestation, low platelet count, and a positive lupus anticoagulant test during the first trimester. “The patients who tended to be more sick at the outset, tended to be those who might have an adverse pregnancy outcome. The highest risk factor is the presence of something called a lupus anticoagulant. The presence of this abnormal blood test is very important and one that absolutely all doctors should test for,” Dr. Buyon said. In addition, race and ethnicity — black, Hispanic and Asian — contributed to poor outcomes and was in and of itself, a risk factor. Dr. Buyon said she doubts it is due to socioeconomic factors because the patients were treated by similar doctors in tertiary care centers. She suspects it may be due to genetics, which needs to be explored. Although the findings point to the possibility of healthy pregnancies for this population, Dr. Buyon cautioned women who have high protein levels in urine due to uncontrolled kidney disease could still face significant problems with pregnancy. These women are typically advised to postpone pregnancy until their kidney disease improves. Ten to 15 percent of patients had a moderate flare requiring minimal medication changes, but less than 5 percent of patients had a flare that required high dose steroids or hospitalization. About one in five patients had a renal flare. “The other optimistic perspective was that 225 patients never had kidney disease, but many of them had anti DNA antibodies which is an antibody we worry about in developing renal disease. Only four people developed de novo renal disease. For people who had previous kidney disease ... but were in complete remission, they too had very few renal flares. I think this is very encouraging news for women with past renal disease who really are so worried that maybe they’ll never have a healthy pregnancy, that simply is not true (14:01),” Dr. Buyon said. The hope, she said, is that these findings can be used to inform discussions between doctors and their patients with lupus who are also interested in pursuing pregnancy. Dr. Buyon discusses the study, its findings and implications in the following video with Rheumatology Network. http://www.rheumatologynetwork.com/lupus/women-lupus-overwhelmingly-have-healthy-pregnancies REFERENCES Jill P. Buyon, MD; Mimi Y. Kim, ScD; Marta M. Guerra, MS, et al. "Predictors of Pregnancy Outcomes in Patients With Lupus: A Cohort Study," Annals of Internal Medicine, Aug. 4, 2015. DOI: 10.7326/M14-2235
  10. Systemic lupus erythematosus increases risk for cervical neoplasia June 15, 2016 LONDON — Women with systemic lupus erythematosus, or SLE, are at a greater risk for cervical neoplasia, especially those treated with immunosuppressive drugs, according to a speaker here at the EULAR Annual Congress. “Women with SLE appear to be at increased risk for cervical neoplasia. It is more pronounced for premalignant and invasive cancers,” Johan Askling, MD, PhD,from the department of medicine at Karolinska Institutet in Stockholm, Sweden, said during a press conference. “Treatment with SLE is a marker of further increasing the risk. In fact, it contains the overall increase for invasive cancers, but whether this is due to drugs or the indication, we do not really know.” Askling and colleagues identified 4,450 women with SLE from Swedish registries and 28,113 matched controls from the general population. The Swedish National Cervical Screening Registry was used to collect data on cervical screenings. Patients were further divided by whether they used antimalarial drugs (n = 1,783) or other immunosuppressive treatments (n = 1,981), as defined by the Swedish Prescribed Drug Register. At follow-up, the Swedish National Cervical Screening Registry and Swedish Cancer Registry were used to determine outcomes of cervical dysplasia and invasive cervical cancer. Other outcomes assessed separately included cervical intraepithelial neoplasia grades 1 and 2/3, and invasive malignancy. Askling and colleagues used Cox models to estimate hazard ratios. Investigators found women with SLE had a doubled rate for cervical dysplasia or invasive cancer compared with the general population. Women treated with systemic immunosuppressive drugs vs. those treated with antimalarial drugs had a higher rate for cancer. Immunosuppressives were correlated with a higher chance of cervical dysplasia or neoplasms compared with women treated with antimalarials. “Women with SLE should be screened for cervical cancer, and if there is a population-based screening program … [it] is particularly good to adhere to that program,” Askling said. “We do not think, at this stage, additional measures should be taken.” – by Monica Jaramillo Reference: Wadström H, et al. Abstract #OP0189. Presented at: EULAR Annual Congress; June 8-11, 2016; London. Disclosure: Askling reports no relevant financial disclosures.
  11. UK rheumatologists use factors other than NICE guidelines to treat patients with RA June 27, 2016 LONDON — Rheumatologists from the United Kingdom consider other factors apart from the National Institute for Health and Care Excellence, or NICE, clinical guidelines on cost to make decisions on anti-tumor necrosis factor therapy prescription doses, according to a speaker here at the EULAR Annual Congress. “Rheumatologists’ … experiences come into some of this as well, so if they are used to using one particular treatment they would be more likely to use it subsequently,” Sean Gavan, PhD, of the Manchester Centre for Health Economics, United Kingdom,said during a press conference. “There was a sense from all of my participants that, to some extent, NICE guidance was restrictive of what they could do, and so to combat this, they were selective to what treatments they gave patients earlier on to free up more treatments down the line. Occasionally, they would manipulate the DAS28 score to give [anti-tumor necrosis factor] therapy to patients who, according to NICE guidance, would not be allowed to have that treatment.” Gavan and colleagues conducted telephone interviews with 11 consultant rheumatologists from hospitals in England. Rheumatologists were asked to speak of factors that influence their decisions for treatment of patients with rheumatoid arthritis (RA), which included the decision to initiate anti-tumor necrosis factor (anti-TNF) therapy, choice of first-line anti-TNF therapy and treatment options in remission. Investigators used thematic framework analysis to analyze interview transcripts. Results showed that the participants’ choice for first-line anti-TNF treatment was rarely influenced by costs, except when local service commissioners offered a less expensive anti-TNF. Gavan and colleagues found when it came to first-line biosimilar anti-TNF agents, participants’ expressed cautious optimism due to potential cost savings. Participants’ tried to maintain clinical autonomy and involved patients in decision-making when use of cheapest anti-TNF was considered. “A lot of the participants suggested the clinical evidence base was, perhaps, slightly ahead of what NICE was saying currently in its guidance, but then when they decided to implement certain treatments decisions they were selective over which pieces of evidence they used to guide certain decisions,” Gavan said. – by Monica Jaramillo Reference: Gavan S, et al. Abstract #OP0198-HPR. Presented at: EULAR Annual Congress; June 8-11, 2016; London. Disclosure: Gavan reports no relevant financial disclosures.
  12. Staying Ahead of Multiple Autoimmune Disorders Healio Rheumatology, August 2016 There is a well-established body of evidence cataloguing the co-occurrence of autoimmune disorders. Patients with rheumatoid arthritis, multiple sclerosis, autoimmune thyroiditis, Sjögren’s syndrome or a host of other such conditions carry a substantially increased risk for another autoimmune disease. Although some pairings are reported more frequently than others, the likelihood that a patient with any autoimmune disorder will ultimately acquire another autoimmune disorder is high. The question, then, is why. Regina Berkovich, PhD, MD assistant professor of clinical neurology at Keck Medicine at the University of Southern California, laid out some of the principal arguments. “It is a case of mistaken and activated immune system,” she said. “If the immune system already follows the autoimmune pattern, it is just a higher possibility that there will be another target.” This seems to be the main reason autoimmune disorders tend to coincide, according to Berkovich, who has studied multiple sclerosis (MS) extensively. “A second scenario is that when we use immunomodulatory drugs to treat MS, the initial landscape of the immune system changes,” she said. “When we create changes to the immune system, it may predispose them to further complications.” Other researchers, including Emily C. Somers, PhD, ScM an associate professor of internal medicine, environmental health sciences and obstetrics and gynecology at the University of Michigan, have suggested genetic factors are in play. However, untangling the myriad genetic associations in patients who have multiple disorders has remained elusive to the clinical and research communities. “A current line of thinking is there are certain genetic and environmental factors that may disrupt the immune system in a manner that may set the stage for future development of autoimmune diseases,” she said. However, she noted there are no concrete answers on the genetic front. Regina Berkovich Healio Rheumatology lays out the issues and associations, beginning with a look at trends in comorbid autoimmune diseases. Overview of Associations Cojocaru and colleagues outlined factors involved in multiple autoimmune syndrome, which they defined as the existence of three or more of these conditions. “Disorders of autoimmune pathogenesis occur with increased frequency in patients with a history of another autoimmune disease,” they wrote, suggesting the rate of a second disorder may be about 25%. “At least one of them is usually a skin disease, such as psoriasis or scleroderma.” Although some patients may experience as many as five of these conditions, it is unlikely, according to Cojocaru and colleagues. Multiple autoimmune disorder may be the result of familial or genetic factors, along with immunological or psychological factors. However, environmental triggers may set in motion the occurrence of a second disorder. “The pathogenesis of multiple autoimmune disorders is not known,” they wrote. Multiple autoimmune syndrome can be classified into three types, according to the authors. “Type 1 [multiple autoimmune syndrome] includes myasthenia gravis, thymoma, polymyositis and giant cell myocarditis,” they wrote. “Type 2 [multiple autoimmune syndrome] includes Sjögren’s syndrome, [rheumatoid arthritis] RA, primary biliary cirrhosis, scleroderma and autoimmune thyroid disease. Type 3 [multiple autoimmune syndrome] groups together autoimmune thyroid disease, myasthenia gravis and/or thymoma, Sjögren’s syndrome, pernicious anemia, idiopathic thrombopenic purpura, Addison’s disease, type 1 diabetes mellitus, vitiligo, autoimmune hemolytic anemia, [systemic lupus erythematosus] SLE and dermatitis herpetiformis.” Antoine G. Sreih, MD, assistant professor of clinical medicine in rheumatology at the University of Pennsylvania, echoed this point. “Clusters of autoimmune disorders can occur together, such as Schmidt syndrome or other autoimmune polyendocrine syndromes, which are often due to genetic predisposition,” he said. “Once the immune system loses its tolerance to self, it becomes more prone to causing other autoimmune diseases.” Eric Matteson Speaking more specifically, researchers have suggested inflammatory bowel disease is commonly associated with autoimmune comorbidities. For example, hypothyroidism, primary sclerosing cholangitis, vitiligo and alopecia areata frequently occur in ulcerative colitis. Multiple sclerosis is common in the third type of multiple autoimmune disorder, according to Cojocaru and colleagues. An association of Reynolds syndrome and the lupus erythematosus/lichen planus-overlap syndrome is a hallmark of the second type of this disorder. Overall, vitiligo is often the first autoimmune disease diagnosed, while bullous pemphigoid is the most common blistering skin disease. “The significance of the association of bullous pemphigoid with other autoimmune diseases is still unknown,” they wrote. “The most frequent associations are those with [primary biliary cirrhosis] PBC, psoriasis.” Sjögren’s syndrome frequently occurs with SLE and RA, according to Cojocaru and colleagues. “The presence of Sjögren’s syndrome influences the expression of the other autoimmune disease to some degree, for instance by increasing fatigue and lymphoma risk,” they wrote. “The underlying mechanisms for this syndrome are not yet understood, but it may be more prevalent than currently recorded.” “Overlapping syndromes between two or more autoimmune diseases in rheumatology are not uncommon,” Sreih said. “We see this with SLE, RA, scleroderma, Sjögren’s syndrome, vasculitis and polymyositis.” Other common combinations include pemphigus and autoimmune thyroid disease in type 1 [multiple autoimmune syndrome]; chronic active hepatitis, SLE, pemphigus, bullous pemphigoid, [autoimmune hemolytic anemia], [idiopathic thrombopenic purpura], alopecia areata and Addison’s disease in type 2 [multiple autoimmune syndrome]; and acquired primary hypogonadism, hypophysitis, RA, PBC, relapsing polychondritis, multiple sclerosis, [congenital adrenal hyperplasia] CAH, ulcerative colitis and scleroderma in type 3 [multiple autoimmune syndrome],” they wrote. Cojocaru and colleagues suggested clinicians may find the pathogenesis of ulcerative colitis in clusters of autoimmune diseases, and the presence of one of these disorders may likely lead to discovery of another. They urged ongoing surveillance. “The underlying mechanisms for this syndrome are not yet understood, but it may be more prevalent than currently recoded,” they wrote. “I would point out that only some, but certainly not all, of the clustering they suggest is based on pathophysiological understanding of the diseases and so is in the end opinion of the authors,” Eric Matteson, MD, a rheumatologist at the Mayo Clinic in Rochester, Minn., told Healio Rheumatology. “The practical clinical implications of the clustering could include making clinicians aware of certain associations, such as Sjögren’s syndrome and rheumatoid arthritis as they follow patients, and may be helpful in unraveling some of the common pathophysiological basis for them. Some other associations may not have a practical value in terms of understanding the disease causation of management.” A number of data sets validate the findings described by Cojocaru and colleagues. Sardu and colleagues described the prevalence of 12 autoimmune diseases in a general population sample from Sardinia, Italy that included data for more than 25,000 individuals. Results were calculated in terms of prevalence per 100,000. Investigators found RA occurred in 552 individuals per 100,000, while the rate was 124 for ulcerative colitis, 15 for Crohn’s disease, 464 for type 1 diabetes, 81 for SLE, 124 celiac disease, 35 for myasthenia gravis, 939 for psoriasis/psoriatic arthritis, 35 for systemic sclerosis, 224 for MS, 31 Sjögren’s syndrome and 2,619 for autoimmune thyroiditis. “An overall association between autoimmune disorders was highlighted,” the researchers wrote. “People already affected by a first autoimmune disease have a higher probability of being affected by a second autoimmune disorder.” Antoine G. Sreih “This paper recapitulates findings from other populations which also show this interrelatedness of autoimmune diseases, and is not surprising,” Matteson said. “It is necessary to keep in mind that some of the autoimmune diseases have low frequencies, so that lack of an association can be real or spurious.” Sreih built on this point. “The findings in this paper support the notion that having one autoimmune disease increases the risk of having another autoimmune disease and that the majority of the autoimmune diseases examined in this paper are more common in women than men,” he said. “It is important, however, to indicate that findings in one specific population — in this case South Sardinia — may not apply to another population because of differences in genetic composition.” Another caveat is that despite the broad nature of the study, there are still a finite number of autoimmune disorders that underwent analysis, according to Sreih. “Therefore, the findings apply only to those studied autoimmune diseases,” he said. “Also, observation bias may exist since patients with an autoimmune disease are frequently seen and tested by their physicians and therefore more diseases can be detected.” Autoimmune Therapies Berkovich and colleagues investigated the frequency of comorbid diseases in MS. They suggested certain MS drugs may be preferable to others when comorbid autoimmune conditions are present. Moreover, comorbid autoimmune conditions could predict response to MS therapies. “Treatment with interferon beta has been reported to precipitate immune-mediated abnormalities or to exacerbate existing autoimmune diseases,” they wrote. “In comparison, there are fewer reported cases of treatment-associated comorbidities linked with autoimmune disease in patients taking glatiramer acetate. Knowledge of the factors influencing autoimmune comorbidities may provide insights into the complex pathogenesis of MS and help inform treatment choices.” “According to what we know, some immunomodulatory therapies may contribute to a second autoimmune disorder,” Berkovich told Healio Rheumatology. “The association has been noticed with interferon-based therapies. Another more recent medication that may predispose patients to autoimmune complications is alemtuzumab (Lemtrada, Genzyme). We found that if patients already had MS and one other autoimmune condition, such as psoriasis or lupus, interferon was not the best choice of drug.” This information can have practical implications for the clinic, according to Berkovich. “The evidence tells us that interferon may exacerbate the conditions,” she said. “Evidence of those complications should be used as a surrogate biomarker to be careful when using interferon in these patients.” That said, Berkovich is hopeful novel therapies, such as teriflunomide (Aubagio, Genzyme) or, dimethyl fumarate (Tecfidera, Biogen) or glatiramer acetate injection (Copaxone, Teva), may improve this situation. “Some of these new immunomodulatory therapies have known risks,” she said. “The symptomatology of MS can overlap with other conditions.” Clinicians weight the benefit-risk ratioassociated with treating a primary autoimmune disorder, according to Berkovich. “Treatment is justified, first, by the efficacy of the drugs for the primary potentially progressive condition — MS,” she said. “If we give medicine to treat MS, we are well aware that it has associated risks, and always discuss this with patients. It is worth it because if we do not treat the MS, patients are highly likely to progress and develop advanced disability. We have no choice but to address the primary condition. The risk for a second condition is relatively minor and manageable when compared to what happens when MS takes its natural course, which may be a grave prognosis.” Genetic Factors Many experts, including Sreih, have suggested genetic factors may be worth investigating. “Patients with one autoimmune disease may be predisposed to acquiring another autoimmune disease,” he said. “Genetic predispositions to having an autoimmune disorder can be common among several autoimmune diseases.” Somers acknowledged the understanding of these associations is increasing, albeit slowly. “Over the last decade, several genetic factors have been found in common between multiple autoimmune diseases,” she said. “However, the particular combinations of genetic and environmental factors will influence the way that autoimmunity is expressed, or what we refer to as the disease phenotype.” Matteson agreed. “This is likely because in some cases common genetic predisposition exposures, such as possibly infections, and common inflammatory pathways of many of these diseases also have overlapping features, like rheumatoid arthritis, Sjögren’s syndrome, and lupus erythematous, to name three,” he said. Conflicting Data Although the overwhelming consensus is that autoimmune diseases co-occur, there are data sets that show the opposite or at least muddy the picture. Farez and colleagues suggested results investigating comorbid autoimmune disorders have been “controversial.” They added this phenomenon has not been studied in patients in Latin America. Results from their case-control study indicated no significant differences in autoimmune disease prevalence in patients with MS compared to controls. Patients with one or more autoimmune disorders did not experience an increased likelihood of acquiring MS (odds ratio = 0.85), according to their findings. “Our results indicate absence of increased comorbid autoimmune disease prevalence in MS patients, as well as of increased risk of MS in patients suffering from other autoimmune disorders,” they concluded. Somers and colleagues conducted a series of population-based cohort studies with data from the United Kingdom General Practice Research Database between 1990 and 1999. The aim was to evaluate risks for co-occurrence of RA, autoimmune thyroiditis, MS and insulin-dependent diabetes mellitus. The analysis included outcomes for 22,888 patients with RA, 26,198 patients with autoimmune thyroiditis, 4,332 patients with MS and 6,170 patients with diabetes whose outcomes were compared with those reported in the general population. Among patients in the diabetes group, adjusted rates of autoimmune thyroiditis were increased among men (standardized incidence ratio[SIR] = 646) and women (SIR = 409.6). Rates of RA also were higher among women with diabetes (SIR = 181.6). Autoimmune thyroiditis and RA showed a trend for coexistence regardless of the disease sequence (sex-specific SIRs = 130.4 to 162). However, the researchers noted an inverse relationship between RA and MS. “The strongest association we found was between type 1 diabetes and autoimmune thyroiditis, with rates of coexistence up to six-times higher than expected,” Somers said. “Since these are both endocrine disorders, this indicates that they may share risk factors relevant to disruption of the endocrine system.” Somers noted that RA and autoimmune thyroiditis are among the most common autoimmune disorders in the general population. “Therefore, detection of comorbidity between this pair of diseases is easiest to detect statistically,” she said. “We found that for someone with RA or autoimmune thyroiditis, their risk of developing the other one is approximately 1.5-times higher than expected by chance.” The inverse relationship in this data set should not be ignored, according to Somers. “The inverse association between RA and MS is puzzling and we do not have a firm explanation for this, although genetic variants have been reported that are negatively correlated between these two diseases,” she said. “That is, variants associated with increased susceptibility for one but decreased susceptibility for the other.” The other noteworthy data from the study involve gender differences in comorbid autoimmune disorders, according to Somers. Emily C. Somers “Females have a much greater risk of autoimmune disease overall compared to males, and the female excess holds true for most individual autoimmune disorders,” she said. “For example, 90% of lupus patients are female. Thus, the risk of developing a second disorder should be examined separately for each sex, given the higher underlying risk among females. We believe that our data support similar patterns of coexistence for both sexes, but given the rarity of autoimmune diseases in males, the associations among males are more challenging to detect.” Regarding other conflicting evidence, there are also data demonstrating that autoimmune therapies may not always lead to increased risk for further disorders. Chouhfeh and colleagues investigated how disease modifying therapies impact comorbid autoimmune diseases in MS using data from a cohort of 1,792 patients in the New York State MS Consortium registry. There were 1,478 patients with no other autoimmune diseases and 314 with a comorbid condition that occurred after enrollment. The researchers grouped the patients into those with a disorder after initiation of disease modifying therapies (n = 281) and patients with a disorder who were naïve to disease modifying therapies (n = 33). Disease-modifying therapies failed to alter the frequency of self-reported autoimmune disorders (17.2 vs. 20.4%), according to the results. However, the duration between initial symptoms of MS and the initial report of a comorbid autoimmune condition was 192 ± 115 months among patients treated with disease-modifying therapies and 262 ± 107 months among those who were not. “The findings of this paper are interesting,” Sreih said. “One would expect that the use of disease-modifying therapies in general would decrease the incidence of autoimmune diseases given that many of these medications are therapies given to autoimmune diseases.” Sreih highlighted this paper also shows that women are at higher risk of developing autoimmune diseases than men. He also had some comments about the limitations of the paper. “The number of patients with autoimmune disorders who are naïve to disease-modifying therapies is relatively small compared to patients with autoimmune disorders who are on those drugs,” he said. “Also, the authors lumped different medications with different mechanisms of action under one category of disease-modifying therapies. However, some medications may cause autoimmune diseases more than others and therefore one cannot generalize to all medications. It would have been interesting to know which medications were more associated with autoimmune disorders or with shorter duration to developing an autoimmune disorder than others.” The final point Sreih made is there may have been a bias by indication of therapy. “Patients who are sicker or have a specific disease receive therapy or certain medications as opposed to patients who are not as sick or have another subtype of multiple sclerosis,” he said. Commonly Reported Associations A number of comorbid autoimmune conditions have been described extensively. Boelaert and colleagues conducted a multicenter, cross-section study that included 2,791 patients with Graves’ disease and 495 patients with Hashimoto’s thyroiditis at a center in the United Kingdom. The aim was to assess prevalence rates of coexisting autoimmune disorders. A second autoimmune disorder occurred in 9.67% of Graves’ disease index cases and 14.3% of Hashimoto’s thyroiditis index cases. RA was the most frequently reported comorbid condition, occurring in 3.15% of Graves’ disease and 4.24% of Hashimoto’s thyroiditis cases. Increases in relative risk for a number of other autoimmune disorders were reported for both Graves’ disease and Hashimoto’s thyroiditis, according to the findings (greater than 10 for pernicious anemia, SLE, Addison’s disease, celiac disease and vitiligo). The parents of index cases also experienced increased relative risks for a number of other coexisting autoimmune disorders. “There was relative ‘clustering’ of Graves’ disease in the index case with parental hyperthyroidism and of Hashimoto’s thyroiditis in the index case with parental hypothyroidism,” the researchers wrote. “These risks highlight the importance of screening for other autoimmune diagnoses if subjects with autoimmune thyroid disease present with new or nonspecific symptoms.” For Berkovich, this makes clinical decision-making of utmost importance. “We should cooperate and collaborate with other clinicians treating these patients,” she said. “Early screening and diagnosis along with early intervention can mitigate further risk.” Gill and colleagues investigated prevalence of comorbid autoimmune diseases in a cohort of 1,098 patients with vitiligo at Henry Ford Health System in Detroit during January 2002 and October 2012. Around 20% of the group had at least one comorbid autoimmune disease. The researchers reported increased rates of a number of conditions in vitiligo patients compared with the general population, including thyroid disease (12.9%), alopecia areata (3.8%), inflammatory bowel disease (0.9%), pernicious anemia (0.5%), SLE (0.3%), Guillain-Barre syndrome (0.3%), discoid lupus (0.2%), linear morphea (0.2%), myasthenia gravis (0.2%) and Sjögren’s syndrome (0.2%). “We observed a high prevalence of comorbid autoimmune diseases in patients with vitiligo and report several new associations,” the researchers concluded. “These associations can tell us about the immune landscape we are dealing with in these patients,” Berkovich said. “The presence of multiple conditions gives us valuable information to help define therapies and understand these diseases.” Sreih said vitiligo can accompany many autoimmune diseases and may be associated with many autoimmune polyendocrinopathies. “The study was relatively large, but unfortunately lacked a control group, and used the general population autoimmune diseases’ estimates for comparison,” he said. “One can potentially compare to the general population if the assumption is the population being studied is representative of the general population, which is probably not the case for this study. The studied population in this paper belongs to one hospital and one specific geographic area of Detroit.” Another key point was thyroid disease was the most common comorbid disease in this population, according to Sreih. “However, hypo- and hyperthyroidism, which are not necessarily caused by autoimmune processes, were included in the definition of thyroid disease and therefore lead to possible overestimation of the true number,” he said. Lauret and Rodrigo addressed approaches to dealing with celiac disease, which remains poorly understood. “Remarkable breakthroughs have been achieved in the last decades, due to a greater interest in the diagnosis of atypical and asymptomatic patients, which are more frequent in adults,” they wrote. “The known presence of several associated diseases provides guidance in the search of oligosymptomatic cases, as well as studies performed in relatives of patients with [celiac disease].” However, they cautioned there is diversity in the etiology of associated diseases. “Some share a similar genetic base, like type 1 diabetes mellitus; others share pathogenic mechanisms, and yet, others are of unknown nature,” they wrote, and warned the disease may present with extra-intestinal manifestations. A gluten-free diet has demonstrated the capacity to improve clinical symptoms of celiac disease, including associated conditions, according to Lauret and Rodrigo. This diet may eliminate anemia or offer improved control of type 1 diabetes. Moving Forward “According to data sets in a number of publications, there is strong evidence that patients with one autoimmune disease have a higher probability of developing another,” Berkovich said. “In my professional experience — 95% of my patients have MS — it is common to see coexisting autoimmune conditions, such as psoriasis. The presence of other autoimmune conditions gives us a lot of information about these patients. We should be paying attention to this.” The good news is drug developers are investigating drugs that minimize the risk of a second condition in patients with MS and other primary disorders, according to Berkovich. “This is the high possible priority in the pipeline right now,” she said. “While I believe it is impossible to create a medication without the potential side effect or risks of complications, I believe we learn to mitigate and stratify the risks. Patients’ safety is always our priority – and this means safety from complications of treatment and also safety from the potentially debilitating complications of MS progression.” -by Rob Volansky References: Berkovich R, et al. US Neurology. 2011doi:10.17925/USN.2011.07.02.132. Boelaert K, et al. Am J Med. 2010;doi:10.1016/j.amjmed.2009.06.030. Chouhfeh L, et al. Multiple Sclerosis and Related Disorders.2015;doi:10.1016/j.msard.2015.02.004. Cojocaru M, et al. Maedica (Buchar). 2010;5:132-134. Farez MF, et al. Multiple Sclerosis International. 2014;doi:10.1155/2014/828162. Gill L, et al. J Am Acad Dermatol. 2016;doi:10.1016/j.jaad.2015.08.063. Lauret E, et al. BioMed Research International. 2013;doi:10.1155/2013/127589. Ni C, et al. Clin Cosmet Investig Dermatol. 2014;doi:10.2147/CCID.S44843 Sardu C, et al. Plos. 2012;doi:10.1371/journal.pone.0032487. Somers EC, et al. Am J Epidemiol. 2009:doi:10.1093/aje/kwn408. For more information: Regina Berkovich, PhD, MD, can be reached at 1520 San Pablo St, #3000, Los Angeles, CA 90033; email: regina.berkovich@med.usc.edu. Eric Matteson, MD, can be reached at 701 Fairview Blvd., Red Wing, MN 55066; email: theimer.sharon@mayo.edu. Emily C. Somers, PhD, ScM, can be reached at the Division of Rheumatology, University of Michigan, 3918 Taubman Center, 1500 East Medical Center Dr., Ann Arbor, MI, 48109; email: emsomers@umich.edu. Antoine G. Sreih, MD, can be reached at Perelman Center for Advanced Medicine, South Pavilion, 1st Floor, 3400 Civic Center Blvd., Philadelphia, PA 19104; email: greg.richter@uphs.upenn.edu. Disclosures: Berkovich reports she is a consultant on advisory boards for Acorda, Bayer, Biogen Idec, Questcor and Teva; and receives research support from Biogen Idec, Questcor, Teva and the National Multiple Sclerosis Society. Matteson and Somers report no relevant financial disclosures. Sreih reports research funding from Glaxo SmithKline, Roche/Genentech, Celgene, Chemocentryx and Bristol-Myers Squibb; and has consulted for Genentech, Krogg and Partners, Rupert Case Management and Naxion.
  13. Multiple sclerosis study reveals possible trigger Israeli scientists discover an abnormality in neurons’ protective membrane may enable the immune system to launch a mistaken attack. By ISRAEL21c Staff June 20, 2017, 9:00 am Multiple sclerosis, one of the most devastating neurodegenerative diseases, affects some 2.5 million people worldwide and has no known cure. Researchers have long speculated that MS is triggered by the body’s own immune system unleashing an uncontrolled attack on myelin sheaths that protect nerve cells (neurons). A study published by Israeli scientists in the Journal of the American Chemical Society (JACS) pinpoints a structural instability in the myelin membranes, the “insulating tape” surrounding neurons. This vulnerability seems to be what gives the immune system access to otherwise protected regions. “We found that small modifications in the myelin sheaths create structural instabilities that may help the immune system to enter and attack neurons,” said principal investigator Prof. Roy Beck of Tel Aviv University’s School of Physics and Astronomy and Sagol School of Neurosciences. “Current therapeutic approaches have focused on the autoimmune response without identifying a clear mechanism. Our research suggests a new avenue for multiple sclerosis therapies and diagnostics,” Beck said. Breaking down the insulation Axons, which carry electrical impulses in neurons, are surrounded by protective myelin sheaths. In MS, an autoimmune “error” mistakenly identifies these sheaths as hostile foreign entities and breaks them down. The research, conducted by Rona Shaharabani, a doctoral student in Prof. Beck’s lab, pinpoints the precise alterations to the myelin sheaths that result in structural instabilities, creating “easy access” for autoimmune attacks. “After years of research, we were amazed to discover that a possible trigger for the outbreak of the disease could be found in the membrane’s physical structure,” said Beck. Cylindrical instead of flat He explained that the lipid-and-protein building blocks of the myelin sheaths give the membrane a shape that is critical to their functioning. “If the basic building blocks are straight, the membrane will be flat, which is the preferred structure for a neuron’s ‘insulating tape,’” said Beck. “However, if they exhibit a more cone-like shape, the membrane will tend to form closed round cylinders. These produce spontaneous holes in the surface of the sheath, rendering it vulnerable to attack.” For the purpose of the research, the scientists harnessed X-ray light to examine hundreds of membrane model systems that mimicked those of healthy and diseased animal models. In collaboration with Prof. Ruth Arnon of the Weizmann Institute of Science in Rehovot, co-developer of the leading MS drug Copaxone, and Prof. Yeshayahu Talmon of the Technion-Israel Institute of Technology in Haifa, the team also used electron microscopy to determine the different nanoscopic structures of both natural myelin sheaths and model system membranes. “The next step is to find a way to reverse the disease progression and find new techniques for early detection,” said Beck. MS is "lupus of the myelin sheath." In SLE, the autommune system causes the body to attack itself via inflammation. In SLE, every body system, not just the myelin sheath, can be attacked, including body organs.
  14. EULAR publishes recommendations for women with lupus Andreoli L, et al. Ann Rheum Dis. 2017;doi:10.1136/annrheumdis-2016-209770. March 9, 2017 A team of EULAR researchers published recommendations for health issues and family planning for women with lupus or antiphospholipid syndrome. Laura Andreoli, PhD, in the Department of Clinical and Experimental Sciences at the University of Brescia in Italy, and colleagues performed a systematic review of evidence and compiled questions and expert opinions to reach a consensus. According to a published extended report, they made the following recommendations for women with lupus or antiphospholipid syndrome: family planning should be discussed after disease diagnosis; most women can have successful pregnancies, and steps can be taken to reduce adverse maternal or fetal outcomes; risk stratification includes disease activity, autoantibody profile, previous vascular morbidity, previous pregnancy morbidity, hypertension and drug use — with an emphasis on the use of hydroxychloroquine and anti-platelets or anti-coagulants; for patients with stable and inactive disease and a low risk for thrombosis, hormonal contraception and menopause replacement therapy can be used; fertility preservation with gonadotropin-releasing hormone analogues should be considered before use of alkylating agents; assisted reproduction techniques are safe for patients with stable and inactive disease; anticoagulants or low-dose aspirin should be given to patients with positive antiphospholipid antibodies; assessment of disease activity, renal function and serological markers is important to diagnose disease flares and monitor adverse obstetrical results; fetal monitoring includes Doppler ultrasonography and fetal biometry — especially in the third trimester — to screen for placental insufficiency and fetuses that are small given gestational age; gynecological malignancy screens are similar to that of the general population, but with increased vigilance for cervical premalignant lesions if patients exposed to immunosuppressive drugs; and the human papillomavirus vaccine can be given in women with stable and inactive disease. – by Will Offit Disclosure : The researchers report no relevant financial disclosures. Perspective This helpful review from EULAR represents a paradigm shift in the management of reproductive health in patients with systemic lupus erythematosus (SLE). We as physicians can ensure patients with SLE achieve healthy pregnancies starting with knowledge of contraception to prevent unwanted pregnancies, and appropriate prenatal risk stratification. With wider availability of varied contraception methods, we can offer IUDs, particularly non-hormonal copper, to all SLE patients of reproductive age. While hormonal contraception methods, such as oral contraceptive pills and patches, have been shown to be safe and effective in patients with stable disease and no APL antibodies, these methods should be used with caution in patients with increased thrombotic risk. In women who wish to become pregnant, fertility counseling should be offered with special attention to treatments which may limit fertility, including alkylating agents, and need to delay pregnancy due to disease activity. If alkylating agents cannot be avoided, preservation of fertility techniques, such as administration of gonadotropin-releasing hormone analogues can be considered. Importantly, SLE patients without risk factors such as active disease (including nephritis), antiphospholipid antibody syndrome, and Ro antibodies most often have healthy pregnancies. Strategies to prevent pregnancy complications include ensuring 6 disease-inactive prenatal months, continuing hydroxychloroquine during pregnancy, and low dose aspirin particularly in antiphospholipid antibody (APL) positive patients. Perinatal SLE may be managed using low-dose oral glucocorticoids, azathioprine or calcineurin inhibitors. APL-positive patients should get ultrasounds and biometric parameters, particularly during the third trimester to screen for placental insufficiency and small for gestational age fetuses. Ro-positive patients should be screened for fetal congenital heart block in the second trimester. Emerging evidence suggests hydroxychloroquine may significantly reduce CHB risk particularly in Ro-positive mothers with prior affected pregnancies. Finally, apart from cervical dysplasia due to human papillomavirus (HPV), gynecological malignancies do not have increased prevalence in SLE, therefore screening should follow age appropriate protocols. All young women with SLE should be offered HPV vaccination. Ashira D. Blazer, MD Instructor of Medicine Division of Rheumatology NYU Langone Medical Center New York Disclosures: Blazer reports no relevant financial disclosures.
  15. Longterm hydroxychloroquine therapy may reduce cardiovascular events in SLE June 16, 2017 MADRID — Long-term use of hydroxychloroquine was associated with reduced cardiovascular risks in a cohort of patients with systemic lupus erythematosus,according to findings presented at the EULAR Annual Congress. “[Systemic lupus erythematosus] SLE may be considered a coronary heart disease condition,” Serena Fasano, MD, of the Rheumatology Unit at the University of Campania Luigi Vanvitelli in Naples, said. “Patients should be investigated for traditional and SLE-related risk factors. SLE patients are candidates for aspirin prophylaxis and long-term hydroxychloroquine. Statins are recommended for patients with persistently high LDL cholesterol levels.” The aim of the study was to assess the role of aspirin, hydroxychloroquine and statins as primary prophylaxis of cardiovascular events in SLE. The study included clinical chart reviews of 291 patients with 8 years of follow-up. “The primary outcome was the first cardiovascular event,” Fasano said. Results showed 16 events in that time. There were seven myocardial infarctions and two strokes in the group. The event-free rate was higher in the 120 patients treated with low-dose aspirin (hazard ratio = 0.27) and hydroxychloroquine for more than 5 years (HR = 0.26) than in 98 patients who were treated with aspirin alone or hydroxychloroquine for fewer than 5 years. “Low-dose aspirin and hydroxychloroquine were negative predictors of events,” Fasano said. No such association was reported for statins. Smoking, obesity, hypertriglyceridemia, diabetes mellitus, disease activity, severe SLE, or use of immunosuppressive agents or steroids failed to demonstrate any kind of association with cardiovascular events, according to Fasano. Multivariable analysis results showed the associations between low-dose aspirin (HR = 0.24) or hydroxychloroquine use for longer than 5 years (HR = 0.27) and reduced incidence of cardiovascular events persisted. — by Rob Volansky Reference: Fasano S, et al. Abstract #OP0233. Presented at: EULAR Annual Congress; June 14-17, 2017; Madrid. Disclosure: The researchers report no relevant financial disclosures. Measure Measure
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