Lupus SK Society Inc.

Working together to conquer Lupus - 1 in 1000 persons in Canada have Lupus

A Proud Member Organization of Lupus Canada

SLE Information


Lupus Canada Fact Sheets - Lupus Canada is in the process of producing a series of Fact Sheets that aim to provide concise and up-to-date information on a variety of lupus-related issues including:

Please visit Lupus Canada's LIVING WELL WITH LUPUS page to view the current fact sheets and watch for additional topics to be covered.

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FIRST NEW LUPUS TREATMENT IN ALMOST 50 YEARS!

MARKHAM, ON – July, 12, 2011 – Health Canada’s recent approval of BENLYSTA™ marks the first new treatment available in almost 50 years to the over 1:1000 Canadian men, women and children who are living with Systemic Lupus Erythematosus (SLE) an autoimmune disease with no known cause or cure. Lupus most often affects women of childbearing age (15-45) but can affect men, children and the elderly. Nine times more women than men will however be diagnosed with lupus.

“Lupus is a life-altering and life-threatening diagnosis” says Catherine Madden, Executive Director of Lupus Canada. “This incurable disease impacts and destroys many organs in the body and can cause constant pain, immobility, organ failure and even death. Lupus is seriously under-recognized and under-funded, but dedication to new therapies and new research fuels our hope for a cure. While Lupus Canada works towards a vision of life without lupus, we concentrate our efforts on ensuring people with lupus are living well. The approval of BENLYSTA™ means there is a new treatment option for Canadians living with lupus.”

Known as the “disease with 1000 faces”, because its symptoms vary so greatly from person to person, lupus affects over 1:1000 Canadian men, women and children, yet many people are still unaware of the disease. Because of the varied symptoms, lupus can be extremely difficult to diagnose. The symptoms of lupus often mimic other illnesses, and it can attack any tissue or organ in the body including skin, muscles, joints, blood and blood vessels, lungs, heart, kidneys and the brain. Common and often chronic symptoms of lupus include joint pain and inflammation, skin rashes, sun sensitivity, extreme fatigue, fever, chest pain and hair loss.

“As a child, I understood only that my father suffered from lupus – he couldn’t play ball, ride a bike or walk to the store… many days he was in too much pain to be able to get out of bed” says Kendra MacDonald, President, Board of Directors, Lupus Canada. “It was not only my father that suffered from lupus for over 20 years, our entire family was touched by the disease and the constant fear that the next complication would take his life which it ultimately did in 2001. The arrival of a new treatment helps to bring hope for other families like ours!”

Lupus Canada, working together with its provincial partners, is a national voluntary organization dedicated to improving the lives of people living with lupus through advocacy, education, public awareness, support and research. We provide educational and support resources for people whose lives are touched by lupus, raise awareness of Lupus and provide funding for research. Through the support of events such as Walk for Lupus and generous, engaged individual and corporate donors, we are able to continue our work on behalf of people living with lupus.

To learn more about lupus, Lupus Canada, our member organizations and divisions, visit www.lupuscanada.org or contact us at 1-800-661-1468. To learn more about BENLYSTA™, contact your doctor.

BENLYSTA™ Overview

What is BENLYSTA™?
BENLYSTA™ is a new drug for the treatment of systemic lupus erythematosus (SLE), or simply ‘lupus’. It is the first in a new class of drugs called ‘BLyS inhibitors’ that specifically binds to and inhibits the biological activity of BLyS or the B-lymphocyte stimulator – a protein thought to contribute to the biological activity of BLyS or the B-lymphocyte stimulator – a protein thought to contribute to the production of autoantibodies (antibodies that attack the body’s own healthy tissues) in lupus.

BENLYSTA™ (belimumab), a human monoclonal antibody, is indicated in addition to standard therapy for reducing disease activity in adult patients with active, autoantibody-positive systemic lupus erythematosus. The safety and efficacy of BENLYSTA™ have not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus. The efficacy of BENLYSTA™ in patients of black African heritage has not been clearly established.

BENLYSTA™ is the first FDA and now Health Canada-authorized treatment for lupus in almost 50 years; it is the first drug developed specifically for lupus.

How does BENLYSTA™ work?
Patients with active lupus may have elevated levels of a naturally-occurring protein called ‘BLyS’ (B-lymphocyte stimulator), a B cell survival factor. Autoreactive B cells produce antibodies that attack normal healthy tissue, which leads to inflammation (the body’s normal response to injury or infection) in many parts of the body. BENLYSTA™, a human monoclonal antibody administered by intravenous infusion, specifically binds to and inhibits the biological activity of BLyS which inhibits the survival of B cells, including autoreactive B cells.

What is BLyS?
BLyS (B-lymphocyte-stimulator) is a naturally-occurring protein.

What are the potential advantages of BENLYSTA™ over existing treatment options for lupus?
BENLYSTA™ is a new targeted therapy that focuses on the underlying aspects of the disease by selectively targeting and inhibiting soluble BLyS. When given together with other drugs for lupus, BENLYSTA™ decreased lupus disease activity more than the other drugs alone.

Who should be considered for BENLYSTA™?
BENLYSTA™ is indicated in addition to standard therapy for reducing disease activity in adult patients (18 years of age and older) with active, autoantibody-positive systemic lupus erythematosus (SLE, or simply ‘lupus’).

The efficacy of BENLYSTA™ has not been established in the following groups:

• Patients with severe active lupus nephritis
• Patients with severe active central nervous system lupus
• Patients of black African heritage
• Patients less than 18 years of age.

Can BENLYSTA™ be used during pregnancy?
There are no adequate and well controlled clinical studies using BENLYSTA™ in pregnant women and therefore the effects of BENLYSTA™ on pregnant women are not yet known. Immunoglobulin G antibodies, including belimumab, can cross the placenta, therefore BENLYSTA™ should not be used during pregnancy unless the potential benefit to the mother justifies the potential risk to the fetus. Women of childbearing potential should use adequate contraception while using BENLYSTA™ and for at least four months after the final treatment. Safety and efficacy have not been established in patients less than 18 years of age. A Pregnancy Registry to monitor maternal-fetal outcomes of pregnant women exposed to BENLYSTA™ has been established. Women who are nursing should talk to their health care provider about whether or not to use BENLYSTA™ as it is likely it can pass into human breast milk.

What are the warnings and precautions associated with BENLYSTA™?
Immunization: Live vaccines should not be given for 30 days before, or concurrently with BENLYSTA™ as clinical safety has not been established. No data is available on the secondary transmission of infection from persons receiving live vaccines to patients receiving BENLYSTA™. Because of its mechanism of action, BENLYSTA™ may interfere with the response to immunizations. The efficacy of concurrent vaccination in patients receiving BENLYSTA™ is not known. Limited data suggests that BENLYSTA™ does not significantly affect the ability to maintain a protective immune response to immunizations received prior to administration of BENLYSTA™.

What is the rationale behind the exclusion of patients with severe renal and CNS lupus?
Patients with severe active lupus kidney disease or active CNS lupus were excluded from the trials because of the likelihood that these patients would require changes in medications and therefore not be considered to be on a stable lupus treatment regimen required for enrolment in the Phase 3 trial. Efficacy studies in these lupus populations would require a different primary endpoint than those for overall disease activity trials in SLE.

The benefit of BENLYSTA™ has been described as modest; how much of a difference will BENLYSTA™ make for patients?
We believe that BENLYSTA™ will be an important addition to the available treatments for appropriate patients with lupus. In the Phase 3 trials of BENLYSTA™, the patient had to demonstrate improvement on the SLE Responder Index (SRI) meaning that one or more symptoms had to have complete resolution (i.e. significant decrease of disease activity within a year, no organ worsening and a physician assessment finding no deterioration in a patient’s overall condition).

Is the data adequate to demonstrate efficacy in organ involvement associated with poor outcome and mortality, such as kidneys, central nervous system, and blood vessels?
The Phase 3 studies were not designed or powered to determine improvement or worsening in individual organ systems. Patients with severe active lupus kidney disease or active CNS lupus were excluded from the trials because of the likelihood that these patients would require changes in medications and therefore not be considered to be on a stable lupus treatment regimen required for enrolment in the Phase 3 trial. Efficacy studies in these lupus populations would require a different primary endpoint than those for overall disease activity trials in SLE. The reduction in disease activity seen in the SRI was related primarily to improvement in the most commonly involved organ systems namely, mucocutaneous, musculoskeletal, and immunology. A lupus nephritis study is planned in the post-marketing setting.

How will patients who are unable to afford BENLYSTA™ obtain access to it?
The BENLYSTA™ Monarch Program is a patient support program which will support patients with educational information, reimbursement and navigation services as well as infusion services. GSK is fully committed to working with payers/insurance companies to encourage policies that provide coverage of BENLYSTA™ for appropriate patients who could benefit from therapy. GSK will also provide standard reimbursement and navigation services and information regarding coverage verification to healthcare professionals and patients. GSK will further support patients’ access to BENLYSTA™ through financial assistance programs, including co-pay assistance.

What challenges do you expect from managed care organizations and reimbursement agencies?
In Canada, GSK hopes that most provincial governments will provide coverage because they will recognize the potential value of BENLYSTA™ for the appropriate patients.

What can we expect to be paying for BENLYSTA™?
The cost will depend on BENLYSTA™’s inclusion in government assisted drug plans.

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What is SLE?

Systemic Lupus Erythematosus (SLE) is a chronic inflammatory disease which may affect many different organs and tissues in the body. Women of child bearing age are typically affected, but individuals of any age, sex or race may develop the disease.

SLE while uncommon, is not rare, with an estimated disease prevalence of 1 in every 1,000 population. It is a condition which appears to be increasing in prominence especially over the last 15 - 20 years. This is likely explained by the earlier recognition of milder cases because of increased patient and physician awareness and by the enhanced availability of sensitive laboratory tests helpful in the diagnosis.

Although the exact cause is unknown, most of the features of the disease seem to be due to fundamental abnormality of the body's immune system. The immune system is the body's defense mechanism against foreign substances entering the body. It depends on the formation of compounds called antibodies on white cells called lymphocytes which rise to the defense of the body in case of invasion by foreign agents such as germs or viruses. This is a normal and desirable process in the healthy individual. In patients with SLE, there seems to be a defect in the body's immune system whereby antibodies are mistakenly formed against the body's own tissues. This leads to inflammation and damage in the tissues so affected. Patients with SLE can be identified by the presence of thse abnormal antibodies in their blood stream.

It is not clear what triggers this immune abnormality but several factors seem to be contributory on some patients. These include infection, hormonal, genetic, and unidentified environmental factors. Some drugs including those used to treat tuberculosis (isoniazid), high blood pressure (hydralazine), and convulsions (dilantin) have also occasionally been associated with the development of SLE.

Clinical Features

The majority of patients with SLE have very mild symptoms which can be easily controlled with simple measures. A small minority have more serious manifestations which may require more aggressive forms of treatment.

The seriousness of the disease is frequently related to the type and number of organs affected.

The following is a summary of some of the signs and symptoms that may occur in lupus patients grouped according to the organs or tissues affected:

  1. General symptoms - fever and unusual fatigue occur in up to 80% or 90% of SLE patients at some time during the course of their illness.

  2. Skin rash - a very common feature occurring in many patients. The classic rash is called a "butterfly rash" because it occurs in a butterfly- like a patch over the bridge of the nose and cheeks. This type of rash is in fact quite common with most lupus rashes being far less specific and accruing anywhere on the body but especially over sun exposed areas.

    Many lupus rashes appear to be provoked or aggravated by direct sun exposure. Sores may also occur in the nose and mouth, and scalp hair loss may occur in some individuals.

    In a closely related condition called Discoid Lupus Erythematosus (DLE), the rash may arise as distinct scaly and reddish patches which may heal with scarring. Patients with DLE are frequently otherwise well. They demonstrate few, if any, of the symptoms of SLE and usually have a nearly normal laboratory profile.

  3. Joints - stiffness, pain, and swelling may commonly occur. Unlike Rheumatoid Arthritis however, permanent damage to the joints is almost unheard of.

  4. Membranes of the heart and lungs - the linings of the heart and lungs may occasionally become inflamed in SLE patients leading to sharp chest pains and shortness of breath. If it involves the lung, the condition is called pleuritis. If it affects the heart, the condition is called pericarditis.

  5. Blood cells - a number of abnormalities may occur in the blood including anemia or a fall in the red blood cell count and/or falls in the white cell count or platelet count (particles in the blood that help with clotting) and thus lead to potential problems with bleeding.

  6. Kidneys - often a sign of more serious disease, inflammation of the kidney may lead to loss of protein in the urine, increased blood pressure and occasionally kidney failure.

  7. Brain and nerves - fortunately, a relatively rare problem, patients so affected may have trouble with headaches, convulsions, emotional disturbances, weakness or numbness of extremities.

Diagnosis

The diagnosis of SLE is suspected in any individual who presents with one or more of the clinical features outlined in Clinical Features. A diagnosis is confirmed by laboratory tests which show the presence of one or more abnormal circulating antibodies in the blood stream. These antibodies may be directed against the tissue in the body. The most important of these however, is an antibody directed against the centre or nucleus of the cells in the body, the so-called anti-nuclear antibody or ANA. ANAs are normally not present or present only barely detectable quantities in healthy individuals. Thus, this test is very helpful to the doctor if he is suspicious about the possibility of SLE. It is very important however, to stress that presence of ANAs doesn't specifically point to a diagnosis of SLE since abnormal antibodies of this type may occur in other conditions such as rheumatoid arthritis, certain infections and inflammation of the liver. Thus the diagnosis of SLE requires both the presence of abnormal antibodies (especially ANAs) as well as sign and symptoms suggesting inflammation of several organs of tissues in the body.

Although, all lupus patients have elevated levels of ANA, not all people with elevated ANA have lupus. Increased levels of ANA generally indicate that the physician should follow up with an anti-DNA antibody test.

To assist in the diagnosis of SLE, the American Rheumatism Association (ARA) in 1982 adopted a set of criteria for the classification of this disease. (See table 1 in the conclusion) It should be noted that while a variable number of these features may occur during the course of the disease, they need not occur at the same time. Moreover, it is quite unpredictable as to which patient may develop which particular symptom or grouping of symptoms at any particular time.

Management and Treatment

The management of patients with SLE has three important components:

1. Education of Patient and Family

Educating the patient and the family is essential in the management of SLE. Patients and the family are frequently misinformed about the disease and the time taken to correct and clarify any early misconceptions is greatly rewarding. A great deal of helpful information and support by persons similarly affected is also available through patient self-help groups such as the Lupus Erythematosus Society of Saskatchewan.

It is also important for patients with SLE to realize the importance of good health habits in the control of their illness. This includes a well balanced diet, adequate rest, as well as physical activities tailored to the individual's tolerance. Most patients should also reduce direct sun exposure and consider the use of effective sun screen preparations. Preparations with a sun protection factor (SPF) of at least 15 and which block both UVA and UVB rays are recommended.

2. Medical Treatment

SLE is typically a disease which shows a fluctuating course characterized by long periods of relative inactivity (remission) punctuated flares of inflammation involving one or more organ system (exacerbation). Fortunately for a majority of SLE patients, the symptoms are so mild as to require little or no specific treatment. The choice of therapy will therefore depend both on the nature as well as the severity of the symptoms. The initial treatment of minor joint aches and pains may often consist of a simple anti-arthritic medications sometimes known as non-steroidal anti-inflammatory drugs or NSAIDs. Skin rash can frequently be managed by avoidance of sunlight as well as the use of topical steroid creams as directed by the family physician. If the rash or arthritis is more troublesome, your doctor may consider a class of drugs used for the treatment of malaria such as hydroxychloroquine or Plaquenil.

For patients with more serious symptoms such as severe fever, pleurisy or pericaritis, of falling blood count, it may be necessary to resort to the use of corticosteroids by mouth for a variable length of time.

Unfortunately corticosteroids have a variety of side effects and your doctor will endeavor to taper and reduce the dosage as quickly as is medically possible. A relatively new approach called pulse steroid therapy involves the administration of very large does of corticosteroids either orally or intravenously over a short periods such as 1 - 3 days. Pulse steroid therapy would seem to have the advantage of being relatively free of immediate and long term side effects.

For the rare patients where steroids are inadequate, treatment is available with a number of more potent drugs specifically directed at suppressing the information of the abnormal antibodies which occur in SLE. These drugs, examples of which include Imuran and Cyclophosphamide, are called cytotoxic or immunosuppressive agents. These drugs are frequently effective but may have serious effects including the suppression of the body's normal ability to fight infection.

An alternative non-drug approach to the management of SLE, especially severe kidney disease, may be sometimes considered. This procedure, which is called plasmapheresis, involves as exchange type transfusion whereby the red blood cells are removed from the blood and returned to the body while undesirable antibodies and complexes and the liquid part of the body's blood (plasma) are discarded. This treatment seems most effective when combined with one of the cytotoxic or immunosuppressive drugs.

3. Follow-up

As the course of SLE may be unpredictable, close medical follow-up is essential. This involves periodic assessment of disease activity by clinical history, physical examination and specific laboratory tests ordered by your doctor.

Close follow-up during pregnancy and the immediate postpartum period is especially important as the risk of disease flare is increased during these periods. Inactive disease at the time of conception is associated with the best prognosis for both mother and baby. There is a slight but definite increased risk of miscarriage in mothers with lupus and their babies may have an increased chance of being born premature or with low birth weights.

Babies born to lupus mothers may also be at risk of developing lupus (neonatal lupus). This is due probably to the passage of abnormal antibodies through the placenta into the fetal blood stream. Neonatal lupus almost always resolves within 4 - 6 months of delivery.

Babies born to lupus mothers may also be at increased risk of being born with an abnormality to the conduction system of the heart muscle. This may or may not be associated with other signs of neonatal lupus and seems to correlate closely with a very specific type of antibody in the other's circulation called the anti-Ro antibody.

Conclusion

Although there is no specific cure for SLE, there is much room for optimism. Patients are now being identified far earlier and therapy, if necessary, is generally more effective. Moreover, as physicians have gained experience with the disease and it's management, many of the past complications which often as not arose from overzealous treatment can now be avoided. More importantly, fundamental advances are being made in the understanding of the specific immune abnormalities in SLE, which undoubtedly will lead to steady improvements both in the management and the overall prognosis.

Table 1 - 1982 Revised ARA Criteria for Classifications of SLE*

  1. Butterfly rash
  2. Discoid rash
  3. Sun sensitive rash
  4. Mouth ulcers
  5. Arthritis
  6. Pleuritis / Pericaritis
  7. Kidney disorder
  8. Brain or nerve disorder
  9. Blood disorder
  10. Presence's of one or more antibodies to various tissues
  11. Presence of anti-nuclear antibodies (ANA)

* For the purpose of identifying patients, a person shall be said to have SLE if any 4 or more of the 11 criteria are present serially or simultaneously.