Systemic lupus erythematosus


We are a disruptor in Immunology

Our ambition is to bring forth new transformational therapies for multiple immune-mediated diseases. We aim to move beyond symptom control to drive clinical remission and, eventually, cure in immune-mediated diseases with high unmet need, such as systemic lupus erythematosus (SLE).

We intend to show the world what science can do... as we strive to transform outcomes for those living with immune-mediated diseases.



What is systemic lupus erythematosus?

SLE is a chronic disease in which the body’s immune system attacks healthy tissue in any part of the body.1 It’s experienced differently by each person and can cause a wide range of debilitating symptoms, including skin rash, joint pain, swelling and fevers.2 There have been very few new medicines for SLE, and the significant physical, emotional and socio-economic burden remains high for people living with the disease.3,4




Unlocking the science of systemic lupus erythematosus

In people living with SLE, their immune system dysfunctions and inappropriately attacks healthy tissue within the body.1 SLE disease activity involves B, T and dendritic cells, as well as inflammatory cytokines such as type 1 interferons (IFN-1), IL-6 and B-cell activating factor.5 Cytokines are molecules that act as immune signallers, regulating processes along immune pathways that coordinate the overall immune response.5 Normally, these cells come together to act as a defence network that protects us from infection.6 In SLE, this dysfunction results in the immune system attacking tissues in the body.6 This can lead to inflammation, and in some cases permanent tissue damage, which can be widespread, affecting the skin, joints, heart, lung kidneys, blood cells and brain.7 Up to 60-80% of adults with SLE have an elevated IFN-1 gene signature, which can be associated with increased disease severity.8,9

By understanding the role key cytokines play in the inflammatory cascade, we can begin to further unlock the complex nature of this challenging disease. 

Scientists at AstraZeneca are building on existing disease knowledge and emerging biology, applying learnings from other therapeutic areas, such as cancer, to advance new treatment approaches for SLE. These efforts are critical for those people with SLE who continue to experience inadequate disease control with current therapies. Advanced modalities, such as novel antibody approaches and cell therapies, are being explored to help control the underlying processes that cause SLE with the goal of achieving lasting disease remission.




The biological mechanism behind SLE. Dysregulation in the innate immune system and adaptive immune responses results in chronic autoimmune conditions and disease progression.9




The burden of systemic lupus erythematosus 

Over 3.4 million people worldwide are affected by SLE.10 The chronic and complex disease is known as ‘the great imitator’ because its symptoms mimic many other illnesses, and it can take up to six years for a patient to be diagnosed after first experiencing symptoms.11,12




Addressing unmet needs in the lupus community

SLE is a remitting and relapsing disorder (meaning symptoms come and go) characterised by unpredictable flares of worsening pain and inflammation.4,19,20 Even with treatment many patients with lupus may face permanent organ damage, uncontrolled disease activity and even death.1

Patients often rely on prolonged use of treatments, such as oral corticosteroids (OCS) that offer some relief from symptoms but do not target the underlying drivers of lupus.21 OCS are used by approximately 80% of people with SLE to control flares, yet OCS use contributes to irreversible organ damage.22 As a result, many have an inadequate treatment response and few experience remission.21 Data show that reducing OCS use may reduce organ damage and healthcare costs, and that achieving remission is associated with improved prognosis, mortality and health-related quality of life.23

Recent recommendations by the European Alliance of Associations for Rheumatology (EULAR) advocate aiming for a treatment target of remission or low disease activity to reduce the risk of organ damage and adverse outcomes in patients. To achieve these goals EULAR advises clinicians take an OCS-sparing approach to treatment.24

There is an urgent need to improve patient outcomes and address the unmet medical needs associated with the condition.




Our ambition in lupus: making remission a reality 

EULAR defines remission in SLE according to the Definition of Remission in SLE (DORIS) criteria, as having no disease activity while receiving treatment of antimalarials, immunosuppressives or biologics, but low dose or no OCS.24,25

We’re unlocking the science of the immune system to address the significant unmet needs in lupus. By investigating the underlying drivers of this complex disease we aim to bring scientific advancements to the lupus community – including remission – and challenge boundaries that have been accepted for too long.

Our ambition is to disrupt Immunology by achieving increased rates of remission in under-served diseases like lupus. We want to bring in a new generation of therapeutics, aiming to reverse and repair damage, treat patients earlier, modify the course of disease, and one day offer a cure.

Caterina Brindicci Senior Vice President and Global Head of Late Respiratory & Immunology at AstraZeneca



Living with lupus

Lupus affects each person differently and can be unpredictable. Hear from people with SLE on how the disease has impacted their lives since diagnosis, and their hope for scientific advancements in the field.




Looking to the future

Although clinical research in Immunology is fast-growing, there remains a high unmet need for many people living with immune-mediated diseases.26 As a disruptor in Immunology, we aspire to help patients with immune-mediated diseases move beyond symptom control to achieve remission, and one day, cure. We are investigating pathways in other immune-mediated diseases such as Crohn’s disease, myositis, systemic sclerosis and eosinophilic granulomatosis with polyangiitis (EGPA) to deepen our understanding of their drivers.




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References

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