ORIGINALLY PUBLISHED:
6 November 2023
There is an increasing need to improve treatment approaches for people living with immune-mediated diseases who continue to face uncertain and unacceptable outcomes such as permanent organ damage, uncontrolled disease activity and even death.1-4
Over recent years, immunology has emerged as one of the fastest-growing fields of clinical research – second only to oncology – in terms of ongoing clinical trials.5
At AstraZeneca, our ambition is to transform care for immune-mediated diseases by moving beyond symptom control to achieve disease modification, remission and, one day, a cure for millions of people worldwide.
Following the science in immune-driven disease areas
Although clinical research in immunology is fast-growing, there remains a high unmet need for treatments for many people living with immune-mediated diseases who do not achieve disease control with existing therapies.3,6,7 Immune-mediated diseases occur when the immune system mistakenly attacks tissues in the body. This dysfunction causes inflammation, and in some cases permanent tissue damage, which can impact a wide range of body parts including the skin, joints, intestinal system, kidneys, lungs and brain.8
Our deep experience and scientific understanding of the immune system has led us to examine the impact of disease pathway imbalances across a number of conditions to help us understand the genetic drivers of disease. We are following the science to discover how we can intervene by resetting the activity within these key pathways, reducing inflammation, repairing damaged tissue and stabilising the immune system.
Our bold ambition in immunology – to make remission a treatment goal
We are continuing to follow the science to further unlock our understanding of complex immune-driven diseases. Our bold ambition in Immunology is to disrupt current treatment paradigms and make remission – not just symptom management – a goal for as many patients as possible.
The current challenge for patients living with immune-mediated diseases
Complex immune-mediated diseases like systemic lupus erythematosus (SLE), eosinophilic granulomatosis with polyangiitis (EPGA) and inflammatory bowel disease (IBD) remain challenging to diagnose and treat, and many patients today do not achieve remission.1,3,9-11 For example, people living with EGPA can often take more than four years to receive a diagnosis, and in lupus the path to diagnosis can be even longer (up to six years or more).1,12 For these patients, achieving disease control can be particularly challenging, and an estimated 10-15% will die prematurely due to lupus-related complications.1,9 Similarly, up to 50% of people living with Crohn’s disease, a type of IBD, have no response to treatment and up to 80% fail to achieve remission.13
Despite the introduction of updated treatment strategies and the development of novel therapies in SLE and EGPA, oral corticosteroid (OCS) use still remains high.2,3,10 Although OCS can improve symptoms, long-term use is associated with poor quality of life and serious side effects, with an estimated 50% of patients with SLE developing irreversible organ damage within five years of diagnosis due to their disease and existing treatments.3,10,14-16 In Crohn’s disease, studies have shown that the use of OCS works well to reduce and control symptoms during flare-ups, but may not be as effective in achieving lasting remission.17
Treatment goals for the future of immune-mediated diseases
Remission is a treatment goal in guidelines for SLE, EGPA and IBD, including Crohn’s disease and ulcerative colitis (UC).
SLE
The recently updated international SLE treatment recommendations from the European Alliance of Associations for Rheumatology (EULAR) emphasise the need for prompt initiation of treatment aiming at remission, which is associated with improved clinical outcomes including reduced organ damage, fewer flares, reduced hospitalisation, reduced mortality and improved health-related quality of life.9,18,19 The revised SLE treatment recommendations advise an OCS-sparing approach (a threshold of 5mg per day or less) to significantly reduce disease progression and improve quality of life for patients.16
EGPA
Similarly, treatment of EGPA is focused on preventing relapses and increasing the time spent in remission, as the number of relapses and duration of OCS use are associated with long-term organ damage.20,21 Global EGPA guidelines recognise both inducing and maintaining remission as a treatment goal and recommend that OCS use is kept to a minimum.22,23
IBD
Finally, the aim of IBD treatment for both Crohn’s disease and UC is to induce and maintain remission. While European Crohn’s and Colitis Organisation (ECCO) guidelines consider OCS effective in inducing remission, they note use-limiting adverse events and the inability to prevent disease relapse.24 As more therapies become available, it may be possible to use targets based on objective measures to work toward effective and lasting disease control.25
A growing body of evidence is emerging, including examples from other chronic diseases, that could further inform guidelines to drive greater adoption of OCS-sparing strategies and enable physicians to safely and effectively taper their patients from OCS.
Patients living with immune-mediated diseases deserve improved outcomes and sustained relief. We hope to unlock opportunities to better target these conditions, leading to new treatment approaches, and through earlier intervention and personalised medicine, ultimately change the natural course of these diseases.
Shifting mindsets and implementing the latest treatment recommendations could bring clinical practice closer to other disease areas that have had success, and, ultimately, make a significant impact on the long-term health of people living with chronic immune-driven diseases. At AstraZeneca, we won’t stop until we deliver clinical remission for the majority of those living with these complex diseases.
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References
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Veeva ID: Z4-65791
Date of preparation: June 2024