«Skip to content ‘+ Skip to navigation * Skip to footer AstraZeneca. Search Enter your search What scien © Stories © Publications © R&D © Our approach © Precision medicine © Transformative science © Data science & Al © Clinical innovation ¢ Digital health © Our technologies © Next generation therapeutics R&D strategic centres Our therapy areas © All therapy areas © Oncology © BioPharmaceuticals Ir Cardiovascular, Renal and Metabolism Respiratory & Immunology Vaccines and Immune Therapies Rare Disease Pipeline All medicines Our company ‘Our company ‘Our people ‘Our leadership Cambridge Gothenburg Gaithersburg Careers © Careers website © Working with us © Inclusion and diversity Investors VAN © Investor Relations (Global) Za © Investor Relations (Sweden) © ResourcesGovernance Shareholder information Dividend policy Key facts FAQs Debt Investors ADR Programme ia Press Releases Media centre Articles Statements Image library Broadcast videos Archive Media contact: Sustainability Sustainability Access to healthcare Environmental protection Ethics and transparency Partnerships, alliances and recognition ‘Supporting our communities Resources Partnering Partnering with AstraZeneca Our business development teams Our areas of partnering interest Why partner with AstraZeneca? ‘Supplier Information A Catalyst Network * AstraZeneca Websites Taking a precision medicine approach in immune- mediated diseases PUBLISHED 11 November 2022 Topics: Disease understanding Next generation therapeutics Written by:Tatiana Ort Executive Director and Head of Bioscience Immunology, AstraZenca { 2 Adam Platt Vice President and Head of Translational Science and Experimental Medicine, Respiratory and Immunology, AstraZeneca Building on decades of research, we are starting to unravel complex inflammatory cell signalling pathways and uncover key drivers that cause an imbalance in immune- mediated diseases. With an estimated 5 million people worldwide living with lupus? and 6.8 million with inflammatory bowel disease?, well-known immune-mediated diseases, there is a significant need for new innovative therapies to help improve outcomes for these patients. Precisely targeting disease drivers in immune-mediated diseases Moving away from the traditional stepwise treatment approach, the next-wave of therapeutic discovery is embracing the potential that precision medicine can offer - ensuring the right patient, gets the right medicine, at the right time. We are rapidly building our knowledge of disease biomarkers to help differentiate patient subgroups within a single disease, and develop diagnostic tests and precision medicines, which are targeted to the underlying causes of disease. What is precision medicine in chronic diseases? Inflammatory Bowel Disease Our precision medicine approach in Inflammatory Bowel Disease (IBD) focuses on selecting distinct patient subpopulations through identifying biomarkers of disease. IBD is an umbrella term for conditions with chronic inflammation of the gastrointestinal tract and includes ulcerative colitis and Crohn's disease. To date, our core research has focused on inflammatory cytokines called interleukins, known to be increased in these conditions, so we can identify patients who are failing to respond to treatment or become intolerant over time®The pro-inflammatory cytokine interleukin 23 (IL-23) is a known driver of inflammation and is mainly secreted by activated macrophages and dendritic cells located in tissues like skin, lung and the intestinal mucosa’. IL- 23 potently enhances local inflammation by increasing T helper (Th) cells which are responsible for many of the autoimmune responses in IBD. Crohn's Disease is driven by a Th1/Th17 interaction where IL-23 plays a key part and this is supported by genome-wide association studies that have strongly connected IL-23 to the pathogenesis of Crohn's Disease. The levels of IL-23 in the blood, even when elevated in disease, are hard to detect with easy-to-use technologies. An alternative biomarker is needed to clinically determine patients who have IL-23 driven disease. The effector cytokine IL-22 is a downstream product of IL-23 and has roles maintaining the integrity of the mucosal barrier and stimulating epithelial cell proliferation. It is also a direct indicator of IL-23 activity and therefore has potential as a disease biomarker’, We believe that a significant reduction in IL-22 levels could be indicative of both disease activity and potential post-treatment disease modification. In collaboration with Roche Diagnostics, we are currently progressing the development of an accurate, non-invasive diagnostic test for IL-22 and exploring the interconnection between biomarker levels and clinical outcomes across a broad range of patients. Systemic Lupus Erythematosus Systemic Lupus Erythematosus (SLE) is a complex, chronic disease in which the body's immune system attacks healthy tissue in any part of the body. It is estimated that at least five million people worldwide have a form of lupus’, which can manifest in a range of symptoms including skin rash, joint pain, swelling and fevers. Lupus remains poorly understood and the significant physical, emotional and socio-economic burden remains high for people living with the disease‘. SLE involves over activity of B-cells, T-cells and dendritic cells, as well as inflammatory cytokines such as type 1 interferons (IFN), IL-6 and B-cell activating factor. Cytokines regulate and coordinate the overall inflammatory response and in people with SLE over production results in a prolonged autoimmune response, leading to injury, inflammation and long-term organ damage "° Research has shown an association between an elevated IFN gene signature and disease as well as a correlation between IFN protein levels and serological and clinical manifestations of SLE"’. These data underscore our focus on IFN as a biomarker of SLE disease activity and is helping to guide our precision medicine approach. Research has shown that by measuring IFN mRNA levels instead of protein it was possible to detect an elevated IFN gene signature in over three quarters of adults in our patient cohort’, We've successfully deployed this blood-based biomarker test for IFN activity in clinical study programs to stratify patients with SLE and understand their underlying disease drivers'2, Moving forward, our scientists are also investigating other immune-mediated diseases where an IFN gene signature may enrich for patient populations likely to benefit from targeted treatments and improve their disease outcomes. Bringing precision medicines to patients There remains a huge unmet need for patients and healthcare systems in immune-mediated diseases. Providing access to routine diagnostics and precision medicines targeted to the underlying disease will be a powerful enabler of better patient outcomes and more sustainable care. Innovative financing, regulatory and clinical mechanisms will be necessary to support access and uptake, We are committed to working collaboratively with the immunology community to realise this potential and deliver precision medicine research to improve lives of those living with immune-mediated diseases.Topic: Related stories Where technology meets precision medicine Targeting the drivers of immune-mediated diseases Why we need longitudinal patient cohorts to transform respiratory research Get email alerts for new What Science Can Do stories. Sign up to email alerts Your email address will only be used to provide you with services from AstraZeneca that you requested. You can opt out for email subscriptions at any time. Your personal information will not be provided to any third party without your permission, First name Last name Email You may also like Precision medicin Systemic Lupus Erythematosus Precision medicine: Glossary of terms References 1. Lupus Foundation of America. Lupus facts and statistics. https://www.lupus.org/resources/lupus-facts-and- statistics#:~:text=The%20L upus%20Foundation%200f%20America have%20a%20form%200f%20lupus. 2, Global burden of inflammatory bowel disease. Lancet Gastroenterology and Hepatology 2020 Jan;5(1):2-3. 3. Efficacy and Safety of MEDI2070, an Antibody Against Interleukin 23, in Patients With Moderate to Severe Crohn's Disease: A Phase 2a Study, Gastroenterology, 2017; 153 (1): 77-86 4. Al Sawah S, Daly RP, Foster SA, et al. The caregiver burden in lupus: findings from UNVEIL, a national online lupus survey in the United States. Lupus. 2017 Jan;26(1):54-61 5. Crow MK. Type | interferon in the pathogenesis of lupus. J /mmunol. 2014;192(12):5459-5468. Accessed April 20216. Lauwerys BR, Ducreux J, Houssiau FA. Type | interferon blockade in systemic lupus erythematosus: where do we stand? Rheumatol. 2014;53(8):1369-1376. 7. Hoffman RW, Merrill JT, Alarcén-Riquelme MM, et al. Gene expression and pharmacodynamic changes in 1,760 systemic lupus erythematosus patients from two phase Ill trials of BAFF blockade with tabalumab. Arthritis Rheumatol. 2017;69(3):643-654. 8. Becker AM, Dao KH, Han BK, et al. SLE peripheral blood B cell, T cell and myeloid cell transcriptomes display unique profiles and each subset contributes to the interferon signature. PLoS One. 2013;8(6):e67003. 9. Jefferies CA. Regulating IRFs in IFN driven disease. Front Immunol. 2019;10:325. 10. Mai L, Asaduzzaman A, Noamani B, et al. The baseline interferon signature predicts disease severity over the subsequent 5 years in systemic lupus erythematosus. Arthritis Res Ther. 2021;23:29 11, Hammond ER, Tummala R, Berglind A, Syed F, Wang X, Desta B, Nab H. Study protocol for the international Systemic Lupus Erythematosus Prospective Observational Cohort Study (SPOCS): understanding lupus and the role of type | interferon gene signature. BMJ Open. 2020 1;10(9) 12, Type | interferon inhibitor anifrolumab in active systemic lupus erythematosus (TULIP=1): a randomised, controlled, phase 3 trial, The Lancet Rheumatology, Volume 1, Issue 4, 2019 Veeva ID: 24-5004 Date of preparation: October 2022 You are now leaving AstraZeneca.com You have selected a link that will take you to a site maintained by a third party who is solely responsible for its contents. AstraZeneca provides this link as a service to website visitors. AstraZeneca is not responsible for the privacy policy of any third party websites. We encourage you to read the privacy policy of every website you visit Click ‘cancel’ to return to AstraZeneca’s site or ‘continue’ to proceed. Important notice for users You are about to access AstraZeneca historic archive material. Any reference in these archives to AstraZeneca products or their uses may not reflect current medical knowledge and should not be used as a source of information on the present product label, efficacy data or safety data. Please refer to your approved national product label (SmPC) for current product information. I have read this warning and will not be using any of the contained product information for clinical purposes.