Transforming autoimmune treatment: How data-driven therapies are changing patient outcomes

These are not short-term conditions; they shape patients’ lives, have a major impact on global health, and require many years of long-term therapies1,2,3. For example, the estimated 5 million people each with lupus and IBD are primarily diagnosed before the age of 45, requiring life-long therapy to manage pain and many other debilitating symptoms4,5,6. Meanwhile, COPD is one of the leading causes of death worldwide, responsible for approximately 3.5 million deaths per year7.

For many patients, today’s treatments are not enough. They manage symptoms, but rarely change the trajectory of the disease. People with these conditions need effective, sustainable therapeutic options. That is why Roche’s Pharma Research and Early Development (pRED) is adopting a patient-centric and data-driven approach to develop lasting treatments for autoimmune diseases.

Although IBD and COPD are different diseases, affecting the gastrointestinal tract and the lung, respectively, they share some scientific similarities. Both arise from abnormal interactions between the immune system, the mucous membrane lining these organs, and pathogens, including bacteria and viruses. Epithelial cells that secrete mucus are often impaired in these diseases, reducing the first line of defense against pathogens. Impaired or exaggerated immune responses to bacteria or viruses contribute to persistent and damaging inflammation in these diseases, as well as leading to acute flares or exacerbations. The traditional therapeutic approach has been to tamp down the immune system to prevent these attacks, but these medicines do not work for everyone, and the immune system still needs to respond to external threats like pathogens, particularly in organs like the intestine and lung that are very susceptible to pathogens.

“There’s a large unmet need because it is not so simple to figure out which parts of the immune system to suppress and which ones to boost,” Kara said. “Our goal for the next generation of therapies is about restoring  balance to the immune system and epithelial cells, rather than just increasing suppression of the immune system.”

To determine what to target to create this balance, pRED scientists are using innovative tools and data. They have learned that understanding what is happening inside tissues, like the gut and lungs, is key to their work. Because much about the immune system can be learned from patient samples, including blood draws, routine biopsies, and other samples,  a wealth of information already exists that allows researchers to test their hypotheses about the disease and potential therapies with computational models. From those computational results, the most exciting ideas can be tested in human cell models known as organoids, which closely resemble human tissue, and targeted experiments in animal models where needed. Roche’s Institute of Human Biology is a leader in developing organoid models of tissues such as the gut and lung, enabling close collaboration to test new therapeutic approaches.

Kara’s team is also thinking differently about how to make better medicines. Rather than just making therapies that are increasingly stronger suppressants of the immune system, they are using human data to understand exactly how current therapies work. They design more specific therapies to increase safety and tolerability, develop therapies that target more than one molecular pathway or cell type to make a broader impact on the disease, and define better molecular and cellular targets. Despite their many similarities, each autoimmune disease requires a different strategy based on its biology.

For example, the team’s newest approach to lupus focuses on deeper targeting of disease-relevant cell types compared to previous therapies. Developing this medicine rests on a long Roche history of therapies that seek to deplete the number of a particular type of immune cell known as B cells. This breakthrough is one step towards resetting the immune system in patients with lupus, hopefully working towards a future with drug-free remission. “This is a story of perseverance and following the science,” Kara said. “When you find the right key to unlock our understanding of the disease, you can transform the patient experience, and the successes we’re now seeing in lupus, we hope, will help us unlock other autoimmune diseases.”

Ultimately, the team’s goal is a deep understanding of each disease that will lead to transformative medicines.