Kori Wallace is the vice president of Clinical Development for AbbVie Immunology
The promise of precision medicine in immunology is both daunting and profound: tailoring treatment to each person’s unique biology to achieve better outcomes. This approach has revolutionized oncology, demonstrating the success of matching treatments to molecular biomarkers. Immunology brings new challenges: immune‑mediated conditions are heterogeneous, influenced by multiple overlapping immune and inflammatory pathways, and can change over time. Yet even in the face of that complexity, new approaches grounded in reverse translation, rational combination strategies, and molecular profiling can pave a path toward higher remission rates and more predictable, patient‑centered care.
Current therapies for many immune-mediated diseases often plateau at similar efficacy levels. Even when a new mechanism adds a meaningful bump, a substantial portion of people still do not achieve or maintain response at one year. This “efficacy ceiling” reflects multifactorial biology: suppressing one pathway can leave others active, allowing symptoms to persist or return. For patients, that reality translates into cycling through treatments, preventable flares, and uncertainty. A more precise strategy, built around a person’s molecular drivers, aims to reduce that uncertainty and deliver steadier relief with treatment that reflects the diversity and complexity of each individual’s immune system. At AbbVie, this ambition is shaping how we think about the future of immunology.
Reverse Translation: Closing the Gap Between Research and Patient Care
Reverse translation is increasingly reshaping immunology research by turning real-world evidence and knowledge generated from ongoing clinical trials of investigational medicines into discovery insights and then cycling those insights back into drug development. Instead of relying solely on preclinical hypotheses, researchers can now systematically analyze clinical data and patient samples to uncover new patterns and mechanisms that might otherwise remain hidden. This approach acknowledges the multifactorial and evolving nature of immune-mediated diseases, where a single pathway rarely tells the whole story.
However, the process is not without hurdles. Obtaining tissue samples, for example, can be invasive and logistically challenging, limiting the granularity of findings. In addition, the heterogeneity intrinsic to autoimmune diseases means that relevant signals are often subtle and complex, not easily captured by a single biomarker. As a result, reverse translation increasingly relies on advanced analytical approaches, using large datasets and sophisticated modeling techniques, to uncover patterns.
Despite these challenges, the approach is paving the path toward more precise care in immunology, ensuring that discoveries are continually informed and refined by real-world outcomes.
Rational Combination Strategies: Breaking the Efficacy Ceiling
The insights gained from reverse translation are now fueling a new era of therapeutic innovation in immunology, the design of rational combination strategies that pair complementary mechanisms to overcome efficacy ceilings. The goal is not simply to “stack” drugs, but to identify pathway synergies that produce biological effects neither agent achieves alone.
It is the lessons learned from nonresponders that are proving particularly valuable. By examining what continues to drive disease when symptoms persist, researchers can uncover which immune pathways remain active or insufficiently suppressed. That knowledge informs the design of rational combination approaches that maintain control of the original pathway while adding a second or even a third mechanism to address residual drivers of disease. In immunology, this concept is still maturing, but early data suggest that such combinations can sometimes uncover previously unrecognized biological interactions.
Yet even the most promising combinations must ultimately prove their value where it matters most—for real patients in the clinic. The emergence of novel biology is only meaningful if it translates into tangible improvements in remission rates, durability of response, or quality of life. Achieving this requires not just new therapies, but also new ways of identifying which patients are most likely to benefit, which is a challenge that brings molecular profiling to the forefront of precision immunology.
Molecular Profiling: Designing Studies That Impact the Biology Driving Disease
Molecular profiling is shifting immunology beyond broad diagnostic categories toward a more nuanced, biology-driven approach. By analyzing molecular signatures—unique patterns of genes, proteins, and other biomarkers—researchers can stratify people into subgroups that are more likely to respond to specific therapies. This approach can make it possible to match the right drug, or combination of drugs, to the right person at the right time.
In clinical trials, molecular profiling can enable researchers to test insights gained from reverse translation, focusing on whether a targeted pathway is mechanistically relevant to a specific subgroup. These mechanistic trials are key to validating such hypotheses, but they are challenging. Unlike oncology, where tumor shrinkage offers a clear signal, immunology endpoints often involve subjective measures, such as joint tenderness or abdominal pain, and variable biomarkers, making efficacy harder to detect in small cohorts. Regulatory frameworks add complexity, as current standards still favor large, all-comer studies. Adapting regulations to support mechanistic trials will be critical for accelerating innovation.
When mechanistic trials confirm a pathway’s relevance, they feed directly into larger studies designed to establish safety and efficacy—steps required before new therapies can reach patients. Molecular profiling can help identify the right patients for early studies, and evidence from these trials can then shape broader programs. Over time, this approach could reduce trial-and-error prescribing and bring us closer to personalized care that reflects the biology driving each person’s disease. This is the direction AbbVie believes is essential for translating scientific insight into sustained patient benefit.
Looking Ahead: The Next Frontier in Immunology
One of the most promising prospects about precision medicine in immunology is the ability to use molecular signatures that transcend traditional disease boundaries, enabling us to recognize patterns that cross several autoimmune conditions. This “plug and play” approach means that, armed with a growing arsenal of treatments, we can match therapies to the specific molecular profile of an individual, regardless of their primary diagnosis. Importantly, we know that molecular profiles can change over time, so the ability to quickly pivot treatments will become a cornerstone of future care.
The integration of vast datasets with computational modeling and machine learning enables hypothesis generation and simulation of complex tissue environments using advanced in vitro systems and rank-order potential therapy combinations for specific subgroups. By harnessing these technologies judiciously, we can make smarter, faster decisions about which therapies to advance, achieving better predictions and faster learning cycles without placing additional burden on patients.
The prospect of precision medicine in immunology could mean that deep, durable, and even drug-free remission becomes a reality for more patients, allowing individuals to live free from the burden of chronic illness. Much of this work remains in early stages, and not all hypotheses will translate clinically, but this iterative model enables faster learning from both success and failure.
