Rheumatoid arthritis is a chronic autoimmune disease affecting millions of people worldwide, progressively impairing joint function and quality of life. Although biological therapies have significantly improved disease management, about 40% of patients do not respond adequately to currently available treatments. The lack of tools capable of accurately predicting therapeutic response remains one of the main challenges in clinical practice.

A study published on last July in Nature Communications proposes an innovative approach to treatment personalization, based on molecular profiling of the synovial tissue (i.e., the connective tissue that lines the inner surface of the joint capsules of movable joints) in the multicentric, randomised trial called STRAP (Synovial Tissue RNA Analysis for Predicting Response to Anti-Rheumatic Therapy). The study was coordinated by Costantino Pitzalis, Full Professor of Rheumatology at Humanitas University, where he also directs the new School of Specialization in Rheumatology, and at Queen Mary University of London, where he carries out his clinical and scientific work.

The STRAP Project: The Molecular Signature of Synovial Tissue Guides Therapy

The STRAP project involved 208 patients with rheumatoid arthritis, aiming to identify, through RNA sequencing of synovial tissue taken before the start of therapy, specific molecular profiles predictive of response to three commonly used biological drugs: etanercept (anti-TNF), tocilizumab (anti-IL6R), and rituximab (anti-CD20).

The models developed showed high predictive accuracy, highlighting the clinical potential of this approach. “The results obtained show that, as already happens in Oncology, the molecular profile of diseased tissue can also guide therapeutic choices in rheumatic diseases,” commented Costantino Pitzalis. “This strategy allows us to move beyond the traditional trial-and-error approach, reducing the time needed to control the disease, limiting exposure to ineffective therapies and, ultimately, bringing us closer to a more rational and patient-centered medicine.” A decisive step towards personalized management of rheumatoid arthritis, and a methodology that could also be applied to other autoimmune diseases, paving the way for a new era of Precision Medicine in rheumatology.

Towards Precision Medicine in Rheumatology

The STRAP project is part of a broader framework of Horizon Europe research programs aiming to revolutionize the therapeutic approach to rheumatoid arthritis. In this context, Costantino Pitzalis is also the Chief Investigator in three major Horizon projects ongoing at Humanitas: 3TR, focused on the differential treatment of patients based on the presence of specific biomarkers identified through synovial tissue analysis; SQUEEZE, which explores genetic and molecular differences among patients who respond differently to various biological drugs; and MDR RA, a project coordinated by Humanitas University that tackles the problem of drug resistance through the integration of clinical, immunological, and molecular data.

In the latter project, Elisa Gremese, Associate Professor of Rheumatology at Humanitas University, is the Principal Investigator of the clinical trials and is responsible for conducting the prospective studies. “The MDR RA project offers us a unique opportunity to better understand drug resistance, one of the major challenges in the management of rheumatoid arthritis,” says Gremese. “By integrating clinical and molecular data, we will be able to develop more effective and targeted personalized therapies, significantly improving the quality of life of those patients who currently benefit the least from available treatments.”

Humanitas’ role in MDR RA reinforces Italy’s contribution to European research, consolidating the link between scientific innovation and clinical practice in the journey towards precision medicine in rheumatology. Supporting the potential of this evolution is also Carlo Selmi, Full Professor of Internal Medicine at Humanitas University and Head of Rheumatology and Clinical Immunology at Humanitas Research Hospital, where patients participating in the clinical trials of the three projects – 3TR, SQUEEZE, and MDR RA – are enrolled. “The prospects for rheumatoid arthritis are concrete and highly impactful,” Selmi emphasizes. “Thanks to advances in precision medicine, we will be able to offer treatments that are increasingly targeted, personalised, and, above all, effective. Research will enable us to make a qualitative leap in the care of autoimmune diseases – likely not only in rheumatoid arthritis.”