Unraveling the Risk Factors of Rheumatoid Arthritis

By Vandana Suresh | March 4, 2025

The quest to find the root cause of diseases has kept humans occupied since antiquity. Ancient Greeks thought illness was due to imbalances of bodily bile and phlegm, but it was only hundreds of years later, during the rise of empirical science, that concrete answers to disease origin began to emerge. Today, the causes of many diseases, including rheumatoid arthritis (RA), have yet to be fully unraveled, and they pose a major hurdle in guiding appropriate treatments.

To fill this knowledge gap, the Arthritis Foundation awarded a 2024 Rheumatoid Arthritis Research Program award to Mehmet Hocaoglu, MD, a fellow in the rheumatology and clinical immunology division at the University of Pittsburgh. The funding will allow him to investigate the unique and shared risk factors between preclinical rheumatoid arthritis patients and patients with RA.

Before individuals get full-blown RA, their immune systems already show signs of dysregulation. During this preclinical stage, patients produce antibodies against their own bodies, called anti-citrullinated protein antibodies (ACPA) and rheumatoid factors (RF) that can be detected in blood tests. This phase lasts for an average of three to five years but can be as long as 10 years, providing an opportunity for intervention to prevent the onset of rheumatoid arthritis altogether.

Dr. Hocaoglu notes that, adding to the complexity, not all individuals who are positive for ACPA and RF in the preclinical phase eventually develop rheumatoid arthritis. Therefore, attempts to prevent the onset of disease have not been successful.

“There have been several clinical trials in the United States that have tried different rheumatoid arthritis medications to treat people early, before they show clinical signs of the disease, so that they don’t develop rheumatoid arthritis. But unfortunately, they’ve all failed,” says Dr. Hocaoglu. “Whenever you stop therapy, the disease happens anyway. We need reliable indicators that can predict rheumatoid arthritis if we are to deliver preventative care that truly works.”

For his research, Dr. Hocaoglu will investigate genetic and environmental risk factors that underlie the development of preclinical rheumatoid arthritis and the progression from this stage to full-blown disease. He will tap into a very large database of over 30,000 individuals with pre-RA. This group of patients, with more than 10 years of clinical follow-up, are presymptomatic for RA but are positive for rheumatoid factor.

Using this data, Dr. Hocaoglu will use advanced machine learning techniques to build mathematical models that can predict the progression from preclinical RA to RA. 

“I’m quite excited about the grant award,” says Dr. Hocaoglu. “When I read the Foundation’s request for applications for the RA Research Program, I was delighted that it aligned perfectly with my research interests. My hope is that this research will contribute to solving one of the major challenges in the field, which is building accurate prediction models to risk-stratify individuals with pre-rheumatoid arthritis for rheumatoid arthritis development.”