Looking Forward
Beyond improving risk stratification and understanding RA pathogenesis, researchers are also considering novel therapeutic approaches for future trials. Glucagon-like peptide 1 (GLP-1) receptor agonists could be worth exploring in RA prevention and treatment, said Jeffrey A. Sparks, MD, MMSc, a rheumatologist at Brigham and Women’s Hospital, Boston, Massachusetts.
These drugs — initially developed for diabetes — have already shown anti-inflammatory effects, and one study suggested that GLP-1s lowered the risk for major adverse cardiovascular events and all-cause mortality in individuals with immune-mediated inflammatory diseases. Obesity is a known risk factor for RA, so weight loss aided by GLP-1 drugs could also help reduce risk in certain patients. Clinical trials are needed to explore GLP-1s for both RA prevention and treatment, he said.
While prevention trials up to this point have used one-time, time-limited interventions, longer durations of medication or multiple rounds of therapy may be more efficacious. Even for trials that demonstrated the intervention arms had less progression to RA, this effect diminished once participants stopped the medication. In the ARIAA and APIPPRA trials using abatacept, “it wasn’t like we hit a reset button and [patients] just permanently now did not get rheumatoid arthritis,” Deane said, suggesting that alternative approaches should be explored.
“Future studies need to look at potentially longer doses of drug or lower doses of drug, or some combination that might be effective,” he said.
Deane received honoraria from Bristol-Myers Squibb, Thermo Fisher, and Werfen and grant funding from Janssen Research and Development and Gilead Sciences. Mankia received grant support from Gilead, Lilly, AstraZeneca, and Serac Life Sciences and honoraria or consultant fees from AbbVie, UCB, Lilly, Galapagos, DeepCure, Serac Life Sciences, AstraZeneca, and Zura Bio. Sparks received research support from Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, and Sonoma Biotherapeutics. He consulted for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Gilead, Inova Diagnostics, Janssen, Merck, Mustang, Optum, Pfizer, ReCor Medical, Sana, Sobi, and UCB.
A version of this article first appeared on Medscape.com.