Preventive Strategies, Novel Treatments & More

The latest in rheumatoid arthritis

BARCELONA—Over the past two years, thousands of articles have been published in the medical literature on rheumatoid arthritis (RA). This summer during EULAR 2025, Diane van der Woude, MD, PhD, professor of translational rheumatology at the Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, The Netherlands, reviewed this massive cache of knowledge in her presentation, Rheumatoid Arthritis: What Is New.

Supplements & RA

Dr. van der Woude began her lecture discussing RA prevention.

Vitamin D, she noted, has been of interest to scientists given its role in regulating genes involved in inflammation. In animal models, some studies have shown a possible benefit in the prevention of autoimmune disease, though observational studies in humans have shown conflicting results.^1,2  Fish oil consumption, specifically in the form of omega-3 polyunsaturated fatty acids, has demonstrated immunomodulatory and anti-inflammatory effects that may have implications for autoimmune diseases, such as systemic lupus erythematosus, and type 1 diabetes.^3,4

In the VITAL study from Hahn et al., more than 12,000 men aged 50 and older and more than 13,000 women aged 55 and older were randomized to receive either 2,000 IU/day of vitamin D or matched placebo and 1,000 mg/day of omega-3 fatty acids or matched placebo. Then, participants were asked to report all incident autoimmune diseases from baseline to a median of 5.3 years of follow up. A medical record review was used to confirm the reported histories. In the initial study, vitamin D and omega 3 fatty acid supplementation reduced the autoimmune disease rate by 22% and 15%, respectively.⁵

An additional study during the post-intervention, follow-up period, found the protective effect of vitamin D supplementation on autoimmune disease incidence was no longer observed. Meanwhile, fatty acid supplementation demonstrated a sustained reduction in autoimmune disease incidence.⁶ Dr. van der Woude noted that further studies are needed to evaluate if and when such effects persist over longer periods of time.

Preventive Therapy

Next, Dr. van der Woude tackled the growing number of clinical trials that use existing disease-modifying anti-rheumatic drugs (DMARDs) and biologic therapies for RA prevention.

In the APIPPRA study, more than 200 patients with inflammatory joint pain, antibodies to citrullinated protein antigens (ACPA) and rheumatoid factor were randomized to receive either abatacept or placebo for 12 months. Patients were then followed for an additional 12 months. After 24 months, 37% of patients in the placebo group developed RA vs. 25% of patients in the abatacept group.⁷

In the ARIAA study, patients with ACPA positivity and signs of inflammation on magnetic resonance imaging were randomized to receive abatacept or placebo for six months and then followed for an additional 12-month period without treatment. By six months, about 35% of participants in the placebo group developed RA vs. about 8% of those in the abatacept treatment group.⁸

Based on these studies, Dr. van der Woude explained that abatacept appears to be effective as an RA prevention strategy in patients with ACPA-positive arthralgias. However, the sustained effect of this medication in the long term remains to be determined.

For comparison, methotrexate has a more complicated story. In the TREAT EARLIER trial, methotrexate did not prevent the development of RA over a two-year period compared with placebo. But the study showed a signal of possible benefit in patients with ACPA-negative arthralgias and a high inflammatory burden.⁹ To Dr. van der Woude, this finding implies that stratifying patients who are at risk of RA into different groups may better enable clinicians to predict which patients will benefit from preventative therapy.

More Research

Dr. van der Woude also addressed a variety of other interesting, RA-related studies.

In a study on telemedicine, Jackson et al. found that the satisfaction with regard to telemedicine of a large, diverse group of patients was not noninferior to in-person rheumatology visits. When the authors looked at satisfaction levels based on patient gender, men were equally satisfied with both types of visits, whereas women were more likely to be satisfied with in-person visits.¹⁰

In a study on renal disease from Fukui et al., higher RA disease activity was associated with an accelerated decline in estimated glomerular filtration rate (eGFR), as well as an increased risk of clinically relevant kidney dysfunction.¹¹ These findings are important because among older patients with chronic kidney disease, the risk of serious adverse events has been found to be higher in those treated with low-dose methotrexate—a favorite medication of rheumatologists across the world—compared with those treated with hydroxychloroquine.¹²

In a study on the risk of lung cancer in RA, Brooks et al. found that patients with RA had a more than 50% increased risk of lung cancer compared with age and gender-matched controls without RA. The risk was highest in patients with RA and interstitial lung disease (ILD), with an approximately three-fold increased risk of disease compared with patients without ILD.¹³

Novel Treatments

The final portion of the lecture discussed novel therapies for RA. With chimeric antigen receptor (CAR) T cell therapy clearly on everyone’s mind, Dr. van der Woude noted this mode of treatment represents a promising, potentially long-lasting intervention for the disease.

Based on at least one case in the literature, the fact that ACPA levels decline following CD19-CAR T cell treatment implies that ACPA autoreactivity resides in the CD19 cellular subset.¹⁴ Innovative constructs, such as a new, autologous, fourth-generation CD19-targeted CAR T cell that secretes antibodies against interleukin (IL) 6 and tumor necrosis factor (TNF) α, are also being tested.¹⁵ However, Dr. van der Woude reminded the audience that the conditioning regimen and costs associated with CAR T cell therapy may still be barriers to this therapy being used for RA on a broader scale.

Bispecific T cell engagers, or BiTEs, also represent a novel therapy for patients with RA. BiTEs can simultaneously bind to T cells—typically via CD3—and a disease-relevant target, such as an autoantigen or a cell-surface molecule on autoreactive B or T cells, thereby bringing T cells into close proximity with pathogenic immune cells. This approach leads to targeted cytotoxicity or immune modulation of the autoreactive population while sparing non-pathogenic cells.

 Dr. van der Woude’s key takeaways on BiTEs are:

1. They appear to be effective and capable of deep B cell depletion in tissue;
2. They may be an option for treatment-resistant patients;
3. They have an effect that is not long lasting and, thus, may require re-treatment; and
4. They are still finding their place in the therapeutic landscape.

Among other potential new therapies in RA are S1PR1 agonists, PD1 agonists (note: development was halted for peresolimab, other agents are being investigated) and FcRn blockers, such as nipocalimab.

Jason Liebowitz, MD, FACR, is an assistant professor of medicine in the Division of Rheumatology at Columbia University Vagelos College of Physicians and Surgeons, New York.

References

1. Deluca HF, Cantorna MT. Vitamin D: Its role and uses in immunology. FASEB J. 2001 Dec;15(14):2579–2585.
2. Dankers W, Colin EM, van Hamburg JP, et al. Vitamin D in autoimmunity: Molecular mechanisms and therapeutic potential. Front Immunol. 2017 Jan 20;7:697.
3. Liu A, Li Z, Zeng J, et al. ω-3 polyunsaturated fatty acid alleviates systemic lupus erythematosus by suppressing autoimmunity in a murine model. Int Immunopharmacol. 2024 Jan 5;126:111299.
4. Bi X, Li F, Liu S, et al. ω-3 polyunsaturated fatty acids ameliorate type 1 diabetes and autoimmunity. J Clin Invest. 2017 May 1;127(5):1757–1771.
5. Hahn J, Cook NR, Alexander EK, et al. Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: VITAL randomized controlled trial. BMJ. 2022 Jan 26;376:e066452.
6. Costenbader KH, Cook NR, Lee IM, et al. Vitamin D and marine n-3 fatty acids for autoimmune disease prevention: Outcomes two years after completion of a double-blind, placebo-controlled trial. Arthritis Rheumatol. 2024 Jun;76(6):973–983.
7. Cope AP, Jasenecova M, Vasconcelos JC, et al. Abatacept in individuals at high risk of rheumatoid arthritis (APIPPRA): A randomised, double-blind, multicentre, parallel, placebo-controlled, phase 2b clinical trial. Lancet. 2024 Mar 2;403(10429):838–849.
8. Rech J, Tascilar K, Hagen M, et al. Abatacept inhibits inflammation and onset of rheumatoid arthritis in individuals at high risk (ARIAA): A randomised, international, multicentre, double-blind, placebo-controlled trial. Lancet. 2024 Mar 2;403(10429):850–859.
9. Krijbolder DI, Verstappen M, van Dijk BT, et al. Intervention with methotrexate in patients with arthralgia at risk of rheumatoid arthritis to reduce the development of persistent arthritis and its disease burden (treat earlier): A randomised, double-blind, placebo-controlled, proof-of-concept trial. Lancet. 2022 Jul 23;400(10348):283–294.
10. Jackson LE, Yazdany J, Leach JM, et al. Satisfaction with telemedicine versus in-person visits in rheumatology: A noninferiority randomised controlled trial. Ann Rheum Dis. 2025 May 7:S0003–4967(25)00820-9.
11. Fukui S, Winkelmayer WC, Tedeschi SK, et al. Disease activity of rheumatoid arthritis and kidney function decline: A large prospective registry study. Ann Rheum Dis. 2025 Feb;84(2):201–209.
12. Muanda FT, Blake PG, Weir MA, et al. Low-dose methotrexate and serious adverse events among older adults with chronic kidney disease. JAMA Netw Open. 2023 Nov 1;6(11):e2345132.
13. Brooks RT, Luedders B, Wheeler A, et al. The risk of lung cancer in rheumatoid arthritis and rheumatoid arthritis-associated interstitial lung disease. Arthritis Rheumatol. 2024 Dec;76(12):1730–1738.
14. Haghikia A, Hegelmaier T, Wolleschak D, et al. Clinical efficacy and autoantibody seroconversion with CD19-CAR T cell therapy in a patient with rheumatoid arthritis and coexisting myasthenia gravis. Ann Rheum Dis. 2024 Oct 21;83(11):1597–1598.
15. Li Y, Li S, Zhao X, et al. Fourth-generation chimeric antigen receptor T-cell therapy is tolerable and efficacious in treatment-resistant rheumatoid arthritis. Cell Res. 2025 Mar;35(3):220–223.