(Vienna, 06-03-2025) Recently published analyses led by Josef Smolen of MedUni Vienna provide new insights into how certain blood values can influence the effectiveness of medications for rheumatoid arthritis (RA). The results are based on an evaluation of the large-scale international EXXELERATE study and a supplementary investigation that offers further insights into the role of rheumatoid factor and other biomarkers. These findings, published in the journal "Rheumatology", open up new approaches for individually tailored therapy planning.
The analyses focus on rheumatoid factor (RF), an autoantibody found in the blood of many people with RA. High RF levels are associated with a more severe disease course and increased disease activity. A subanalysis of the EXXELERATE study now showed that patients with high RF levels (>204 IU/ml) achieved better clinical outcomes when treated with a monoclonal antibody targeting tumour necrosis factor (TNF) named certolizumab pegol (CZP) than when treated with another one named adalimumab (ADA). While the concentration of ADA in the blood was significantly lower in these patients, the CZP levels remained stable, indicating sustained high efficacy.
In a supplementary analysis, Josef Smolen (Department of Medicine III, MedUni Vienna) confirmed these observations and also investigated the influence of other autoantibodies, including anti-citrullinated protein antibodies (ACPA). The results suggest that only high RF levels appear to cause a more rapid elimination of so-called Fc-containing TNF inhibitors such as ADA. CZP, which does not contain an Fc fragment, does not appear to be affected by this mechanism, leading to more stable drug levels and better treatment outcomes. "One of the main research objectives of our department is to develop better treatment strategies that are tailored to the individual characteristics of each patient," says Daniel Aletaha, head of the Clinical Division of Rheumatology at MedUni Vienna's Department of Medicine III.
Rheumatoid arthritis is a chronic inflammatory disease that causes pain and swelling and can even lead to the loss of joint function. If left untreated, RA can result in significant restrictions to quality of life and permanent joint damage. Treatment includes the use of so-called TNF inhibitors such as CZP and ADA, for example, but their effectiveness depends heavily on individual factors. Josef Smolen: "Our analyses show that the rheumatoid factor could be used as an important biomarker in therapy planning and provide an important contribution to better aligning therapy decisions with the individual needs of patients and to increase quality of life in the long term."
Publications:
Rheumatology
Poor prognostic factors and unmet needs in rheumatoid arthritis.
Josef S. Smolen
https://doi.org/10.1093/rheumatology/keae701
Rheumatology
Impact of high rheumatoid factor levels on treatment outcomes with certolizumab pegol and adalimumab in patients with rheumatoid arthritis.
Josef S. Smolen1*, Peter C. Taylor , Yoshiya Tanaka , Tsutomu Takeuchi, Motomu Hashimoto, Carlos Cara, Bernard Lauwerys, Nicola Tilt, Baran Ufuktepe, Ricardo M. Xavier, Alejandro Balsa, Jeffrey R. Curtis, Ted R. Mikuls, Michael Weinblatt
https://doi.org/10.1093/rheumatology/keae435