Biomarkers for the Prediction of Therapy Response in Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent joint inflammation, pain and progressive joint damage. First-line treatment typically consists of classical synthetic disease-modifying antirheumatic drugs (csDMARDs), such as methotrexate (MTX), often combined with short-term glucocorticoids. However, approximately 30% of RA patients do not adequately respond to these therapies and subsequently require escalation to more expensive biological (bDMARD) therapies.
Early identification of patients unlikely to respond to first-line treatment remains a major unmet clinical need. Predictive biomarkers enabling earlier treatment stratification could help optimize therapeutic decision-making, reduce unnecessary exposure to ineffective therapies, and potentially improve long-term patient outcomes.
Technology Overview
Researchers at Hasselt University and KU Leuven identified three novel antibody biomarkers directed against the UH-RA.305, UH-RA.318 and UH-RA.329 antigens. Baseline antibody reactivity against these biomarkers was associated with failure to achieve remission or low disease activity after first-line RA therapy.
The biomarkers were evaluated using established disease activity measures, including DAS28CRP, DAS28ESR, SDAI and CDAI. Testing for baseline antibody reactivity identified approximately 36% of RA patients who failed to reach DAS28CRP remission already at early treatment time points such as week 8. Antibody positivity against any of the three antigens significantly discriminated between patients failing to achieve remission and responders (36% versus 13%, p=0.0031).
Importantly, the biomarkers demonstrated particularly strong predictive value in seronegative RA patients lacking rheumatoid factor and anti-citrullinated protein antibodies. In this subgroup, antibody reactivity identified 57% of patients who failed to achieve week 8 remission, compared with only 7% in responders, and was significantly associated with treatment failure in both univariate and multivariate analyses.
The biomarker panel may therefore support earlier identification of patients at risk for insufficient treatment response and facilitate more personalized treatment strategies.
Figure 1: Baseline anti-UH-RA.305/318/329 Ab reactivity according to disease remission at w8. The percentage of anti-UH-RA.305/318/329 positive baseline samples from total (A) and RF/ACPA seronegative (B) RA patients that did (rem+) or did not (rem-) reach remission according to different disease activity criteria at w8.* p-value <0.05. CDAI: clinical disease activity index; SDAI: simplified disease activity index; DAS28ESR: disease activity score with assessment of 28 joints and erythrocyte sedimentation rate (ESR); DAS28 CRP: disease activity score with assessment of 28 joints and C-reactive protein (CRP)
Benefits
- Addresses a significant unmet need in RA treatment stratification
- Blood-based, minimally invasive serum or plasma test
- Enables early prediction of first-line treatment failure
- Potential to support personalized treatment selection and earlier therapy optimization
Relevant Publications
- Fadlallah et al., RDM Open 2026
- Vandormael et al., RMD Open 2024
Opportunity
Licensing / Research Collaboration