Rheumatoid arthritis (RA) is a severe autoimmune disease that is mainly characterized by inflammation of multiple peripheral joints. If left untreated, this inflammation leads to chronic pain and irreversible damage to cartilage and bone in the affected joints. Therefore, the main goal in the current management of RA is to gain rapid control of the ongoing inflammation in an early disease phase.
For newly diagnosed RA patients, current guidelines recommend a first-line therapy consisting of conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs), often combined with glucocorticoids. These first-line combination therapies are relatively low cost, and can induce early disease remission in about two-thirds of RA patients. Still, the remaining non-responding patients experience a prolonged period of high disease activity, leading to additional joint damage. Finding out which patients respond well to first-line csDMARDs still largely depends on trial and error, and would greatly benefit from novel biomarkers that predict this therapy response at baseline, before treatment is initiated.
To address this problem, we used baseline samples of the CareRA trial, which evaluated different first-line combination therapies, to screen for antibodies that could predict lack of disease remission after 16 weeks of therapy. Three novel Hasselt University (UH) antibodies were identified whose presence was significantly higher in baseline samples of RA patients that failed to reach disease remission according to the disease activity score (DAS28CRP) at week 16, compared to RA patients that did reach disease remission. At least one of these 3 antibodies were present in about 30% of the non-responders at week 16, which increased up to 50% in non-responding RA patients that were seronegative for rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA). Finally, presence of these 3 UH antibodies at baseline was correlated with absence of DAS28CRP remission as early as 8 weeks and up to 40 weeks after treatment initiation.
We have identified a set of 3 antibody biomarkers which can predict failure of early disease remission after first-line combination therapy in RA. Patients which are positive for these antibody biomarkers might thus be advised to use an alternative therapy instead of the classic first-line csDMARDs. Therefore, these antibodies provide a novel tool for rheumatologists, allowing them to make a personalized therapy decision.