Cellular biomarkers predict failure to respond to rituximab in rheumatoid arthritis
Rheumatoid arthritis (RA) is the most common type of autoimmune arthritis. It is triggered by a faulty immune system and affects the wrist and small joints of the hand, including the knuckles and the middle joints of the fingers.
But, with the introduction of biologic disease modifying anti-rheumatic drugs (bDMRDs), the armamentarium to fight RA has been dramatically enlarged. It has been shown that B cell depletion with the chimeric monoclonal antibody rituximab (RTX) is an effective treatment strategy for rheumatoid arthritis.
However, B cell depletion with RTX is an effective treatment strategy in RA. One third of patients does not achieve remission or low disease activity (LDA). Thus, identifying patients who will benefit from RTX is highly desirable.
A study was done based on the investigation, in which lymphocyte subsets other than B cells are predictors of a clinical response to RTX treatment. The RA patients who were receiving RTX for the first time were included in the study. Clinical assessments, complete blood count and flow cytometry of lymphocyte subsets were obtained at baseline and at week 24 after RTX. Complete data were available for 44 patients. Logistic regression and receiver operating characteristic curve analyses were computed to analyze the predictive value of lymphocyte subsets for European League Against Rheumatism (EULAR) response and LDA at week 24. It was observed that EULAR responders had lower total lymphocyte counts, T cells and CD4+ T cells at baseline. Although, these parameters were independent predictors of EULAR response, they failed in determining who would reach LDA. In contrast, LC >2910/μl or plasmablast frequency >2.85% at baseline predicted a significantly higher DAS28 at week 24 after RTX and identified patients not achieving LDA at week 24 with sensitivity of 93.3% and specificity of 44.8%.
It was concluded that a combination of LC and plasmablast frequency identifies patients with RA who will not benefit from RTX with high probability. Although, there are several bDMARDs available for RA treatment, but despite a plethora of data from different studies, no single biomarker has emerged that might predict the response to different therapies. Combination of biomarkers with high LC and plasma blast frequency at baseline, that reliably identify patients who are likely to fail to respond to RTX treatment.