A combination of cellular biomarkers predicts failure to respond to rituximab in rheumatoid arthritis: a 24-week observational study

Estándar

Martin H. Stradner, Christian Dejaco, Kerstin Brickmann, Winfried B. Graninger and Hans Peter BrezinschekEmail authorView ORCID ID profile
Arthritis Research & Therapy201618:190
DOI: 10.1186/s13075-016-1091-1© The Author(s). 2016
Received: 14 May 2016Accepted: 8 August 2016Published: 24 August 2016

Abstract

Background

Although B cell depletion with rituximab (RTX) is an effective treatment strategy in rheumatoid arthritis (RA), one third of patients do not achieve remission or low disease activity (LDA). Thus, identifying patients who will benefit from RTX is highly desirable. In the present study we investigated whether lymphocyte subsets other than B cells are predictors of a clinical response to RTX treatment.

Methods

Patients with RA who were receiving RTX for the first time were included in an observatory registry. 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 (defined as disease activity score in 28 joints (DAS28) ≤3.2) at week 24.

Results

EULAR responders had lower total lymphocyte counts (LC), 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 %.

Conclusions

A combination of LC and plasmablast frequency identifies patients with RA who will not benefit from RTX with high probability.

Keywords

Rheumatoid arthritis Biomarker Rituximab T cells Plasmablasts Lymphocytes

Anti‑citrullinated peptide antibodies and their value for predicting responses to biologic agents: a review

Estándar

Rheumatol Int DOI 10.1007/s00296-016-3506-3

Emilio Martin‑Mola1,7 · Alejandro Balsa1 · Rosario García‑Vicuna2 · Juan Gómez‑Reino3 · Miguel Angel González‑Gay4 · Raimon Sanmartí5 · Estíbaliz Loza

Abstract Anti-citrullinated peptide antibodies (ACPAs) play an important pathogenic role both at the onset and during the disease course. These antibodies precede the clinical appearance of rheumatoid arthritis (RA) and are associated with a less favorable prognosis, both clinically and radiologically. The objective of this work was to conduct a comprehensive review of studies published through September 2015 of ACPAs’ role as a predictor of the therapeutic response to the biological agents in RA patients. The review also includes summary of the biology and detection of ACPAs as well as ACPAs in relation to joint disease and CV disease and the possible role of seroconversion. The reviews of studies examining TNF inhibitors and tocilizumab yielded negative results. In the case of rituximab, the data indicated a greater probability of clinical benefit in ACPA+ patients versus ACPA− patients, as has been previously described for rheumatoid factor. Nonetheless, the effect is discreet and heterogeneous. Another drug that may have greater effectiveness in ACPA+ patients is abatacept. Some studies have suggested that the drug is more efficient in ACPA+ patients and that those patients show greater drug retention. In a subanalysis of the AMPLE trial, patients with very high ACPA titers who were treated with abatacept had a statistically significant response compared to patients with lower titers. In summary, the available studies suggest that the presence of or high titers of ACPA may predict a better response to rituximab and/or abatacept. Evidence regarding TNFi and tocilizumab is lacking. However, there is a lack of studies with appropriate designs to demonstrate that some drugs are superior to others for ACPA+ patients.