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Characterization and Changes of Lymphocyte Subsets in Baricitinib-Treated Patients With Rheumatoid Arthritis: An Integrated Analysis.

Tanaka Y, McInnes IB, Taylor PC, Byers NL, Chen L, de Bono S, Issa M, Macias WL, Rogai V, Rooney TP, Schlichting DE, Zuckerman SH, Emery P. - Arthritis Rheumatol. 2018 Dec;70(12):1923-1932. doi: 10.1002/art.40680

This review shows that changes in lymphocyte subsets were largely within normal reference ranges and were not associated with efficacy or safety end points.

BARI is a selective JAK1/JAK2 inhibitor, approved for the treatment of moderate to severe RA. BARI treatment is associated with changes to circulating lymphocyte and lymphocyte subsets, however detailed analyses of these effects, and their relevance to efficacy and safety is lacking. This study investigated the changes in lymphocyte cell subsets during BARI treatment, and correlates these changes with clinical outcomes.

An integrated analysis was conducted by pooling data from three phase III RA trials comparing placebo with BARI treatment (RA-BEAM, RA-BUILD and, RA-BEACON), and one ongoing long-term extension study (RA-BEYOND).
BARI treatment was associated with an early transient increase in total lymphocyte, T cell count and significant increase in B cells at week 4 for both 2 and 4 mg/day doses, which returned to or decreased below baseline by week 12 through weeks 24–32. NK cells however, significantly increased temporarily at week 4 with BARI treatment compared to the placebo, before decreasing below baseline by week 12 through 24–32.

Compared to patients who never experienced a low NK cell count during placebo treatment, increases in frequency of overall infection were seen in both BARI groups and an increase in frequency of Herpes Zoster infection was seen in BARI 4 mg/day group (2.1%). However, the rate of serious infection was similar among all 3 groups. Patients who experienced ≥1 low NK cell value during the treatment period exhibited a dose-related increase in overall infections with BARI versus placebo.

This study shows distinct changes in different lymphocyte populations, including B cell increases, variable changes in T cell counts and transient reduction in NK cells, without strong association with efficacy or safety end points. The long-term kinetics of these analytes of continued BARI treatment, and clinical correlations, continue to be evaluated.

Keywords: JAK, Baricitinib, Clinical, Safety

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Upload date: January 2019

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