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Characterization and changes of lymphocyte subsets in baricitinib-treated patients with rheumatoid arthritis: an integrated analysis

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Tanaka Y1, McInnes IB2, Taylor PC3, Byers NL4, Chen L4, de Bono S4, Issa M4, Macias WL4, Rogai V4, Rooney TP4, Schlichting DE4, Zuckerman SH4, Emery P5. Arthritis Rheumatol. 2018 Jul 29. doi: 10.1002/art.40680. [Epub ahead of print]

Abstract

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1 The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.

2 Institue of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.

3 Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.

4 Eli Lilly and Company, Indianapolis, Indiana, USA.

5 Leeds Institute of Rheumatic and Musculoskeletal Medicine, NIHR Leeds Musculoskeletal Biomedical Research Centre, LTHT, University of Leeds, Leeds, UK.

Abstract

OBJECTIVE: Baricitinib is an oral selective inhibitor of Janus kinase (JAK) 1 and JAK2 that is efficacious in patients with rheumatoid arthritis (RA). This study analyzed changes in lymphocyte cell subsets during baricitinib treatment and correlated such changes with clinical outcomes of baricitinib treatment.

METHODS: An integrated analysis was conducted by pooling data from three completed Phase 3 trials comparing placebo and baricitinib treatment (RA-BEAM, RA-BUILD, and RA-BEACON) and one ongoing long-term extension study (RA-BEYOND) in patients (N=2,186) with active RA.

RESULTS: Baricitinib treatment was associated with an early transient increase in total lymphocyte count at week 4, which returned to baseline by week 12. Up to week 104, transient changes within normal reference ranges in T cells and subsets were observed with baricitinib treatment. B cells and relevant subpopulations increased after 4 weeks of baricitinib treatment with no further increases noted through 104 weeks of treatment. Natural killer (NK) cells transiently increased after 4 weeks of baricitinib treatment, before decreasing below baseline levels and then stabilizing over time. Few correlations were observed between changes in lymphocyte subsets and clinical endpoints with baricitinib treatment, and most were also observed within the placebo arm. A modest potential association was observed for baricitinib 4-mg between low NK cells and treatment emergent infections but not serious infections or herpes zoster.

CONCLUSION: Overall, changes in lymphocyte subsets were largely within normal reference ranges across the baricitinib Phase 3 RA clinical program, and were not associated with increased risk of serious infections.