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Statins do not influence clinical response and B cell depletion after rituximab treatment in rheumatoid arthritis
  1. Sudipto Das1,
  2. Meritxell Fernandez Matilla1,
  3. Shouvik Dass1,
  4. Maya H Buch1,
  5. Andrew C Rawstron2,
  6. Edward M Vital1,
  7. Paul Emery1
  1. 1Division of Rheumatic & Musculoskeletal Disease, NIHR Leeds Biomedical Research Unit, Leeds Institute of Molecular Medicine, Leeds Teaching Hospitals NHS Trust and University of Leeds, Leeds, UK
  2. 2Haematological Malignancy Diagnostic Service, Leeds Teaching Hospitals NHS Trust, Leeds, UK
  1. Correspondence to Professor Paul Emery, Division of Rheumatic & Musculoskeletal Disease, NIHR Leeds Biomedical Research Unit, Leeds Institute of Molecular Medicine, Academic Unit of Musculoskeletal Disease, Leeds Teaching Hospitals NHS Trust and University of Leeds, Chapel Allerton Hospital, Leeds LS7 4SA, UK; p.emery{at}leeds.ac.uk

https://doi.org/10.1136/annrheumdis-2012-202454

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    B cell depletion by rituximab requires cross linking of CD20, which induces redistribution of CD20 to lipid rafts. This redistribution is correlated with efficiency of complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) in previous studies. The integrity of the lipid rafts may also be important in induction of apoptosis. In vitro, statins interfere with the formation of cholesterol-rich micro domains within the plasma membrane- the lipid rafts, which impairs lymphoma cell killing by ADCC and CDC by rituximab.1 We previously demonstrated that pre- and post-treatment numbers of plasmablasts were associated with clinical response to rituximab.2 Statins were recently reported to inhibit rituximab's clinical efficacy in rheumatoid arthritis (RA).3 We therefore tested for an association of statin use and both …

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    Footnotes

    • Contributors All authors contributed to the planning, conduct and reporting of the work.

    • Funding This work was funded by the Leeds Musculoskeletal Biomedical Research Unit. EMV, SD, MHB and PE have received honoraria from Roche. MFM was sponsored by the Valencian Society of Rheumatology & Spanish Society of Rheumatology.

    • Competing interests PE has received consultancy fees from Pfizer, MSD, Abbott, UCB BMS, Roche and Novartis, and lecture fees from Pfizer, MSD, Abbott and UCB. SD has received funding from Roche, Pfizer. MFM has received a funding grant from Valencia Society of Rheumatology and Spanish Society of Rheumatology. EV has received a funding grant and lecture fees from Roche. SDass has received consultancy and lecture fees from Roche. MB has received consultancy fees from Abbot, BMS, Roche; lecture fees from Abbott, BMS, Roche, Pfizer and a pending grant from Pfizer.

    • Provenance and peer review Not commissioned; externally peer reviewed.