PMID- 31848169 OWN - NLM STAT- MEDLINE DCOM- 20201112 LR - 20220129 IS - 2044-6055 (Electronic) IS - 2044-6055 (Linking) VI - 9 IP - 12 DP - 2019 Dec 16 TI - Belimumab after B cell depletion therapy in patients with systemic lupus erythematosus (BEAT Lupus) protocol: a prospective multicentre, double-blind, randomised, placebo-controlled, 52-week phase II clinical trial. PG - e032569 LID - 10.1136/bmjopen-2019-032569 [doi] LID - e032569 AB - INTRODUCTION: Few treatment options exist for patients with systemic lupus erythematosus (SLE) who fail conventional therapy. Although widely used to treat lupus, the efficacy of B cell depletion therapy using rituximab has not been demonstrated in randomised clinical trials. Following rituximab, elevated levels of serum B cell activating factor (BAFF) have been associated with failure to remit or subsequent lupus relapse. The administration of belimumab, a monoclonal antibody specific for BAFF and approved for lupus therapy, could potentiate the efficacy of rituximab and enable longer periods of disease remission. The aim of this trial is to assess the safety and efficacy of belimumab following rituximab in patients with SLE. METHODS AND ANALYSIS: BEAT Lupus is a double-blind, randomised, placebo controlled, phase II clinical trial. Patients with SLE commencing a treatment cycle of rituximab (two 1g infusions, 2 weeks apart) as standard of care will be randomised to receive belimumab or placebo, 4 to 8 weeks following the first rituximab infusion. Belimumab or placebo infusions are administered for 52 weeks. The primary outcome measure is anti-double stranded DNA (anti-dsDNA) antibody levels at 52 weeks. Secondary outcomes include measures of adverse events, lupus disease activity and cumulative steroid dose. The kinetics of B cell repopulation will be assessed in a subgroup of participants. Belimumab administration after rituximab may provide a novel therapeutic pathway for patients with active lupus if safety is demonstrated in this proof of concept study, and lower anti-dsDNA antibodies levels are achieved in those patients treated with belimumab compared with placebo. ETHICS AND DISSEMINATION: The protocol has been reviewed and approved by the Hampstead Research Ethics Committee - London (reference 16/LO/1024). Trial information is available at https://www.isrctn.com/ISRCTN47873003, and the results of this trial will be submitted for publication in relevant peer-reviewed journals. Key findings will also be presented at national and international conferences. TRIAL REGISTRATION NUMBER: ISRCTN47873; date assigned to the registry: 28 November 2016. The stage is pre-results. CI - (c) Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ. FAU - Jones, Alexis AU - Jones A AD - Centre for Rheumatology, Division of Medicine, University College London, London, UK. FAU - Muller, Patrick AU - Muller P AUID- ORCID: 0000-0002-6824-578X AD - Comprehensive Clinical Trials Unit, University College London, London, UK. FAU - Dore, Caroline J AU - Dore CJ AD - Comprehensive Clinical Trials Unit, University College London, London, UK. FAU - Ikeji, Felicia AU - Ikeji F AD - Comprehensive Clinical Trials Unit, University College London, London, UK. FAU - Caverly, Emilia AU - Caverly E AD - Comprehensive Clinical Trials Unit, University College London, London, UK. FAU - Chowdhury, Kashfia AU - Chowdhury K AD - Comprehensive Clinical Trials Unit, University College London, London, UK. FAU - Isenberg, David A AU - Isenberg DA AUID- ORCID: 0000-0001-9514-2455 AD - Centre for Rheumatology, Division of Medicine, University College London, London, UK. FAU - Gordon, Caroline AU - Gordon C AD - Rheumatology Research Team - Inflammation and Ageing (IIA), University of Birmingham Research Laboratories, New Queen Elizabeth Hospital, Birmingham, UK. FAU - Ehrenstein, Michael R AU - Ehrenstein MR AUID- ORCID: 0000-0003-1673-743X AD - Centre for Rheumatology, Division of Medicine, University College London, London, UK m.ehrenstein@ucl.ac.uk. LA - eng SI - ISRCTN/ISRCTN47873003 SI - EudraCT/2015-005543-14 GR - 20873/VAC_/Versus Arthritis/United Kingdom GR - MC_UU_12023/14/MRC_/Medical Research Council/United Kingdom PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20191216 PL - England TA - BMJ Open JT - BMJ open JID - 101552874 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (B-Cell Activating Factor) RN - 0 (Immunosuppressive Agents) RN - 4F4X42SYQ6 (Rituximab) RN - 73B0K5S26A (belimumab) SB - IM MH - Adult MH - Antibodies, Monoclonal/*administration & dosage MH - Antibodies, Monoclonal, Humanized/*administration & dosage/adverse effects MH - B-Cell Activating Factor/blood MH - Double-Blind Method MH - Drug Therapy, Combination MH - Female MH - Humans MH - Immunosuppressive Agents/*administration & dosage MH - Lupus Erythematosus, Systemic/*drug therapy MH - Male MH - Middle Aged MH - Prospective Studies MH - Rituximab/*administration & dosage MH - Severity of Illness Index PMC - PMC6937022 OTO - NOTNLM OT - immunology OT - rheumatology COIS- Competing interests: MRE has received grant/research support from GSK. CG has been a member of the speakers bureau for GSK and has received consultancy fees for attending advisory boards. EDAT- 2019/12/19 06:00 MHDA- 2020/11/13 06:00 PMCR- 2019/12/16 CRDT- 2019/12/19 06:00 PHST- 2019/12/19 06:00 [entrez] PHST- 2019/12/19 06:00 [pubmed] PHST- 2020/11/13 06:00 [medline] PHST- 2019/12/16 00:00 [pmc-release] AID - bmjopen-2019-032569 [pii] AID - 10.1136/bmjopen-2019-032569 [doi] PST - epublish SO - BMJ Open. 2019 Dec 16;9(12):e032569. doi: 10.1136/bmjopen-2019-032569.