PMID- 36477362
OWN - NLM
STAT- MEDLINE
DCOM- 20221215
LR  - 20230111
IS  - 2379-3708 (Electronic)
IS  - 2379-3708 (Linking)
VI  - 7
IP  - 23
DP  - 2022 Dec 8
TI  - A randomized, phase II study of sequential belimumab and rituximab in primary 
      Sjogren's syndrome.
LID - 10.1172/jci.insight.163030 [doi]
LID - e163030
AB  - BACKGROUNDPrimary Sjogren's syndrome (pSS) is characterized by B cell 
      hyperactivity and elevated B-lymphocyte stimulator (BLyS). Anti-BLyS treatment 
      (e.g., belimumab) increases peripheral memory B cells; decreases naive, 
      activated, and plasma B cell subsets; and increases stringency on B cell 
      selection during reconstitution. Anti-CD20 therapeutics (e.g., rituximab) bind 
      and deplete CD20-expressing B cells in circulation but are less effective in 
      depleting tissue-resident CD20+ B cells. Combined, these 2 mechanisms may achieve 
      synergistic effects.METHODSThis 68-week, phase II, double-blind study (GSK study 
      201842) randomized 86 adult patients with active pSS to 1 of 4 arms: placebo, 
      s.c. belimumab, i.v. rituximab, or sequential belimumab + 
      rituximab.RESULTSOverall, 60 patients completed treatment and follow-up until 
      week 68. The incidence of adverse events (AEs) and drug-related AEs was similar 
      across groups. Infections/infestations were the most common AEs, and no serious 
      infections of special interest occurred. Near-complete depletion of minor 
      salivary gland CD20+ B cells and a greater and more sustained depletion of 
      peripheral CD19+ B cells were observed with belimumab + rituximab versus 
      monotherapies. With belimumab + rituximab, reconstitution of peripheral B cells 
      occurred, but it was delayed compared with rituximab. At week 68, mean (+/- 
      standard error) total EULAR Sjogren's syndrome disease activity index scores 
      decreased from 11.0 (1.17) at baseline to 5.0 (1.27) for belimumab + rituximab 
      and 10.4 (1.36) to 8.6 (1.57) for placebo.CONCLUSIONThe safety profile of 
      belimumab + rituximab in pSS was consistent with the monotherapies. Belimumab + 
      rituximab induced enhanced salivary gland B cell depletion relative to the 
      monotherapies, potentially leading to improved clinical outcomes.TRIAL 
      REGISTRATIONClinicalTrials.gov NCT02631538.FUNDINGFunding was provided by GSK.
FAU - Mariette, Xavier
AU  - Mariette X
AD  - Department of Rheumatology, Universite Paris-Saclay, Hopital Bicetre, Assistance 
      Publique - Hopitaux de Paris, INSERM UMR1184, Le Kremlin Bicetre, Paris, France.
FAU - Barone, Francesca
AU  - Barone F
AD  - Institute of Inflammation and Ageing, College of Medical and Dental Sciences, 
      University of Birmingham, Birmingham, United Kingdom.
FAU - Baldini, Chiara
AU  - Baldini C
AD  - Centro Farmacologia Clinica AOUP, Rheumatology Unit, Department of Clinical and 
      Experimental Medicine, University of Pisa, Pisa, Italy.
FAU - Bootsma, Hendrika
AU  - Bootsma H
AD  - Department of Rheumatology and Clinical Immunology, University of Groningen, 
      University Medical Center Groningen, Groningen, The Netherlands.
FAU - Clark, Kenneth L
AU  - Clark KL
AD  - Clinical Science, GSK, Stevenage, Hertfordshire, United Kingdom.
FAU - De Vita, Salvatore
AU  - De Vita S
AD  - Rheumatology Clinic, Department of Medical Area, Azienda Ospedaliera 
      Universitaria di Udine, Udine, Italy.
FAU - Gardner, David H
AU  - Gardner DH
AD  - Institute of Inflammation and Ageing, College of Medical and Dental Sciences, 
      University of Birmingham, Birmingham, United Kingdom.
FAU - Henderson, Robert B
AU  - Henderson RB
AD  - Clinical Pharmacology and Experimental Medicine, GSK, Stevenage, Hertfordshire, 
      United Kingdom.
FAU - Herdman, Michael
AU  - Herdman M
AD  - Clinical Pharmacology and Experimental Medicine, GSK, Stevenage, Hertfordshire, 
      United Kingdom.
FAU - Lerang, Karoline
AU  - Lerang K
AD  - Department of Rheumatology, Oslo University Hospital, Oslo, Norway.
FAU - Mistry, Prafull
AU  - Mistry P
AD  - R&D Biostatistics, GSK, Stevenage, Hertfordshire, United Kingdom.
FAU - Punwaney, Raj
AU  - Punwaney R
AD  - Pharmaceutical Research and Development, GSK, Collegeville, Pennsylvania, USA.
FAU - Seror, Raphaele
AU  - Seror R
AD  - Department of Rheumatology, Universite Paris-Saclay, Hopital Bicetre, Assistance 
      Publique - Hopitaux de Paris, INSERM UMR1184, Le Kremlin Bicetre, Paris, France.
FAU - Stone, John
AU  - Stone J
AD  - R&D, GSK, Stevenage, Hertfordshire, United Kingdom.
FAU - van Daele, Paul LA
AU  - van Daele P
AD  - Department of Internal Medicine and Department of Immunology, Erasmus Medical 
      Center, Rotterdam, The Netherlands.
FAU - van Maurik, Andre
AU  - van Maurik A
AD  - Clinical Pharmacology and Experimental Medicine, GSK, Stevenage, Hertfordshire, 
      United Kingdom.
FAU - Wisniacki, Nicolas
AU  - Wisniacki N
AD  - Discovery Medicine, GSK, Stevenage, Hertfordshire, United Kingdom.
FAU - Roth, David A
AU  - Roth DA
AD  - R&D, GSK, Collegeville, Pennsylvania, USA.
FAU - Tak, Paul Peter
AU  - Tak PP
AD  - R&D, GSK, Stevenage, Hertfordshire, United Kingdom.
LA  - eng
SI  - ClinicalTrials.gov/NCT02631538
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20221208
PL  - United States
TA  - JCI Insight
JT  - JCI insight
JID - 101676073
RN  - 4F4X42SYQ6 (Rituximab)
SB  - IM
MH  - Humans
MH  - Rituximab/therapeutic use
MH  - *Sjogren's Syndrome/drug therapy
PMC - PMC9746921
OTO - NOTNLM
OT  - Autoimmune diseases
OT  - Clinical Trials
OT  - Drug therapy
OT  - Immunology
COIS- Conflict of interest: XM has received grant/research support from Ose and has 
      been a paid consultant for AstraZeneca, BMS, Galapagos, GSK, Novartis, Pfizer, 
      and Sanofi. FB has received grant/research support from GSK, UCB, Roche, and 
      Actelion; has been a paid consultant for GSK, UCB, Roche, and Actelion; and has 
      been an employee of Kintai Therapeutics and Candel Therapeutics. HB has received 
      grant/research support from BMS and Roche; has been a paid consultant for BMS, 
      Roche, Novartis, MedImmune, UCB, and Servier; and has been a paid speaker for BMS 
      and Novartis. RBH, PM, RP, AVM, NW, and DAR are employees of GSK and hold shares 
      in the company. PPT, KLC, and MH were employees of GSK and held shares in the 
      company at the time of study design and execution. SDV has been a paid consultant 
      for GSK, Novartis, and Roche. KL has participated in advisory boards for GSK and 
      AstraZeneca. RS has been a paid consultant for GSK, Boehringer, Novartis, 
      Janssen, BMS, and AbbVie; has received support to attend meetings from GSK and 
      Amgen; and has been involved with clinical trials for GSK, Servier, USB, and 
      Novartis. JS was an employee of GSK, holds shares in the company, and is 
      currently an employee of AstraZeneca and holds shares in the company. GSK was 
      involved in study design, collection, analysis, and interpretation of data, as 
      well as publication development.
EDAT- 2022/12/09 06:00
MHDA- 2022/12/15 06:00
PMCR- 2022/12/08
CRDT- 2022/12/08 11:37
PHST- 2022/06/24 00:00 [received]
PHST- 2022/10/26 00:00 [accepted]
PHST- 2022/12/08 11:37 [entrez]
PHST- 2022/12/09 06:00 [pubmed]
PHST- 2022/12/15 06:00 [medline]
PHST- 2022/12/08 00:00 [pmc-release]
AID - 163030 [pii]
AID - 10.1172/jci.insight.163030 [doi]
PST - epublish
SO  - JCI Insight. 2022 Dec 8;7(23):e163030. doi: 10.1172/jci.insight.163030.