PMID- 32173512
OWN - NLM
STAT- MEDLINE
DCOM- 20200424
LR  - 20200424
IS  - 1873-0183 (Electronic)
IS  - 1568-9972 (Linking)
VI  - 19
IP  - 5
DP  - 2020 May
TI  - Severe infections in patients with anti-neutrophil cytoplasmic 
      antibody-associated vasculitides receiving rituximab: A meta-analysis.
PG  - 102505
LID - S1568-9972(20)30057-4 [pii]
LID - 10.1016/j.autrev.2020.102505 [doi]
AB  - INTRODUCTION: The efficacy of rituximab (RTX) for remission induction and 
      maintenance in patients with anti-neutrophil cytoplasmic antibody 
      (ANCA)-associated vasculitides (AAV) is now established, but the safety, 
      particularly concerning severe infection risk, is not well known. OBJECTIVE: The 
      purpose of this meta-analysis is to assess the prevalence and incidence of severe 
      infections and the factors explaining heterogeneity in AAV patients treated with 
      RTX. METHODS: PubMed and Embase were searched up to December 2017. Prevalence and 
      incidence was pooled using a random-effects model in case of significant 
      heterogeneity (I(2) > 50%). Severe infection was defined as severe when it led to 
      hospitalization, intravenous antibiotics therapy, and/or death. The heterogeneity 
      was explored by subgroup analyses and meta-regression. RESULTS: The included 
      studies encompassed 1434 patients with a median age of 51.9 years. The overall 
      prevalence and incidence of severe infections was 15.4% (95% CI [8.9; 23.3], 
      I(2) = 90%, 33 studies) and 6.5 per 100 person-years (PY) (95% CI [2.9; 11.4], 
      I(2) = 76%, 18 studies), respectively. The most common infections were bacterial 
      (9.4%, 95% CI [5.1; 14.8]). The prevalence of opportunistic infection was 1.5% 
      (95% CI [0.5; 3.1], I(2) = 58%) including pneumocytis jirovecii infections (0.2%, 
      95% CI [0.0; 0.6], I(2) = 0), irrespective of prophylaxis administration. 
      Mortality related to infection was estimated at 0.7% (95% CI [0.2; 1.2], 
      I(2) = 27%). The RTX cumulative dose was positively associated with prevalence of 
      infections (13 studies, prevalence increase of 4% per 100 mg, p < .0001). The 
      incidence of infection was negatively associated with duration of follow-up (8 
      studies, incidence decrease of 9% per year, p = .03). CONCLUSION: Prevalence and 
      incidence of severe infections, mainly bacterial ones, were high in AAV patients 
      treated with RTX. This meta-analysis highlights the need for prospective studies 
      to stratify infectious risk and validate cumulative RTX dose and duration of 
      follow-up as modifying factors.
CI  - Copyright (c) 2020 Elsevier B.V. All rights reserved.
FAU - Thery-Casari, Clemence
AU  - Thery-Casari C
AD  - Department of Internal and Vascular Medicine, National Referral Centre for Rare 
      Juvenile Rheumatological and Autoimmune Diseases (RAISE), Hopital Lyon Sud, 
      Hospices Civils de Lyon, Pierre-Benite, France; Faculty of Medicine, Universite 
      de Lyon, Universite Lyon 1, France; Lyon Immunopathology Federation (LIFE), 
      University of Lyon, Hospices Civils de Lyon, France.
FAU - Euvrard, Romain
AU  - Euvrard R
AD  - Department of Internal and Vascular Medicine, National Referral Centre for Rare 
      Juvenile Rheumatological and Autoimmune Diseases (RAISE), Hopital Lyon Sud, 
      Hospices Civils de Lyon, Pierre-Benite, France; Faculty of Medicine, Universite 
      de Lyon, Universite Lyon 1, France; Lyon Immunopathology Federation (LIFE), 
      University of Lyon, Hospices Civils de Lyon, France.
FAU - Mainbourg, Sabine
AU  - Mainbourg S
AD  - Department of Internal and Vascular Medicine, National Referral Centre for Rare 
      Juvenile Rheumatological and Autoimmune Diseases (RAISE), Hopital Lyon Sud, 
      Hospices Civils de Lyon, Pierre-Benite, France; Faculty of Medicine, Universite 
      de Lyon, Universite Lyon 1, France; Lyon Immunopathology Federation (LIFE), 
      University of Lyon, Hospices Civils de Lyon, France; Universite de Lyon, 
      Universite Lyon 1, CNRS, Laboratoire de Biometrie et Biologie Evolutive UMR 5558, 
      F-69622 Villeurbanne, France.
FAU - Durupt, Stephane
AU  - Durupt S
AD  - Department of Internal and Vascular Medicine, National Referral Centre for Rare 
      Juvenile Rheumatological and Autoimmune Diseases (RAISE), Hopital Lyon Sud, 
      Hospices Civils de Lyon, Pierre-Benite, France; Lyon Immunopathology Federation 
      (LIFE), University of Lyon, Hospices Civils de Lyon, France.
FAU - Reynaud, Quitterie
AU  - Reynaud Q
AD  - Department of Internal and Vascular Medicine, National Referral Centre for Rare 
      Juvenile Rheumatological and Autoimmune Diseases (RAISE), Hopital Lyon Sud, 
      Hospices Civils de Lyon, Pierre-Benite, France; Faculty of Medicine, Universite 
      de Lyon, Universite Lyon 1, France; Lyon Immunopathology Federation (LIFE), 
      University of Lyon, Hospices Civils de Lyon, France; Univ Lyon, Health Services 
      and Performance Research EA7425, Claude Bernard University Lyon, F-69003, France.
FAU - Durieu, Isabelle
AU  - Durieu I
AD  - Department of Internal and Vascular Medicine, National Referral Centre for Rare 
      Juvenile Rheumatological and Autoimmune Diseases (RAISE), Hopital Lyon Sud, 
      Hospices Civils de Lyon, Pierre-Benite, France; Faculty of Medicine, Universite 
      de Lyon, Universite Lyon 1, France; Lyon Immunopathology Federation (LIFE), 
      University of Lyon, Hospices Civils de Lyon, France; Univ Lyon, Health Services 
      and Performance Research EA7425, Claude Bernard University Lyon, F-69003, France.
FAU - Belot, Alexandre
AU  - Belot A
AD  - Department of Internal and Vascular Medicine, National Referral Centre for Rare 
      Juvenile Rheumatological and Autoimmune Diseases (RAISE), Hopital Lyon Sud, 
      Hospices Civils de Lyon, Pierre-Benite, France; Faculty of Medicine, Universite 
      de Lyon, Universite Lyon 1, France; INSERM U1111, National Referral Centre for 
      rare Juvenile Rheumatological and Autoimmune Diseases (RAISE) and Department of 
      Paediatric Rheumatology, Lyon University Hospital, University of Lyon, France.
FAU - Lobbes, Herve
AU  - Lobbes H
AD  - Department of Internal and Vascular Medicine, National Referral Centre for Rare 
      Juvenile Rheumatological and Autoimmune Diseases (RAISE), Hopital Lyon Sud, 
      Hospices Civils de Lyon, Pierre-Benite, France; Internal Medicine Department, 
      University Hospital Clermont-Ferrand, 1 place Lucie et Raymond Aubrac, 63003 
      Clermont-Ferrand, France.
FAU - Cabrera, Natalia
AU  - Cabrera N
AD  - Faculty of Medicine, Universite de Lyon, Universite Lyon 1, France; Lyon 
      Immunopathology Federation (LIFE), University of Lyon, Hospices Civils de Lyon, 
      France; Universite de Lyon, Universite Lyon 1, CNRS, Laboratoire de Biometrie et 
      Biologie Evolutive UMR 5558, F-69622 Villeurbanne, France.
FAU - Lega, Jean-Christophe
AU  - Lega JC
AD  - Department of Internal and Vascular Medicine, National Referral Centre for Rare 
      Juvenile Rheumatological and Autoimmune Diseases (RAISE), Hopital Lyon Sud, 
      Hospices Civils de Lyon, Pierre-Benite, France; Faculty of Medicine, Universite 
      de Lyon, Universite Lyon 1, France; Lyon Immunopathology Federation (LIFE), 
      University of Lyon, Hospices Civils de Lyon, France; Universite de Lyon, 
      Universite Lyon 1, CNRS, Laboratoire de Biometrie et Biologie Evolutive UMR 5558, 
      F-69622 Villeurbanne, France. Electronic address: 
      jean-christophe.lega@chu-lyon.fr.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
DEP - 20200312
PL  - Netherlands
TA  - Autoimmun Rev
JT  - Autoimmunity reviews
JID - 101128967
RN  - 4F4X42SYQ6 (Rituximab)
SB  - IM
MH  - Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/*complications/*drug 
      therapy
MH  - Humans
MH  - Infections/*complications
MH  - Middle Aged
MH  - Remission Induction
MH  - Rituximab/*therapeutic use
MH  - Treatment Outcome
OTO - NOTNLM
OT  - ANCA-associated vasculitis
OT  - Infection
OT  - Pneumocystis
OT  - Rituximab
OT  - Safety
EDAT- 2020/03/17 06:00
MHDA- 2020/04/25 06:00
CRDT- 2020/03/17 06:00
PHST- 2019/12/28 00:00 [received]
PHST- 2019/12/31 00:00 [accepted]
PHST- 2020/03/17 06:00 [pubmed]
PHST- 2020/04/25 06:00 [medline]
PHST- 2020/03/17 06:00 [entrez]
AID - S1568-9972(20)30057-4 [pii]
AID - 10.1016/j.autrev.2020.102505 [doi]
PST - ppublish
SO  - Autoimmun Rev. 2020 May;19(5):102505. doi: 10.1016/j.autrev.2020.102505. Epub 
      2020 Mar 12.