PMID- 29950327
OWN - NLM
STAT- MEDLINE
DCOM- 20190819
LR  - 20191210
IS  - 1468-2060 (Electronic)
IS  - 0003-4967 (Print)
IS  - 0003-4967 (Linking)
VI  - 77
IP  - 10
DP  - 2018 Oct
TI  - Trimethoprim-sulfamethoxazole prophylaxis prevents severe/life-threatening 
      infections following rituximab in antineutrophil cytoplasm antibody-associated 
      vasculitis.
PG  - 1440-1447
LID - 10.1136/annrheumdis-2017-212861 [doi]
AB  - OBJECTIVE: We aimed to assess risk factors for the development of severe 
      infection in patients with antineutrophil cytoplasm antibody-associated 
      vasculitis (AAV) receiving rituximab. METHODS: 192 patients with AAV were 
      identified. Univariate and multivariate analyses were performed to identify risk 
      factors for severe infection following rituximab. Severe infections were 
      classified as grade >/=3 as proposed by the Common Terminology Criteria for Adverse 
      Events V.4.0. RESULTS: 95 severe infections were recorded in 49 (25.52%) 
      patients, corresponding to an event rate of 26.06 per 100 person-years. The 
      prophylactic use of trimethoprim-sulfamethoxazole was associated with a lower 
      frequency of severe infections (HR 0.30, 95% CI 0.13 to 0.69), while older age 
      (HR 1.03, 95% CI 1.01 to 1.05), endobronchial involvement (HR 2.21, 95% CI 1.14 
      to 4.26), presence of chronic obstructive pulmonary disease (HR 6.30, 95% CI 1.08 
      to 36.75) and previous alemtuzumab use (HR 3.97, 95% CI 1.50 to 10.54) increased 
      the risk. When analysis was restricted to respiratory tract infections (66.3% of 
      all infections), endobronchial involvement (HR 4.27, 95% CI 1.81 to 10.06), 
      severe bronchiectasis (HR 6.14, 95% CI 1.18 to 31.91), higher neutrophil count 
      (HR 1.19, 95% CI 1.06 to 1.33) and major relapse (HR 3.07, 95% CI 1.30 to 7.23) 
      as indication for rituximab use conferred a higher risk, while refractory disease 
      (HR 0.25, 95% CI 0.07 to 0.90) as indication had a lower frequency of severe 
      infections. CONCLUSIONS: We found severe infections in one quarter of patients 
      with AAV receiving rituximab. Trimethoprim-sulfamethoxazole prophylaxis reduced 
      the risk, while especially bronchiectasis and endobronchial involvement are risk 
      factors for severe respiratory infections.
CI  - (c) Article author(s) (or their employer(s) unless otherwise stated in the text of 
      the article) 2018. All rights reserved. No commercial use is permitted unless 
      otherwise expressly granted.
FAU - Kronbichler, Andreas
AU  - Kronbichler A
AUID- ORCID: 0000-0002-2945-2946
AD  - Vasculitis and Lupus Clinic, Addenbrooke's Hospital, Cambridge, UK.
AD  - Department of Internal Medicine IV (Nephrology and Hypertension), Anichstrasse, 
      Innsbruck, Austria.
FAU - Kerschbaum, Julia
AU  - Kerschbaum J
AD  - Department of Internal Medicine IV (Nephrology and Hypertension), Anichstrasse, 
      Innsbruck, Austria.
FAU - Gopaluni, Seerapani
AU  - Gopaluni S
AUID- ORCID: 0000-0002-1584-6186
AD  - Vasculitis and Lupus Clinic, Addenbrooke's Hospital, Cambridge, UK.
FAU - Tieu, Joanna
AU  - Tieu J
AD  - Vasculitis and Lupus Clinic, Addenbrooke's Hospital, Cambridge, UK.
FAU - Alberici, Federico
AU  - Alberici F
AD  - Vasculitis and Lupus Clinic, Addenbrooke's Hospital, Cambridge, UK.
AD  - Renal Medicine and Vasculitis Clinic, San Carlo Borromeo Hospital, Milan, Italy.
FAU - Jones, Rachel Bronwen
AU  - Jones RB
AUID- ORCID: 0000-0003-4790-283X
AD  - Vasculitis and Lupus Clinic, Addenbrooke's Hospital, Cambridge, UK.
FAU - Smith, Rona M
AU  - Smith RM
AD  - Vasculitis and Lupus Clinic, Addenbrooke's Hospital, Cambridge, UK.
FAU - Jayne, David R W
AU  - Jayne DRW
AD  - Vasculitis and Lupus Clinic, Addenbrooke's Hospital, Cambridge, UK.
AD  - Department of Medicine, University of Cambridge, Cambridge, UK.
LA  - eng
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180627
PL  - England
TA  - Ann Rheum Dis
JT  - Annals of the rheumatic diseases
JID - 0372355
RN  - 0 (Immunologic Factors)
RN  - 4F4X42SYQ6 (Rituximab)
RN  - 8064-90-2 (Trimethoprim, Sulfamethoxazole Drug Combination)
CIN - Ann Rheum Dis. 2020 Feb;79(2):e19. PMID: 30472653
CIN - Ann Rheum Dis. 2020 Apr;79(4):e40. PMID: 30700422
CIN - Ann Rheum Dis. 2020 Apr;79(4):e41. PMID: 30700424
CIN - Ann Rheum Dis. 2020 Feb;79(2):e20. PMID: 30700426
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/*drug therapy
MH  - Antibiotic Prophylaxis/*methods
MH  - Female
MH  - Humans
MH  - Immunologic Factors/*adverse effects
MH  - Male
MH  - Middle Aged
MH  - Multivariate Analysis
MH  - Respiratory Tract Infections/chemically induced/*prevention & control
MH  - Risk Factors
MH  - Rituximab/*adverse effects
MH  - Treatment Outcome
MH  - Trimethoprim, Sulfamethoxazole Drug Combination/*therapeutic use
MH  - Young Adult
PMC - PMC6161662
OTO - NOTNLM
OT  - ANCA
OT  - infections
OT  - rituximab
OT  - trimethoprim-sulfamethoxazole
OT  - vasculitis
COIS- Competing interests: AK has received travel support from Roche/Genentech. DRWJ 
      has received research grants and consulting fees from Roche/Genentech and Terumo 
      BCT and is supported by the Cambridge Biomedical Research Centre.
EDAT- 2018/06/29 06:00
MHDA- 2019/08/20 06:00
PMCR- 2018/09/28
CRDT- 2018/06/29 06:00
PHST- 2017/12/16 00:00 [received]
PHST- 2018/06/11 00:00 [accepted]
PHST- 2018/06/29 06:00 [pubmed]
PHST- 2019/08/20 06:00 [medline]
PHST- 2018/06/29 06:00 [entrez]
PHST- 2018/09/28 00:00 [pmc-release]
AID - annrheumdis-2017-212861 [pii]
AID - 10.1136/annrheumdis-2017-212861 [doi]
PST - ppublish
SO  - Ann Rheum Dis. 2018 Oct;77(10):1440-1447. doi: 10.1136/annrheumdis-2017-212861. 
      Epub 2018 Jun 27.