PMID- 36702528
OWN - NLM
STAT- MEDLINE
DCOM- 20230414
LR  - 20230515
IS  - 1468-2060 (Electronic)
IS  - 0003-4967 (Print)
IS  - 0003-4967 (Linking)
VI  - 82
IP  - 5
DP  - 2023 May
TI  - Risk factors for serious infections in ANCA-associated vasculitis.
PG  - 681-687
LID - 10.1136/ard-2022-223401 [doi]
AB  - OBJECTIVES: Severe infections contribute to morbidity and mortality in 
      antineutrophil cytoplasm antibody-associated vasculitis (AAV). This study aimed 
      to identify risk factors associated with severe infections in participants of the 
      Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis (RAVE) trial. 
      METHODS: Data on 197 patients recruited into the RAVE trial were analysed. 
      Participants received either rituximab (RTX) or cyclophosphamide (CYC), followed 
      by azathioprine (AZA). Clinical and laboratory data of patients with and without 
      severe infections (>/=grade 3, according to the Common Terminology Criteria for 
      Adverse Events version 3.0) were compared. Risk factors for severe infections 
      were investigated using Cox-regression models. RESULTS: Eighteen of 22 (82%) 
      severe infections occurred within 6 months after trial entry, most commonly 
      respiratory tract infections (15/22, 68%). At baseline, lower absolute numbers of 
      CD19+ cells were observed in patients with severe infections either receiving RTX 
      or CYC/AZA at baseline, while CD5+B and CD3+T cells did not differ between 
      groups. In Cox-regression analysis, higher baseline serum immunoglobulin M levels 
      were associated with the risk of severe infections, whereby a higher baseline 
      total CD19+B cell number and prophylaxis against Pneumocystis jirovecii with 
      trimethoprim-sulfamethoxazole (TMP/SMX) with decreased risk of severe infections. 
      Use of TMP/SMX was associated with lower risk of severe infections in both 
      groups, receiving either RTX or CYC/AZA. CONCLUSIONS: The use of low-dose TMP/SMX 
      is associated with reduced risk of severe infections in patients with AAV treated 
      with either RTX or CYC/AZA. Reduced B cell subpopulations at start of treatment 
      might be a useful correlate of reduced immunocompetence.
CI  - (c) Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published 
      by BMJ.
FAU - Odler, Balazs
AU  - Odler B
AD  - Department of Medicine, University of Cambridge, Cambridge, UK.
AD  - Division of Nephrology, Department of Internal Medicine, Medical University of 
      Graz, Graz, Austria.
FAU - Riedl, Regina
AU  - Riedl R
AD  - Institute for Medical Informatics, Statistics and Documentation, Medical 
      University of Graz, Graz, Austria.
FAU - Gauckler, Philipp
AU  - Gauckler P
AUID- ORCID: 0000-0002-5964-0307
AD  - Department of Internal Medicine IV, Nephrology and Hypertension, Medical 
      University Innsbruck, Innsbruck, Austria.
FAU - Shin, Jae Il
AU  - Shin JI
AD  - Yonsei University College of Medicine and Severance Children's Hospital, Seoul, 
      Republic of Korea.
FAU - Leierer, Johannes
AU  - Leierer J
AD  - Department of Internal Medicine IV, Nephrology and Hypertension, Medical 
      University Innsbruck, Innsbruck, Austria.
FAU - Merkel, Peter A
AU  - Merkel PA
AD  - Division of Rheumatology, University of Pennsylvania, Philadelphia, Pennsylvania, 
      USA.
FAU - St Clair, William
AU  - St Clair W
AD  - Division of Rheumatology and Immunology, Duke University, Durham, North Carolina, 
      USA.
FAU - Fervenza, Fernando
AU  - Fervenza F
AD  - Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA.
FAU - Geetha, Duvuru
AU  - Geetha D
AUID- ORCID: 0000-0001-8353-5542
AD  - Division of Nephrology, Johns Hopkins University, Baltimore, Maryland, USA.
FAU - Monach, Paul
AU  - Monach P
AD  - VA Boston Healthcare System, West Roxbury, Massachusetts, USA.
FAU - Jayne, David
AU  - Jayne D
AUID- ORCID: 0000-0002-1712-0637
AD  - Department of Medicine, University of Cambridge, Cambridge, UK.
FAU - Smith, Rona M
AU  - Smith RM
AD  - Department of Medicine, University of Cambridge, Cambridge, UK.
FAU - Rosenkranz, Alexander
AU  - Rosenkranz A
AD  - Division of Nephrology, Department of Internal Medicine, Medical University of 
      Graz, Graz, Austria.
FAU - Specks, Ulrich
AU  - Specks U
AD  - Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, 
      Minnesota, USA.
FAU - Stone, John H
AU  - Stone JH
AUID- ORCID: 0000-0001-6588-9435
AD  - Division of Rheumatology Allergy, and Immunology, Massachusetts General Hospital, 
      Harvard Medical School, Boston, Massachusetts, USA.
FAU - Kronbichler, Andreas
AU  - Kronbichler A
AUID- ORCID: 0000-0002-2945-2946
AD  - Department of Medicine, University of Cambridge, Cambridge, UK ak2283@cam.ac.uk.
CN  - RAVE-ITN Research Group
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230126
PL  - England
TA  - Ann Rheum Dis
JT  - Annals of the rheumatic diseases
JID - 0372355
RN  - 4F4X42SYQ6 (Rituximab)
RN  - 8064-90-2 (Trimethoprim, Sulfamethoxazole Drug Combination)
RN  - 0 (Antibodies, Monoclonal, Murine-Derived)
RN  - 8N3DW7272P (Cyclophosphamide)
RN  - MRK240IY2L (Azathioprine)
SB  - IM
MH  - Humans
MH  - Rituximab/therapeutic use
MH  - *Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use
MH  - Antibodies, Monoclonal, Murine-Derived
MH  - Remission Induction
MH  - *Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications/drug 
      therapy
MH  - Cyclophosphamide/therapeutic use
MH  - Azathioprine/therapeutic use
MH  - Risk Factors
MH  - Treatment Outcome
PMC - PMC10176387
OTO - NOTNLM
OT  - ANCA
OT  - Infections
OT  - Vasculitis
OT  - cyclophosphamide
OT  - rituximab
COIS- Competing interests: BO received speaker fees and travel support from Otsuka. 
      Fernando Fervenza reports receiving research grants from Genentech. PG reports 
      receiving speaker fees from Otsuka and consulting fees from Vifor Pharma, UriSalt 
      and Delta4. DG received consulting fees from ChemoCentryx, Aurinia and GSK. DJ 
      has received research grants, consultancy or lecture fees from Amgen, 
      Astra-Zeneca, BMS, Boehringer-Ingelheim, Chemocentryx, GSK, Kessai, NICE, 
      Novartis, Otsuka, Roche/Genentech, Takeda, UCB and Vifor. AK reports receiving 
      research grants from Vifor Pharma and Otsuka, speaking fees from Vifor Pharma, 
      and Terumo BCT, and consulting fees from Vifor Pharma, Otsuka, UriSalt, Delta4 
      and Catalyst Biosciences.
EDAT- 2023/01/27 06:00
MHDA- 2023/04/14 06:41
PMCR- 2023/05/12
CRDT- 2023/01/26 20:43
PHST- 2022/09/26 00:00 [received]
PHST- 2023/01/06 00:00 [accepted]
PHST- 2023/04/14 06:41 [medline]
PHST- 2023/01/27 06:00 [pubmed]
PHST- 2023/01/26 20:43 [entrez]
PHST- 2023/05/12 00:00 [pmc-release]
AID - ard-2022-223401 [pii]
AID - 10.1136/ard-2022-223401 [doi]
PST - ppublish
SO  - Ann Rheum Dis. 2023 May;82(5):681-687. doi: 10.1136/ard-2022-223401. Epub 2023 
      Jan 26.