Induction and maintenance of remission with mycophenolate mofetil in ANCA-associated vasculitis: a systematic review and meta-analysis.


Journal

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
ISSN: 1460-2385
Titre abrégé: Nephrol Dial Transplant
Pays: England
ID NLM: 8706402

Informations de publication

Date de publication:
19 10 2022
Historique:
received: 13 09 2021
pubmed: 16 12 2021
medline: 25 10 2022
entrez: 15 12 2021
Statut: ppublish

Résumé

Uncertainties exist about the use of mycophenolate mofetil (MMF) in anti-neutrophil cytoplasmatic antibody (ANCA)-associated vasculitis (AAV), particularly for remission maintenance. Systematic review and meta-analysis of phase II and III trials assessing the use of MMF in AAV, granulomatosis with polyangiitis and microscopic polyangiitis (MPA). A comprehensive search of several databases (Medline, EMBASE, Cochrane, Web of Science, Scopus) from inception to 5 May 2020 has been conducted. Trial data were extracted to estimate odds ratios (ORs) and estimates (ES) for MMF efficacy (remission-induction and maintenance). Severe adverse effects (SAEs) were collected. From 565 articles captured, 10 met the predefined criteria, 5 phase II and 5 III trials; 4 assessed remission-induction, 3 remission maintenance and 3 both. The pooled OR for remission-induction at 6 months was 1.06 (95% confidence interval 0.74, 1.52), with no significant difference by subgroup meta-analysis of trials stratified by different study-level features (i.e. kidney disease, MPA, myeloperoxidase-ANCA positivity, newly diagnosed disease) (P > 0.05). The overall ES for remission maintenance at the end of follow-up ranged between 51% and 91% (I2 = 74.8%). Subgroup meta-analysis identified kidney involvement as a possible source of heterogeneity, yielding a significantly higher rate of sustained remission in trials enrolling only patients with kidney involvement (92%, 76-100%) versus those enrolling patients with and without kidney involvement (56%, 45-66%). Results were similar in multiple sensitivity analyses. During follow-up, the frequency of SAEs in MMF-based treatment arms was 31.8%. In AAV, MMF use was significantly associated with higher sustained remission rates in trials enrolling only patients with kidney involvement. These findings might influence clinical practice.

Sections du résumé

BACKGROUND
Uncertainties exist about the use of mycophenolate mofetil (MMF) in anti-neutrophil cytoplasmatic antibody (ANCA)-associated vasculitis (AAV), particularly for remission maintenance.
METHODS
Systematic review and meta-analysis of phase II and III trials assessing the use of MMF in AAV, granulomatosis with polyangiitis and microscopic polyangiitis (MPA). A comprehensive search of several databases (Medline, EMBASE, Cochrane, Web of Science, Scopus) from inception to 5 May 2020 has been conducted. Trial data were extracted to estimate odds ratios (ORs) and estimates (ES) for MMF efficacy (remission-induction and maintenance). Severe adverse effects (SAEs) were collected.
RESULTS
From 565 articles captured, 10 met the predefined criteria, 5 phase II and 5 III trials; 4 assessed remission-induction, 3 remission maintenance and 3 both. The pooled OR for remission-induction at 6 months was 1.06 (95% confidence interval 0.74, 1.52), with no significant difference by subgroup meta-analysis of trials stratified by different study-level features (i.e. kidney disease, MPA, myeloperoxidase-ANCA positivity, newly diagnosed disease) (P > 0.05). The overall ES for remission maintenance at the end of follow-up ranged between 51% and 91% (I2 = 74.8%). Subgroup meta-analysis identified kidney involvement as a possible source of heterogeneity, yielding a significantly higher rate of sustained remission in trials enrolling only patients with kidney involvement (92%, 76-100%) versus those enrolling patients with and without kidney involvement (56%, 45-66%). Results were similar in multiple sensitivity analyses. During follow-up, the frequency of SAEs in MMF-based treatment arms was 31.8%.
CONCLUSIONS
In AAV, MMF use was significantly associated with higher sustained remission rates in trials enrolling only patients with kidney involvement. These findings might influence clinical practice.

Identifiants

pubmed: 34910216
pii: 6462928
doi: 10.1093/ndt/gfab357
doi:

Substances chimiques

Mycophenolic Acid HU9DX48N0T
Antibodies, Antineutrophil Cytoplasmic 0
Peroxidase EC 1.11.1.7
Immunosuppressive Agents 0

Types de publication

Meta-Analysis Systematic Review Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

2190-2200

Informations de copyright

© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.

Auteurs

Alvise Berti (A)

Santa Chiara Regional Hospital and Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Rheumatology, Trento, Italy.

Mouaz Alsawas (M)

Evidence-Based Practice Center, Mayo Clinic, Rochester, MN, USA.
Department of Pathology, University of Iowa, IA City, IA, USA.

Tabinda Jawaid (T)

Evidence-Based Practice Center, Mayo Clinic, Rochester, MN, USA.

Larry J Prokop (LJ)

Mayo Clinic Libraries, Mayo Clinic, Rochester, MN, USA.

Jiwon M Lee (JM)

Korea Disease Control and Prevention Agency, Division of Rare Disease Management, Cheongju-si, Republic of Korea.

Gwang Hun Jeong (GH)

College of Medicine, Gyeongsang National University, Jinju, Republic of Korea.

Luis F Quintana (LF)

Reference Center in Complex Glomerular Disease of the National Health System (CSUR), Nephrology and Renal Transplantation Department, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain, Institut d'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Barcelona, Spain.

Sergey Moiseev (S)

Tareev Clinic of Internal Diseases, Sechenov First Moscow State Medical University, Moscow, Russia.

Augusto Vaglio (A)

Department of Biomedical Experimental and Clinical Sciences 'Mario Serio', University of Firenze, and Nephrology Unit, Meyer Children's Hospital, Firenze, Italy.

Vladimir Tesar (V)

Department of Nephrology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czechia.

Duvuru Geetha (D)

Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Jae I L Shin (JIL)

Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea.

Andreas Kronbichler (A)

Department of Medicine, University of Cambridge, Cambridge, UK.
Vasculitis and Lupus Clinic, Addenbrooke's Hospital, Cambridge University Hospitals, Cambridge, UK.

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