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

Author:

Berti Alvise1,Alsawas Mouaz23,Jawaid Tabinda2,Prokop Larry J4,Lee Jiwon M5,Jeong Gwang Hun6,Quintana Luis F7ORCID,Moiseev Sergey8,Vaglio August9,Tesar Vladimir10,Geetha Duvuru11,Shin Jae Il12ORCID,Kronbichler Andreas1314

Affiliation:

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

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

3. Department of Pathology, University of Iowa, IA City, IA, USA

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

5. Korea Disease Control and Prevention Agency, Division of Rare Disease Management, Republic of Korea

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

7. 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

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

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

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

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

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

13. Department of Medicine, University of Cambridge, Cambridge, UK

14. Vasculitis and Lupus Clinic, Addenbrooke's Hospital, Cambridge University Hospitals, Cambridge, UK

Abstract

Abstract 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 (GPA) and microscopic polyangiitis (MPA)). A comprehensive search of several databases (Medline, EMBASE, Cochrane, Web of Science, Scopus) from inception to May 5th, 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, five phase II and five III trials, 4 assessed remission-induction, 3 remission-maintenance, 3 both. The pooled OR for remission-induction at 6 months was 1.06 (95% CI: [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%-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 significantly associated with higher sustained remission rates in trials enrolling only patients with kidney involvement. These findings might influence clinical practice.

Publisher

Oxford University Press (OUP)

Subject

Transplantation,Nephrology

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