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Comparative efficacy and safety of mycophenolate mofetil versus cyclophosphamide in patients with active antineutrophil cytoplasmic antibody-associated vasculitis: a meta-analysis of randomized trials

Relative Wirksamkeit und Sicherheit von Mycophenolatmofetil vs. Cyclophosphamid bei Patienten mit aktiver, mit antineutrophilen zytoplasmatischen Antikörpern assoziierter Vaskulitis: Metaanalyse randomisierter Studien

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Abstract

Objective

This study aimed to assess the efficacy and safety of mycophenolate mofetil (MMF) versus cyclophosphamide (CYC) in patients with active antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

Methods

We performed a meta-analysis of four randomized clinical trials (RCTs; 300 patients) to examine the relative efficacy and safety of MMF compared to CYC in patients with active AAV.

Results

There was no significant difference in remission at 6 months between MMF and CYC (odds ratio [OR] 1.311, 95% confidence interval [CI] 0.570–3.017, P = 0.524). Additionally, the relapse rate did not differ between the MMF and CYC groups (OR 1.331, 95% CI 0.497–3.568, P = 0.570). There was no significant difference in serious adverse event (SAE; OR 1.232, 95% CI 0.754–2.014, P = 0.404) and infection rates (OR 0.958, 95% CI 0.561–1.634, P = 0.873) between the MMF and CYC groups. Some heterogeneity was found in the meta-analysis of remission and relapse rates (I2 = 57.4%, 63.4%), but no between-study heterogeneity was found during the meta-analysis of SAE and infection rate. Egger’s regression test showed no evidence of publication bias (Egger’s regression test P-values >0.1).

Conclusion

MMF was an equally effective alternative treatment to CYC and MMF was comparable to CYC in patients with active AAV in terms of safety, suggesting that MMF can be used as an alternative to CYC for remission induction in AAV.

Zusammenfassung

Ziel

Ziel der vorliegenden Studie war es, die Wirksamkeit und Sicherheit von Mycophenolatmofetil (MMF) vs. Cyclophosphamid (CYC) bei Patienten mit aktiver, mit antineutrophilen zytoplasmatischen Antikörpern (ANCA) assoziierter Vaskulitis (AAV) zu untersuchen.

Methoden

Es wurde eine Metaanalyse von 4 randomisierten klinischen Studien (300 Patienten) durchgeführt, um die relative Wirksamkeit und Sicherheit von MMF im Vergleich zu CYC bei Patienten mit aktiver AAV zu untersuchen.

Ergebnisse

Bei der Remission nach 6 Monaten gab es keinen signifikanten Unterschied zwischen MMF und CYC (Odds Ratio, OR: 1,311; 95%-Konfidenzintervall, 95%-KI: 0,570–3,017; p = 0,524). Darüber hinaus unterschied sich die Rezidivrate nicht zwischen der MMF- und der CYC-Gruppe (OR: 1,331; 95%-KI: 0,497–3,568; p = 0,570). Auch gab es keinen signifikanten Unterschied bei der Rate an schweren unerwünschten Ereignissen (SAE; OR: 1,232; 95%-KI: 0,754–2,014; p = 0,404) und Infektionen (OR: 0,958; 95%-KI: 0,561–1,634; p = 0,873) zwischen der MMF- und der CYC-Gruppe. Eine gewisse Heterogenität in der Metaanalyse der Remissions- und Rezidivraten war festzustellen (I2 = 57,4%; 63,4%), aber es bestand keine Heterogenität zwischen den Studien bei der Metaanalyse der Rate an SAE und Infektionen. Im Regressionstest nach Egger zeigte sich kein Anhalt für Publikations-Bias (p-Werte >0,1 im Regressionstest nach Egger).

Schlussfolgerung

Der Behandlungsansatz mit MMF erwies sich als Alternative zu CYC mit gleicher Wirksamkeit, und in Bezug auf die Sicherheit war MMF vergleichbar mit CYC bei Patienten mit aktiver AAV, was darauf hindeutet, dass MMF als Alternative zu CYC für die Induktion einer Remission bei AAV eingesetzt werden kann.

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Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Division of Rheumatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea (Republic of)

    G. G. Song & Y. H. Lee MD, PhD

  2. Department of Rheumatology, Korea University Anam Hospital, Korea University College of Medicine, 73, Goryeodae-ro, 02841, Seoul, Seongbuk-gu, Korea (Republic of)

    Y. H. Lee MD, PhD

Authors
  1. G. G. Song
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Correspondence to Y. H. Lee MD, PhD.

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Conflict of interest

G.G. Song and Y.H. Lee declare that they have no competing interests.

For this article no studies with human participants or animals were performed by any of the authors. All studies performed were in accordance with the ethical standards indicated in each case.

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U. Müller-Ladner, Bad Nauheim

U. Lange, Bad Nauheim

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Song, G.G., Lee, Y.H. Comparative efficacy and safety of mycophenolate mofetil versus cyclophosphamide in patients with active antineutrophil cytoplasmic antibody-associated vasculitis: a meta-analysis of randomized trials. Z Rheumatol 80, 425–431 (2021). https://doi.org/10.1007/s00393-020-00803-5

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