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Relative efficacy and safety of calcineurin inhibitor, mycophenolate mofetil, and azathioprine as maintenance therapies for lupus nephritis: a network meta-analysis

Relative Wirksamkeit und Sicherheit von Calcineurin-Inhibitoren, Mycophenolatmofetil und Azathioprin als Erhaltungstherapie bei Lupusnephritis: eine Netzwerk-Metaanalyse

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Abstract

Objective

This study aimed to assess the relative efficacy and safety of calcineurin inhibitor (CNI), mycophenolate mofetil (MMF), and azathioprine (AZA) as maintenance therapies for lupus nephritis.

Methods

Randomized controlled trials (RCTs) examining the efficacy and safety of CNI, MMF, and AZA as maintenance therapies in patients with lupus nephritis were included. We performed a Bayesian random-effects network meta-analysis to combine the direct and indirect evidence from RCTs.

Results

Ten RCTs comprising 884 patients were included in the study. Although the difference was not statistically significant, MMF showed a trend toward a lower relapse rate compared with AZA (odds ratio [OR] 0.72, 95% credible interval [CrI] 0.45–1.22). Similarly, tacrolimus showed a trend toward a lower relapse rate compared with AZA (OR 0.85, 95% CrI 0.34–2.00). Ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that MMF had the highest probability of being the best treatment based on the relapse rate, followed by CNI and AZA. The incidence of leukopenia in the MMF and CNI groups was significantly lower than that in the AZA group (OR 0.12, 95% CrI 0.04–0.34; OR 0.16, 95% CrI 0.04–0.50; respectively). Fewer patients with infections were observed in the MMF group than in the AZA group, although the difference was not statistically significant. The analysis of withdrawals due to adverse events showed a similar pattern.

Conclusion

Lower relapse rates combined with a more favorable safety profile suggest that CNI and MMF are superior to AZA as maintenance treatments in lupus nephritis patients.

Zusammenfassung

Zielsetzung

Ziel dieser Studie war es, die relative Wirksamkeit und Sicherheit von Calcineurin-Inhibitoren (CNI), Mycophenolatmofetil (MMF) und Azathioprin (AZA) als Erhaltungstherapie bei Lupusnephritis zu bewerten.

Methoden

Eingeschlossen wurden randomisierte kontrollierte Studien (RCTs), welche die Wirksamkeit und Sicherheit von CNI, MMF und AZA als Erhaltungstherapie bei Patienten mit Lupusnephritis untersuchten. Wir führten eine Bayessche Netzwerk-Metaanalyse mit zufälligen Effekten durch, um die direkte und indirekte Evidenz aus den RCTs zu kombinieren.

Ergebnisse

Es wurden 10 RCTs mit 884 Patienten in die Studie aufgenommen. Obwohl der Unterschied statistisch nicht signifikant war, zeigte MMF im Vergleich zu AZA die Tendenz zu einer niedrigeren Rückfallrate (Odds-Ratio [OR] 0,72; 95 % Konfidenzintervall [KI] 0,45‑1,22). Auch bei Tacrolimus zeigte sich ein Trend zu einer niedrigeren Rückfallrate im Vergleich zu AZA (OR 0,85; 95 % KI 0,34‑2,00). Die Rangwahrscheinlichkeit auf Grundlage der Fläche unter der kumulativen Rangkurve (SUCRA) zeigte, dass MMF die höchste Wahrscheinlichkeit hatte, die beste Behandlung auf der Grundlage der Rückfallrate zu sein, gefolgt von CNI und AZA. Die Inzidenz von Leukopenien war in der MMF- und CNI-Gruppe signifikant niedriger als in der AZA-Gruppe (OR 0,12; 95 % KI 0,04‑0,34; OR 0,16; 95 % KI 0,04‑0,50; jeweils). In der MMF-Gruppe wurden weniger Patienten mit Infektionen beobachtet als in der AZA-Gruppe, obwohl der Unterschied statistisch nicht signifikant war. Die Analyse der Abbrüche aufgrund von unerwünschten Ereignissen ergab ein ähnliches Muster.

Schlussfolgerung

Geringere Rückfallraten in Verbindung mit einem günstigeren Sicherheitsprofil deuten darauf hin, dass CNI und MMF als Erhaltungstherapie bei Patienten mit Lupusnephritis gegenüber AZA überlegen sind.

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Acknowledgements

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. Department of Rheumatology, Korea University Anam Hospital, Korea University College of Medicine, 73, Inchon-ro, 136-705, Seoul, Seongbuk-gu, Korea (Republic of)

    Young Ho Lee MD, PhD & Gwan Gyu Song

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  1. Young Ho Lee MD, PhD
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  2. Gwan Gyu Song
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Correspondence to Young Ho Lee MD, PhD.

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Conflict of interest

Y.H. Lee and G.G. Song 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 mentioned were in accordance with the ethical standards indicated in each case.

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Ulf Müller-Ladner, Bad Nauheim

Uwe Lange, Bad Nauheim

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Lee, Y.H., Song, G.G. Relative efficacy and safety of calcineurin inhibitor, mycophenolate mofetil, and azathioprine as maintenance therapies for lupus nephritis: a network meta-analysis. Z Rheumatol 83 (Suppl 1), 140–147 (2024). https://doi.org/10.1007/s00393-023-01374-x

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