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A network meta-analysis of randomized controlled trials comparing the effectiveness and safety of voclosporin or tacrolimus plus mycophenolate mofetil as induction treatment for lupus nephritis

Netzwerk-Metaanalyse randomisierter kontrollierter Studien zum Vergleich der Wirksamkeit und Sicherheit von Voclosporin oder Tacrolimus plus Mycophenolat-Mofetil als Induktionstherapie bei Lupusnephritis

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Abstract

Aim

This study aimed to compare the effectiveness and safety of voclosporin + mycophenolate mofetil (MMF), tacrolimus + MMF, and monotherapy with MMF or cyclophosphamide as induction treatment for lupus nephritis.

Methods

The study included randomized controlled trials (RCTs) that evaluated the effectiveness and safety of voclosporin + MMF, tacrolimus + MMF, and monotherapy for induction treatment in patients with lupus nephritis. To incorporate direct and indirect evidence from RCTs, we used a Bayesian network meta-analysis.

Results

Four RCTs, including 936 participants, met the inclusion criteria. Tacrolimus + MMF substantially increased the incidence of complete remission relative to that following monotherapy (odds ratio [OR] 2.85; 95% credible interval [CrI] 1.87–4.39). Tacrolimus + MMF was also more effective than voclosporin + MMF (OR 1.43; 95% CrI 0.80–2.57). Tacrolimus + MMF showed the greatest chance of being the optimal treatment for overall response (surface under the cumulative ranking curve [SUCRA] = 0.942), followed by voclosporin + MMF (SUCRA = 0.558) and monotherapy (SUCRA = 0.001). In terms of safety based on severe event rates, monotherapy had the greatest chance of being the safest treatment (SUCRA = 0.903), followed by voclosporin + MMF (SUCRA = 0.517) and tacrolimus + MMF (SUCRA = 0.081).

Conclusion

Tacrolimus + MMF and voclosporin + MMF were more effective than monotherapy, and tacrolimus + MMF was the most effective induction treatment for lupus nephritis patients. However, tacrolimus + MMF did pose a greater risk of serious adverse events than monotherapy.

Zusammenfassung

Ziel der Arbeit

Ziel der vorliegenden Studie war es, die Wirksamkeit und Sicherheit von Voclosporin + Mycophenolat-Mofetil (MMF) zum einen, Tacrolimus + MMF zum anderen und einer Monotherapie mit MMF oder Cyclophosphamid als Induktionstherapie bei Lupusnephritis zu vergleichen.

Methoden

In die Studie wurden randomisierte kontrollierte Studien (RCT) einbezogen, in denen die Wirksamkeit und Sicherheit von Voclosporin + MMF, Tacrolimus + MMF und einer Monotherapie als Induktionstherapie bei Patienten mit Lupusnephritis verglichen wurde. Um direkte und indirekte Evidenz aus RCT zu erfassen, wurde eine Bayes-Netzwerk-Metaanalyse durchgeführt.

Ergebnisse

Von 4 RCT mit 936 Teilnehmern wurden die Einschlusskriterien erfüllt. Tacrolimus + MMF führten zu einer wesentlich erhöhten Inzidenz kompletter Remissionen im Verhältnis zur Situation nach Monotherapie (Odds Ratio [OR] 2,85; 95%-Glaubwürdigkeitsintervall, Credibility Interval [CrI] 1,87–4,39). Tacrolimus + MMF erwiesen sich auch als wirksamer denn Voclosporin + MMF (OR 1,43; 95%-CrI 0,80–2,57). Bei Tacrolimus + MMF bestand die höchste Wahrscheinlichkeit, die optimale Therapie in Bezug auf das Gesamtansprechen darzustellen (Oberfläche unter der kumulativen Ranking-Kurve [SUCRA] = 0,942), dann folgten Voclosporin + MMF (SUCRA = 0,558) und die Monotherapie (SUCRA = 0,001). In Hinsicht auf die Sicherheit, basierend auf der Rate schwerer unerwünschter Ereignisse, bestand die höchste Wahrscheinlichkeit, die sicherste Therapie darzustellen, für die Monotherapie (SUCRA = 0,903), dann folgten Voclosporin + MMF (SUCRA = 0,517) und Tacrolimus + MMF (SUCRA = 0,081).

Schlussfolgerung

Tacrolimus + MMF und Voclosporin + MMF waren wirksamer als die Monotherapie, und Tacrolimus + MMF erwies sich als die wirksamste Induktionstherapie bei Patienten mit Lupusnephritis. Allerdings war das Risiko schwerer unerwünschter Ereignisse unter Tacrolimus + MMF größer als unter Monotherapie.

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Authors and Affiliations

  1. Division of Rheumatology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, 73, Goryeodae-ro, Seongbuk-gu, 02841, Seoul, 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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Correspondence to Young Ho Lee MD, PhD.

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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 performed 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. A network meta-analysis of randomized controlled trials comparing the effectiveness and safety of voclosporin or tacrolimus plus mycophenolate mofetil as induction treatment for lupus nephritis. Z Rheumatol 82, 580–586 (2023). https://doi.org/10.1007/s00393-021-01087-z

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