Abstract
Aims
This study aimed to assess the relative efficacy and safety of tacrolimus, mycophenolate mofetil (MMF), azathioprine (AZA), and cyclophosphamide (CYC) as maintenance therapy for lupus nephritis.
Methods
Randomized controlled trials (RCTs) examining the efficacy and safety of tacrolimus, MMF, AZA, and CYC for maintenance therapy in lupus nephritis patients were included. We performed a Bayesian random-effects network meta-analysis to combine direct and indirect evidence from the RCTs.
Results
Five RCTs including 525 patients were included. Although the difference was not statistically significant, tacrolimus showed a trend toward a lower renal relapse rate than AZA or CYC. Similarly, MMF showed a trend toward a lower relapse rate than AZA or CYC. Renal relapse tended to be lower in the AZA group than in the CYC group. Ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that tacrolimus had the highest probability of being the best treatment based on the renal relapse, followed by MMF, AZA, and CYC. Analysis of withdrawal due to adverse events showed the same pattern. The leukopenia incidence was significantly lower in the MMF group than in the AZA group. Similarly, it tended to be lower in the tacrolimus group than in the AZA group. Ranking probability based on SUCRA indicated that MMF had the highest probability of being the safest treatment based on leukopenia incidence, followed by tacrolimus and AZA.
Conclusions
Lower renal relapse rates combined with a more favorable safety profile suggest that tacrolimus and MMF are superior to AZA and CYC as maintenance treatments in these patients.
Zusammenfassung
Ziele
Ziel dieser Studie war es, die relative Wirksamkeit und Sicherheit von Tacrolimus, Mycophenolat-Mofetil (MMF), Azathioprin (AZA) und Cyclophosphamid (CYC) als Erhaltungstherapie bei Lupusnephritis zu untersuchen.
Methoden
Randomisierte kontrollierte Studien (RCTs), welche die Wirksamkeit und Sicherheit von Tacrolimus, MMF, AZA und CYC als Erhaltungstherapie bei Patienten mit Lupusnephritis untersuchten, wurden eingeschlossen. Es wurde eine Netzwerk-Metaanalyse nach Bayes mit Zufallseffekten durchgeführt, um die direkte und indirekte Evidenz der RCTs zu kombinieren.
Ergebnisse
Insgesamt wurden 5 RCTs mit 525 Patienten eingeschlossen. Obwohl die Differenz statistisch nicht signifikant war, zeigte Tacrolimus die Tendenz einer niedrigeren renalen Rezidivrate als AZA oder CYC. Ähnlich verhielt es sich mit MMF, das eine tendenziell niedrigere renale Rezidivrate zeigte als AZA oder CYC. Das Auftreten renaler Rezidive war in der AZA-Gruppe tendenziell geringer als in der CYC-Gruppe. Die Ranking-Wahrscheinlichkeit basierend auf der „surface under the cumulative ranking curve“ (SUCRA) zeigte, dass Tacrolimus hinsichtlich der renalen Rezidivrate die höchste Wahrscheinlichkeit aufwies, die beste Behandlung zu sein, gefolgt von MMF, AZA und CYC. Die Analyse der Studienabbrüche aufgrund unerwünschter Ereignisse zeigte das gleiche Muster. Die Inzidenz einer Leukopenie war in der MMF-Gruppe signifikant niedriger als in der AZA-Gruppe. Ebenso war sie in der Tacrolimus-Gruppe tendenziell niedriger als in der AZA-Gruppe. Die Ranking-Wahrscheinlichkeit basierend auf SUCRA zeigte, dass MMF hinsichtlich der Inzidenz einer Leukopenie die höchste Wahrscheinlichkeit aufwies, die beste Behandlung zu sein, gefolgt von Tacrolimus und AZA.
Schlussfolgerung
Die niedrigere renale Rezidivrate gepaart mit einem günstigeren Sicherheitsprofil zeigte, dass bei den untersuchten Patienten eine Erhaltungstherapie mit Tacrolimus und MMF einer Behandlung mit AZA und CYC überlegen ist.
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Acknowledgements
This study was supported by a Korea University grant.
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Y. H. Lee and G. G. Song state that they have no competing interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
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U. Müller-Ladner, Bad Nauheim
U. Lange, Bad Nauheim
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Lee, Y.H., Song, G.G. Comparative efficacy and safety of tacrolimus, mycophenolate mofetil, azathioprine, and cyclophosphamide as maintenance therapy for lupus nephritis. Z Rheumatol 76, 904–912 (2017). https://doi.org/10.1007/s00393-016-0186-z
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DOI: https://doi.org/10.1007/s00393-016-0186-z