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Comparative efficacy and tolerability of sarilumab 150 and 200 mg in patients with active rheumatoid arthritis

A Bayesian network meta-analysis of randomized controlled trials

Vergleichbare Wirksamkeit und Verträglichkeit von Sarilumab 150 und 200 mg bei Patienten mit aktiver rheumatoider Arthritis

Eine Bayes-Netzwerk-Metaanalyse randomisierter kontrollierter Studien

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Abstract

Objective

This study aimed to assess the relative efficacy and tolerability of every other week (q2w) dosing of sarilumab 150 and 200 mg in patients with active rheumatoid arthritis (RA).

Methods

In this network meta-analysis, randomized controlled trials (RCTs) examining the efficacy and tolerability of sarilumab in patients with active RA were included. A Bayesian network meta-analysis was conducted to combine the direct and indirect evidence from the RCTs.

Results

Four RCTs, involving 2667 patients, met the inclusion criteria. The American College of Rheumatology (ACR)50 response rate was significantly higher in the sarilumab 200 mg and sarilumab 200 mg + methotrexate (MTX) groups than in the placebo + MTX group (odds ratio, OR, of 4.05, 95% credible interval, CrI, of 2.04–8.33 and OR of 3.75, 95% CrI of 2.37–5.72, respectively). Compared to the placebo + MTX group, the sarilumab 150 mg + MTX and adalimumab 40 mg groups showed a significantly higher ACR50 response rate. The ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that sarilumab 200 mg was likely to achieve the best ACR50 response rate (SUCRA = 0.8518), followed by sarilumab 200 mg + MTX (SUCRA = 0.8225), sarilumab 150 mg + MTX (SUCRA = 0.5112), adalimumab 40 mg (SUCRA = 0.3072), and placebo + MTX (SUCRA = 0.0072). The ACR50 and ACR70 response rate distributions were comparable, except that sarilumab 200 mg + MTX was likely to achieve the best ACR70 response rate. The tolerability based on the number of patient withdrawals due to adverse events (AEs) did not differ significantly between the treatments, except that placebo + MTX was likely to be the best tolerated.

Conclusion

Sarilumab 150 and 200 mg are efficacious treatments for active RA and are well tolerated.

Zusammenfassung

Ziel

Ziel der vorliegenden Studie war es, die relative Wirksamkeit und Verträglichkeit von Sarilumab in einer Dosierung von 150 bzw. 200 mg alle 2 Wochen bei Patienten mit aktiver rheumatoider Arthritis (RA) zu untersuchen.

Methoden

In diese Netzwerk-Metaanalyse wurden randomisierte kontrollierte Studien (RCT) eingeschlossen, in denen die Wirksamkeit und Verträglichkeit von Sarilumab bei Patienten mit aktiver RA untersucht wurden. Um die direkt und die indirekte Evidenz aus den RCT zu kombinieren, wurde eine Bayes-Netzwerk-Metaanalyse durchgeführt.

Ergebnisse

Die Einschlusskriterien wurden von 4 RCT mit 2667 Patienten erfüllt. Die Ansprechrate gemäß den American-College-of-Rheumatologists(ACR)50-Kriterien war in der Gruppe mit Sarilumab 200 mg und Sarilumab 200 mg + Methotrexat (MTX) signifikant höher als in der Gruppe mit Placebo + MTX; Odds Ratio (OR): 4,05; 95%-Crl (95%-Bayes-Konfidenzintervall, „credible interval“): 2,04–8,33 bzw. OR: 3,75; 95%-CrI: 2,37–5,72. Im Vergleich zu der Gruppe mit Placebo + MTX wies die Gruppe mit Sarilumab 150 mg + MTX und die Gruppe mit Adalimumab 40 mg eine signifikant höhere ACR50-Ansprechrate auf. Die Rangordnungswahrscheinlichkeit, basierend auf der Oberfläche unter der kumulativen Ranglistenkurve („surface under the cumulative ranking curve“, SUCRA), zeigte, dass Sarilumab 200 mg wahrscheinlich die beste ACR50-Ansprechrate erzielte (SUCRA = 0,8518), dem folgten Sarilumab 200 mg + MTX (SUCRA = 0,8225), Sarilumab 150 mg + MTX (SUCRA = 0,5112), Adalimumab 40 mg (SUCRA = 0,3072) und Placebo + MTX (SUCRA = 0,0072). Die ACR50- und ACR70-Ansprechratenverteilungen waren vergleichbar, außer dass Sarilumab 200 mg + MTX wahrscheinlich die beste ACR70-Ansprechrate erzielte. Die Verträglichkeit, basierend auf der Anzahl der Studienabbrüche durch Patienten aufgrund unerwünschter Ereignisse, unterschied sich nicht signifikant zwischen den Therapieoptionen, außer dass Placebo + MTX wahrscheinlich am besten vertragen wurde.

Schlussfolgerung

Sarilumab 150 und 200 mg sind wirksame Behandlungsoptionen bei aktiver RA und werden gut vertragen.

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Acknowledgements

This study was supported in part by a grant from the Korea Healthcare Technology R&D Project, Ministry for Health and Welfare, Republic of Korea (HI15C2958).

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Authors and Affiliations

  1. Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea

    S.-C. Bae

  2. Division of Rheumatology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, 73, Inchon-ro, 02841, Seoul, Republic of Korea

    Y. H. Lee MD, PhD

Authors
  1. S.-C. Bae
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Correspondence to Y. H. Lee MD, PhD.

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S.-C. Bae and Y. H. Lee declare that they have no competing interests.

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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Bae, SC., Lee, Y.H. Comparative efficacy and tolerability of sarilumab 150 and 200 mg in patients with active rheumatoid arthritis. Z Rheumatol 77, 421–428 (2018). https://doi.org/10.1007/s00393-017-0292-6

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