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Comparative efficacy and safety of 15 and 30 mg upadacitinib administered to patients with active rheumatoid arthritis: a Bayesian network meta-analysis of randomized controlled trials

  • G. G. Song
  • Y. H. LeeEmail author
Originalien
  • 34 Downloads

Abstract

Objectives

We assessed the relative efficacy and safety of once-daily administration of 15 and 30 mg upadacitinib (a JAK1-selective inhibitor) in patients with active rheumatoid arthritis (RA).

Methods

We conducted a Bayesian network meta-analysis to combine the direct and indirect evidence from randomized controlled trials (RCTs) that examined the efficacy and safety of upadacitinib in patients with active RA.

Results

Five RCTs involving 4381 patients met the inclusion criteria. There were 15 pairwise comparisons, including eight direct comparisons and six interventions. The ACR20 response rate was significantly higher in the upadacitinib 15 and 30 mg + MTX (methotrexate) groups than in the MTX group (OR: 4.98, 95% CrI: 2.66–10.10; OR: 4.73, 95% CrI: 2.25–10.98). Adalimumab 40 mg + MTX, upadacitinib 30 mg, and upadacitinib 15 mg groups showed a significantly higher ACR20 response rate than did the MTX group. Ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that upadacitinib 15 mg + MTX was likely to achieve the best ACR20 response rate (SUCRA = 0.838), followed by upadacitinib 30 mg + MTX, adalimumab 40 mg + MTX, upadacitinib 30 mg, upadacitinib 15 mg, and MTX (SUCRA = 0.784, 0.495, 0.471, 0.404, and 0.008, respectively). The safety based on the number of serious adverse events (SAEs) did not differ significantly among the six interventions.

Conclusions

Upadacitinib 15 and 30 mg administration once daily in combination with MTX was the most efficacious intervention for active RA, with no significant risk for SAEs.

Keywords

Upadacitinib Efficacy Safety Rheumatoid arthritis Network meta-analysis 

Vergleichbare Wirksamkeit und Sicherheit von 15 und 30 mg Upadacitinib bei Patienten mit aktiver rheumatoider Arthritis: eine Bayes-Netzwerk-Metaanalyse randomisierter kontrollierter Studien

Zusammenfassung

Ziel der Arbeit

Untersucht wurden die relative Wirksamkeit und Sicherheit der Gabe von 15 und 30 mg Upadacitinib (ein selektiver JAK1-Inhibitor) einmal täglich bei Patienten mit aktiver rheumatoider Arthritis (RA).

Methoden

Es erfolgte eine Bayes-Netzwerk-Metaanalyse zur Kombination direkter und indirekter Evidenz aus randomisierten kontrollierten Studien (RCT), in denen die Wirksamkeit und Sicherheit von Upadacitinib bei Patienten mit aktiver RA untersucht wurde.

Ergebnisse

Die Einschlusskriterien wurden von 5 RCT mit 4381 Patienten erfüllt. Es gab 15 paarweise erfolgende Vergleiche, einschließl. 8 direkter Vergleiche und 6 Interventionen. Die ACR20-Ansprechrate (gemäß American College of Rheumatology) war in den Gruppen mit Upadacitinib 15 bzw. 30 mg + MTX signifikant höher als in der MTX-Gruppe (Odds Ratio, OR: 4,98; 95%-Bayes-Konfidenzintervall, „credible interval“, 95%-CrI: 2,66–10,10; OR: 4,73, 95%-CrI: 2,25–10,98). Die Gruppen mit Adalimumab 40 mg + MTX, Upadacitinib 30 mg und Upadacitinib 15 mg zeigten eine signifikant höhere ACR20-Ansprechrate als die MTX-Gruppe. Wie die Rangfolgewahrscheinlichkeit („ranking probability“), basierend auf SUCRA („surface under the cumulative ranking curve“), ergab, ließ sich am ehesten mit Upadacitinib 15 mg + MTX die beste ACR20-Ansprechrate (SUCRA = 0,838) erreichen, dem folgten Upadacitinib 30 mg + MTX, Adalimumab 40 mg + MTX, Upadacitinib 30 mg, Upadacitinib 15 mg und MTX (SUCRA = 0,784; 0,495; 0,471; 0,404 bzw. 0,008). Die Sicherheit basierte auf der Anzahl schwerer Nebenwirkungen und unterschied sich nicht signifikant zwischen den 6 Interventionen.

Schlussfolgerung

Die Gabe von Upadacitinib 15 und 30 mg einmal täglich in Kombination mit MTX stellte sich als die wirksamste Intervention bei aktiver RA heraus, dabei bestand kein wesentliches Risiko für schwere Nebenwirkungen.

Schlüsselwörter

Upadacitinib Wirksamkeit Sicherheit Rheumatoide Arthritis Netzwerkmetaanalyse 

Notes

Compliance with ethical guidelines

Conflict of interest

G. G. Song 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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Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2019

Authors and Affiliations

  1. 1.Department of RheumatologyKorea University College of MedicineSeoulKorea (Republic of)
  2. 2.Division of Rheumatology, Department of Internal Medicine, Korea University Anam HospitalKorea University College of MedicineSeongbuk-gu, SeoulKorea (Republic of)

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