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Comparison of the efficacy and safety of tofacitinib and baricitinib in patients with active rheumatoid arthritis: a Bayesian network meta-analysis of randomized controlled trials

  • S.-C. Bae
  • Y. H. LeeEmail author
Originalien

Abstract

Objectives

The relative efficacy and safety of tofacitinib and baricitinib were assessed in patients with rheumatoid arthritis (RA) with an inadequate response to disease-modifying anti-rheumatic drugs (DMARDs) or biologics.

Methods

We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) to examine the efficacy and safety of tofacitinib and baricitinib in combination with DMARDs in RA patients with an inadequate DMARD or biologic response.

Results

Twelve RCTs including 5883 patients met the inclusion criteria. There were 15 pairwise comparisons including 10 direct comparisons of 6 interventions. Tofacitinib 10 mg + methotrexate (MTX) and baricitinib 4 mg + MTX were among the most effective treatments for active RA with an inadequate DMARD or biologic response, followed by baricitinib 2 mg + MTX, tofacitinib 5 mg + MTX, and adalimumab + MTX. The ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that tofacitinib 10 mg + MTX had the highest probability of being the best treatment to achieve the ACR20 response rate (SUCRA = 0.865), followed by baricitinib 4 mg + MTX (SUCRA = 0.774), baricitinib 2 mg + MTX (SUCRA = 0.552), tofacitinib 5 mg + MTX (SUCRA = 0.512), adalimumab + MTX (SUCRA = 0.297), and placebo + MTX (SUCRA <0.001). No significant differences were observed in the incidence of serious adverse events after treatment with tofacitinib + MTX, baricitinib + MTX, adalimumab + MTX, or placebo + MTX.

Conclusions

In RA patients with an inadequate response to DMARDs or biologics, tofacitinib 10 mg + MTX and baricitinib 4 mg + MTX were the most efficacious interventions and were not associated with a significant risk of serious adverse events.

Keywords

Tofacitinib Baricitinib Rheumatoid arthritis Network meta-analysis Janus kinase inhibitors 

Vergleich der Wirksamkeit und Sicherheit von Tofacitinib und Baricitinib bei Patienten mit aktiver rheumatoider Arthritis: Bayes-Netz-Metaanalyse randomisierter kontrollierter Studien

Zusammenfassung

Ziel

Bei Patienten mit rheumatoider Arthritis (RA) und unzureichendem Ansprechen auf krankheitsmodifizierende Medikamente („disease-modifying anti-rheumatic drugs“, DMARD) oder Biologika wurden die relative Wirksamkeit und Sicherheit von Tofacitinib und Baricitinib ermittelt.

Methoden

Die Autoren führten eine Bayes-Netz-Metaanalyse zur Kombination direkter und indirekter Evidenz aus randomisierten kontrollierten Studien („randomized controlled trials“, RCT) durch, die der Untersuchung der Wirksamkeit und Sicherheit von Tofacitinib und Baricitinib zusätzlich zu DMARD bei RA-Patienten mit unzureichendem Ansprechen auf DMARD oder Biologika diente.

Ergebnisse

Die Einschlusskriterien erfüllten 12 RCT mit 5883 Patienten. Es wurden 15 paarweise erfolgende Vergleiche einschließlich 10 direkter Vergleiche von 6 Interventionen durchgeführt. Tofacitinib 10 mg + Methotrexat (MTX) und Baricitinib 4 mg + MTX gehörten zu den wirksamsten Therapien bei aktiver RA mit unzureichendem Ansprechen auf DMARD oder Biologika, nächstwirksam waren Baricitinib 2 mg + MTX, Tofacitinib 5 mg + MTX und Adalimumab + MTX. Die auf dem SUCRA-Wert („surface under the cumulative ranking curve“) basierende Rangfolgewahrscheinlichkeit ergab für Tofacitinib 10 mg + MTX die größte Wahrscheinlichkeit, die beste Behandlung zur Erzielung einer Ansprechrate mit 20%iger Linderung der Symptome (ACR20) zu sein (SUCRA = 0,865); es folgten Baricitinib 4 mg + MTX (SUCRA = 0,774), Baricitinib 2 mg + MTX (SUCRA = 0,552), Tofacitinib 5 mg + MTX (SUCRA = 0,512), Adalimumab + MTX (SUCRA = 0,297) und Placebo + MTX (SUCRA <0,001). Bei der Inzidenz schwerer unerwünschter Ereignisse nach Behandlung mit Tofacitinib + MTX, Baricitinib + MTX, Adalimumab + MTX oder Placebo + MTX wurden keine signifikanten Unterschiede festgestellt.

Schlussfolgerung

Bei RA-Patienten mit unzureichendem Ansprechen auf DMARD oder Biologika stellten Tofacitinib 10 mg + MTX und Baricitinib 4 mg + MTX die wirksamsten Interventionen dar, sie waren dabei nicht mit einem signifikanten Risiko für schwere unerwünschte Ereignisse verbunden.

Schlüsselwörter

Tofacitinib Baricitinib Rheumatoide Arthritis Netzwerk-Metaanalyse Januskinase-Inhibitoren 

Notes

Acknowledgements

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

Compliance with ethical guidelines

Conflict of interest

S.-C. Bae and Y. H. Lee have no financial or non-financial conflict of interest to declare.

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 2018

Authors and Affiliations

  1. 1.Department of RheumatologyHanyang University Hospital for Rheumatic DiseasesSeoulKorea
  2. 2.Department of Rheumatology, Korea University Anam HospitalKorea University College of MedicineSeoulKorea (Republic of)

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