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Comparative efficacy and safety of tofacitinib, baricitinib, upadacitinib, and filgotinib in active rheumatoid arthritis refractory to biologic disease-modifying antirheumatic drugs

Relative Wirksamkeit und Sicherheit von Tofacitinib, Baricitinib, Upadacitinib und Filgotinib bei aktiver rheumatoider Arthritis mit Refraktärität gegen biologische krankheitsmodifizierende Antirheumatika

Zeitschrift für Rheumatologie volume 80, pages 379–392 (2021)Cite this article

Abstract

Objective

The relative efficacy and tolerability of tofacitinib, baricitinib, upadacitinib, and filgotinib were assessed in patients with rheumatoid arthritis (RA) with inadequate responses to biologic disease-modifying antirheumatic drugs (bDMARDs).

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, baricitinib, upadacitinib, and filgotinib in RA patients with inadequate responses to bDMARDs.

Results

Four RCTs comprising 1399 patients met the inclusion criteria. Tofacitinib, baricitinib, upadacitinib, and filgotinib achieved significant American College of Rheumatology 20% (ACR20) responses versus placebo. The ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that upadacitinib 15 mg had the highest probability of being the best treatment for achieving the ACR20 response rate, followed by filgotinib 200 mg, baricitinib 4 mg, filgotinib 100 mg, tofacitinib 5 mg, and placebo. The ranking in SUCRA based on the ACR50 response rate indicated that baricitinib 4 mg had the highest probability of achieving the ACR50 response rate, followed by filgotinib 200 mg, tofacitinib 5 mg, upadacitinib 15 mg, filgotinib 100 mg, and placebo. Tofacitinib 5 mg showed a significantly higher ACR70 response rate than filgotinib 100 mg and upadacitinib 15 mg. Tofacitinib 5 mg, filgotinib 200 mg, and placebo showed a significantly lower serious adverse event rate than upadacitinib 15 mg.

Conclusion

Tofacitinib, baricitinib, upadacitinib, and filgotinib were effective treatment options for RA patients with an inadequate response to bDMARDs but with different efficacy and safety profiles.

Zusammenfassung

Ziel

Bei Patienten mit rheumatoider Arthritis (RA) und inadäquater Reaktion auf biologische krankheitsmodizifierende Antirheumatika (bDMARD) wurde die relative Wirksamkeit und Verträglichkeit von Tofacitinib, Baricitinib, Upadacitinib und Filgotinib ermittelt.

Methoden

Eine Bayes-Netzwerk-Metaanalyse wurde durchgeführt, um direkte und indirekte Evidenz aus randomisierten kontrollierten Studien (RCT) zu kombinieren und so die Wirksamkeit und Sicherheit von Tofacitinib, Baricitinib, Upadacitinib und Filgotinib bei RA-Patienten mit inadäquatem Ansprechen auf bDMARD zu untersuchen.

Ergebnisse

Die Einschlusskriterien wurden von 4 RCT mit 1399 Patienten erfüllt. Unter Tofacitinib, Baricitinib, Upadacitinib und Filgotinib zeigte sich eine signifikant höhere ACR20-Ansprechrate (gemäß American College of Rheumatology) als unter Placebo. Wie die Rangfolgewahrscheinlichkeit, basierend auf der Oberfläche unter der kumulativen Rangfolgenkurve (SUCRA, „surface under the cumulative ranking curve“), ergab, stellte Upadacitinib 15 mg mit größter Wahrscheinlichkeit die beste Behandlung zur Erzielung der ACR20-Ansprechrate dar, es folgten Filgotinib 200 mg, Baricitinib 4 mg, Filgotinib 100 mg, Tofacitinib 5 mg und Placebo. Die auf der ACR50-Ansprechrate basierende SUCRA-Rangfolge zeigte, dass für Baricitinib 4 mg die höchste Wahrscheinlichkeit bestand, die ACR50-Ansprechrate zu erzielen, es folgten Filgotinib 200 mg, Tofacitinib 5 mg, Upadacitinib 15 mg, Filgotinib 100 mg und Placebo. Tofacitinib 5 mg wies eine signifikant höhere ACR70-Ansprechrate auf als Filgotinib 100 mg und Upadacitinib 15 mg. Für Tofacitinib 5 mg, Filgotinib 200 mg und Placebo zeigte sich eine signifikant niedrigere Rate schwerer unerwünschter Ereignisse als für Upadacitinib 15 mg.

Schlussfolgerung

Für RA-Patienten mit inadäquater Reaktion auf bDMARD erwiesen sich Tofacitinib, Baricitinib, Upadacitinib und Filgotinib als wirksame Therapieoptionen, jedoch mit unterschiedlichen Wirksamkeits- und Sicherheitsprofilen.

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Funding

This research received no specific grants from any public, commercial, or not-for-profit sector funding agencies.

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Authors and Affiliations

  1. Division of Rheumatology, Department of Internal Medicine, Korea University College of Medicine, 73, Goryeodae-ro, Seongbuk-gu, 02841, Seoul, Korea (Republic of)

    Y. H. Lee MD, PhD & G. G. Song

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  1. Y. H. Lee MD, PhD
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  2. G. G. Song
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Correspondence to Y. H. 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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Lee, Y.H., Song, G.G. Comparative efficacy and safety of tofacitinib, baricitinib, upadacitinib, and filgotinib in active rheumatoid arthritis refractory to biologic disease-modifying antirheumatic drugs. Z Rheumatol 80, 379–392 (2021). https://doi.org/10.1007/s00393-020-00796-1

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  • DOI: https://doi.org/10.1007/s00393-020-00796-1

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