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Relative remission rates of Janus kinase inhibitors in comparison with adalimumab in patients with active rheumatoid arthritis: a network meta-analysis

Relative Remissionsraten von Januskinaseinhibitoren im Vergleich zu Adalimumab bei Patienten mit aktiver rheumatoider Arthritis: eine Netzwerk-Metaanalyse

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Abstract

Objectives

The relative remission rates of tofacitinib, baricitinib, upadacitinib, and filgotinib compared with those of adalimumab were assessed in patients with rheumatoid arthritis (RA) who responded poorly to methotrexate (MTX).

Methods

We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) to examine the Disease Activity Score in 28 joints with C‑reactive protein (DAS28-CRP), the Clinical Disease Activity Index (CDAI), the Simplified Disease Activity Index (SDAI), and the Boolean remission of tofacitinib, baricitinib, upadacitinib, filgotinib, and adalimumab in RA patients with inadequate responses to MTX.

Results

Four RCTs, comprising 3507 patients, met the inclusion criteria. The filgotinib 200 mg + MTX and upadacitinib 15 mg + MTX groups showed a significantly higher DAS28-CRP < 2.6 than adalimumab 40 mg + MTX. Upadacitinib 15 mg + MTX showed a significantly higher CDAI (≤ 2.8) than adalimumab 40 mg + MTX (odds ratio [OR]: 1.62; 95% credible interval [CrI]: 1.16–2.29). The ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that upadacitinib 15 mg + MTX had the highest probability of being the best treatment as it achieved a CDAI ≤ 2.8, followed by filgotinib 200 mg + MTX, baricitinib 4 mg + MTX, tofacitinib 5 mg + MTX, and adalimumab 40 mg + MTX. The Boolean remission showed the same distribution pattern as that of the CDAI ≤ 2.8. Upadacitinib 15 mg + MTX showed a significantly higher SDAI ≤ 3.3 than adalimumab 40 mg + MTX (OR: 1.62; 95% CrI: 1.16–2.28). SUCRA ranking based on SDAI ≤ 3.3 indicated that upadacitinib 15 mg + MTX had the highest probability of being the best treatment for achieving an SDAI ≤ 3.3, followed by baricitinib 4 mg + MTX, filgotinib 200 mg + MTX, tofacitinib 5 mg + MTX, and adalimumab 40 mg + MTX.

Conclusions

In RA patients with an inadequate response to MTX, remission rates with JAK inhibitors were significantly higher; there is evidence for differences in efficacy regarding remission among the different JAK inhibitors.

Zusammenfassung

Ziel

Die relativen Remissionsraten von Tofacitinib, Baricitinib, Upadacitinib und Filgotinib im Vergleich zu denen von Adalimumab wurden bei Patienten mit rheumatoider Arthritis (RA) untersucht, die schlecht auf Methotrexat (MTX) ansprachen.

Methoden

Es wurde eine Bayes-Netzwerk-Metaanalyse durchgeführt, um direkte und indirekte Evidenz aus randomisierten kontrollierten Studien (RCT) zu kombinieren mit dem Ziel, den Disease Activity Score in 28 Gelenken mit C‑reaktivem Protein (DAS28-CRP), den Clinical Disease Activity Index (CDAI), den Simplified Disease Activity Index (SDAI) und die boolesche Remission von Tofacitinib, Baricitinib, Upadacitinib, Filgotinib und Adalimumab bei RA-Patienten mit unzureichendem Ansprechen auf MTX zu untersuchen.

Ergebnisse

Die Einschlusskriterien wurden von 4 RCT mit 3507 Patienten erfüllt. Die Gruppe mit Filgotinib 200 mg + MTX und die Gruppe mit Upadacitinib 15 mg + MTX wiesen einen signifikant höheren Anteil mit einem DAS28-CRP < 2,6 auf als Adalimumab 40 mg + MTX. Unter Upadacitinib 15 mg + MTX zeigte sich ein signifikant höherer Anteil mit einem CDAI ≤ 2,8 als unter Adalimumab 40 mg + MTX (Odds Ratio [OR]: 1,62; 95%-Kredibilitätsintervall [CrI]: 1,16–2,29). Die Ranglistenwahrscheinlichkeit, die auf der Oberfläche unter der kumulativen Rangkurve (SUCRA) basierte, zeigte, dass Upadacitinib 15 mg + MTX die höchste Wahrscheinlichkeit dafür aufwies, die beste Behandlung zu sein, da es einen CDAI ≤ 2,8 erzielte, es folgten Filgotinib 200 mg + MTX, Baricitinib 4 mg + MTX, Tofacitinib 5 mg + MTX und Adalimumab 40 mg + MTX. Die boolesche Remission wies das gleiche Verteilungsmuster auf wie bei einem CDAI ≤ 2,8. Unter Upadacitinib 15 mg + MTX zeigte sich ein signifikant höherer Anteil mit SDAI ≤ 3,3 als unter Adalimumab 40 mg + MTX (OR: 1,62; 95%-CrI: 1,16–2,28). Das SUCRA-Ranking auf der Basis eines SDAI ≤ 3,3 zeigte, dass Upadacitinib 15 mg + MTX die höchste Wahrscheinlichkeit dafür aufwies, die beste Behandlung zu sein, um einen SDAI ≤ 3,3 zu erzielen, es folgten Baricitinib 4 mg + MTX, Filgotinib 200 mg + MTX, Tofacitinib 5 mg + MTX und Adalimumab 40 mg + MTX.

Schlussfolgerung

Bei RA-Patienten mit unzureichendem Ansprechen auf MTX waren mit JAK-Inhibitoren signifikant höhere Remissionsraten zu erzielen; es gab Hinweise auf einen Unterschied hinsichtlich der Remissionswirksamkeit zwischen den verschiedenen JAK-Inhibitoren.

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Authors and Affiliations

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

    Young Ho Lee MD PhD & Gwan Gyu Song

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  1. Young Ho Lee MD PhD
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  2. Gwan Gyu Song
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Correspondence to Young Ho Lee MD PhD.

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Y.H. Lee and G.G. Song declare that they have no financial or non-financial conflict of interest to declare.

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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Ulf Müller-Ladner, Bad Nauheim

Uwe Lange, Bad Nauheim

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Lee, Y.H., Song, G.G. Relative remission rates of Janus kinase inhibitors in comparison with adalimumab in patients with active rheumatoid arthritis: a network meta-analysis. Z Rheumatol 83 (Suppl 1), 88–96 (2024). https://doi.org/10.1007/s00393-022-01165-w

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