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Are all JAK inhibitors for the treatment of rheumatoid arthritis equivalent? An adjusted indirect comparison of the efficacy of tofacitinib, baricitinib, upadacitinib, and filgotinib

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Abstract

Introduction

Comparisons of Janus kinase inhibitors (JAKi) for treatment of rheumatoid arthritis in patients with inadequate response to biologic disease-modifying anti-rheumatic drugs are lacking. We assessed the relative efficacy and safety of four JAKi (tofacitinib, baricitinib, upadacitinib, and filgotinib) in this context.

Method

We performed an adjusted indirect comparison (IC) of randomized clinical trials using Bucher’s method with an IC and mixed calculator. Endpoints were Disease Activity Score C-reactive protein (DAS28-CRP) and American College of Rheumatology-20 (ACR20). Equivalence was assessed using the equivalent therapeutic alternatives (ETA) guidelines.

Results

We included four of 133 potentially relevant studies. IC showed no statistically significant differences between the four JAKi regarding DAS28-CRP < 3.2. Results were similar in terms of ACR20 except for tofacitinib showing lower efficacy than upadacitinib (RAR −18.4% [IC95% −33.4 to −3.5], p=0.0157). Statistically significant differences were related to the relevant difference for tofacitinib in both endpoints. Despite no statistical differences for baricitinib, we observed a probably clinically relevant difference regarding DAS28-CRP. Probably clinically relevant differences were found for tofacitinib vs. upadacitinib in both endpoints, and for baricitinib vs. upadacitinib in DAS28-CRP. Safety, drug-drug interactions, and convenience considerations did not modify the result of therapeutic equivalence assessment based on efficacy data.

Conclusions

In conclusion, our results show that filgotinib and upadacitinib are ETA. Baricitinib and upadacitinib are also ETA due to a lack of clear differences and for showing superiority over placebo. The results for tofacitinib and upadacitinib show some inconsistency and more data are needed.

Key Points

• To date, neither a head-to-head comparison nor an indirect comparison between the Janus kinase inhibitors has been performed in patients with rheumatoid arthritis and an inadequate response to biologic disease-modifying anti-rheumatic drugs.

• We performed an adjusted indirect comparison that included randomized clinical trials of tofacitinib, baricitinib, upadacitinib, and filgotinib to assess their equivalence in this scenario.

• Our results show that baricitinib and filgotinib are equivalent therapeutic alternatives compared to upadacitinib. However, there is some inconsistency in the results of tofacitinib in front of upadacitinib.

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Authors and Affiliations

  1. Pharmacy Department, Hospital de la Santa Creu i Sant Pau (HSCSP), 08025, Barcelona, Spain

    Lucía Vallez-Valero, Ingrid Gasó-Gago, Ángel Marcos-Fendian, Adrián Plaza Diaz, Cristina Martinez-Molina & Maria Antònia Mangues-Bafalluy

  2. Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), 08041, Barcelona, Spain

    Lucía Vallez-Valero, Ingrid Gasó-Gago, Ángel Marcos-Fendian, Adrián Plaza Diaz, Cristina Martinez-Molina, Maria Antònia Mangues-Bafalluy & Hèctor Corominas

  3. Medicines Strategy and Coordination Unit, Catalan Health Institute, Barcelona, Spain

    Gemma Garrido-Alejos

  4. Pharmacy Department, Hospital de Sant Pau i Santa Tecla, 43003, Tarragona, Spain

    Adrià Riera-Magallón

  5. Department of Medicine, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain

    Cristina Martinez-Molina & Hèctor Corominas

  6. Department of Rheumatology and Systemic Autoimmune Diseases, Hospital de la Santa Creu i Sant Pau (HSCSP), 08041, Barcelona, Spain

    Hèctor Corominas

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  1. Lucía Vallez-Valero
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Contributions

L. V. V.: conceptualization and design, data collection, data analysis and interpretation, the first and final draft of the manuscript; I. G. G.: data analysis and interpretation, the first and final draft of the manuscript; A. M. F.: the first and final draft of the manuscript and critical review of the manuscript; A. R. M., A. P. D., C. M. M.: data collection, G. G. A., H. C. M., M. A. M. B.: critical review of the manuscript. All authors were involved in the critical assessment of the final manuscript. All authors have read and agreed to the present version of the manuscript.

Corresponding author

Correspondence to Lucía Vallez-Valero.

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This work has not been previously published and is not under consideration in the same or a substantially similar form (in print or electronically, including on a website), in any other peer-reviewed media. The present version of the manuscript has been seen and approved by all the authors who ensure the integrity of the work. This research has not received external funding. The manuscript does not contain clinical studies or patient data.

Conflict of interest

L. V. V., I. G. G., A. M. F., G. G. A., A. R. M., A. P. D., C. M. M., and M. A. M. B. declare no conflict of interest. H. C. has received consultancy fees, research grants, and speaker’s fees from Lilly, Galapagos, Abbvie, and Pfizer.

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We report that part of this manuscript has previously been published as an abstract in the 67th Sociedad Española de Farmacia Hospitalaria Congress. Vallez Valero L, Gaso Gago I, Garrido Alejos G et al. 411. Comparación indirecta ajustada de la eficacia de los inhibidores de Janus quinasas para el tratamiento de la artritis reumatoide. 67 Congreso Nacional de la Sociedad Española de Farmacia Hospitalaria. Barcelona, noviembre 2022. https://67congreso.sefh.es/img/libro-comunicaciones-67-congreso.pdf

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Vallez-Valero, L., Gasó-Gago, I., Marcos-Fendian, Á. et al. Are all JAK inhibitors for the treatment of rheumatoid arthritis equivalent? An adjusted indirect comparison of the efficacy of tofacitinib, baricitinib, upadacitinib, and filgotinib. Clin Rheumatol 42, 3225–3235 (2023). https://doi.org/10.1007/s10067-023-06787-2

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