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

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, an...

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Autores: Vallez-Valero, Lucía|||0000-0001-9163-302X, Gasó-Gago, Ingrid, Marcos Fendian, Ángel|||0000-0003-2595-5906, Garrido-Alejos, Gemma|||0000-0001-8249-2771, Riera-Magallón, Adrià, Plaza Díaz, Adrián|||0000-0002-5316-5090, Martinez-Molina, Cristina|||0000-0001-5079-613X, Mangues-Bafalluy, Maria Antònia, Corominas, Hèctor|||0000-0002-7738-6787
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:302730
Acceso en línea:https://ddd.uab.cat/record/302730
https://dx.doi.org/urn:doi:10.1007/s10067-023-06787-2
Access Level:acceso abierto
Palabra clave:Rheumatoid arthritis
Indirect comparison
Janus Kinase inhibitors
Equivalent therapeutic alternatives
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spelling Are all JAK inhibitors for the treatment of rheumatoid arthritis equivalent? An adjusted indirect comparison of the efficacy of tofacitinib, baricitinib, upadacitinib, and filgotinibVallez-Valero, Lucía|||0000-0001-9163-302XGasó-Gago, IngridMarcos Fendian, Ángel|||0000-0003-2595-5906Garrido-Alejos, Gemma|||0000-0001-8249-2771Riera-Magallón, AdriàPlaza Díaz, Adrián|||0000-0002-5316-5090Martinez-Molina, Cristina|||0000-0001-5079-613XMangues-Bafalluy, Maria AntòniaCorominas, Hèctor|||0000-0002-7738-6787Rheumatoid arthritisIndirect comparisonJanus Kinase inhibitorsEquivalent therapeutic alternativesIntroduction: 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. 22023-01-0120232023-01-01Articlehttp://purl.org/coar/resource_type/c_6501AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/302730https://dx.doi.org/urn:doi:10.1007/s10067-023-06787-2reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest material està protegit per drets d'autor i/o drets afins. Podeu utilitzar aquest material en funció del que permet la legislació de drets d'autor i drets afins d'aplicació al vostre cas. Per a d'altres usos heu d'obtenir permís del(s) titular(s) de drets.https://rightsstatements.org/vocab/InC/1.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:3027302026-06-06T12:50:31Z
dc.title.none.fl_str_mv Are all JAK inhibitors for the treatment of rheumatoid arthritis equivalent? An adjusted indirect comparison of the efficacy of tofacitinib, baricitinib, upadacitinib, and filgotinib
title Are all JAK inhibitors for the treatment of rheumatoid arthritis equivalent? An adjusted indirect comparison of the efficacy of tofacitinib, baricitinib, upadacitinib, and filgotinib
spellingShingle Are all JAK inhibitors for the treatment of rheumatoid arthritis equivalent? An adjusted indirect comparison of the efficacy of tofacitinib, baricitinib, upadacitinib, and filgotinib
Vallez-Valero, Lucía|||0000-0001-9163-302X
Rheumatoid arthritis
Indirect comparison
Janus Kinase inhibitors
Equivalent therapeutic alternatives
title_short Are all JAK inhibitors for the treatment of rheumatoid arthritis equivalent? An adjusted indirect comparison of the efficacy of tofacitinib, baricitinib, upadacitinib, and filgotinib
title_full Are all JAK inhibitors for the treatment of rheumatoid arthritis equivalent? An adjusted indirect comparison of the efficacy of tofacitinib, baricitinib, upadacitinib, and filgotinib
title_fullStr Are all JAK inhibitors for the treatment of rheumatoid arthritis equivalent? An adjusted indirect comparison of the efficacy of tofacitinib, baricitinib, upadacitinib, and filgotinib
title_full_unstemmed Are all JAK inhibitors for the treatment of rheumatoid arthritis equivalent? An adjusted indirect comparison of the efficacy of tofacitinib, baricitinib, upadacitinib, and filgotinib
title_sort Are all JAK inhibitors for the treatment of rheumatoid arthritis equivalent? An adjusted indirect comparison of the efficacy of tofacitinib, baricitinib, upadacitinib, and filgotinib
dc.creator.none.fl_str_mv Vallez-Valero, Lucía|||0000-0001-9163-302X
Gasó-Gago, Ingrid
Marcos Fendian, Ángel|||0000-0003-2595-5906
Garrido-Alejos, Gemma|||0000-0001-8249-2771
Riera-Magallón, Adrià
Plaza Díaz, Adrián|||0000-0002-5316-5090
Martinez-Molina, Cristina|||0000-0001-5079-613X
Mangues-Bafalluy, Maria Antònia
Corominas, Hèctor|||0000-0002-7738-6787
author Vallez-Valero, Lucía|||0000-0001-9163-302X
author_facet Vallez-Valero, Lucía|||0000-0001-9163-302X
Gasó-Gago, Ingrid
Marcos Fendian, Ángel|||0000-0003-2595-5906
Garrido-Alejos, Gemma|||0000-0001-8249-2771
Riera-Magallón, Adrià
Plaza Díaz, Adrián|||0000-0002-5316-5090
Martinez-Molina, Cristina|||0000-0001-5079-613X
Mangues-Bafalluy, Maria Antònia
Corominas, Hèctor|||0000-0002-7738-6787
author_role author
author2 Gasó-Gago, Ingrid
Marcos Fendian, Ángel|||0000-0003-2595-5906
Garrido-Alejos, Gemma|||0000-0001-8249-2771
Riera-Magallón, Adrià
Plaza Díaz, Adrián|||0000-0002-5316-5090
Martinez-Molina, Cristina|||0000-0001-5079-613X
Mangues-Bafalluy, Maria Antònia
Corominas, Hèctor|||0000-0002-7738-6787
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Rheumatoid arthritis
Indirect comparison
Janus Kinase inhibitors
Equivalent therapeutic alternatives
topic Rheumatoid arthritis
Indirect comparison
Janus Kinase inhibitors
Equivalent therapeutic alternatives
description 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.
publishDate 2023
dc.date.none.fl_str_mv 2
2023-01-01
2023
2023-01-01
dc.type.none.fl_str_mv Article
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https://dx.doi.org/urn:doi:10.1007/s10067-023-06787-2
dc.language.none.fl_str_mv Inglés
eng
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