Dual anti-cytokine biologic and/or targeted synthetic therapy combination in spondyloarthritis: a narrative review. Are we missing the opportunity for higher remission rates?

Spondyloarthritis (SpA) is a phenotypically heterogeneous group of diseases that share genetic and immune-mediated inflammatory pathways, affecting various organs/and tissues such as the synovium, enthesis, bone marrow, skin, eye, and bowel. Advances in understanding tissue-specific cytokine imbalan...

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Main Authors: Elsa Vieira-Sousa, Pedro Ávila-Ribeiro, João Eurico Fonseca
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Medicine
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Online Access:https://www.frontiersin.org/articles/10.3389/fmed.2025.1576411/full
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author Elsa Vieira-Sousa
Elsa Vieira-Sousa
Pedro Ávila-Ribeiro
Pedro Ávila-Ribeiro
João Eurico Fonseca
João Eurico Fonseca
author_facet Elsa Vieira-Sousa
Elsa Vieira-Sousa
Pedro Ávila-Ribeiro
Pedro Ávila-Ribeiro
João Eurico Fonseca
João Eurico Fonseca
author_sort Elsa Vieira-Sousa
collection DOAJ
description Spondyloarthritis (SpA) is a phenotypically heterogeneous group of diseases that share genetic and immune-mediated inflammatory pathways, affecting various organs/and tissues such as the synovium, enthesis, bone marrow, skin, eye, and bowel. Advances in understanding tissue-specific cytokine imbalance in SpA have unveiled an opportunity to foster higher remission rates through a more tailored cytokine blockade. Furthermore, over the years, the accumulated knowledge of the safety profile of approved anti-cytokine treatments has instilled confidence in considering the combination of two cytokine blockade agents for more severe musculoskeletal (MSK) or extra-MSK manifestations/in refractory patients. The rationale for these dual-targeted therapy combination strategies has largely depended on the predominant SpA manifestations and the known efficacy of these therapeutics in monotherapy. More recently, the addition of a targeted synthetic (ts) to a biologic (b) disease-modifying anti-rheumatic drug (DMARD) has also been considered. Additionally, newer bispecific anti-cytokine antibodies and tsDMARDs with dual mechanisms of action have been developed and assessed. Despite limited evidence from randomized controlled trials, real-world data from retrospective cohorts and case series/reports indicate that b/tsDMARD combinations are being used in clinical practice to overcome efficacy limitations of b/tsDMARD monotherapies in more severe either/or difficult-to-treat SpA patients, particularly in the presence of extra-MSK recalcitrant manifestations such as inflammatory bowel disease or psoriasis.
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spelling doaj-art-89db195b815b43f490e6a567960779cc2025-08-20T03:07:17ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2025-06-011210.3389/fmed.2025.15764111576411Dual anti-cytokine biologic and/or targeted synthetic therapy combination in spondyloarthritis: a narrative review. Are we missing the opportunity for higher remission rates?Elsa Vieira-Sousa0Elsa Vieira-Sousa1Pedro Ávila-Ribeiro2Pedro Ávila-Ribeiro3João Eurico Fonseca4João Eurico Fonseca5Faculdade de Medicina, Universidade de Lisboa, Centro Académico de Medicina de Lisboa, Lisboa, PortugalRheumatology Department, Hospital de Santa Maria, Unidade Local de Saúde de Santa Maria, Centro Académico de Medicina de Lisboa, Lisboa, PortugalFaculdade de Medicina, Universidade de Lisboa, Centro Académico de Medicina de Lisboa, Lisboa, PortugalRheumatology Department, Hospital de Santa Maria, Unidade Local de Saúde de Santa Maria, Centro Académico de Medicina de Lisboa, Lisboa, PortugalFaculdade de Medicina, Universidade de Lisboa, Centro Académico de Medicina de Lisboa, Lisboa, PortugalRheumatology Department, Hospital de Santa Maria, Unidade Local de Saúde de Santa Maria, Centro Académico de Medicina de Lisboa, Lisboa, PortugalSpondyloarthritis (SpA) is a phenotypically heterogeneous group of diseases that share genetic and immune-mediated inflammatory pathways, affecting various organs/and tissues such as the synovium, enthesis, bone marrow, skin, eye, and bowel. Advances in understanding tissue-specific cytokine imbalance in SpA have unveiled an opportunity to foster higher remission rates through a more tailored cytokine blockade. Furthermore, over the years, the accumulated knowledge of the safety profile of approved anti-cytokine treatments has instilled confidence in considering the combination of two cytokine blockade agents for more severe musculoskeletal (MSK) or extra-MSK manifestations/in refractory patients. The rationale for these dual-targeted therapy combination strategies has largely depended on the predominant SpA manifestations and the known efficacy of these therapeutics in monotherapy. More recently, the addition of a targeted synthetic (ts) to a biologic (b) disease-modifying anti-rheumatic drug (DMARD) has also been considered. Additionally, newer bispecific anti-cytokine antibodies and tsDMARDs with dual mechanisms of action have been developed and assessed. Despite limited evidence from randomized controlled trials, real-world data from retrospective cohorts and case series/reports indicate that b/tsDMARD combinations are being used in clinical practice to overcome efficacy limitations of b/tsDMARD monotherapies in more severe either/or difficult-to-treat SpA patients, particularly in the presence of extra-MSK recalcitrant manifestations such as inflammatory bowel disease or psoriasis.https://www.frontiersin.org/articles/10.3389/fmed.2025.1576411/fulldual combination therapybiologic DMARDtargeted synthetic DMARDsbispecific antibodiesdual mechanism of action
spellingShingle Elsa Vieira-Sousa
Elsa Vieira-Sousa
Pedro Ávila-Ribeiro
Pedro Ávila-Ribeiro
João Eurico Fonseca
João Eurico Fonseca
Dual anti-cytokine biologic and/or targeted synthetic therapy combination in spondyloarthritis: a narrative review. Are we missing the opportunity for higher remission rates?
Frontiers in Medicine
dual combination therapy
biologic DMARD
targeted synthetic DMARDs
bispecific antibodies
dual mechanism of action
title Dual anti-cytokine biologic and/or targeted synthetic therapy combination in spondyloarthritis: a narrative review. Are we missing the opportunity for higher remission rates?
title_full Dual anti-cytokine biologic and/or targeted synthetic therapy combination in spondyloarthritis: a narrative review. Are we missing the opportunity for higher remission rates?
title_fullStr Dual anti-cytokine biologic and/or targeted synthetic therapy combination in spondyloarthritis: a narrative review. Are we missing the opportunity for higher remission rates?
title_full_unstemmed Dual anti-cytokine biologic and/or targeted synthetic therapy combination in spondyloarthritis: a narrative review. Are we missing the opportunity for higher remission rates?
title_short Dual anti-cytokine biologic and/or targeted synthetic therapy combination in spondyloarthritis: a narrative review. Are we missing the opportunity for higher remission rates?
title_sort dual anti cytokine biologic and or targeted synthetic therapy combination in spondyloarthritis a narrative review are we missing the opportunity for higher remission rates
topic dual combination therapy
biologic DMARD
targeted synthetic DMARDs
bispecific antibodies
dual mechanism of action
url https://www.frontiersin.org/articles/10.3389/fmed.2025.1576411/full
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