Dual 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-Sousa^*Pedro Ávila-RibeiroJoão Eurico Fonseca

• Rheumatology Department, Hospital de Santa Maria, ULSSM; EULAR Center of Excellence for research in Rheumatology; Faculdade de Medicina, Universidade de Lisboa; Centro Académico de Medicina de Lisboa, Lisbon, Portugal

Spondyloarthritis (SpA) is a phenotypically heterogeneous group of diseases that share genetic and immune-mediated inflammatory pathways, affecting a diversity of organs/tissues such as the synovium, enthesis, bone marrow, skin, eye, and bowel. Progresses in the understanding of 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 on the safety profile of approved anti-cytokine treatments brought confidence to consider the combination of two cytokine blockade agents in more severe musculoskeletal (MSK) or extra MSK manifestations/refractory patients. The rationale for these dual-targeted therapy combination strategies has been largely dependent on the predominant SpA manifestations and the known efficacy of these therapeutics in monotherapy. More recently, adding a targeted synthetic (ts) to a biologic (b) disease-modifying antirheumatic drug (DMARDs) has also been considered. Additionally, newer bispecific anticytokine antibodies and tsDMARDs with dual mechanisms of action have also been developed and assessed. Despite scarce evidence from randomized controlled trials, real-world data retrospective cohorts and case series/reports show that b/tsDMARDs combinations are being used in clinical practice to overcome efficacy limitations from b/tsDMARDs monotherapies in more severe/difficult-to-treat SpA patients, namely in the presence of extra-MSK recalcitrant manifestations such as inflammatory bowel disease or psoriasis.