JAK Inhibitors, Anti-IL-6R Antagonists, Secukinumab, Abatacept, and Rituximab in Polymyalgia Rheumatica: What Insights Emerge from Phase 2 and 3 Randomized Controlled Trials?
Year: 2026
Type: article
Abstract: Background: Glucocorticoids (GCs) remain the cornerstone of polymyalgia rheumatica (PMR) management, but their cumulative toxicity necessitates effective GC-sparing strategies. Recent randomized controlled trials (RCTs) evaluating targeted therapies with diverse mechanisms of action have offered an unprecedented opportunity to dissect the disease’s underlying immunobiological architecture. Methods: A focused narrative literature search was conducted within PubMed to analyze Phase 2 and Phase 3 RCTs and long-term extension studies investigating Janus Kinase (JAK) inhibitors, secukinumab (anti-IL-17A), abatacept, anti-CD20 monoclonal antibody rituximab, and anti-IL-6 receptor (IL-6R) antagonists in PMR patients. Results: This scoping analysis highlighted how distinct molecular pathways demonstrated highly divergent efficacy profiles. Specifically, baricitinib and tofacitinib (two JAK inhibitors), along with sarilumab and tocilizumab (anti-IL-6 receptor), achieved robust short-term clinical response and acute-phase reactant normalization, though anti-IL-6 receptor extension data revealed persistent localized musculoskeletal symptoms in a patient subgroup. In chronic, relapsing, GC-dependent settings, the anti-IL-17a monoclonal antibody secukinumab significantly increased sustained GC-free remission. The placebo-controlled Phase 2 BRIDGE-PMR trial and its subsequent 1-year extension study demonstrated the efficacy of a single intravenous infusion of rituximab: a significantly higher rate of sustained, GC-free clinical remission was observed compared to the placebo group. Conversely, the T-cell co-stimulation modulator abatacept failed to demonstrate significant therapeutic efficacy. All these high-impact trials confirmed that precision cytokine and cellular targeting could provide a safe and highly tolerable alternative to conventional GC management. Methodologically, however, some of these trials had a primary limitation, and this was the reliance on short-term 24-week endpoints, which introduced a critical “temporal blind spot” that masked late relapses during advanced GC tapering. Conclusions: PMR is hypothesized to represent a complex syndrome of compartmentalized phenotypic convergence, where distinct molecular axes could drive pathology across different chronological stages (modeled as an acute/IL-6-driven phase vs. a chronic/Th17-dependent phase). While these therapeutic differences suggest a novel conceptual framework, head-to-head comparative research is strictly required to establish clear clinical hierarchies. In addition, upcoming clinical trial designs should systematically extend evaluation periods to 52 weeks to accurately assess sustained remission and differentiate between short-term suppression and long-term therapeutic efficacy.
Source: Medicines
Author: Ciro Manzo
Institution: ASL Roma
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,689
OpenAlex ID: W7222202063
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