Add-on Baricitinib in Omalizumab-refractory Chronic Rhinosinusitis with Nasal Polyps as a Dual-pathway Strategy

Abstract

A subset of patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) remains refractory to omalizumab, necessitating alternative therapeutic strategies. Blocking downstream interleukin (IL)-4 and IL-13 signaling via Janus kinase (JAK) inhibition represents a plausible approach, particularly in settings where the IL-4/IL-13 receptor blocker dupilumab is unavailable. This study aimed to evaluate the efficacy and safety of add-on baricitinib, an oral JAK1/2 inhibitor, in patients with severe, omalizumab-refractory CRSwNP.
In this open-label pilot case series, 10 adults with severe, refractory CRSwNP despite standard medical treatment and at least 1 endoscopic sinus surgery, who demonstrated poor control after a 6-month trial of omalizumab, received add-on baricitinib (4 mg daily) for 6 months while continuing omalizumab. Outcomes included the 22-item Sinonasal Outcome Test (SNOT-22), Lund-Mackay (LMK) CT score, lung function (forced expiratory volume in 1 second [FEV₁]% predicted), and safety monitoring.
The addition of baricitinib was associated with clinically meaningful improvements from baseline in all patients. Mean SNOT-22 scores decreased from 41.7 to 25.9, LMK scores improved from 14.5 to 11.5, and FEV₁% predicted increased from 77.1% to 79.7%. The combination was well tolerated; adverse events included transient hypercholesterolemia (n=3) and 1 self-limited oral herpes simplex recurrence, with no thromboembolic events observed.
This first-in-human case series provides preliminary evidence that dual-pathway blockade with add-on baricitinib may be a viable and well-tolerated therapeutic strategy for patients with omalizumab-refractory CRSwNP, especially in resource-constrained environments. These findings warrant further investigation in controlled trials.