Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 09 13 1 5 Morteza Fallahpour Department of Allergy, Rasool Akram Hospital, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Mohammad Nabavi Department of Allergy, Rasool Akram Hospital, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Babak Ghalehbaghi The Five Senses Institute, ENT and Head and Neck Surgery Research Center, Iran University of Medical Sciences, Tehran, Iran Somayeh Heydari Ghadikolaii Department of Allergy, Rasool Akram Hospital, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Mohammad Hasan Bemanian Department of Allergy, Rasool Akram Hospital, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Maryam Jalessi Skull Base Research Center, The Five Senses Institute, Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran 2026 05 28 2026 07 28 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. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4860 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4860/2421