Successful Treatment of Chronic Rhinosinusitis With Nasal Polyps ( CRSwNP ) With Tezepelumab: A Case Report

Chronic rhinosinusitis (CRS) is a persistent inflammatory condition affecting the paranasal sinuses and their adjacent nasal cavity, characterised by symptoms lasting for at least 12 weeks [1]. Furthermore, the release of TSLP leads to the proliferation of the nasal epithelium by activating fibroblasts, resulting in smooth muscle hypertrophy and increased tissue remodelling, characteristic of nasal polyposis [2]. The patient was a 73-year-old Caucasian woman with rhinoconjunctivitis, chronic sinusitis and uncontrolled asthma since the age of 60 with frequent exacerbations. The total serum IgE levels were 80.10 KU/I (normal value < 100 KU/I) with specific IgE for Alternaria and 600 eosinophils/μL. Despite the optimised high-dose inhaled corticosteroid-long-acting beta2 agonist (ICS-LABA) plus long-acting muscarinic antagonist (LAMA) therapy, she complained of dyspnea at rest, which was worse on exercise or at night, frequent episodes of shortness of breath, chest tightness and cough. According to the Global Initiative for Asthma (GINA) guidelines [3], the fractional concentration of exhaled nitric oxide (FeNO) is modestly associated with levels of sputum and blood eosinophils. It was performed showing values of 55, higher than the established positivity limit (25 ppb). Findings from a maxillofacial CT scan showed mucosal hypertrophy with newly formed tissue in the bilateral ethmoid sinuses associated with the hypertrophy of the inferior turbinates. An accurate exam with flexible-fiberoptic fibrolaryngoscopy (FFL) confirmed the presence of polypoid formations of the bilateral inferior meatus with a Nasal Polyps Score (NPS) [4] of four. The total subjective nasal and Sino-Nasal Outcome Test (SNOT-22) [5] score was 62. All these data led to a diagnosis of adult-onset (late-onset) asthma and severe eosinophilic chronic rhinosinusitis. Regarding the clinical scenario, we added on Benralizumab (anti-IL5 receptor α) 30 mg by subcutaneous injection every 4 weeks for the first three injections, and then every 8 weeks thereafter. It is indicated for maintenance treatment of adult patients with severe eosinophilic asthma, which is not controlled with their current medicines, and showed efficacy in eosinophilic granulomatosis with polyangiitis (EGPA) [6]. After 1 year of therapy, despite the good initial asthma control with an important reduction of symptoms like dyspnea and cough, the number of exacerbations with the necessity to resort to oral corticosteroid (OCS) therapy did not reduce. Furthermore, the nasal obstruction remained almost unchanged, confirmed by the FFL that showed almost the same grading to the NPS score. Given the high impact on the quality of life and work activity reported by the patient, we decided to replace the biological therapy with tezepelumab (anti-TSLP, a bronchial epithelial cell-derived alarmin implicated in multiple downstream processes involved in asthma pathophysiology [7]). After 3 months from the introduction of this biological therapy, the FFL control reported the complete regression of the polyps in both nasal cavities (NPS score 0—Figure 1), confirmed by a CT scan performed at 6 months. From the asthmatic point of view, both respiratory symptom control and reduction of OCS cycles improved. After 6 months of therapy, the SNOT-22 score decreased to 20, with a reduction of 42 points, the blood eosinophilia was less than 150 cells/μL and the fractional exhaled nitric oxide level was decreased to normal (12 ppb). After switching to tezepelumab, which targets TSLP at the top of the inflammatory cascade, effectively addressed the multiple drivers of epithelial-driven inflammatory diseases and it was effective in regressing NP in a few months, as shown by NPS. Up to now, our patient no longer took systemic corticosteroids, in contrast with SOURCE [8] Phase 3 results, where no significant improvement in oral corticosteroid-sparing with tezepelumab versus placebo was observed, although an improvement was effectively evaluated in participants with baseline blood eosinophil counts of at least 150 cells/μL. No adverse events were registered. In literature, there are only two clinical cases that recorded a reduction of NPS after the administration of tezepelumab. Kawashima et al. [9] and Yamashita et al. [10] reported a significant reduction of NPs, a better control of bronchial asthma and ACT score, the reduction of FeNO level, needlessness to resort to OCS. Characteristics of CRS are epithelial dysfunction and persistent inflammation that hinder the ability of the epithelium to act as a physical and immunological barrier against the external environment [11]. TSLP is an epithelial cytokine implicated in shared pathophysiological processes underlying severe asthma and CRSwNP [12]. Nagarkar et al. [13] demonstrated that TSLP mRNA levels were significantly increased in NP tissue from patients with CRSwNP compared with uncinate tissue from patients with CRSsNP or control subjects and significantly correlated with markers of Th2 inflammation in the nasal mucosa. Furthermore, recent studies have shown that TSLP induces dendritic cells to express OX40L, a protein of the TNF superfamily. Neutralisation of this protein by antibodies has been demonstrated to inhibit interleukins associated with Th2-profile, and to increase the production of IL-10. This could be another possible mechanism of action that explains the improvement of chronic inflammatory diseases in nasal polyposis. In addition, inducing the release of Th17 cells, which are involved in both Type 2 and non-Type 2 inflammation, TSLP has a broad spectrum of action suitable for different and not always well-defined conditions. This could explain its usefulness when other conventional treatments do not achieve better results. A sub-analysis of the NAVIGATOR trial [14], a Phase 3 multicenter randomised double-blind placebo-controlled study, evaluated the effect of tezepelumab on asthma exacerbation rate and SNOT-22 score in patients (12–89 years old) with any reported history of NP, compared to asthma without NP. Nearly one-third of tezepelumab recipients achieved a complete response, showing clinically meaningful responses across all five criteria evaluated (decrease in Asthma Control Questionnaire-6 total score ≥ 0.5, increase in FEV1 ≥ 100 mL or ≥ 5%, ≥ 50% reduction in exacerbations from the previous year, a Clinical Global Impression of Change score, decrease in SNOT-22 total score ≥ 8.9). This case report highlights successful control of refractory asthma and comorbid Type 2 inflammatory diseases with tezepelumab treatment, with no side effects. Tezepelumab could be an encouraging option for those patients with CRSwNP who do not respond well to conventional treatment because it acts upstream of the Type 2 inflammation pathway. The authors have nothing to report. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.