Table 1.

Relevant studies in CRSwNP

Target	Drug name	Status of approval	Relevant studies in CRSwNP
			Author	Study design	Subjects	Outcomes	Adverse events
IgE	Omalizumab	Approved by FDA for treatment of severe allergic asthma. Under investigation for use in allergic rhinitis and CRS.	Pinto et al. 2010 [32]	Randomized, placebo-controlled, double-blind study. Duration of trial—6 months. Subcutaneous injection of omalizumab (0.016 mg/kg per IU total serum IgE/ml) or placebo.	Adults with CRS with total serum IGE between 30 and 700 IU/ml. N = 14 (treatment group = 7, placebo group = 7).	No significant changes on CT scan evaluation (P < 0.391), in QoL (P < 0.60), in olfaction (P < 0.31), endoscopy scores (P < 0.58), in eosinophils in nasal lavage (P < 0.47), NPNIF (P < 0.31), sinonasal symptoms (P < 0.21). Trend towards less use of rescue medications in treatment group.	No side effects during the study.
			Gevaert et al. 2013 [33]	Randomized, double-blind, placebo-controlled, 2-center study. Duration of trial—20 weeks. Subcutaneous injection of omalizumab every 2 weeks (8 injections in total) or every month (4 injections in total) based on total IgE levels and body weight (max dose 375 mg) or placebo.	Adults with CRSwNP and comorbid asthma for more than 2 years. N = 24 (treatment group = 16 subjects, placebo group = 8 subjects).	Significant reduction in the treatment group: polyp size (P = 0.02), Lund-Mackay score (P = 0.04), nasal congestion (P = 0.002), anterior rhinorrhea (P = 0.003), loss of sense of smell (P = 0.004), wheeze (P = 0.02), dyspnea (P = 0.02). Cough and spirometric results did not reach significant differences. Mental health did not improve significantly. Physical health (P = 0.02), sleep (P = 0.03), general symptoms (P = 0.01), AQLQ (P = 0.003), activity limitations (P = 0.002), symptoms (P = 0.01) and emotional function (P = 0.02) significantly improved in treatment group).	Common cold appeared significantly more often in the treatment group (P = 0.02). Asthma attack (n = 1, placebo group). Fatal lymphoblastic lymphoma 1 year after finishing the study (n = 1, treatment group).
	Ligelizumab		No trials for CRSwNP yet.
IL-5	Mepolizumab	Approved by FDA for treatment of severe eosinophilic asthma.	Bachert et al. 2017 [43]	Randomized, double-blind, placebo-controlled, multicenter study. Duration of trial—25 weeks. Intravenous infusion of 750 mg mepolizumab or placebo every 4 weeks, 6 doses.	Adult patients with severe recurrent bilateral polyposis who required surgery. N = 105 (treatment = 54, placebo = 51).	Mepolizumab significantly reduced the number of patients who needed surgery (P = 0.006), improved VAS score of nasal polyposis (P = 0.001), endoscopic polyp score (P = 0.031), mean individual symptom VAS scores (rhinorrhea, mucus in the throat, nasal blockage, loss of smell), SNOT-22 scores, PNIF (P = 0.026). No significant differences between mepolizumab in EQ-5D index scores, olfaction, lung function.	AEs more frequent in placebo group: headache, nasopharyngitis. AEs more frequent in treatment group: oropharyngeal pain, back pain, influenza, pyrexia.
	Reslizumab	Approved by FDA for treatment of severe eosinophilic asthma.	Gevaert et al. 2006 [42]	Phase I. single-dose, randomized, double-blind, placebo-controlled, 3-arm, parallel-group, 2-center safety and pharmacokinetic study. Duration of the trial—36 weeks. Intravenous infusion of reslizumab 3 mg/kg or 1 mg/kg or placebo.	Adult patients with massive bilateral nasal polyposis or recurrent nasal polyposis after surgery. N = 24	(Study was not designed and powered to detect treatment differences in efficacy variables.) No significant differences in symptom scores or in nasal peak inspiratory flow values. Significant decrease in blood eosinophil counts in both treatment groups. Significant suppression of nasal IL-5.	AEs: upper respiratory tract infection (treatment groups = 5 each, placebo group = 4). No major differences in other AEs.
IL-5Rα receptor	Benralizumab	Approved by FDA for treatment of severe eosinophilic asthma.	No trials for CRSwNP yet.
Anti-IL-4/IL-13	Dupilumab	Approved by FDA for treatment of eczema.	Bachert et al. 2016 [50]	Randomized, double-blind, placebo-controlled parallel-group study. Duration of the trial—32 weeks. Subcutaneous dupilumab (loading dose 600 mg followed by 15 weekly doses of 300 mg) and placebo.	Adult patients with bilateral nasal polyposis and chronic symptoms of sinusitis despite intranasal corticosteroid treatment for at least 2 months. N = 60 (30 patients in each group).	Significant improvement in the treatment group in polyp score (P < 0.001), Lund-Mackay CT score (P < 0.001), peak inspiratory flow (P = 0.002), SNOT-22 (P < 0.001).	AEs: 25 of 30 patients in placebo group and 30 of 30 patients in the treatment group. AEs: mild-to-moderate nasopharyngitis, injection site reactions, headache. No serious adverse events were considered to be related to dupilumab.
	Tralokinumab	In phase III trials for severe asthma (unsatisfactory results of STRATOS 2 and TROPOS trials).	No trials for CRSwNP yet.
	Lebrikizumab	In phase II for atopic dermatitis, idiopathic pulmonary fibrosis. Discontinued for asthma, COPD, Hodgkin’s disease.	No trials for CRSwNP yet.
Siglec-8		Phase II trial is underway.	No trials for CRSwNP yet.
CRTh2/DRP			No trials for CRSwNP yet.
CXCR2 receptors			No trials for CRSwNP yet.
IL-17A	Brodalumab	Approved by FDA for treatment patients with moderate-to-severe plaque psoriasis.	No trials for CRSwNP yet.