Table 1 Results of biologic randomized controlled trials for CRSwNP

Effect of Subcutaneous Dupilumab on Nasal Polyp Burden in Patients With Chronic Sinusitis and Nasal Polyposis: A Randomized Clinical Trial

Bachert et al. [3]

Dupilumab (anti-IL-4/IL-13)

N = 60

(Placebo n = 30, Treatment n = 30)

16 weeks

(study endpoint)

CRSwNP refractory to intranasal corticosteroid therapy

Asthma: n = 35 Allergies: n = 38

Aspirin

intolerance: n = 12

Placebo

Asthma: n = 19 (63.3%)

Aspirin sensitization: n = 9 (30%)

Treatment

Asthma: n = 16 (53.3%)

Aspirin sensitization: n = 6 (20%)

Endoscopic NPS, SNOT-22, VAS, NPIF, UPSIT, CT (LMK), FEV1, ACQ-5

Statistically significant improvement in SNOT-22 and UPSIT in the dupilumab group versus placebo

Statistically significant difference of least squares mean change in bilateral endoscopic nasal polyp score and LMK CT total scores between the treatment and placebo group

Statistically significant reduction of IgE, and plasma eotaxin-3 with dupilumab versus placebo

Asthma:

Dupilumab and mometasone improved lung function and asthma control by FEV1, ACQ-5, UPSIT, SNOT22

Efficacy and safety of dupilumab in patients with chronic rhinosinusitis with nasal polyps: results from the randomized phase 3 SINUS-24 study

Bachert et al. [4]

Dupilumab (anti-IL-4/IL-13)

N = 276 (Placebo n = 133, Treatment n = 143)

24 weeks (study endpoint) with 24 weeks follow-up

CRSwNP

58% comorbid asthma

30% comorbid AERD

VAS, SNOT-22, adverse events, patient-reported outcomes, ACQ- 6, total nasal polyp score, UPSIT, FEV1, LMK score, blood and serum markers

Dupilumab significantly improved nasal polyp score, LMK score, Snot- 22 score, patient reported nasal congestion, and UPSIT scores from baseline compared to placebo

Asthma patients on dupilumab had improved lung function (FEV1) and ACQ-6 scores

By week 24, significant decrease in NPS by 1.89 points and decrease congestion by 1.34 points was observed

Week 4–8 showed significant improvement in NPS and congestion

After stopping injections at 24 weeks, all metrics trended back towards baseline

A randomized phase 3 study, SINUS-52, evaluating the efficacy and safety of dupilumab in patients with

severe chronic rhinosinusitis with nasal polyps

Han et al. (2019)⁵

Dupilumab (anti-IL-4/IL- 13)

N = 448 (Placebo n = 153, Treatment Q2W/Q4W n = 145, Treatment Q2W n = 150)

52 weeks (study endpoint)

CRSwNP

60% comorbid asthma

27% comorbid AERD

VAS, SNOT-22, adverse events, patient-reported outcomes, ACQ- 6, total nasal polyp score, UPSIT, FEV1, LMK score, blood and serum markers,

Dupilumab significantly improved nasal polyp score, LMK score, Snot- 22 score, patient reported nasal congestion, and UPSIT scores from baseline compared to placebo

Asthma patients on dupilumab had improved lung function (FEV1) and ACQ-6 scores

By week 24, significant dec NPS by 1.71 points and decrease in congestion by 1.25 points was observed

When injections continued after 24 weeks, patients continued to see benefit and was greatest in q2w versus q4w

By week 4–8, patients showed significant improvement in NPS and congestion

In 2/3 patients, surgical procedure was no longer necessary

Dupilumab reduces opacification across all sinuses and related symptoms in patients with CRSwNP

Bachert et al. [6]

Dupilumab

(anti-IL-4/IL-13)

N = 60

(Placebo n = 30, Treatment n = 30)

16 weeks (study endpoint)

CRSwNP

Comorbid asthma

Placebo: n = 19(63.3%)

Treatment:

N = 16(53.3%)

Placebo n = 19

Treatment n = 16

zLMK, LMK score, bilateral endoscopic nasal polyp score, UPSIT, SNOT-22, VAS, patient reported symptoms of nasal congestion and/or obstruction

After 16 weeks, Dupilumab significantly decreased opacification across all sinuses measured using the LMK and zLMK scoring systems, and significantly improved nasal polyp score, SNOT-22 score, VAS score, and UPSIT score

At baseline opacification measured by total LMK score correlated with other assessed outcomes but not at 16 weeks

A randomized, double-blind, placebo-controlled trial of anti-IgE for chronic rhinosinusitis

Pinto et al. [7]

Omalizumab

(anti-IgE)

N = 14

(Placebo n = 7,

Treatment n = 7)

6 months (study endpoint)

CRSwNP

Asthma: All patients

Snot-22, SF-36, nasal polyp size, CT scan opacification percentage, adverse events, NPIF, eosinophil count, UPSIT

No significant differences in polyp size, CT scan opacification percentage, SNOT-22 score, NPIF in the omalizumab group compared to placebo

Improvement in UPSIT smell test score but not statistically significant and no significant differences in SF-36 except for the one domain, Vitality, between omalizumab and placebo group

Omalizumab is effective in allergic and nonallergic patients with nasal polyps and asthma

Gevaert et al. [8]

Omalizumab

(anti-IgE)

N = 24

(Placebo n = 8, Treatment n = 15)

16 weeks (study endpoint)

CRSwNP with asthma

Asthma: All patients

Allergies: n = 13 (placebo n = 7 (47%), treatment n = 6 (75%))

Aspirin

intolerance: n = 12

Placebo 9 (53%), treatment = 4(50%)

Disease symptom scores, adverse events, RSOM-31, AQLQ, SF-36, polyp size and total overall polyp score, LMK Score, FEV1 and PEF, and blood and serum markers

Significant reduction in polyp size, improvement in LMK scores in Omalizumab group after 16 weeks

Significant decrease in symptom scores for Omalizumab group: nasal congestion, anterior rhinorrhea, loss of sense of smell, dyspnea

Significant improvement in SF-36 of physical health, RSOM-31 of sleep and general symptoms and AQLQ after Omalizumab treatment

No significant changes in blood and serum markers were observed at study endpoint

No significant differences were observed in outcomes between allergic, non-allergic and AERD patients

Efficacy and safety of omalizumab in nasal polyposis: 2 randomized phase 3 trials

(POLYP 1)

Gevaert et al. [9]

Omalizumab (anti-IgE)

N = 138

(Placebo n = 66, Treatment n = 72)

24 weeks (study endpoint)

CRSwNP

Asthma

Placebo: N = 32 (48.5%), treatment: N = 42 (58.3%)

AERD:

Placebo: N = 11 (16.7%), treatment N = 16 (22.2%)

endoscopic NPS, NCS, NOT-22, UPSIT, TNSS, % requiring rescue therapy, comorbid asthma, number of asthma exacerbations, AQLQ

Significant improvement in mean NPS and daily NCS at week 24 and as early as week 4, week 8 for UPSIT

Comorbid asthma and AERD showed similar improvements in comparison to those without AERD

Significant improvement in SNOT-22, UPSIT, TNSS and individual nasal symptoms were observed

There was a 62.5% relative reduction in rescue steroid use in treatment group

There was a reduced need for surgery and reduced number of asthma exacerbations observed after treatment

Efficacy and safety of omalizumab in nasal polyposis: 2 randomized phase 3 trials

(POLYP 2)

Gevaert et al. [9]

Omalizumab (anti-IgE)

N = 127

(Placebo n = 65, Treatment n = 62)

24 weeks (study endpoint) with 24 weeks follow-up

CRSwNP

Asthma:

Placebo: n = 39 (60%), treatment: n = 38 (61.3%)

AERD:

Placebo: n = 21 (32.3%), treatment: n = 24 (38.7%)

endoscopic NPS, NCS, NOT-22, UPSIT, TNSS, % requiring rescue therapy, comorbid asthma, AQLQ

There was a significant improvement in mean NPS and daily NCS at week 24 and as early as week 4, week 8 for UPSIT

Comorbid asthma and AERD showed similar improvements in comparison to those without AERD

Significant improvement in SNOT-22, UPSIT, TNSS and individual nasal symptoms

62.5% patients demonstrated relative reduction in rescue steroid use, reduced need for surgery and reduced number of asthma exacerbations

Continued safety/efficacy of omalizumab in chronic rhinosinusitis with nasal polyps: an open-label extension study

Gevaert et al. [16]

Omalizumab (anti-IgE)

N = 249 (Placebo n = 126, Treatment n = 123)

76 weeks (study endpoint, 24 weeks of follow-up after 52 weeks)

CRSwNP

Same patients from Polyp I and II

endoscopic NPS, NCS, NOT-22, UPSIT, TNSS, % requiring rescue therapy, comorbid asthma, AQLQ

Patients who received omalizumab in Polyp 1 or Poly 2 trials experienced continued improvement in NPS, NCS, and SNOT-22 through week 52 in comparison to placebo

After omalizumab withdrawal at 52 weeks, all outcomes worsened/trended back to baseline, but remained below pre-treatment levels at week 76

Safety and efficacy profile of omalizumab same as previous studies

Reduced need for surgery in severe nasal polyposis with mepolizumab: randomized trial

Bachert et al. [10]

Mepolizumab

(anti-IL-5)

N = 105

(Placebo n = 51,

Treatment n = 54)

25 weeks (study endpoint)

CRSwNP

 Asthma n = 82

VAS, SNOT-22, adverse events, avoidance of surgery, endoscopic nasal polyp score, EQ-5D, Sniffin’ Sticks Screening-12, and lung function assessments

Significant improvement endoscopic nasal polyp score, all individual VAS symptom scores, and SNOT-22 score in the mepolizumab compared with placebo group

The was no statistically significant difference in olfaction via Sniffin’ Sticks Screening-12, and lung function tests

A reduction in blood eosinophil counts in the mepolizumab but not in the placebo

After 25 weeks of dosing every 4 weeks, 5% patients required surgery compared to 30% of patients in the placebo group

Mepolizumab, a humanized anti-IL-5 mAb, as a treatment option for severe nasal polyposis

Gevaert et al. [11]

Mepolizumab

(anti-IL-5)

N = 30

(Placebo n = 10,

Treatment n = 20)

48 weeks (study endpoint)

CRSwNP refractory to corticosteroid therapy

Asthma: n = 23

Allergies: n = 14

Aspirin

intolerance: n = 5

Disease symptom scores, Adverse events, nasal polyp score, CT scan score, NPIF, blood and serum markers

Significant improvement in total polyp score and CT scan scores from baseline in the mepolizumab group compared to placebo

No significant difference in disease symptoms scores or NPIF

Significant reduction of blood eosinophil counts and serum ECP and serum IL-5Rα levels at week 8 in mepolizumab group

Nasal IL-5Rα, IL-6, IL-1β, and MPO levels were significantly reduced in the mepolizumab group

Mepolizumab for CRSwNP (SYNAPSE): a randomised, double-blind, placebo-controlled phase 3 trial

Han et al. [12]

Mepolizumab

(anti-IL-5)

N = 407 (Placebo n = 201, Treatment n = 206)

52 weeks (study endpoint)

CRSwNP refractory to medical and surgical management

Asthma:

Placebo: N = 149 (74%), treatment N = 140 (68%)

AERD:

Placebo: N = 63 (31%), treatment: N = 45 (22%)

NPS, nasal obstruction. SNPT22, Peak nasal inspiratory flow, UPSIT, blood samples, ECG

Mepolizumab treatment improved nasal polyp size, nasal obstruction VAS compared with placebo

41% of patients treated with mepolizumab required a course of antibiotics in comparison to 50% of patients in the placebo group

Subgroup analyses of the coprimary endpoints suggested that the efficacy of mepolizumab is higher with higher baseline blood eosinophil count

The risk of nasal surgery was lower in the mepolizumab group (9%) versus the placebo group (23%)

Patients demonstrated relative reduction in rescue steroid use, reduced need for surgery and reduced number of asthma exacerbations

Efficacy of benralizumab in CRSwNP with nasal polyps: A randomized placebo-controlled trial (OSTRO)

Bachert et al. [13]

Benralizumab

(anti-IL-5/Ra)

N = 413 (Placebo n = 206, Treatment n = 207)

40 weeks (study endpoint) extended to 60 and 80 weeks for follow-up

CRSwNP refractory to ICS

Asthma:

Placebo: n = 142 (68.6%), treatment: n = 59(29.1%)

AERD

Placebo: n = 62 (30%), treatment: n = 59 (29.1%)

NPS, NBS, SNOT22, DSS, LMS, UPSIT, SCS use, ACQ-6, Adverse events, ADA

There was a significant improvement in NPS and Nasal blockage score at week 40 in treatment group

There were no significant improvements in SNOT22, time to first nasal polyp surgery and/or SCS use

At week 40, a decrease in baseline ACQ-6 was observed for the treatment group and not the placebo group

Treatment favoured benralizumab up to week 56 in comparison to placebo

A Phase II, multicenter, randomized placebo-controlled study of benralizumab, in patients with eosinophilic CRS

Takabayashi [14]

Benralizumab

(anti-IL-5/Ra)

N = 56

(Placebo n = 11, Single dose n = 22, q4w n = 23)

12 weeks (study endpoint) with 12 weeks follow-up

ECRS (eosinophilic CRSwNP)

Asthma:

Placebo: n = 10 (90.9%), treatment one: n = 18(81.8%), treatment 2: n = 19(82.6%)

AERD

Placebo: n = 5(45.5%), treatment one: n = 6 (27.3%), treatment 2: n = 6 (26.1%)

NPS, LMK, Symptoms severity, blood eosinophil

There was no significant difference in change in nasal polyp score from baseline at week 12

There was a decrease in NPS of > 2 points in 42.2% eosinophilic CRS patients

High blood eosinophil level was associated with improved response to biologic treatment (eosinophil count significantly decreased and remained at 0/uL up to week 8 with a single dose and week 12 with 3 doses)

Benralizumab effect on severe CRSwNP: A randomized double-blind placebo-controlled trial

Tversky et al. [15]

Benralizumab

(anti-IL-5/Ra)

N = 24

(Placebo n = 12, Treatment n = 12)

20 weeks (study endpoint) with 4 weeks follow-up

CRSwNP, refractory to medical and surgical management

Asthma:

Placebo: n = 10 (83%), treatment: n = 12 (100%)

AERD

Placebo: n = 3 (25%), treatment: n = 8(67%)

Polyp score, CT, SNOT22, Sniffin’ Stick smell test

There were significant improvement in NP score observed in patients in the treatment group

There was a dec in NP size in the treatment group, but was not found to be statistically significant

The ratio of blood eosinophil count to allergen skin test positivity correlated with polyp reduction in the treatment group

There was a 42% improvement in all outcomes observed in the treatment group