Clinical trial NCT02898454: Controlled Clinical Study of Dupilumab in Patients With Nasal Polyps
Official title: A Randomized, Double-blind, 52-week, Placebo Controlled Efficacy and Safety Study of Dupilumab, in Patients With Bilateral Nasal Polyposis on a Background Therapy With Intranasal Corticosteroids
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Rhinosinusitis Phenotype With Nasal Polyps (CRSwNP)
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2016-09-13
Enrollment: 448
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary Objective:

To evaluate the efficacy of dupilumab 300 mg every 2 weeks (q2w) compared to placebo on a background of mometasone furoate nasal spray (MFNS) in reducing nasal congestion (NC)/obstruction severity and endoscopic nasal polyp score (NPS) in participants with bilateral nasal polyps (NP). In addition for Japanese participants, reduction in computed tomography (CT) scan opacification of the sinuses was a co-primary objective.

Secondary Objectives:

* To evaluate the efficacy of dupilumab in improving total symptoms score.
* To evaluate the efficacy of dupilumab in improving sense of smell.
* To evaluate the efficacy of dupilumab in reducing CT scan opacification of the sinuses (primary objective for Japanese participants).
* To evaluate ability of dupilumab in reducing proportion of participants who required treatment with systemic corticosteroids (SCS) or surgery for NP.
* To evaluate the effect of dupilumab on participant reported outcomes and health related quality of life.
* To evaluate the efficacy of dupilumab 300 mg q2w up to Week 52.
* To evaluate the efficacy of dupilumab 300 mg q2w up to Week 24 followed by 300 mg every 4 weeks (q4w) up to Week 52.
* To evaluate the effect of dupilumab in the subgroups of participants with prior surgery and comorbid asthma including non-steroid anti-inflammatory drug exacerbated respiratory disease.
* To evaluate the safety of dupilumab in participants with bilateral NP.
* To evaluate functional dupilumab concentrations (systemic exposure) and incidence of treatment emergent anti-drug antibodies.

Detailed description: The total study duration per participant was up to 68 weeks that consisted of a 4-weeks run-in period, 52-weeks treatment period, and a 12-weeks post treatment period.

Eligibility criteria: Inclusion criteria :

* Participants with bilateral sino-nasal polyposis that despite prior treatment with SCS anytime within the past 2 years; and/or had a medical contraindication/intolerance to SCS; and/or had prior surgery for NP at the screening visit, had:
* An endoscopic bilateral NPS at Visit 1 (V1) of at least 5 out of a maximum score of 8 (with a minimum score of 2 in each nasal cavity).
* Ongoing symptoms (for at least 8 weeks before V1) of NC/blockage/obstruction with moderate or severe symptom severity (score 2 or 3) at V1 and a weekly average severity of greater than 1 at time of randomization (V2), and another symptom such as loss of smell, rhinorrhea (anterior/posterior).
* Signed written informed consent.

Exclusion criteria:

* Participants \<18 years of age.
* Participant who had been previously treated in dupilumab studies.
* Participant who had taken:

  * Biologic therapy/ systemic immunosuppressant to treat inflammatory disease or autoimmune disease (eg, rheumatoid arthritis, inflammatory bowel disease, primary biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis, etc.) within 2 months before V1 or 5 half-lives, whichever was longer.
  * Any experimental monoclonal antibody within 5 half-lives or within 6 months before V1 if the half-life was unknown.
  * Anti-immunoglobulin E therapy (omalizumab) within 130 days prior to V1.
  * Participants who received leukotriene antagonists/modifiers at V1 unless they were on a continuous treatment for at least 30 days prior to V1.
* Initiation of allergen immunotherapy within 3 months prior to V1 or a plan to begin therapy or change its dose during the run-in period or the randomized treatment period.
* Participants who underwent any and/or sinus surgery (including polypectomy) within 6 months before V1.
* Participants who had a sino-nasal or sinus surgery changing the lateral wall structure of the nose making impossible the evaluation of NPS.
* Participants with conditions/concomitant diseases making them non evaluable at V1 or for the primary efficacy endpoint such as:

  * Antrochoanal polyps,
  * Nasal septal deviation that would occlude at least one nostril,
  * Acute sinusitis, nasal infection or upper respiratory infection,
  * Ongoing rhinitis medicamentosa,
  * Allergic granulomatous angiitis (Churg-Strauss syndrome), granulomatosis with polyangiitis (Wegener's granulomatosis),Young's syndrome, Kartagener's syndrome or other dyskinetic ciliary syndromes, concomitant cystic fibrosis,
  * Radiologic suspicion, or confirmed invasive or expansive fungal rhinosinusitis.
* Participants with nasal cavity malignant tumor and benign tumors (eg, papilloma, blood boil etc.).
* Participants with forced expiratory volume 50% or less (of predicted normal).
* Participants who received concomitant treatment prohibited in the study.
* Treatment with a live (attenuated) vaccine within 4 weeks before the baseline visit.
* Treatment with a live (attenuated) vaccine within 12 weeks before the baseline visit.
* History of human immunodeficiency virus (HIV) infection or positive HIV serology at screening.
* Positive with hepatitis B surface antigen or hepatitis C antibody at the screening visit.
* Active chronic or acute infection requiring systemic treatment within 2 weeks before the baseline visit.
* Known or suspected history of immunosuppression.
* Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study.
* Women unwilling to use adequate birth control, if of reproductive potential and sexually active.

The above information was not intended to contain all considerations relevant to a Participant's potential participation in a clinical trial.

Primary outcomes:
measure: Change From Baseline at Week 24 in Nasal Congestion/Obstruction Symptom Severity Score
timeFrame: Baseline, Week 24
measure: Change From Baseline at Week 24 in Nasal Polyp Score
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Change From Baseline at Week 24 in Opacification of Sinuses Measured by Lund Mackay (LMK) Score
timeFrame: Baseline, Week 24
measure: Change From Baseline at Week 24 in Total Symptom Score (TSS)
timeFrame: Baseline, Week 24
measure: Change From Baseline at Week 24 in the University of Pennsylvania Smell Identification Test (UPSIT) Score
timeFrame: Baseline, Week 24
measure: Change From Baseline at Week 24 in Severity of Decreased/Loss of Smell as Assessed by Participant Daily
timeFrame: Baseline, Week 24
measure: Change From Baseline at Week 24 in 22-item Sino-nasal Outcome Test (SNOT-22) Scores
timeFrame: Baseline, Week 24
measure: Change From Baseline at Week 52 in Nasal Polyp Score
timeFrame: Baseline, Week 52
measure: Change From Baseline at Week 52 in Nasal Congestion/Obstruction Symptom Severity Score
timeFrame: Baseline, Week 52
measure: Change From Baseline at Week 52 in 22-item Sino-nasal Outcome Test Scores
timeFrame: Baseline, Week 52
measure: Rescue Treatment Use: Estimate of Percentage of Participants With Greater Than or Equal to (>=) 1 Event by Week 52 Obtained Using Kaplan-Meier Method
timeFrame: Baseline up to 52 weeks
measure: Change From Baseline at Week 52 in Total Symptom Score
timeFrame: Baseline, Week 52
measure: Change From Baseline at Week 52 in the University of Pennsylvania Smell Identification Test Score
timeFrame: Baseline, Week 52
measure: Change From Baseline at Week 52 in Severity of Decreased/Loss of Smell
timeFrame: Baseline, Week 52
measure: Change From Baseline at Week 52 in Opacification of Sinuses Measured by Lund-Mackay Score
timeFrame: Baseline, Week 52
measure: Change From Baseline at Week 24 in Visual Analogue Scale (VAS) for Rhinosinusitis
timeFrame: Baseline, Week 24
measure: Change From Baseline at Week 52 in Visual Analogue Scale for Rhinosinusitis
timeFrame: Baseline, Week 52
measure: Change From Baseline at Week 24 in Nasal Peak Inspiratory Flow (NPIF)
timeFrame: Baseline, Week 24
measure: Change From Baseline at Week 24 in Rhinorrhea Daily Symptom Score
timeFrame: Baseline, Week 24
measure: Change From Baseline at Week 52 in Rhinorrhea Daily Symptom Score
timeFrame: Baseline, Week 52
measure: Mean Total Systemic Corticosteroids Rescue Dose Prescribed During Treatment Period
timeFrame: Baseline to Week 52
measure: Total Systemic Corticosteroids Rescue Intake Duration: Average Duration Per Participant
timeFrame: Baseline to Week 52
measure: Changed From Baseline at Week 24 in Forced Expiratory Volume in 1 Second (FEV1) for Participants With Asthma
timeFrame: Baseline, Week 24
measure: Change From Baseline at Week 52 in Forced Expiratory Volume in 1 Second for Participants With Asthma
timeFrame: Baseline, Week 52
measure: Change From Baseline at Week 24 in Asthma Control Questionnaire-6 (ACQ-6) for Participants With Asthma
timeFrame: Baseline, Week 24
measure: Change From Baseline at Week 52 in Asthma Control Questionnaire-6 for Participants With Asthma
timeFrame: Baseline, Week 52
measure: Change From Baseline at Week 24 in Nasal Congestion/Obstruction Symptom Severity Score: Subgroup of Participants With Asthma
timeFrame: Baseline, Week 24
measure: Change From Baseline at Week 52 in Nasal Congestion/Obstruction Symptom Severity Score: Subgroup of Participants With Asthma
timeFrame: Baseline, Week 52
measure: Change From Baseline at Week 24 in Nasal Congestion/Obstruction Symptom Severity Score: Subgroup of Participants With Prior Nasal Polyp Surgery
timeFrame: Baseline, Week 24
measure: Change From Baseline at Week 52 in Nasal Congestion/Obstruction Symptom Severity Score: Subgroup of Participants With Prior Nasal Polyp Surgery
timeFrame: Baseline, Week 52
measure: Change From Baseline at Week 24 in Nasal Polyp Score: Subgroup of Participants With Asthma
timeFrame: Baseline, Week 24
measure: Change From Baseline at Week 52 in Nasal Polyp Score: Subgroup of Participants With Asthma
timeFrame: Baseline, Week 52
measure: Change From Baseline at Week 24 in Nasal Polyp Score: Subgroup of Participants With Prior Nasal Polyp Surgery
timeFrame: Baseline, Week 24
measure: Change From Baseline at Week 52 in Nasal Polyp Score: Subgroup of Participants With Prior Nasal Polyp Surgery
timeFrame: Baseline, Week 52
measure: Change From Baseline at Week 24 in Opacification of Sinuses Measured by Lund Mackay Score: Subgroup of Participants With Asthma
timeFrame: Baseline, Week 24
measure: Change From Baseline at Week 52 in Opacification of Sinuses Measured by Lund Mackay Score: Subgroup of Participants With Asthma
timeFrame: Baseline, Week 52
measure: Change From Baseline at Week 24 in Opacification of Sinuses Measured by Lund Mackay Score: Subgroup of Participants With Prior Nasal Polyp Surgery
timeFrame: Baseline, Week 24
measure: Change From Baseline at Week 52 in Opacification of Sinuses Measured by Lund Mackay Score: Subgroup of Participants With Prior Nasal Polyp Surgery
timeFrame: Baseline, Week 52
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEAEs Leading to Treatment Discontinuation
timeFrame: Baseline up to 84 days after last dose of study drug (up to 64 weeks)
measure: Change From Baseline at Week 24 in European Quality of Life 5 Dimension Scale (EQ-5D) Visual Analog Scale Score
timeFrame: Baseline, Week 24
measure: Change From Baseline at Week 52 in European Quality of Life 5 Dimension Scale Visual Analog Scale Score
timeFrame: Baseline, Week 52
measure: Functional Dupilumab Concentration in Serum
timeFrame: Baseline, Week 2, Week 4, Week 16, Week 24, Week 40, End of treatment (Week 52), End of study (Week 64)
measure: Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies Response (ADA)
timeFrame: Baseline to Week 52
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Investigational Site Number 8400019
state: Alabama
city: Fresno
country: United States
facility: Investigational Site Number 8400011
state: California
city: Huntington Beach
country: United States
facility: Investigational Site Number 8400008
state: California
city: Rolling Hills Estates
country: United States
facility: Investigational Site Number 8400004
state: California
city: Walnut Creek
country: United States
facility: Investigational Site Number 8400012
state: California
city: Colorado Springs
country: United States
facility: Investigational Site Number 8400017
state: Colorado
city: Denver
country: United States
facility: Investigational Site Number 8400006
state: Colorado
city: New Haven
country: United States
facility: Investigational Site Number 8400022
state: Connecticut
city: Louisville
country: United States
facility: Investigational Site Number 8400002
state: Kentucky
city: Boston
country: United States
facility: Investigational Site Number 8400021
state: Massachusetts
city: Kansas City
country: United States
facility: Investigational Site Number 8400014
state: Missouri
city: Bronx
country: United States
facility: Investigational Site Number 8400024
state: New York
city: North Charleston
country: United States
facility: Investigational Site Number 8400016
state: North Carolina
city: Bethlehem
country: United States
facility: Investigational Site Number 8400013
state: Pennsylvania
city: Philadelphia
country: United States
facility: Investigational Site Number 8400005
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Investigational Site Number 8400003
state: Pennsylvania
city: Salt Lake City
country: United States
facility: Investigational Site Number 8400009
state: Utah
city: Bellevue
country: United States
facility: Investigational Site Number 8400010
state: Washington
city: Milwaukee
country: United States
facility: Investigational Site Number 8400007
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: Investigational Site Number 0320006
city: Buenos Aires
country: Argentina
facility: Investigational Site Number 0320004
city: Caba
country: Argentina
facility: Investigational Site Number 0320005
city: Caba
country: Argentina
facility: Investigational Site Number 0320001
city: Caba
country: Argentina
facility: Investigational Site Number 0320007
city: Mendoza
country: Argentina
facility: Investigational Site Number 0320003
city: Rosario
country: Argentina
facility: Investigational Site Number 0320008
city: San Miguel De Tucumán
country: Argentina
facility: Investigational Site Number 0320002
city: Clayton
country: Australia
facility: Investigational Site Number 0360002
city: Herston
country: Australia
facility: Investigational Site Number 0360004
city: Murdoch
country: Australia
facility: Investigational Site Number 0360005
city: Parkville
country: Australia
facility: Investigational Site Number 0360001
city: Prahran
country: Australia
facility: Investigational Site Number 0360003
city: Bruxelles
country: Belgium
facility: Investigational Site Number 0560003
city: Gent
country: Belgium
facility: Investigational Site Number 0560001
city: Leuven
country: Belgium
facility: Investigational Site Number 0560002
city: Kingston
country: Canada
facility: Investigational Site Number 1240007
city: Montreal
country: Canada
facility: Investigational Site Number 1240002
city: Montreal
country: Canada
facility: Investigational Site Number 1240006
city: Ottawa
country: Canada
facility: Investigational Site Number 1240005
city: Quebec
country: Canada
facility: Investigational Site Number 1240003
city: Quebec
country: Canada
facility: Investigational Site Number 1240004
city: Trois-Rivieres
country: Canada
facility: Investigational Site Number 1240008
city: Vancouver
country: Canada
facility: Investigational Site Number 1240001
city: Quillota
country: Chile
facility: Investigational Site Number 1520009
city: San Fernando
country: Chile
facility: Investigational Site Number 1520010
city: Santiago
country: Chile
facility: Investigational Site Number 1520005
city: Santiago
country: Chile
facility: Investigational Site Number 1520011
city: Santiago
country: Chile
facility: Investigational Site Number 1520008
city: Santiago
country: Chile
facility: Investigational Site Number 1520006
city: Santiago
country: Chile
facility: Investigational Site Number 1520001
city: Santiago
country: Chile
facility: Investigational Site Number 1520014
city: Talca
country: Chile
facility: Investigational Site Number 1520003
city: Viña Del Mar
country: Chile
facility: Investigational Site Number 1520007
city: Hadera
country: Israel
facility: Investigational Site Number 3760001
city: Nahariya
country: Israel
facility: Investigational Site Number 3760003
city: Petah-Tikva
country: Israel
facility: Investigational Site Number 3760002
city: Rehovot
country: Israel
facility: Investigational Site Number 3760005
city: Tel Hashomer
country: Israel
facility: Investigational Site Number 3760004
city: Bunkyo-Ku
country: Japan
facility: Investigational Site Number 3920004
city: Bunkyo-Ku
country: Japan
facility: Investigational Site Number 3920009
city: Bunkyo-Ku
country: Japan
facility: Investigational Site Number 3920026
city: Chiyoda-Ku
country: Japan
facility: Investigational Site Number 3920006
city: Fukuoka-Shi
country: Japan
facility: Investigational Site Number 3920024
city: Hirakata-Shi
country: Japan
facility: Investigational Site Number 3920010
city: Hiroshima-Shi
country: Japan
facility: Investigational Site Number 3920011
city: Iida-Shi
country: Japan
facility: Investigational Site Number 3920007
city: Inzai-Shi
country: Japan
facility: Investigational Site Number 3920015
city: Itabashi-Ku
country: Japan
facility: Investigational Site Number 3920012
city: Izumisano-Shi
country: Japan
facility: Investigational Site Number 3920014
city: Kawasaki-Shi
country: Japan
facility: Investigational Site Number 3920016
city: Kitakyushu-Shi
country: Japan
facility: Investigational Site Number 3920020
city: Kitakyushu-Shi
country: Japan
facility: Investigational Site Number 3920027
city: Kumamoto-Shi
country: Japan
facility: Investigational Site Number 3920002
city: Kumamoto-Shi
country: Japan
facility: Investigational Site Number 3920021
city: Kyoto-Shi
country: Japan
facility: Investigational Site Number 3920003
city: Meguro-Ku
country: Japan
facility: Investigational Site Number 3920023
city: Moriguchi-Shi
country: Japan
facility: Investigational Site Number 3920013
city: Okayama-Shi
country: Japan
facility: Investigational Site Number 3920025
city: Osaka-Shi
country: Japan
facility: Investigational Site Number 3920018
city: Ota-Ku
country: Japan
facility: Investigational Site Number 3920017
city: Sendai-Shi
country: Japan
facility: Investigational Site Number 3920005
city: Sendai-Shi
country: Japan
facility: Investigational Site Number 3920022
city: Shimonoseki-Shi
country: Japan
facility: Investigational Site Number 3920001
city: Shinagawa-Ku
country: Japan
facility: Investigational Site Number 3920029
city: Shinjyuku-Ku
country: Japan
facility: Investigational Site Number 3920030
city: Takatsuki-Shi
country: Japan
facility: Investigational Site Number 3920028
city: Yoshida-Gun
country: Japan
facility: Investigational Site Number 3920019
city: Chihuahua
country: Mexico
facility: Investigational Site Number 4840001
city: Chihuahua
country: Mexico
facility: Investigational Site Number 4840005
city: Durango
country: Mexico
facility: Investigational Site Number 4840004
city: Guadalajara
country: Mexico
facility: Investigational Site Number 4840002
city: Monterrey
country: Mexico
facility: Investigational Site Number 4840003
city: Aveiro
country: Portugal
facility: Investigational Site Number 6200004
city: Guimarães
country: Portugal
facility: Investigational Site Number 6200006
city: Lisboa
country: Portugal
facility: Investigational Site Number 6200002
city: Matosinhos
country: Portugal
facility: Investigational Site Number 6200007
city: Porto
country: Portugal
facility: Investigational Site Number 6200001
city: Viana Do Castelo
country: Portugal
facility: Investigational Site Number 6200005
city: Moscow
country: Russian Federation
facility: Investigational Site Number 6430006
city: Odintsovo
country: Russian Federation
facility: Investigational Site Number 6430003
city: Saint-Petersburg
country: Russian Federation
facility: Investigational Site Number 6430002
city: Stavropol
country: Russian Federation
facility: Investigational Site Number 6430005
city: Yaroslavl
country: Russian Federation
facility: Investigational Site Number 6430001
city: Barcelona
country: Spain
facility: Investigational Site Number 7240001
city: Barcelona
country: Spain
facility: Investigational Site Number 7240006
city: Jerez De La Frontera
country: Spain
facility: Investigational Site Number 7240003
city: Madrid
country: Spain
facility: Investigational Site Number 7240002
city: Sevilla
country: Spain
facility: Investigational Site Number 7240007
city: Valencia
country: Spain
facility: Investigational Site Number 7240009
city: Lund
country: Sweden
facility: Investigational Site Number 7520002
city: Stockholm
country: Sweden
facility: Investigational Site Number 7520001
city: Ankara
country: Turkey
facility: Investigational Site Number 7920004
city: Ankara
country: Turkey
facility: Investigational Site Number 7920005
city: Ankara
country: Turkey
facility: Investigational Site Number 7920008
city: Bursa
country: Turkey
facility: Investigational Site Number 7920013
city: Istanbul
country: Turkey
facility: Investigational Site Number 7920010
city: Istanbul
country: Turkey
facility: Investigational Site Number 7920009
city: Istanbul
country: Turkey
facility: Investigational Site Number 7920003
city: Istanbul
country: Turkey
facility: Investigational Site Number 7920001
city: Istanbul
country: Turkey
facility: Investigational Site Number 7920002
city: Izmir
country: Turkey
facility: Investigational Site Number 7920006
city: Izmir
country: Turkey
facility: Investigational Site Number 7920007
city: Rize
country: Turkey
facility: Investigational Site Number 7920011
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Peters AT, Soler ZM, Kern RC, Heffler E, Maspero JF, Crampette L, Fujieda S, Lane AP, Zhang H, Nash S, Khan AH, Siddiqui S, Jacob-Nara JA, Rowe P, Deniz Y. Improvement in patient-reported "taste" and association with smell in dupilumab-treated patients with severe chronic rhinosinusitis with nasal polyps from the SINUS-24 and SINUS-52 trials. Clin Exp Allergy. 2022 Sep;52(9):1105-1109. doi: 10.1111/cea.14194. Epub 2022 Jul 12. No abstract available.
citation: Wechsler ME, Klion AD, Paggiaro P, Nair P, Staumont-Salle D, Radwan A, Johnson RR, Kapoor U, Khokhar FA, Daizadeh N, Chen Z, Laws E, Ortiz B, Jacob-Nara JA, Mannent LP, Rowe PJ, Deniz Y. Effect of Dupilumab on Blood Eosinophil Counts in Patients With Asthma, Chronic Rhinosinusitis With Nasal Polyps, Atopic Dermatitis, or Eosinophilic Esophagitis. J Allergy Clin Immunol Pract. 2022 Oct;10(10):2695-2709. doi: 10.1016/j.jaip.2022.05.019. Epub 2022 May 28.
citation: Bachert C, Peters AT, Heffler E, Han JK, Olze H, Pfaar O, Chuang CC, Rout R, Attre R, Goga L, Jacob-Nara JA, Rowe PJ, Deniz Y, Chen Z, Kamat S, Siddiqui S. Responder analysis to demonstrate the effect of targeting type 2 inflammatory mechanisms with dupilumab across objective and patient-reported endpoints for patients with severe chronic rhinosinusitis with nasal polyps in the SINUS-24 and SINUS-52 studies. Clin Exp Allergy. 2022 Feb;52(2):244-249. doi: 10.1111/cea.14051. No abstract available.
citation: Lee SE, Hopkins C, Mullol J, Msihid J, Guillemin I, Amin N, Mannent LP, Li Y, Siddiqui S, Chuang CC, Kamat S, Khan AH. Dupilumab improves health related quality of life: Results from the phase 3 SINUS studies. Allergy. 2022 Jul;77(7):2211-2221. doi: 10.1111/all.15222. Epub 2022 Feb 1.
citation: Bachert C, Corren J, Lee SE, Zhang H, Harel S, Cunoosamy D, Khan AH, Jacob-Nara JA, Siddiqui S, Nash S, Rowe PJ, Deniz Y. Dupilumab efficacy and biomarkers in chronic rhinosinusitis with nasal polyps: Association between dupilumab treatment effect on nasal polyp score and biomarkers of type 2 inflammation in patients with chronic rhinosinusitis with nasal polyps in the phase 3 SINUS-24 and SINUS-52 trials. Int Forum Allergy Rhinol. 2022 Sep;12(9):1191-1195. doi: 10.1002/alr.22964. Epub 2022 Jan 31. No abstract available.
citation: Geng B, Bachert C, Busse WW, Gevaert P, Lee SE, Niederman MS, Chen Z, Lu X, Khokhar FA, Kapoor U, Pandit-Abid N, Jacob-Nara JA, Rowe PJ, Deniz Y, Ortiz B. Respiratory Infections and Anti-Infective Medication Use From Phase 3 Dupilumab Respiratory Studies. J Allergy Clin Immunol Pract. 2022 Mar;10(3):732-741. doi: 10.1016/j.jaip.2021.12.006. Epub 2021 Dec 22.
citation: Hellings PW, Peters AT, Chaker AM, Heffler E, Zhang H, Praestgaard A, Nash S, Khan AH, Siddiqui S, Jacob-Nara JA, Rowe PJ, Deniz Y. Rapid and sustained effects of dupilumab in severe chronic rhinosinusitis with nasal polyps. Int Forum Allergy Rhinol. 2022 Jul;12(7):958-962. doi: 10.1002/alr.22944. Epub 2022 Jan 23. No abstract available.
citation: Han JK, Bachert C, Lee SE, Hopkins C, Heffler E, Hellings PW, Peters AT, Kamat S, Whalley D, Qin S, Nelson L, Siddiqui S, Khan AH, Li Y, Mannent LP, Guillemin I, Chuang CC. Estimating Clinically Meaningful Change of Efficacy Outcomes in Inadequately Controlled Chronic Rhinosinusitis with Nasal Polyposis. Laryngoscope. 2022 Feb;132(2):265-271. doi: 10.1002/lary.29888. Epub 2021 Dec 1.
citation: Chuang CC, Guillemin I, Bachert C, Lee SE, Hellings PW, Fokkens WJ, Duverger N, Fan C, Daizadeh N, Amin N, Mannent LP, Khan AH, Kamat S. Dupilumab in CRSwNP: Responder Analysis Using Clinically Meaningful Efficacy Outcome Thresholds. Laryngoscope. 2022 Feb;132(2):259-264. doi: 10.1002/lary.29911. Epub 2021 Nov 24.
citation: Mullol J, Laidlaw TM, Bachert C, Mannent LP, Canonica GW, Han JK, Maspero JF, Picado C, Daizadeh N, Ortiz B, Li Y, Ruddy M, Laws E, Amin N. Efficacy and safety of dupilumab in patients with uncontrolled severe chronic rhinosinusitis with nasal polyps and a clinical diagnosis of NSAID-ERD: Results from two randomized placebo-controlled phase 3 trials. Allergy. 2022 Apr;77(4):1231-1244. doi: 10.1111/all.15067. Epub 2021 Oct 1.
citation: Khan AH, Reaney M, Guillemin I, Nelson L, Qin S, Kamat S, Mannent L, Amin N, Whalley D, Hopkins C. Development of Sinonasal Outcome Test (SNOT-22) Domains in Chronic Rhinosinusitis With Nasal Polyps. Laryngoscope. 2022 May;132(5):933-941. doi: 10.1002/lary.29766. Epub 2021 Aug 26.
citation: Hamilton JD, Harel S, Swanson BN, Brian W, Chen Z, Rice MS, Amin N, Ardeleanu M, Radin A, Shumel B, Ruddy M, Patel N, Pirozzi G, Mannent L, Graham NMH. Dupilumab suppresses type 2 inflammatory biomarkers across multiple atopic, allergic diseases. Clin Exp Allergy. 2021 Jul;51(7):915-931. doi: 10.1111/cea.13954. Epub 2021 Jun 26.
citation: Fujieda S, Matsune S, Takeno S, Ohta N, Asako M, Bachert C, Inoue T, Takahashi Y, Fujita H, Deniz Y, Rowe P, Ortiz B, Li Y, Mannent LP. Dupilumab efficacy in chronic rhinosinusitis with nasal polyps from SINUS-52 is unaffected by eosinophilic status. Allergy. 2022 Jan;77(1):186-196. doi: 10.1111/all.14906. Epub 2021 Jun 4.
citation: Chong LY, Piromchai P, Sharp S, Snidvongs K, Webster KE, Philpott C, Hopkins C, Burton MJ. Biologics for chronic rhinosinusitis. Cochrane Database Syst Rev. 2021 Mar 12;3(3):CD013513. doi: 10.1002/14651858.CD013513.pub3.
citation: Hopkins C, Wagenmann M, Bachert C, Desrosiers M, Han JK, Hellings PW, Lee SE, Msihid J, Radwan A, Rowe P, Amin N, Deniz Y, Ortiz B, Mannent LP, Rout R. Efficacy of dupilumab in patients with a history of prior sinus surgery for chronic rhinosinusitis with nasal polyps. Int Forum Allergy Rhinol. 2021 Jul;11(7):1087-1101. doi: 10.1002/alr.22780. Epub 2021 Feb 21.
citation: Peters AT, Han JK, Hellings P, Heffler E, Gevaert P, Bachert C, Xu Y, Chuang CC, Neupane B, Msihid J, Mannent LP, Guyot P, Kamat S. Indirect Treatment Comparison of Biologics in Chronic Rhinosinusitis with Nasal Polyps. J Allergy Clin Immunol Pract. 2021 Jun;9(6):2461-2471.e5. doi: 10.1016/j.jaip.2021.01.031. Epub 2021 Feb 4.
citation: Laidlaw TM, Bachert C, Amin N, Desrosiers M, Hellings PW, Mullol J, Maspero JF, Gevaert P, Zhang M, Mao X, Khan AH, Kamat S, Patel N, Graham NMH, Ruddy M, Staudinger H, Mannent LP. Dupilumab improves upper and lower airway disease control in chronic rhinosinusitis with nasal polyps and asthma. Ann Allergy Asthma Immunol. 2021 May;126(5):584-592.e1. doi: 10.1016/j.anai.2021.01.012. Epub 2021 Jan 16.
citation: Fujieda S, Matsune S, Takeno S, Asako M, Takeuchi M, Fujita H, Takahashi Y, Amin N, Deniz Y, Rowe P, Mannent L. The Effect of Dupilumab on Intractable Chronic Rhinosinusitis with Nasal Polyps in Japan. Laryngoscope. 2021 Jun;131(6):E1770-E1777. doi: 10.1002/lary.29230. Epub 2020 Nov 23.
citation: Bachert C, Han JK, Desrosiers M, Hellings PW, Amin N, Lee SE, Mullol J, Greos LS, Bosso JV, Laidlaw TM, Cervin AU, Maspero JF, Hopkins C, Olze H, Canonica GW, Paggiaro P, Cho SH, Fokkens WJ, Fujieda S, Zhang M, Lu X, Fan C, Draikiwicz S, Kamat SA, Khan A, Pirozzi G, Patel N, Graham NMH, Ruddy M, Staudinger H, Weinreich D, Stahl N, Yancopoulos GD, Mannent LP. Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials. Lancet. 2019 Nov 2;394(10209):1638-1650. doi: 10.1016/S0140-6736(19)31881-1. Epub 2019 Sep 19.