Clinical trial NCT01854047: An Evaluation of Dupilumab in Patients With Moderate to Severe Uncontrolled Asthma
Official title: A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate Dupilumab in Patients With Moderate to Severe Uncontrolled Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2013-05-15
Enrollment: 776
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 different doses and regimens of dupilumab in participants with moderate to severe uncontrolled asthma.

Secondary Objective:

To evaluate different doses and regimens of dupilumab in participants with moderate to severe uncontrolled asthma, with regard to:

* Safety and tolerability
* Dupilumab systemic exposure and anti-drug antibodies

Detailed description: Total duration per participant of approximately 43 weeks including a screening period (14-21 days), a randomized treatment period (24 weeks), and a post-treatment period (16 weeks).

Eligibility criteria: Inclusion criteria:

Participants with a physician diagnosis of moderate to severe, uncontrolled asthma for \>=12 months, based on the Global Initiative for Asthma (GINA) 2009 Guidelines and:

* Existing treatment with moderate or high-dose inhaled corticosteroid / long-acting beta-2 agonist
* Forced expiratory volume (FEV1) 40 to 80% of predicted normal
* Asthma Control Questionnaire, 5-question version (ACQ-5) score \>=1.5
* Reversibility of at least 12% and 200 mL in forced expiratory volume (FEV1)
* Had experienced, within prior year: hospitalization, emergency or urgent care visit or systemic corticosteroid treatment for worsening asthma

Exclusion criteria:

* Participants \<18 years
* Chronic obstructive pulmonary disease (COPD) or other lung diseases (eg, emphysema, idiopathic pulmonary fibrosis, Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis) which impaired pulmonary function tests
* Chest X-ray within 12 months of screening visit or at screening visit with clinically significant findings of lung disease(s) other than asthma
* Current smoker or cessation of smoking within 6 months prior to Visit 1
* Previous smoker with a smoking history \>10 pack-years

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

Primary outcomes:
measure: Absolute Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 12: High Eosinophils -Intent to Treat (HEos-ITT) Population
timeFrame: Baseline, Week 12
measure: Absolute Change From Baseline in FEV1 at Week 12: ITT Population
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Percent Change From Baseline in FEV1 at Week 12: HEos-ITT Population
timeFrame: Baseline, Week 12
measure: Percent Change From Baseline in FEV1 at Week 12: ITT Population
timeFrame: Baseline, Week 12
measure: Annualized Event Rate of Severe Exacerbation During The Treatment Period: HEos-ITT Population
timeFrame: Baseline to Week 24
measure: Annualized Event Rate of Severe Exacerbation During The Treatment Period: ITT Population
timeFrame: Baseline to Week 24
measure: Time to First Severe Exacerbation: Kaplan-Meier Estimates at Week 12 and 24: HEos-ITT Population
timeFrame: Baseline up to Week 24
measure: Time to First Severe Exacerbation: Kaplan-Meier Estimates at Week 12 and 24: ITT Population
timeFrame: Baseline up to Week 24
measure: Annualized Event Rate of Loss of Asthma Control (LOAC) During The Treatment Period: HEos-ITT Population
timeFrame: Baseline to Week 24
measure: Annualized Event Rate of LOAC During The Treatment Period: ITT Population
timeFrame: Baseline to Week 24
measure: Time to First LOAC Event: Kaplan-Meier Estimates at Week 12 and Week 24: HEos-ITT Population
timeFrame: Baseline up to Week 24
measure: Time to First LOAC Event: Kaplan-Meier Estimates at Week 12 and Week 24: ITT Population
timeFrame: Baseline up to Week 24
measure: Change From Baseline in Morning Asthma Symptom Score at Week 12: HEos-ITT Population
timeFrame: Baseline, Week 12
measure: Change From Baseline in Morning Asthma Symptom Score at Week 12: ITT Population
timeFrame: Baseline, Week 12
measure: Change From Baseline in Evening Asthma Symptom Score at Week 12: HEos-ITT Population
timeFrame: Baseline, Week 12
measure: Change From Baseline in Evening Asthma Symptom Score at Week 12: ITT Population
timeFrame: Baseline, Week 12
measure: Change From Baseline in Asthma Control Questionnaire 5-item Version (ACQ-5) Score at Week 12: HEos-ITT Population
timeFrame: Baseline, Week 12
measure: Change From Baseline in ACQ-5 Score at Week 12: ITT Population
timeFrame: Baseline, Week 12
measure: Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Global Score at Week 12: HEos-ITT Population
timeFrame: Baseline, Week 12
measure: Change From Baseline in AQLQ Global Score at Week 12: ITT Population
timeFrame: Baseline, Week 12
measure: Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: HEos-ITT Population
timeFrame: Baseline, Week 12
measure: Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: ITT Population
timeFrame: Baseline, Week 12
Other outcomes:
Locations:
city: Fullerton
country: United States
facility: Investigational Site Number 840050
state: California
city: Huntington Beach
country: United States
facility: Investigational Site Number 840041
state: California
city: Los Angeles
country: United States
facility: Investigational Site Number 840019
state: California
city: Los Angeles
country: United States
facility: Investigational Site Number 840029
state: California
city: Los Angeles
country: United States
facility: Investigational Site Number 840022
state: California
city: Mission Viejo
country: United States
facility: Investigational Site Number 840013
state: California
city: Newport Beach
country: United States
facility: Investigational Site Number 840044
state: California
city: Riverside
country: United States
facility: Investigational Site Number 840007
state: California
city: Rolling Hills Estates
country: United States
facility: Investigational Site Number 840014
state: California
city: San Jose
country: United States
facility: Investigational Site Number 840036
state: California
city: Colorado Springs
country: United States
facility: Investigational Site Number 840032
state: Colorado
city: Colorado Springs
country: United States
facility: Investigational Site Number 840040
state: Colorado
city: Denver
country: United States
facility: Investigational Site Number 840043
state: Colorado
city: Denver
country: United States
facility: Investigational Site Number 840006
state: Colorado
city: Denver
country: United States
facility: Investigational Site Number 840024
state: Colorado
city: Daytona Beach
country: United States
facility: Investigational Site Number 840027
state: Florida
city: Miami
country: United States
facility: Investigational Site Number 840039
state: Florida
city: Albany
country: United States
facility: Investigational Site Number 840048
state: Georgia
city: River Forest
country: United States
facility: Investigational Site Number 840026
state: Illinois
city: Evansville
country: United States
facility: Investigational Site Number 840053
state: Indiana
city: Louisville
country: United States
facility: Investigational Site Number 840017
state: Kentucky
city: Owensboro
country: United States
facility: Investigational Site Number 840030
state: Kentucky
city: Baltimore
country: United States
facility: Investigational Site Number 840028
state: Maryland
city: Wheaton
country: United States
facility: Investigational Site Number 840052
state: Maryland
city: North Dartmouth
country: United States
facility: Investigational Site Number 840045
state: Massachusetts
city: Novi
country: United States
facility: Investigational Site Number 840046
state: Michigan
city: Novi
country: United States
facility: Investigational Site Number 840051
state: Michigan
city: Minneapolis
country: United States
facility: Investigational Site Number 840018
state: Minnesota
city: Saint Louis
country: United States
facility: Investigational Site Number 840002
state: Missouri
city: Saint Louis
country: United States
facility: Investigational Site Number 840003
state: Missouri
city: Missoula
country: United States
facility: Investigational Site Number 840037
state: Montana
city: Papillion
country: United States
facility: Investigational Site Number 840004
state: Nebraska
city: Princeton
country: United States
facility: Investigational Site Number 840011
state: New Jersey
city: Rochester
country: United States
facility: Investigational Site Number 840016
state: New York
city: Cincinnati
country: United States
facility: Investigational Site Number 840025
state: Ohio
city: Cincinnati
country: United States
facility: Investigational Site Number 840015
state: Ohio
city: Cincinnati
country: United States
facility: Investigational Site Number 840020
state: Ohio
city: Oklahoma City
country: United States
facility: Investigational Site Number 840001
state: Oklahoma
city: Lake Oswego
country: United States
facility: Investigational Site Number 840031
state: Oregon
city: Medford
country: United States
facility: Investigational Site Number 840034
state: Oregon
city: Philadelphia
country: United States
facility: Investigational Site Number 840042
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Investigational Site Number 840010
state: Pennsylvania
city: Upland
country: United States
facility: Investigational Site Number 840009
state: Pennsylvania
city: Spartanburg
country: United States
facility: Investigational Site Number 840021
state: South Carolina
city: Dallas
country: United States
facility: Investigational Site Number 840023
state: Texas
city: El Paso
country: United States
facility: Investigational Site Number 840005
state: Texas
city: San Antonio
country: United States
facility: Investigational Site Number 840008
state: Texas
city: Richmond
country: United States
facility: Investigational Site Number 840035
state: Virginia
city: Everett
country: United States
facility: Investigational Site Number 840054
state: Washington
city: Tacoma
country: United States
facility: Investigational Site Number 840033
state: Washington
city: Buenos Aires
country: Argentina
facility: Investigational Site Number 032004
city: Buenos Aires
country: Argentina
facility: Investigational Site Number 032003
city: Caba
country: Argentina
facility: Investigational Site Number 032008
city: Caba
country: Argentina
facility: Investigational Site Number 032010
city: Caba
country: Argentina
facility: Investigational Site Number 032001
city: La Plata
country: Argentina
facility: Investigational Site Number 032002
city: Rosario
country: Argentina
facility: Investigational Site Number 032005
city: Rosario
country: Argentina
facility: Investigational Site Number 032006
city: Rosario
country: Argentina
facility: Investigational Site Number 032007
city: Santa Fe
country: Argentina
facility: Investigational Site Number 032012
city: Tucumán
country: Argentina
facility: Investigational Site Number 032009
city: Adelaide
country: Australia
facility: Investigational Site Number 036004
city: Brisbane
country: Australia
facility: Investigational Site Number 036002
city: Campbelltown
country: Australia
facility: Investigational Site Number 036005
city: Clayton
country: Australia
facility: Investigational Site Number 036001
city: Frankston
country: Australia
facility: Investigational Site Number 036008
city: Nedlands
country: Australia
facility: Investigational Site Number 036003
city: Prahran
country: Australia
facility: Investigational Site Number 036009
city: Woolloongabba
country: Australia
facility: Investigational Site Number 036006
city: Quillota
country: Chile
facility: Investigational Site Number 152007
city: Santiago
country: Chile
facility: Investigational Site Number 152011
city: Santiago
country: Chile
facility: Investigational Site Number 152001
city: Santiago
country: Chile
facility: Investigational Site Number 152002
city: Santiago
country: Chile
facility: Investigational Site Number 152014
city: Santiago
country: Chile
facility: Investigational Site Number 152003
city: Santiago
country: Chile
facility: Investigational Site Number 152005
city: Santiago
country: Chile
facility: Investigational Site Number 152012
city: Santiago
country: Chile
facility: Investigational Site Number 152013
city: Talca
country: Chile
facility: Investigational Site Number 152008
city: Viña Del Mar
country: Chile
facility: Investigational Site Number 152006
city: Brest Cedex
country: France
facility: Investigational Site Number 250009
city: Grenoble Cedex 09
country: France
facility: Investigational Site Number 250004
city: Lille
country: France
facility: Investigational Site Number 250010
city: Lyon
country: France
facility: Investigational Site Number 250006
city: Marseille
country: France
facility: Investigational Site Number 250001
city: Montpellier
country: France
facility: Investigational Site Number 250002
city: Nantes
country: France
facility: Investigational Site Number 250005
city: Nimes
country: France
facility: Investigational Site Number 250007
city: Pessac
country: France
facility: Investigational Site Number 250003
city: Strasbourg
country: France
facility: Investigational Site Number 250008
city: Vernon
country: France
facility: Investigational Site Number 250011
city: Ancona
country: Italy
facility: Investigational Site Number 380010
city: Catania
country: Italy
facility: Investigational Site Number 380009
city: Ferrara
country: Italy
facility: Investigational Site Number 380004
city: Firenze
country: Italy
facility: Investigational Site Number 380002
city: Foggia
country: Italy
facility: Investigational Site Number 380008
city: Modena
country: Italy
facility: Investigational Site Number 380003
city: Padova
country: Italy
facility: Investigational Site Number 380007
city: Pisa
country: Italy
facility: Investigational Site Number 380001
city: Torino
country: Italy
facility: Investigational Site Number 380005
city: Verona
country: Italy
facility: Investigational Site Number 380006
city: Asahi-Shi
country: Japan
facility: Investigational Site Number 392009
city: Chiyoda-Ku
country: Japan
facility: Investigational Site Number 392037
city: Chuo-Ku
country: Japan
facility: Investigational Site Number 392002
city: Chuoh-Ku
country: Japan
facility: Investigational Site Number 392007
city: Edogawa-Ku
country: Japan
facility: Investigational Site Number 392012
city: Fukuoka-Shi
country: Japan
facility: Investigational Site Number 392017
city: Fukuyama-Shi
country: Japan
facility: Investigational Site Number 392021
city: Habikino-Shi
country: Japan
facility: Investigational Site Number 392030
city: Himeji-Shi
country: Japan
facility: Investigational Site Number 392004
city: Hirakata-Shi
country: Japan
facility: Investigational Site Number 392032
city: Iizuka-Shi
country: Japan
facility: Investigational Site Number 392013
city: Isesaki-Shi
country: Japan
facility: Investigational Site Number 392042
city: Itabashi-Ku
country: Japan
facility: Investigational Site Number 392026
city: Kanazawa-Shi
country: Japan
facility: Investigational Site Number 392023
city: Kitakyushu-Shi
country: Japan
facility: Investigational Site Number 392001
city: Kiyose-Shi
country: Japan
facility: Investigational Site Number 392022
city: Kobe-Shi
country: Japan
facility: Investigational Site Number 392025
city: Kodaira-Shi
country: Japan
facility: Investigational Site Number 392040
city: Kokubunji-Shi
country: Japan
facility: Investigational Site Number 392044
city: Kurashiki-Shi
country: Japan
facility: Investigational Site Number 392010
city: Kyoto-Shi
country: Japan
facility: Investigational Site Number 392036
city: Nagaoka-Shi
country: Japan
facility: Investigational Site Number 392041
city: Naka-Gun
country: Japan
facility: Investigational Site Number 392020
city: Nakano-Ku
country: Japan
facility: Investigational Site Number 392015
city: Naruto-Shi
country: Japan
facility: Investigational Site Number 392005
city: Ohta-Shi
country: Japan
facility: Investigational Site Number 392043
city: Sagamihara-Shi
country: Japan
facility: Investigational Site Number 392019
city: Sakai-Shi
country: Japan
facility: Investigational Site Number 392024
city: Sakaide-Shi
country: Japan
facility: Investigational Site Number 392011
city: Sapporo-Shi
country: Japan
facility: Investigational Site Number 392008
city: Sapporo-Shi
country: Japan
facility: Investigational Site Number 392034
city: Setagaya-Ku
country: Japan
facility: Investigational Site Number 392038
city: Sumida-Ku
country: Japan
facility: Investigational Site Number 392028
city: Tomakomai-Shi
country: Japan
facility: Investigational Site Number 392006
city: Toride-Shi
country: Japan
facility: Investigational Site Number 392003
city: Tsu-Shi
country: Japan
facility: Investigational Site Number 392029
city: Tsukubo-Gun
country: Japan
facility: Investigational Site Number 392018
city: Uruma-Shi
country: Japan
facility: Investigational Site Number 392045
city: Yokohama-Shi
country: Japan
facility: Investigational Site Number 392014
city: Yokohama-Shi
country: Japan
facility: Investigational Site Number 392035
city: Bucheon
country: Korea, Republic of
facility: Investigational Site Number 410002
city: Cheongju
country: Korea, Republic of
facility: Investigational Site Number 410003
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 410004
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 410005
city: Suwon
country: Korea, Republic of
facility: Investigational Site Number 410001
city: Chihuahua
country: Mexico
facility: Investigational Site Number 484006
city: Distrito Federal
country: Mexico
facility: Investigational Site Number 484005
city: Guadalajara
country: Mexico
facility: Investigational Site Number 484001
city: Mexico City
country: Mexico
facility: Investigational Site Number 484004
city: Monterrey
country: Mexico
facility: Investigational Site Number 484003
city: Dunedin
country: New Zealand
facility: Investigational Site Number 554001
city: Wellington
country: New Zealand
facility: Investigational Site Number 554002
city: Bialystok
country: Poland
facility: Investigational Site Number 616006
city: Gdansk
country: Poland
facility: Investigational Site Number 616004
city: Gdansk
country: Poland
facility: Investigational Site Number 616003
city: Krakow
country: Poland
facility: Investigational Site Number 616007
city: Lodz
country: Poland
facility: Investigational Site Number 616001
city: Lodz
country: Poland
facility: Investigational Site Number 616005
city: Warszawa
country: Poland
facility: Investigational Site Number 616008
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643003
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643002
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643007
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643012
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643001
city: Novosibirsk
country: Russian Federation
facility: Investigational Site Number 643006
city: Saint-Petersburg
country: Russian Federation
facility: Investigational Site Number 643010
city: Saint-Petersburg
country: Russian Federation
facility: Investigational Site Number 643011
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number 643009
city: Yaroslavl
country: Russian Federation
facility: Investigational Site Number 643008
city: Cape Town
country: South Africa
facility: Investigational Site Number 710001
city: Cape Town
country: South Africa
facility: Investigational Site Number 710002
city: Barcelona
country: Spain
facility: Investigational Site Number 724005
city: Barcelona
country: Spain
facility: Investigational Site Number 724002
city: Barcelona
country: Spain
facility: Investigational Site Number 724001
city: Cáceres
country: Spain
facility: Investigational Site Number 724004
city: Pozuelo De Alarcón
country: Spain
facility: Investigational Site Number 724006
city: Sabadell
country: Spain
facility: Investigational Site Number 724003
city: Sant Boi De Llobregat
country: Spain
facility: Investigational Site Number 724007
city: Amasya
country: Turkey
facility: Investigational Site Number 792011
city: Ankara
country: Turkey
facility: Investigational Site Number 792002
city: Bursa
country: Turkey
facility: Investigational Site Number 792008
city: Istanbul
country: Turkey
facility: Investigational Site Number 792007
city: Istanbul
country: Turkey
facility: Investigational Site Number 792001
city: Istanbul
country: Turkey
facility: Investigational Site Number 792004
city: Istanbul
country: Turkey
facility: Investigational Site Number 792003
city: Izmir
country: Turkey
facility: Investigational Site Number 792005
city: Kirikkale
country: Turkey
facility: Investigational Site Number 792013
city: Mersin
country: Turkey
facility: Investigational Site Number 792006
city: Donetsk
country: Ukraine
facility: Investigational Site Number 804016
city: Kharkiv
country: Ukraine
facility: Investigational Site Number 804001
city: Kyiv
country: Ukraine
facility: Investigational Site Number 804004
city: Kyiv
country: Ukraine
facility: Investigational Site Number 804003
city: Kyiv
country: Ukraine
facility: Investigational Site Number 804008
city: Kyiv
country: Ukraine
facility: Investigational Site Number 804018
city: Kyiv
country: Ukraine
facility: Investigational Site Number 804020
city: Odessa
country: Ukraine
facility: Investigational Site Number 804006
city: Poltava
country: Ukraine
facility: Investigational Site Number 804002
city: Vinnytsya
country: Ukraine
facility: Investigational Site Number 804019
city: Yalta
country: Ukraine
facility: Investigational Site Number 804015
city: Zaporozhye
country: Ukraine
facility: Investigational Site Number 804012
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Wenzel S, Castro M, Corren J, Maspero J, Wang L, Zhang B, Pirozzi G, Sutherland ER, Evans RR, Joish VN, Eckert L, Graham NM, Stahl N, Yancopoulos GD, Louis-Tisserand M, Teper A. Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high-dose inhaled corticosteroids plus a long-acting beta2 agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial. Lancet. 2016 Jul 2;388(10039):31-44. doi: 10.1016/S0140-6736(16)30307-5. Epub 2016 Apr 27.
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: Bourdin A, Papi AA, Corren J, Virchow JC, Rice MS, Deniz Y, Djandji M, Rowe P, Pavord ID. Dupilumab is effective in type 2-high asthma patients receiving high-dose inhaled corticosteroids at baseline. Allergy. 2021 Jan;76(1):269-280. doi: 10.1111/all.14611. Epub 2020 Oct 21.
citation: Maspero JF, Katelaris CH, Busse WW, Castro M, Corren J, Chipps BE, Peters AT, Pavord ID, Ford LB, Sher L, Rabe KF, Rice MS, Rowe P, Lu Y, Harel S, Jagerschmidt A, Khan AH, Kamat S, Pirozzi G, Amin N, Ruddy M, Graham NMH, Mannent LP, Teper A. Dupilumab Efficacy in Uncontrolled, Moderate-to-Severe Asthma with Self-Reported Chronic Rhinosinusitis. J Allergy Clin Immunol Pract. 2020 Feb;8(2):527-539.e9. doi: 10.1016/j.jaip.2019.07.016. Epub 2019 Jul 24.
citation: Corren J, Castro M, Ford LB, Bernstein JA, Jayawardena S, Maroni J, Rowe P, Amin N, Pirozzi G, Graham NMH, Khan A, Eckert L, Teper A. Dupilumab improves asthma outcomes irrespective of frequency of previous asthma exacerbation history. Ann Allergy Asthma Immunol. 2019 Aug;123(2):222-224.e1. doi: 10.1016/j.anai.2019.04.028. Epub 2019 May 8. No abstract available.
citation: Corren J, Castro M, Chanez P, Fabbri L, Joish VN, Amin N, Graham NMH, Mastey V, Abbe A, Taniou C, Mahajan P, Teper A, Pirozzi G, Eckert L. Dupilumab improves symptoms, quality of life, and productivity in uncontrolled persistent asthma. Ann Allergy Asthma Immunol. 2019 Jan;122(1):41-49.e2. doi: 10.1016/j.anai.2018.08.005. Epub 2018 Aug 21.
citation: Weinstein SF, Katial R, Jayawardena S, Pirozzi G, Staudinger H, Eckert L, Joish VN, Amin N, Maroni J, Rowe P, Graham NMH, Teper A. Efficacy and safety of dupilumab in perennial allergic rhinitis and comorbid asthma. J Allergy Clin Immunol. 2018 Jul;142(1):171-177.e1. doi: 10.1016/j.jaci.2017.11.051. Epub 2018 Jan 31.