Long-Term Efficacy and Safety of Dupilumab in Adolescents with Moderate-to-Severe Atopic Dermatitis: Results Through Week 52 from a Phase III Open-Label Extension Trial (LIBERTY AD PED-OLE)

Andrew Blauvelt; Emma Guttman-Yassky; Amy S. Paller; Eric L. Simpson; Michael J. Cork; Jamie Weisman; John Browning; Weily Soong; Xian Sun; Zhen Chen; Matthew P. Kosloski; Mohamed A. Kamal; Dimittri Delevry; Chien Chia Chuang; John T. O’Malley; Ashish Bansal

doi:10.1007/s40257-022-00683-2

Long-Term Efficacy and Safety of Dupilumab in Adolescents with Moderate-to-Severe Atopic Dermatitis: Results Through Week 52 from a Phase III Open-Label Extension Trial (LIBERTY AD PED-OLE)

Andrew Blauvelt, Emma Guttman-Yassky, Amy S. Paller, Eric L. Simpson, Michael J. Cork, Jamie Weisman, John Browning, Weily Soong, Xian Sun, Zhen Chen, Matthew P. Kosloski, Mohamed A. Kamal, Dimittri Delevry, Chien Chia Chuang, John T. O’Malley, Ashish Bansal^*

^*Corresponding author for this work

Dermatology

Research output: Contribution to journal › Article › peer-review

64 Scopus citations

Abstract

Background: For adolescent patients (aged ≥ 12 to < 18 years) with uncontrolled moderate-to-severe atopic dermatitis (AD), 16 weeks of treatment with dupilumab resulted in substantial clinical benefit compared with placebo, with an acceptable safety profile. However, long-term data on the approved dose regimens of dupilumab in adolescents with AD are lacking. Objectives: This open-label extension study (LIBERTY AD PED-OLE, NCT02612454) reports the long-term safety, efficacy, and pharmacokinetics of dupilumab in adolescents with moderate-to-severe AD who had participated in dupilumab parent trials. Methods: Patients enrolled under the original study protocol received subcutaneous dupilumab according to a weight-based regimen (2 or 4 mg/kg every week). Following protocol amendment, patients were switched to subcutaneous dupilumab 300 mg every 4 weeks (q4w) irrespective of weight, and newly enrolled patients were started on dupilumab 300 mg q4w. Patients with an inadequate clinical response (Investigator’s Global Assessment [IGA] score of 0/1 was not reached) to the q4w regimen could be uptitrated to the approved dupilumab dose regimens of 200 or 300 mg every 2 weeks (body weight < 60 or ≥ 60 kg, respectively). Patients whose IGA score of 0/1 was maintained continuously for a 12-week period after week 40 were discontinued from dupilumab, monitored for relapse, and re-initiated on dupilumab if required. Results: Data for 294 patients (mean age 14.7 years) were analyzed, 102 (34.7%) of whom had completed the 52-week visit at the database lock. The dupilumab long-term safety profile was comparable to that seen in adults and consistent with the known safety profile. Most treatment-emergent adverse events were mild/moderate. By week 52, 42.7% of patients had an IGA score of 0/1 (clear/almost clear), and 93.1%, 81.2%, and 56.4%, respectively, had at least a 50%, 75%, or 90% improvement in Eczema Area and Severity Index (EASI). Most (70.9%) patients required uptitration to the approved dupilumab dose regimen. The proportions of uptitrated patients with an IGA score of 0/1 or 75% improvement in EASI increased over time, reaching 35.7% and 51.9%, respectively, 48 weeks after the first uptitration visit. By week 52, 29.4% of patients had clear/almost clear skin sustained for 12 weeks and had stopped medication; 56.7% relapsed and were subsequently re-initiated on treatment, with a mean time to re-initiation of 17.5 (± standard deviation 17.3) weeks. Conclusions: Consistent with results seen with short-term treatment, long-term treatment with dupilumab showed an acceptable safety profile while providing incremental clinical benefit with continued treatment over time. The high proportion of patients who needed uptitration because of inadequate response to q4w dosing supports the q2w dose regimen as optimal for this age group. Finally, the majority of patients who stopped medication after having clear/almost clear skin sustained over 12 weeks experienced disease recurrence, suggesting the need for continued dupilumab dosing to maintain efficacy. Trial Registration: ClinicalTrials.gov Identifiers: NCT02612454, NCT02407756, NCT03054428, and NCT03050151. Infographic: [Figure not available: see fulltext.] [MediaObject not available: see fulltext.]

Original language	English (US)
Pages (from-to)	365-383
Number of pages	19
Journal	American Journal of Clinical Dermatology
Volume	23
Issue number	3
DOIs	https://doi.org/10.1007/s40257-022-00683-2
State	Published - May 2022

Funding

This research was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. (ClinicalTrials.gov identifier: NCT03345914). The study sponsors participated in the study design; the collection, analysis, and interpretation of the data; the writing of the report; and the decision to submit the article for publication. Medical writing/editorial assistance was provided by Ekaterina Semenova, PhD, of Excerpta Medica, funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc., according to the Good Publication Practice Guideline. Andrew Blauvelt is a scientific advisor and clinical study investigator for AbbVie, Abcentra, Aligos, Almirall, Amgen, Arcutis, Arena, Aslan, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly and Company, Evommune, Forte, Galderma, Incyte, Janssen, Landos, LEO Pharma, Novartis, Pfizer, Rapt, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme, Sun Pharma, UCB Pharma, and Vibliome. Emma Guttman-Yassky has received personal fees from AbbVie, Allergan, Amgen, Asana BioSciences, Celgene, Concert, Dermavant, Dermira, DS Biopharma, Eli Lilly and Company, Escalier BioSciences, Galderma, Glenmark, Kyowa Kirin, LEO Pharma, Mitsubishi Tanabe, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., and Sanofi; and has received grants paid to the institution from AbbVie, Asana Biosciences, Celgene, Concert, Dermavant, Dermira, DS Biopharma, Galderma, Glenmark, Innovaderm, LEO Pharma, Novan, Novartis, Pfizer, Ralexar Therapeutics, and Regeneron Pharmaceuticals, Inc. Amy S. Paller has served as a scientific advisor, clinical study investigator, and/or data safety monitoring board member for AbbVie, Arena, Bausch, Bristol Myers Squibb, Dermavant, Eli Lilly and Company, Forte, Incyte, Janssen, LEO Pharma, Lifemax, Novartis, Pfizer, Rapt, Regeneron Pharmaceuticals, Inc., Sanofi, and UCB. Eric L. Simpson has received personal fees from AbbVie, Boehringer Ingelheim, Collective Acumen LLC, Eli Lilly and Company, Forte Bio, Incyte, Janssen, Kyowa Hakko Kirin, LEO Pharma, Novartis, Ortho Dermatologics, Pfizer, Pierre Fabre Dermo Cosmetique, Regeneron Pharmaceuticals, Inc., Roivant, Sanofi, and Valeant; and grants (or undertaken a principal investigator role) from AbbVie, Eli Lilly and Company, Incyte, Kyowa Hakko Kirin, LEO Pharma, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi, Tioga, and Vanda. Michael J. Cork has been a consultant and/or advisory board member for and/or received research grants from Astellas Pharma, Atopix, Boots, Dermavant, Eli Lilly and Company, Galapagos, Galderma, Hyphens Pharma, Johnson & Johnson, Kymab, L’Oréal, LEO Pharma, Menlo, Novartis, Oxagen, Perrigo (ACO Nordic), Pfizer, Procter & Gamble, Reckitt Benckiser, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme, UCB Pharma, and the National Eczema Society, UK. Jamie Weisman has been an advisory board member or participated in a speaker’s bureau for AbbVie, Eli Lilly and Company, Janssen, Regeneron Pharmaceuticals, Inc., and UCB and received research grants from AbbVie, Allergan, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Dermira, Eli Lilly and Company, Galderma, GlaxoSmithKline, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., and UCB. John Browning has been an investigator for Amryt Pharma, Arcutis Biotherapeutics, Bristol Myers Squibb, Brickell Biotech, ChemoCentryx, Eli Lilly and Company, Galderma, Incyte, Lenus Pharma, LEO Pharma, Mayne Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., and Valeant; has been an advisor for Dermavant and LEO Pharma; and has been a speaker for Dermira, Pfizer, and Regeneron Pharmaceuticals, Inc. Weily Soong has received research funding from AbbVie, AstraZeneca, Cara, Galderma, Genentech, GlaxoSmithKline, Glenmark, Innovaderm, LEO Pharma, Mandala, Menlo, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Relaxar, Sanofi, Symbio, Teva, and Vanda Pharmaceuticals; has received speaker fees from AstraZeneca, GlaxoSmithKline, Optinose, Regeneron Pharmaceuticals, Inc., and Sanofi; and has received consulting fees from AbbVie, Genentech, and Regeneron Pharmaceuticals, Inc. Xian Sun, Zhen Chen, Matthew P. Kosloski, Mohamed A. Kamal, Dimittri Delevry, and Ashish Bansal are employees and shareholder of Regeneron Pharmaceuticals, Inc. Chien-Chia Chuang and John T. O’Malley are employees of and may hold stock and/or stock options in Sanofi. The authors thank the patients and their families for their participation in these studies, their colleagues for their support, and Linda Williams (Regeneron Pharmaceuticals, Inc.), El-Bdaoui Haddad, Adriana Mello, and Abby Gan (Sanofi Genzyme) for their contributions.

ASJC Scopus subject areas

Dermatology

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10.1007/s40257-022-00683-2

Cite this

Blauvelt, A., Guttman-Yassky, E., Paller, A. S., Simpson, E. L., Cork, M. J., Weisman, J., Browning, J., Soong, W., Sun, X., Chen, Z., Kosloski, M. P., Kamal, M. A., Delevry, D., Chuang, C. C., O’Malley, J. T., & Bansal, A. (2022). Long-Term Efficacy and Safety of Dupilumab in Adolescents with Moderate-to-Severe Atopic Dermatitis: Results Through Week 52 from a Phase III Open-Label Extension Trial (LIBERTY AD PED-OLE). American Journal of Clinical Dermatology, 23(3), 365-383. https://doi.org/10.1007/s40257-022-00683-2

@article{c296090521e14cdb83cf3a990745a595,

title = "Long-Term Efficacy and Safety of Dupilumab in Adolescents with Moderate-to-Severe Atopic Dermatitis: Results Through Week 52 from a Phase III Open-Label Extension Trial (LIBERTY AD PED-OLE)",

abstract = "Background: For adolescent patients (aged ≥ 12 to < 18 years) with uncontrolled moderate-to-severe atopic dermatitis (AD), 16 weeks of treatment with dupilumab resulted in substantial clinical benefit compared with placebo, with an acceptable safety profile. However, long-term data on the approved dose regimens of dupilumab in adolescents with AD are lacking. Objectives: This open-label extension study (LIBERTY AD PED-OLE, NCT02612454) reports the long-term safety, efficacy, and pharmacokinetics of dupilumab in adolescents with moderate-to-severe AD who had participated in dupilumab parent trials. Methods: Patients enrolled under the original study protocol received subcutaneous dupilumab according to a weight-based regimen (2 or 4 mg/kg every week). Following protocol amendment, patients were switched to subcutaneous dupilumab 300 mg every 4 weeks (q4w) irrespective of weight, and newly enrolled patients were started on dupilumab 300 mg q4w. Patients with an inadequate clinical response (Investigator{\textquoteright}s Global Assessment [IGA] score of 0/1 was not reached) to the q4w regimen could be uptitrated to the approved dupilumab dose regimens of 200 or 300 mg every 2 weeks (body weight < 60 or ≥ 60 kg, respectively). Patients whose IGA score of 0/1 was maintained continuously for a 12-week period after week 40 were discontinued from dupilumab, monitored for relapse, and re-initiated on dupilumab if required. Results: Data for 294 patients (mean age 14.7 years) were analyzed, 102 (34.7%) of whom had completed the 52-week visit at the database lock. The dupilumab long-term safety profile was comparable to that seen in adults and consistent with the known safety profile. Most treatment-emergent adverse events were mild/moderate. By week 52, 42.7% of patients had an IGA score of 0/1 (clear/almost clear), and 93.1%, 81.2%, and 56.4%, respectively, had at least a 50%, 75%, or 90% improvement in Eczema Area and Severity Index (EASI). Most (70.9%) patients required uptitration to the approved dupilumab dose regimen. The proportions of uptitrated patients with an IGA score of 0/1 or 75% improvement in EASI increased over time, reaching 35.7% and 51.9%, respectively, 48 weeks after the first uptitration visit. By week 52, 29.4% of patients had clear/almost clear skin sustained for 12 weeks and had stopped medication; 56.7% relapsed and were subsequently re-initiated on treatment, with a mean time to re-initiation of 17.5 (± standard deviation 17.3) weeks. Conclusions: Consistent with results seen with short-term treatment, long-term treatment with dupilumab showed an acceptable safety profile while providing incremental clinical benefit with continued treatment over time. The high proportion of patients who needed uptitration because of inadequate response to q4w dosing supports the q2w dose regimen as optimal for this age group. Finally, the majority of patients who stopped medication after having clear/almost clear skin sustained over 12 weeks experienced disease recurrence, suggesting the need for continued dupilumab dosing to maintain efficacy. Trial Registration: ClinicalTrials.gov Identifiers: NCT02612454, NCT02407756, NCT03054428, and NCT03050151. Infographic: [Figure not available: see fulltext.] [MediaObject not available: see fulltext.]",

author = "Andrew Blauvelt and Emma Guttman-Yassky and Paller, {Amy S.} and Simpson, {Eric L.} and Cork, {Michael J.} and Jamie Weisman and John Browning and Weily Soong and Xian Sun and Zhen Chen and Kosloski, {Matthew P.} and Kamal, {Mohamed A.} and Dimittri Delevry and Chuang, {Chien Chia} and O{\textquoteright}Malley, {John T.} and Ashish Bansal",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = may,

doi = "10.1007/s40257-022-00683-2",

language = "English (US)",

volume = "23",

pages = "365--383",

journal = "American Journal of Clinical Dermatology",

issn = "1175-0561",

publisher = "Adis",

number = "3",

}

Blauvelt, A, Guttman-Yassky, E, Paller, AS, Simpson, EL, Cork, MJ, Weisman, J, Browning, J, Soong, W, Sun, X, Chen, Z, Kosloski, MP, Kamal, MA, Delevry, D, Chuang, CC, O’Malley, JT & Bansal, A 2022, 'Long-Term Efficacy and Safety of Dupilumab in Adolescents with Moderate-to-Severe Atopic Dermatitis: Results Through Week 52 from a Phase III Open-Label Extension Trial (LIBERTY AD PED-OLE)', American Journal of Clinical Dermatology, vol. 23, no. 3, pp. 365-383. https://doi.org/10.1007/s40257-022-00683-2

Long-Term Efficacy and Safety of Dupilumab in Adolescents with Moderate-to-Severe Atopic Dermatitis: Results Through Week 52 from a Phase III Open-Label Extension Trial (LIBERTY AD PED-OLE). / Blauvelt, Andrew; Guttman-Yassky, Emma; Paller, Amy S. et al.
In: American Journal of Clinical Dermatology, Vol. 23, No. 3, 05.2022, p. 365-383.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Long-Term Efficacy and Safety of Dupilumab in Adolescents with Moderate-to-Severe Atopic Dermatitis

T2 - Results Through Week 52 from a Phase III Open-Label Extension Trial (LIBERTY AD PED-OLE)

AU - Blauvelt, Andrew

AU - Guttman-Yassky, Emma

AU - Paller, Amy S.

AU - Simpson, Eric L.

AU - Cork, Michael J.

AU - Weisman, Jamie

AU - Browning, John

AU - Soong, Weily

AU - Sun, Xian

AU - Chen, Zhen

AU - Kosloski, Matthew P.

AU - Kamal, Mohamed A.

AU - Delevry, Dimittri

AU - Chuang, Chien Chia

AU - O’Malley, John T.

AU - Bansal, Ashish

PY - 2022/5

Y1 - 2022/5

N2 - Background: For adolescent patients (aged ≥ 12 to < 18 years) with uncontrolled moderate-to-severe atopic dermatitis (AD), 16 weeks of treatment with dupilumab resulted in substantial clinical benefit compared with placebo, with an acceptable safety profile. However, long-term data on the approved dose regimens of dupilumab in adolescents with AD are lacking. Objectives: This open-label extension study (LIBERTY AD PED-OLE, NCT02612454) reports the long-term safety, efficacy, and pharmacokinetics of dupilumab in adolescents with moderate-to-severe AD who had participated in dupilumab parent trials. Methods: Patients enrolled under the original study protocol received subcutaneous dupilumab according to a weight-based regimen (2 or 4 mg/kg every week). Following protocol amendment, patients were switched to subcutaneous dupilumab 300 mg every 4 weeks (q4w) irrespective of weight, and newly enrolled patients were started on dupilumab 300 mg q4w. Patients with an inadequate clinical response (Investigator’s Global Assessment [IGA] score of 0/1 was not reached) to the q4w regimen could be uptitrated to the approved dupilumab dose regimens of 200 or 300 mg every 2 weeks (body weight < 60 or ≥ 60 kg, respectively). Patients whose IGA score of 0/1 was maintained continuously for a 12-week period after week 40 were discontinued from dupilumab, monitored for relapse, and re-initiated on dupilumab if required. Results: Data for 294 patients (mean age 14.7 years) were analyzed, 102 (34.7%) of whom had completed the 52-week visit at the database lock. The dupilumab long-term safety profile was comparable to that seen in adults and consistent with the known safety profile. Most treatment-emergent adverse events were mild/moderate. By week 52, 42.7% of patients had an IGA score of 0/1 (clear/almost clear), and 93.1%, 81.2%, and 56.4%, respectively, had at least a 50%, 75%, or 90% improvement in Eczema Area and Severity Index (EASI). Most (70.9%) patients required uptitration to the approved dupilumab dose regimen. The proportions of uptitrated patients with an IGA score of 0/1 or 75% improvement in EASI increased over time, reaching 35.7% and 51.9%, respectively, 48 weeks after the first uptitration visit. By week 52, 29.4% of patients had clear/almost clear skin sustained for 12 weeks and had stopped medication; 56.7% relapsed and were subsequently re-initiated on treatment, with a mean time to re-initiation of 17.5 (± standard deviation 17.3) weeks. Conclusions: Consistent with results seen with short-term treatment, long-term treatment with dupilumab showed an acceptable safety profile while providing incremental clinical benefit with continued treatment over time. The high proportion of patients who needed uptitration because of inadequate response to q4w dosing supports the q2w dose regimen as optimal for this age group. Finally, the majority of patients who stopped medication after having clear/almost clear skin sustained over 12 weeks experienced disease recurrence, suggesting the need for continued dupilumab dosing to maintain efficacy. Trial Registration: ClinicalTrials.gov Identifiers: NCT02612454, NCT02407756, NCT03054428, and NCT03050151. Infographic: [Figure not available: see fulltext.] [MediaObject not available: see fulltext.]

AB - Background: For adolescent patients (aged ≥ 12 to < 18 years) with uncontrolled moderate-to-severe atopic dermatitis (AD), 16 weeks of treatment with dupilumab resulted in substantial clinical benefit compared with placebo, with an acceptable safety profile. However, long-term data on the approved dose regimens of dupilumab in adolescents with AD are lacking. Objectives: This open-label extension study (LIBERTY AD PED-OLE, NCT02612454) reports the long-term safety, efficacy, and pharmacokinetics of dupilumab in adolescents with moderate-to-severe AD who had participated in dupilumab parent trials. Methods: Patients enrolled under the original study protocol received subcutaneous dupilumab according to a weight-based regimen (2 or 4 mg/kg every week). Following protocol amendment, patients were switched to subcutaneous dupilumab 300 mg every 4 weeks (q4w) irrespective of weight, and newly enrolled patients were started on dupilumab 300 mg q4w. Patients with an inadequate clinical response (Investigator’s Global Assessment [IGA] score of 0/1 was not reached) to the q4w regimen could be uptitrated to the approved dupilumab dose regimens of 200 or 300 mg every 2 weeks (body weight < 60 or ≥ 60 kg, respectively). Patients whose IGA score of 0/1 was maintained continuously for a 12-week period after week 40 were discontinued from dupilumab, monitored for relapse, and re-initiated on dupilumab if required. Results: Data for 294 patients (mean age 14.7 years) were analyzed, 102 (34.7%) of whom had completed the 52-week visit at the database lock. The dupilumab long-term safety profile was comparable to that seen in adults and consistent with the known safety profile. Most treatment-emergent adverse events were mild/moderate. By week 52, 42.7% of patients had an IGA score of 0/1 (clear/almost clear), and 93.1%, 81.2%, and 56.4%, respectively, had at least a 50%, 75%, or 90% improvement in Eczema Area and Severity Index (EASI). Most (70.9%) patients required uptitration to the approved dupilumab dose regimen. The proportions of uptitrated patients with an IGA score of 0/1 or 75% improvement in EASI increased over time, reaching 35.7% and 51.9%, respectively, 48 weeks after the first uptitration visit. By week 52, 29.4% of patients had clear/almost clear skin sustained for 12 weeks and had stopped medication; 56.7% relapsed and were subsequently re-initiated on treatment, with a mean time to re-initiation of 17.5 (± standard deviation 17.3) weeks. Conclusions: Consistent with results seen with short-term treatment, long-term treatment with dupilumab showed an acceptable safety profile while providing incremental clinical benefit with continued treatment over time. The high proportion of patients who needed uptitration because of inadequate response to q4w dosing supports the q2w dose regimen as optimal for this age group. Finally, the majority of patients who stopped medication after having clear/almost clear skin sustained over 12 weeks experienced disease recurrence, suggesting the need for continued dupilumab dosing to maintain efficacy. Trial Registration: ClinicalTrials.gov Identifiers: NCT02612454, NCT02407756, NCT03054428, and NCT03050151. Infographic: [Figure not available: see fulltext.] [MediaObject not available: see fulltext.]

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U2 - 10.1007/s40257-022-00683-2

DO - 10.1007/s40257-022-00683-2

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AN - SCOPUS:85130133660

SN - 1175-0561

VL - 23

SP - 365

EP - 383

JO - American Journal of Clinical Dermatology

JF - American Journal of Clinical Dermatology

IS - 3

ER -

Long-Term Efficacy and Safety of Dupilumab in Adolescents with Moderate-to-Severe Atopic Dermatitis: Results Through Week 52 from a Phase III Open-Label Extension Trial (LIBERTY AD PED-OLE)

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