TY - JOUR
T1 - Conjunctivitis in dupilumab clinical trials
AU - Akinlade, B.
AU - Guttman-Yassky, E.
AU - de Bruin-Weller, M.
AU - Simpson, E. L.
AU - Blauvelt, A.
AU - Cork, M. J.
AU - Prens, E.
AU - Asbell, P.
AU - Akpek, E.
AU - Corren, J.
AU - Bachert, C.
AU - Hirano, I.
AU - Weyne, J.
AU - Korotzer, A.
AU - Chen, Z.
AU - Hultsch, T.
AU - Zhu, X.
AU - Davis, J. D.
AU - Mannent, L.
AU - Hamilton, J. D.
AU - Teper, A.
AU - Staudinger, H.
AU - Rizova, E.
AU - Pirozzi, G.
AU - Graham, N. M.H.
AU - Shumel, B.
AU - Ardeleanu, M.
AU - Wollenberg, A.
N1 - Funding Information:
This research was sponsored by Sanofi and Regen-eron Pharmaceuticals, Inc. Medical writing assistance and editorial support were provided by Vicki Schwartz, PhD, of Excerpta Medica, funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc.
Funding Information:
Conflicts of interest: B.A., J.W., A.K., Z.C., X.Z., J.D.D., J.D.H., N.M.H.G., B.S. and M.A. are employees and shareholders of Regeneron Pharmaceuticals, Inc. E.G.-Y. is an investigator for AbbVie, Celgene, Eli Lilly, Galderma, GlaxoSmithKline, Glen-mark, LEO Pharma, Pfizer, Regeneron Pharmaceuticals, Inc. and Sanofi; a consultant for AbbVie, Anacor, Asana Biosciences, Daiichi Sanckyo, DBV, Dermira, Eli Lilly, Galderma, GlaxoSmithKline, Glenmark, Kiniksa, Kyowa, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, Realm, Regeneron Pharmaceuticals, Inc. and Sanofi; and has received research grants from AbbVie, Celgene, Dermira, Galderma, Innovaderm, Jans-sen, LEO Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc. and Sanofi. M.dB.-W. is a principal investigator, advisory board member and consultant for Regeneron Pharmaceuticals, Inc. and Sanofi Genzyme; and a principal investigator and advisory board member for AbbVie. E.L.S. has received honoraria for consulting services from AbbVie, Anacor, Cel-gene, Dermira, Eli Lilly, Galderma, Genentech, GlaxoSmithK-line, LEO Pharma, Menlo Therapeutics, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme and Valeant; and has received study support from Anacor, Eli Lilly, GlaxoSmithK-line, MedImmune, Novartis, Regeneron Pharmaceuticals, Inc., Roivant Sciences, Tioga and Vanda. A.B. is a scientific advisor and clinical study investigator for AbbVie, Aclaris, Akros, Allergan, Almirall, Amgen, Arena, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermavant, Dermira, Eli Lilly, Gal-derma, Genentech/Roche, GlaxoSmithKline, Janssen, LEO Pharma, Meiji, Merck, Novartis, Pfizer, Purdue Pharma, Regeneron Pharmaceuticals, Inc., Revance, Sandoz, Sanofi Gen-zyme, Sienna Pharmaceuticals, Sun Pharma, UCB, Valeant and Vidac; and a paid speaker for Janssen, Regeneron Pharmaceuticals, Inc. and Sanofi Genzyme. M.J.C. is an investigator and consultant for AbbVie, Astellas, Boots, Dermavant, Galapagos, Galderma Hyphens, Johnson & Johnson, LEO Pharma, L’Oreal, Menlo, Novartis, Oxagen, Pfizer, Procter & Gamble, Reckitt Benckiser, Regeneron Pharmaceuticals, Inc. and Sanofi Gen-zyme. E.P. has received honoraria and/or research grants from AbbVie, Amgen, Celgene, Eli Lilly, Galderma, Janssen-Cilag, Novartis, Pfizer, Regeneron Pharmaceuticals Inc., Sandoz, Sanofi Genzyme and UCB. P.A. has served on advisory boards for Allergan, Bausch & Lomb, Novartis, Regeneron Pharmaceuticals, Inc., Shire and Valeant; is a CME speaker for Med-scape, Santen, ScientiaCME and Vindico; is a consultant for MC2 Therapeutics, Miotech, Rtech and Shire; has received investigator-initiated research grants from Bausch & Lomb, MC2 Therapeutics, Miotech, Novartis, Rtech and Valeant; is a speaker for Oculus; and is Editor-in-Chief and ECL for CLAO. E.A. has received institutional research grants from Allergan and Bausch & Lomb; has served on advisory boards for Novar-tis and Regeneron Pharmaceuticals, Inc.; and is a consultant for Shire. J.C. has received research funding from Sanofi. C.B. is a principal investigator for Regeneron Pharmaceuticals, Inc.; and is a consultant for AstraZeneca, GlaxoSmithKline, Novartis and Sanofi. I.H. is a consultant for Adare, Allakos, Receptos/ Celgene, Regeneron Pharmaceuticals, Inc. and Shire; and has received research funding from Adare, Receptos/Celgene, Regeneron Pharmaceuticals, Inc. and Shire. T.H., L.M., A.T., H.S., E.R. and G.P. are employees, and may hold stock and/or stock options in Sanofi. A.W. is an advisor, speaker or investigator for ALK Abelló, Almirall, Anacor, Beiersdorf AG, Ben-card, Bioderma, Chugai, Eli Lilly, Pierre Fabre, Galderma, GlaxoSmithKline, Hans Karrer, LEO Pharma, L’Oreal, Maruho, MedImmune, Novartis, Pfizer, Sanofi, Regeneron Pharmaceuticals, Inc. and Sienna.
Publisher Copyright:
© 2019 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.
PY - 2019/9/1
Y1 - 2019/9/1
N2 - Background: Dupilumab blocks the shared receptor component for interleukin (IL)-4 and IL-13. It is approved in the U.S.A. for patients aged ≥ 12 years with moderate-to-severe atopic dermatitis (AD) uncontrolled by topical prescription medicines or who cannot use topical medicines, for patients in Japan whose AD is uncontrolled with existing therapies, for patients with moderate-to-severe AD in Europe who are candidates for systemic therapy and for patients aged ≥ 12 years for maintenance treatment of moderate-to-severe asthma uncontrolled with their current medicines. AD trials have reported increased incidence of conjunctivitis for dupilumab vs. placebo. Objectives: To characterize further the occurrence and risk factors of conjunctivitis in dupilumab clinical trials. Methods: We evaluated randomized placebo-controlled trials of dupilumab in AD (n = 2629), asthma (n = 2876), chronic rhinosinusitis with nasal polyps (CRSwNP) (n = 60) and eosinophilic oesophagitis (EoE) (n = 47). Results: In most AD trials, dupilumab-treated patients had higher conjunctivitis incidence than placebo controls. Higher baseline AD severity and previous history of conjunctivitis were associated with increased conjunctivitis incidence. Conjunctivitis was mostly mild to moderate. Most cases recovered or resolved during the treatment period; two patients permanently discontinued dupilumab due to conjunctivitis or keratitis. Common treatments included ophthalmic corticosteroids, antibiotics, and antihistamines or mast cell stabilizers. Most cases were diagnosed by the investigators. In asthma and CRSwNP trials, the incidence of conjunctivitis was lower for both dupilumab and placebo than in AD trials; dupilumab did not increase the incidence compared with placebo. In the EoE trial, no patients had conjunctivitis. Conclusions: Conjunctivitis was more frequent with dupilumab treatment in most AD trials. In dupilumab trials in other type 2 diseases, incidence of conjunctivitis was overall very low, and was similar for dupilumab and placebo. In AD, the incidence of conjunctivitis was associated with AD severity and prior history of conjunctivitis. The aetiology and treatment of conjunctivitis in dupilumab-treated patients require further study. What's already known about this topic?. Ocular disorders, including allergic conjunctivitis, are common in patients with atopic dermatitis (AD). In most dupilumab AD trials, dupilumab-treated patients had higher conjunctivitis incidence than those receiving placebo. Most cases were mild to moderate and recovered or were recovering during study treatment; study treatment discontinuation due to conjunctivitis was rare. Conjunctivitis incidence was very low and similar for dupilumab and placebo in clinical trials in asthma, chronic rhinosinusitis with nasal polyps and eosinophilic oesophagitis. What does this study add?. This analysis confirms and extends the results of the individual clinical trials. Baseline disease-related factors, including AD severity, prior conjunctivitis history and certain biomarkers (thymus and activation-regulated chemokine, IgE, eosinophils), were associated with increased incidence of conjunctivitis. Patients who responded well to dupilumab had reduced incidence of conjunctivitis. Further study is needed to elucidate the aetiology and treatment of conjunctivitis in dupilumab-treated patients with AD.
AB - Background: Dupilumab blocks the shared receptor component for interleukin (IL)-4 and IL-13. It is approved in the U.S.A. for patients aged ≥ 12 years with moderate-to-severe atopic dermatitis (AD) uncontrolled by topical prescription medicines or who cannot use topical medicines, for patients in Japan whose AD is uncontrolled with existing therapies, for patients with moderate-to-severe AD in Europe who are candidates for systemic therapy and for patients aged ≥ 12 years for maintenance treatment of moderate-to-severe asthma uncontrolled with their current medicines. AD trials have reported increased incidence of conjunctivitis for dupilumab vs. placebo. Objectives: To characterize further the occurrence and risk factors of conjunctivitis in dupilumab clinical trials. Methods: We evaluated randomized placebo-controlled trials of dupilumab in AD (n = 2629), asthma (n = 2876), chronic rhinosinusitis with nasal polyps (CRSwNP) (n = 60) and eosinophilic oesophagitis (EoE) (n = 47). Results: In most AD trials, dupilumab-treated patients had higher conjunctivitis incidence than placebo controls. Higher baseline AD severity and previous history of conjunctivitis were associated with increased conjunctivitis incidence. Conjunctivitis was mostly mild to moderate. Most cases recovered or resolved during the treatment period; two patients permanently discontinued dupilumab due to conjunctivitis or keratitis. Common treatments included ophthalmic corticosteroids, antibiotics, and antihistamines or mast cell stabilizers. Most cases were diagnosed by the investigators. In asthma and CRSwNP trials, the incidence of conjunctivitis was lower for both dupilumab and placebo than in AD trials; dupilumab did not increase the incidence compared with placebo. In the EoE trial, no patients had conjunctivitis. Conclusions: Conjunctivitis was more frequent with dupilumab treatment in most AD trials. In dupilumab trials in other type 2 diseases, incidence of conjunctivitis was overall very low, and was similar for dupilumab and placebo. In AD, the incidence of conjunctivitis was associated with AD severity and prior history of conjunctivitis. The aetiology and treatment of conjunctivitis in dupilumab-treated patients require further study. What's already known about this topic?. Ocular disorders, including allergic conjunctivitis, are common in patients with atopic dermatitis (AD). In most dupilumab AD trials, dupilumab-treated patients had higher conjunctivitis incidence than those receiving placebo. Most cases were mild to moderate and recovered or were recovering during study treatment; study treatment discontinuation due to conjunctivitis was rare. Conjunctivitis incidence was very low and similar for dupilumab and placebo in clinical trials in asthma, chronic rhinosinusitis with nasal polyps and eosinophilic oesophagitis. What does this study add?. This analysis confirms and extends the results of the individual clinical trials. Baseline disease-related factors, including AD severity, prior conjunctivitis history and certain biomarkers (thymus and activation-regulated chemokine, IgE, eosinophils), were associated with increased incidence of conjunctivitis. Patients who responded well to dupilumab had reduced incidence of conjunctivitis. Further study is needed to elucidate the aetiology and treatment of conjunctivitis in dupilumab-treated patients with AD.
UR - http://www.scopus.com/inward/record.url?scp=85065473317&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85065473317&partnerID=8YFLogxK
U2 - 10.1111/bjd.17869
DO - 10.1111/bjd.17869
M3 - Article
C2 - 30851191
AN - SCOPUS:85065473317
VL - 181
SP - 459
EP - 473
JO - British Journal of Dermatology
JF - British Journal of Dermatology
SN - 0007-0963
IS - 3
ER -