Analyses of Dupilumab-Related Ocular Adverse Drug Reactions Using the WHO's VigiBase.
Adverse drug reaction
Conjunctivitis
Dry eye
Dupilumab
Interleukin-13
Interleukin-4
Journal
Advances in therapy
ISSN: 1865-8652
Titre abrégé: Adv Ther
Pays: United States
ID NLM: 8611864
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
received:
13
03
2023
accepted:
31
05
2023
medline:
16
8
2023
pubmed:
26
6
2023
entrez:
26
6
2023
Statut:
ppublish
Résumé
Dupilumab is a drug that inhibits the action of interleukin (IL)-4 and IL-13 and is a potent therapeutic drug for allergic diseases such as atopic dermatitis. Although its use has been associated with significant ocular adverse drug reactions (ADRs), the IL-4 and IL-13 inhibition may also have favorable therapeutic effects. The aim of this study was to determine the disease spectrum in which the use of dupilumab may have been associated with an increase or decrease of ocular ADRs. We searched the World Health Organization's VigiBase for ADRs associated with the use of dupilumab for data up to 12 June 2022. The number of all ADRs that were retrieved was compared with the number of ocular ADRs associated with the use of dupilumab. Disproportionate reporting was assessed by calculating the information component (IC) values and odds ratios. Since the introduction of dupilumab, 100,267 ADRs have been reported. Of all the ADRs associated with dupilumab, 28,522 ADRs were ocular complications, and it ranked fourth in the ocular complications by organ level. By assessments of the IC for age ≤ 44 years, the most significantly associated ADRs were dry eye followed by blepharitis including eyelid crusting and dryness and conjunctivitis. Crusting and dryness of the eyelids were the most significant ADRs for all age groups. Other ocular ADRs reported include meibomian gland dysfunction, keratitis, glaucoma, and retinal disorders. In contrast, periorbital edema, neuro-ophthalmic disorders, optic neuritis, and macular edema were significantly reduced by the use of dupilumab. Dupilumab-related ADRs included an increase or decrease of various ocular disorders. The results indicate that dupilumab also has potential therapeutic effects.
Identifiants
pubmed: 37358706
doi: 10.1007/s12325-023-02573-3
pii: 10.1007/s12325-023-02573-3
doi:
Substances chimiques
dupilumab
420K487FSG
Interleukin-13
0
Types de publication
Journal Article
Langues
eng
Pagination
3830-3856Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.
Références
Thaci D, Simpson EL, Beck LA, et al. Efficacy and safety of dupilumab in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments: a randomised, placebo-controlled, dose-ranging phase 2b trial. Lancet. 2016;387(10013):40–52.
doi: 10.1016/S0140-6736(15)00388-8
pubmed: 26454361
Munoz-Bellido FJ, Moreno E, Davila I. Dupilumab: a review of present indications and off-label uses. J Investig Allergol Clin Immunol. 2022;32(2):97–115.
doi: 10.18176/jiaci.0682
pubmed: 33661102
Iwaszko M, Bialy S, Bogunia-Kubik K. Significance of interleukin (IL)-4 and IL-13 in inflammatory arthritis. Cells. 2021;10(11):3000.
doi: 10.3390/cells10113000
pubmed: 34831223
pmcid: 8616130
Simpson EL, Bieber T, Guttman-Yassky E, et al. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016;375(24):2335–48.
doi: 10.1056/NEJMoa1610020
pubmed: 27690741
Brumfiel CM, Patel MH, Zirwas MJ. Development of psoriasis during treatment with dupilumab: a systematic review. J Am Acad Dermatol. 2022;86(3):708–9.
doi: 10.1016/j.jaad.2021.05.013
pubmed: 34022319
Jo CE, Finstad A, Georgakopoulos JR, Piguet V, Yeung J, Drucker AM. Facial and neck erythema associated with dupilumab treatment: a systematic review. J Am Acad Dermatol. 2021;84(5):1339–47.
doi: 10.1016/j.jaad.2021.01.012
pubmed: 33428978
Chretien B, Dolladille C, Alexandre J, et al. Dupilumab-associated arthralgia: an observational retrospective study in VigiBase(®). Br J Dermatol. 2021;185(2):464–5.
doi: 10.1111/bjd.20138
pubmed: 33829495
Kychygina A, Cassagne M, Tauber M, et al. Dupilumab-associated adverse events during treatment of allergic diseases. Clin Rev Allergy Immunol. 2022;62(3):519–33.
doi: 10.1007/s12016-022-08934-0
pubmed: 35275334
Halling AS, Loft N, Silverberg JI, Guttman-Yassky E, Thyssen JP. Real-world evidence of dupilumab efficacy and risk of adverse events: a systematic review and meta-analysis. J Am Acad Dermatol. 2021;84(1):139–47.
doi: 10.1016/j.jaad.2020.08.051
pubmed: 32822798
Hansen PM, Tollenaere MAX, Hedengran A, et al. IL-4 and IL-13 both contribute to the homeostasis of human conjunctival goblet cells in vitro. Allergy. 2022;77(8):2555–8.
doi: 10.1111/all.15326
pubmed: 35474220
Huang SC, Smith AM, Everts B, et al. Metabolic reprogramming mediated by the mTORC2-IRF4 signaling axis is essential for macrophage alternative activation. Immunity. 2016;45(4):817–30.
doi: 10.1016/j.immuni.2016.09.016
pubmed: 27760338
pmcid: 5535820
Wollenberg A, Beck LA, de Bruin WM, et al. Conjunctivitis in adult patients with moderate-to-severe atopic dermatitis: results from five tralokinumab clinical trials. Br J Dermatol. 2022;186(3):453–65.
doi: 10.1111/bjd.20810
pubmed: 34637142
Mahroum N, Damiani G, Watad A, et al. Higher rates of COVID-19 but less severe infections reported for patients on dupilumab: a big data analysis of the World Health Organization VigiBase. Eur Rev Med Pharmacol Sci. 2021;25:5865–70.
pubmed: 34604979
Norén GN, Orre R, Bate A. A hit-miss model for duplicate detection in the WHO drug safety database. Proceeding of the eleventh ACM SIGKDD international conference on knowledge discovery in data mining - KDD '05. 2005:459–468.
Blauvelt A, de Bruin-Weller M, Gooderham M, et al. Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, randomised, double-blinded, placebo-controlled, phase 3 trial. Lancet. 2017;389(10086):2287–303.
doi: 10.1016/S0140-6736(17)31191-1
pubmed: 28478972
de Bruin-Weller M, Thaçi D, Smith CH, et al. Dupilumab with concomitant topical corticosteroid treatment in adults with atopic dermatitis with an inadequate response or intolerance to ciclosporin A or when this treatment is medically inadvisable: a placebo-controlled, randomized phase III clinical trial (LIBERTY AD CAFÉ). Br J Dermatol. 2018;178(5):1083–101.
doi: 10.1111/bjd.16156
pubmed: 29193016
Worm M, Simpson EL, Thaci D, et al. Efficacy and safety of multiple dupilumab dose regimens after initial successful treatment in patients with atopic dermatitis: a randomized clinical trial. JAMA Dermatol. 2020;156(2):131–43.
doi: 10.1001/jamadermatol.2019.3617
pubmed: 31876900
Akinlade B, Guttman-Yassky E, de Bruin-Weller M, et al. Conjunctivitis in dupilumab clinical trials. Br J Dermatol. 2019;181(3):459–73.
doi: 10.1111/bjd.17869
pubmed: 30851191
pmcid: 6850316
Bachert C, Mannent L, Naclerio RM, et al. Effect of subcutaneous dupilumab on nasal polyp burden in patients with chronic sinusitis and nasal polyposis: a randomized clinical trial. JAMA. 2016;315(5):469–79.
doi: 10.1001/jama.2015.19330
pubmed: 26836729
Castro M, Corren J, Pavord ID, et al. Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma. N Engl J Med. 2018;378(26):2486–96.
doi: 10.1056/NEJMoa1804092
pubmed: 29782217
Hirano I, Dellon ES, Hamilton JD, et al. Efficacy of dupilumab in a phase 2 randomized trial of adults with active eosinophilic esophagitis. Gastroenterology. 2020;158(1):111-22.e10.
doi: 10.1053/j.gastro.2019.09.042
pubmed: 31593702
Rabe KF, Nair P, Brusselle G, et al. Efficacy and safety of dupilumab in glucocorticoid-dependent severe asthma. N Engl J Med. 2018;378(26):2475–85.
doi: 10.1056/NEJMoa1804093
pubmed: 29782224
Wenzel S, Castro M, Corren J, et al. 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;388(10039):31–44.
doi: 10.1016/S0140-6736(16)30307-5
pubmed: 27130691
Atherton HC, Jones G, Danahay H. IL-13-induced changes in the goblet cell density of human bronchial epithelial cell cultures MAP kinase and phosphatidylinositol 3-kinase regulation. Am J Physiol Lung Cell Mol Physiol. 2003;285:730–9.
doi: 10.1152/ajplung.00089.2003
Jun I, Kim BR, Park SY, et al. Interleukin-4 stimulates lipogenesis in meibocytes by activating the STAT6/PPARgamma signaling pathway. Ocul Surf. 2020;18(4):575–82.
doi: 10.1016/j.jtos.2020.04.015
pubmed: 32360783
Wilson MM, Roberts PK, Daniell M. Dupilumab-associated ulcerative keratitis. Int J Ophthalmol. 2022;15(6):1020–2.
doi: 10.18240/ijo.2022.06.23
pubmed: 35814891
pmcid: 9203468
Thyssen JP. Could conjunctivitis in patients with atopic dermatitis treated with dupilumab be caused by colonization with demodex and increased interleukin-17 levels? Br J Dermatol. 2018;178(5):1220.
doi: 10.1111/bjd.16330
pubmed: 29333603
de Beer FSA, Bakker DS, Haeck I, et al. Dupilumab facial redness: positive effect of itraconazole. JAAD Case Rep. 2019;5(10):888–91.
doi: 10.1016/j.jdcr.2019.07.020
pubmed: 31681828
pmcid: 6818397
Takakuwa K, Hamanaka T, Mori K, et al. Atopic glaucoma: clinical and pathophysiological analysis. J Glaucoma. 2015;24(9):662–8.
doi: 10.1097/IJG.0000000000000069
pubmed: 25415644
Chen D, Peng C, Ding XM, et al. Interleukin-4 promotes microglial polarization toward a neuroprotective phenotype after retinal ischemia/reperfusion injury. Neural Regen Res. 2022;17(12):2755–60.
doi: 10.4103/1673-5374.339500
pubmed: 35662225
pmcid: 9165374
Baba T, Miyazaki D, Inata K, et al. Role of IL-4 in bone marrow driven dysregulated angiogenesis and age-related macular degeneration. Elife. 2020;9:e54257.
doi: 10.7554/eLife.54257
pubmed: 32366355
pmcid: 7200155
Wu H, Hwang DK, Song X, Tao Y. Association between aqueous cytokines and diabetic retinopathy stage. J Ophthalmol. 2017;2017:9402198.
doi: 10.1155/2017/9402198
pubmed: 28680705
pmcid: 5478856
Chernykh VV, Varvarinsky EV, Smirnov EV, Chernykh DV, Trunov AN. Proliferative and inflammatory factors in the vitreous of patients with proliferative diabetic retinopathy. Indian J Ophthalmol. 2015;63(1):33–6.
doi: 10.4103/0301-4738.151464
pubmed: 25686060
pmcid: 4363955
Yamada T, Komiya I, Miyahara Y, et al. Effect of methimazole treatment for 2 years on circulating IL-4, IgE, TBII, and TSAb in patients with hyperthyroid Graves’ disease. Endocr J. 2006;53(6):783–8.
doi: 10.1507/endocrj.K06-054
pubmed: 16983180
Chen B, Tsui S, Boeglin WE, Douglas RS, Brash AR, Smith TJ. Interleukin-4 induces 15-lipoxygenase-1 expression in human orbital fibroblasts from patients with Graves disease. Evidence for anatomic site-selective actions of Th2 cytokines. J Biol Chem. 2006;281(27):18296–306.
doi: 10.1074/jbc.M603484200
pubmed: 16675443
Alves-Leon SV, Pimentel ML, Sant’Anna G, Malfetano FR, Estrada CD, Quirico-Santos T. Immune system markers of neuroinflammation in patients with clinical diagnose of neuromyelitis optica. Arq Neuropsiquiatr. 2008;66(3B):678–84.
doi: 10.1590/S0004-282X2008000500013
pubmed: 18949261
Seyfizadeh N, Kazemi T, Farhoudi M, et al. Association of IL-13 single nucleotide polymorphisms in Iranian patients to multiple sclerosis. Am J Clin Exp Immunol. 2014;3(3):124–9.
pubmed: 25628961
pmcid: 4299763
Noren GN, Hopstadius J, Bate A. Shrinkage observed-to-expected ratios for robust and transparent large-scale pattern discovery. Stat Methods Med Res. 2013;22(1):57–69.
doi: 10.1177/0962280211403604
pubmed: 21705438
Bihan K, Lebrun-Vignes B, Funck-Brentano C, Salem JE. Uses of pharmacovigilance databases: an overview. Therapie. 2020;75(6):591–8.
doi: 10.1016/j.therap.2020.02.022
pubmed: 32169289