Effect of Dupilumab on Laboratory Parameters in Adolescents with Atopic Dermatitis: Results from a Randomized, Placebo-Controlled, Phase 3 Clinical Trial.
Journal
American journal of clinical dermatology
ISSN: 1179-1888
Titre abrégé: Am J Clin Dermatol
Pays: New Zealand
ID NLM: 100895290
Informations de publication
Date de publication:
Mar 2021
Mar 2021
Historique:
accepted:
16
12
2020
pubmed:
4
3
2021
medline:
13
7
2021
entrez:
3
3
2021
Statut:
ppublish
Résumé
Laboratory testing is typically required for patients with atopic dermatitis (AD) treated with systemic immunosuppressants. A previous analysis of laboratory outcomes in randomized, double-blinded, placebo-controlled clinical trials of dupilumab in adults with moderate-to-severe AD found no clinically important changes in hematologic, serum chemistry, and urinalysis parameters, supporting the use of dupilumab without routine laboratory monitoring. The aim was to assess laboratory results in adolescents with moderate-to-severe AD treated with dupilumab in a phase 3, randomized, double-blind, placebo-controlled trial. Adolescents aged ≥ 12 to < 18 years with moderate-to-severe AD were randomized 1:1:1 to subcutaneous dupilumab 200/300 mg every 2 weeks (q2w) (200 mg for patients < 60 kg at baseline; 300 mg for patients ≥ 60 kg at baseline); dupilumab 300 mg every 4 weeks (q4w); or placebo for 16 weeks. Laboratory evaluations included hematology, serum chemistry, and urinalysis parameters. Of 251 patients enrolled in the study, 250 received treatment and were included in the analysis. 4.7%, 2.4%, and 4.8% of patients receiving placebo, dupilumab 200/300 mg q2w, and dupilumab 300 mg q4w, respectively, had laboratory abnormalities reported as treatment-emergent adverse events, none of which prompted discontinuation of study treatment or study withdrawal. Mean eosinophil counts were elevated at baseline in all treatment groups. Patients in both dupilumab regimens, but not the placebo group, showed mild transient increases in mean eosinophil counts above baseline that returned to near-baseline values by week 16. Mean levels of lactate dehydrogenase trended towards the upper limit of normal at baseline and decreased with treatment; greater decreases were seen in dupilumab-treated patients than placebo-treated patients. There were no meaningful changes in other laboratory parameters, and none of the laboratory abnormalities were clinically significant. No clinically meaningful changes in laboratory parameters were seen in adolescents, similar to that observed in adults. The findings of this study indicate no routine laboratory monitoring is required in this population prior to or during dupilumab treatment. ClinicalTrials.gov: NCT03054428. Video abstract: Effect of Dupilumab on Laboratory Parameters in Adolescents with Atopic Dermatitis: Results from a Randomized Placebo-Controlled Phase 3 Clinical Trial (MP4 175137 KB).
Sections du résumé
BACKGROUND
BACKGROUND
Laboratory testing is typically required for patients with atopic dermatitis (AD) treated with systemic immunosuppressants. A previous analysis of laboratory outcomes in randomized, double-blinded, placebo-controlled clinical trials of dupilumab in adults with moderate-to-severe AD found no clinically important changes in hematologic, serum chemistry, and urinalysis parameters, supporting the use of dupilumab without routine laboratory monitoring.
OBJECTIVE
OBJECTIVE
The aim was to assess laboratory results in adolescents with moderate-to-severe AD treated with dupilumab in a phase 3, randomized, double-blind, placebo-controlled trial.
METHODS
METHODS
Adolescents aged ≥ 12 to < 18 years with moderate-to-severe AD were randomized 1:1:1 to subcutaneous dupilumab 200/300 mg every 2 weeks (q2w) (200 mg for patients < 60 kg at baseline; 300 mg for patients ≥ 60 kg at baseline); dupilumab 300 mg every 4 weeks (q4w); or placebo for 16 weeks. Laboratory evaluations included hematology, serum chemistry, and urinalysis parameters.
RESULTS
RESULTS
Of 251 patients enrolled in the study, 250 received treatment and were included in the analysis. 4.7%, 2.4%, and 4.8% of patients receiving placebo, dupilumab 200/300 mg q2w, and dupilumab 300 mg q4w, respectively, had laboratory abnormalities reported as treatment-emergent adverse events, none of which prompted discontinuation of study treatment or study withdrawal. Mean eosinophil counts were elevated at baseline in all treatment groups. Patients in both dupilumab regimens, but not the placebo group, showed mild transient increases in mean eosinophil counts above baseline that returned to near-baseline values by week 16. Mean levels of lactate dehydrogenase trended towards the upper limit of normal at baseline and decreased with treatment; greater decreases were seen in dupilumab-treated patients than placebo-treated patients. There were no meaningful changes in other laboratory parameters, and none of the laboratory abnormalities were clinically significant.
CONCLUSION
CONCLUSIONS
No clinically meaningful changes in laboratory parameters were seen in adolescents, similar to that observed in adults. The findings of this study indicate no routine laboratory monitoring is required in this population prior to or during dupilumab treatment.
TRIAL REGISTRATION
BACKGROUND
ClinicalTrials.gov: NCT03054428. Video abstract: Effect of Dupilumab on Laboratory Parameters in Adolescents with Atopic Dermatitis: Results from a Randomized Placebo-Controlled Phase 3 Clinical Trial (MP4 175137 KB).
Identifiants
pubmed: 33655423
doi: 10.1007/s40257-020-00583-3
pii: 10.1007/s40257-020-00583-3
pmc: PMC7973645
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Placebos
0
dupilumab
420K487FSG
Banques de données
ClinicalTrials.gov
['NCT03054428']
Types de publication
Clinical Trial, Phase III
Journal Article
Randomized Controlled Trial
Video-Audio Media
Langues
eng
Sous-ensembles de citation
IM
Pagination
243-255Références
Sidbury R, Davis DM, Cohen DE, et al. Guidelines of care for the management of atopic dermatitis: section 3. Management and treatment with phototherapy and systemic agents. J Am Acad Dermatol. 2014;71:327–49.
doi: 10.1016/j.jaad.2014.03.030
Ring J, Alomar A, Bieber T, et al. Guidelines for treatment of atopic eczema (atopic dermatitis) part II. J Eur Acad Dermatol Venereol. 2012;26:1176–93.
doi: 10.1111/j.1468-3083.2012.04636.x
Drucker AM, Eyerick K, de Bruin-Weller M, et al. Use of systemic corticosteroids for atopic dermatitis: International Eczema Council consensus statement. Br J Dermatol. 2018;178:768–75.
doi: 10.1111/bjd.15928
Simpson EL, Bruin-Weller M, Flohr C, et al. When does atopic dermatitis warrant systemic therapy? Recommendations from an expert panel of the International Eczema Council. J Am Acad Dermatol. 2017;77:623–33.
doi: 10.1016/j.jaad.2017.06.042
Liu D, Ahmet A, Ward L, et al. A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. Allergy Asthma Clin Immunol. 2013;9:30.
doi: 10.1186/1710-1492-9-30
Macdonald LE, Karow M, Stevens S, et al. Precise and in situ genetic humanization of 6 Mb of mouse immunoglobulin genes. Proc Natl Acad Sci U S A. 2014;111:5147–52.
doi: 10.1073/pnas.1323896111
Murphy AJ, Macdonald LE, Stevens S, et al. Mice with megabase humanization of their immunoglobulin genes generate antibodies as efficiently as normal mice. Proc Natl Acad Sci U S A. 2014;111:5153–8.
doi: 10.1073/pnas.1324022111
Gandhi NA, Pirozzi G, Graham NMH. Commonality of the IL-4/IL-13 pathway in atopic diseases. Expert Rev Clin Immunol. 2017;13:425–37.
doi: 10.1080/1744666X.2017.1298443
Le Floc’h A, Allinne J, Martin J, et al. Dupilumab protects from type 2 inflammation by impacting both systemic and local inflammatory events downstream of IL-4/IL-13 signalling. Allergy. 2020;75:1188–204.
doi: 10.1111/all.14151
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;375:2335–48.
doi: 10.1056/NEJMoa1610020
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;389:2287–303.
doi: 10.1016/S0140-6736(17)31191-1
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 cyclosporine A or when this treatment is medically inadvisable: a placebo-controlled, randomized phase III clinical trial (LIBERTY AD CAFÉ). Br J Dermatol. 2018;178:1083–101.
doi: 10.1111/bjd.16156
Simpson EL, Paller AS, Siegfried EC, et al. Efficacy and safety of dupilumab in adolescents with uncontrolled moderate to severe atopic dermatitis: a phase 3 randomized clinical trial. JAMA Dermatol. 2020;156:44–56.
doi: 10.1001/jamadermatol.2019.3336
Deleuran M, Thaçi D, Beck LA, et al. Dupilumab shows long-term safety and efficacy in patients with moderate to severe atopic dermatitis enrolled in a phase 3 open-label extension study. J Am Acad Dermatol. 2020;82:377–88.
doi: 10.1016/j.jaad.2019.07.074
Cork MJ, Thaçi D, Eichenfield LF, et al. Dupilumab in adolescents with uncontrolled moderate-to-severe atopic dermatitis: results from a phase IIa open-label trial and subsequent phase III open-label extension. Br J Dermatol. 2020;182:85–96.
doi: 10.1111/bjd.18476
Wollenberg A, Beck LA, Blauvelt A, et al. Laboratory safety of dupilumab in moderate-to-severe atopic dermatitis: results from three phase III trials (LIBERTY AD SOLO 1, LIBERTY AD SOLO 2, LIBERTY AD CHRONOS). Br J Dermatol. 2020;182:1120–35.
doi: 10.1111/bjd.18434
U.S. Department of Health and Human Services. Common Terminology Criteria for Adverse Events (CTCAE); version 5.0. November 27, 2017. https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf . Accessed 20 Dec 2019.
Nordic MPN Study Group. Guidelines for the diagnosis and treatment of eosinophilia. 3rd version. May 2018. https://www.nmpn.org/index.php/guidelines/18-care-program-for-the-diagnosis-and-treatment-of-eosinophilia-3rd-version-may-2018/file . Accessed 20 Aug 2020.
Dogru M, Citli R. The neutrophil-lymphocyte ratio in children with atopic dermatitis: a case-control study. Clin Ter. 2017;168:e262–5.
pubmed: 28703842
Jiang Y, Ma W. Assessment of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in atopic dermatitis patients. Med Sci Monitor. 2017;23:1340–6.
doi: 10.12659/MSM.900212
Uehara M, Izukura R, Sawai T. Blood eosinophilia in atopic dermatitis. Clin Exp Dermatol. 1990;15:264–6.
doi: 10.1111/j.1365-2230.1990.tb02086.x
Kagi MK, Joller-Jemelka H, Wüthrich B. Correlation of eosinophils, eosinophil cationic protein and soluble interleukin-2 receptor with the clinical activity of atopic dermatitis. Dermatology. 1992;185:88–92.
doi: 10.1159/000247419
Kiehl P, Falkenberg K, Vogelbruch M, Kapp A. Tissue eosinophilia in acute and chronic atopic dermatitis: a morphometric approach using quantitative image analysis of immunostaining. Br J Dermatol. 2001;145:720–9.
doi: 10.1046/j.1365-2133.2001.04456.x
Liu F-T, Goodarzi H, Chen H-Y. IgE, mast cells, and eosinophils in atopic dermatitis. Clin Rev Allerg Immunol. 2011;41:298–310.
doi: 10.1007/s12016-011-8252-4
De Grauuw E, Beltraminelli H, Simon HU, et al. Eosinophilia in dermatologic disorders. Immunol Allergy Clin N Am. 2015;35:535–60.
Werfel T, Allam J-P, Biedermann T, et al. Cellular and molecular immunologic mechanisms in patients with atopic dermatitis. J Allergy Clin Immunol. 2016;138:336–49.
doi: 10.1016/j.jaci.2016.06.010
Castro M, Corren J, Pavord I, et al. Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma. N Engl J Med. 2018;378:2486–96.
doi: 10.1056/NEJMoa1804092
Rabe K, Nair P, Brusselle G, et al. Efficacy and safety of dupilumab in glucocorticoid-dependent severe asthma. N Engl J Med. 2018;378:2475–85.
doi: 10.1056/NEJMoa1804093
Bachert C, Han JK, Desrosiers M, et al. 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;394:1638–50.
doi: 10.1016/S0140-6736(19)31881-1
Mukai H, Noguchi T, Kamimura K, Nishioka K, Nishiyama S. Significance of elevated serum LDH (lactate dehydrogenase) activity in atopic dermatitis. J Dermatol. 1990;17:477–81.
doi: 10.1111/j.1346-8138.1990.tb01679.x
Kou K, Alhara M, Matsunaga T, et al. Association of serum interleukin-18 and other biomarkers with disease severity in adults with atopic dermatitis. Arch Dermatol Res. 2012;304:305–12.
doi: 10.1007/s00403-011-1198-9
Thijs J, Krastev T, Weidinger S, et al. Biomarkers for atopic dermatitis: a systemic review and meta-analysis. Curr Opin Allergy Clin Immunol. 2015;15:453–60.
doi: 10.1097/ACI.0000000000000198
Simpson EL, Villarreal M, Jepson B, et al. Patients with atopic dermatitis colonized with Staphylococcus aureus have a distinct phenotype and endotype. J Investig Dermatol. 2018;138:2224–33.
doi: 10.1016/j.jid.2018.03.1517
Turan S, Topcu B, Gökçe İ, et al. Serum alkaline phosphatase levels in healthy children and evaluation of alkaline phosphatase z-scores in different types of rickets. J Clin Res Pediatr Endocrinol. 2011;3:7–11.
doi: 10.4274/jcrpe.v3i1.02
Silverberg JI, Paller AS. Association between eczema and stature in 9 US population-based studies. JAMA Dermatol. 2015;151:401–9.
doi: 10.1001/jamadermatol.2014.3432
JAKAFI
XELJANZ
OLUMIANT