Dupilumab therapy provides clinically meaningful improvement in patient-reported outcomes (PROs): A phase IIb, randomized, placebo-controlled, clinical trial in adult patients with moderate to severe atopic dermatitis (AD)

Journal of the American Academy of Dermatology

Volumn 75, Issue 3, 2016, Pages 506-515

  Simpson, Eric L ^a   Gadkari, Abhijit ^b   Worm, Margitta ^c   Soong, Weily ^d   Blauvelt, Andrew ^e   Eckert, Laurent ^f   Wu, Richard ^b   Ardeleanu, Marius ^b   Graham, Neil M H ^b   Pirozzi, Gianluca ^f   Sutherland, E Rand ^g   Mastey, Vera ^b  

^a OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^b REGENERON PHARMACEUTICALS INC   (United States)

^c CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^d Alabama Allergy and Asthma Center   (United States)

^e OREGON MEDICAL RESEARCH CENTER   (United States)

^f SANOFI   (France)

^g SANOFI   (United States)

Author keywords

adults; atopic dermatitis; disease burden; dupilumab; patient reported outcomes; pruritus; quality of life

Indexed keywords

DUPILUMAB; PLACEBO; MONOCLONAL ANTIBODY;

5 DIMENSION 3 LEVEL EUROQOL; ADULT; ANXIETY; ARTICLE; ATOPIC DERMATITIS; BACKACHE; CLINICAL ASSESSMENT TOOL; CLINICAL EVALUATION; CONTROLLED STUDY; DEPRESSION; DERMATOLOGY LIFE QUALITY INDEX; DISEASE SEVERITY; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG DOSE REGIMEN; DRUG EFFICACY; DRUG SAFETY; DRUG WITHDRAWAL; FEMALE; HEADACHE; HOSPITAL ANXIETY AND DEPRESSION SCALE; HUMAN; INJECTION SITE REACTION; INVESTIGATOR GLOBAL ASSESSMENT SCORE; LOADING DRUG DOSE; MAJOR CLINICAL STUDY; MALE; MINIMAL CLINICALLY IMPORTANT DIFFERENCE; NUMERIC RATING SCALE; PATIENT ORIENTED ECZEMA MEASURE; PATIENT-REPORTED OUTCOME; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PRODUCTIVITY; PRURITUS; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL; RHINOPHARYNGITIS; SLEEP; STATISTICAL ANALYSIS; TREATMENT OUTCOME; TREATMENT RESPONSE; UPPER RESPIRATORY TRACT INFECTION; CLINICAL TRIAL; DERMATITIS, ATOPIC; DRUG ADMINISTRATION; FOLLOW UP; MIDDLE AGED; MULTICENTER STUDY; PATIENT SATISFACTION; PSYCHOLOGY; RISK ASSESSMENT; SEVERITY OF ILLNESS INDEX; STATISTICS AND NUMERICAL DATA; SUBCUTANEOUS DRUG ADMINISTRATION;

ADULT; ANTIBODIES, MONOCLONAL; DERMATITIS, ATOPIC; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; DRUG ADMINISTRATION SCHEDULE; FEMALE; FOLLOW-UP STUDIES; HUMANS; INJECTIONS, SUBCUTANEOUS; MALE; MIDDLE AGED; PATIENT REPORTED OUTCOME MEASURES; PATIENT SATISFACTION; QUALITY OF LIFE; RISK ASSESSMENT; SEVERITY OF ILLNESS INDEX; TREATMENT OUTCOME;

EID: 84971641180     PISSN: 01909622     EISSN: 10976787     Source Type: Journal    
DOI: 10.1016/j.jaad.2016.04.054     Document Type: Article

References (39)

1. Boguniewicz, M., Leung, D.Y., Atopic dermatitis: a disease of altered skin barrier and immune dysregulation. Immunol Rev 242 (2011), 233–246.
2. Gittler, J.K., Shemer, A., Suarez-Farinas, M., et al. Progressive activation of T(H)2/T(H)22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis. J Allergy Clin Immunol 130 (2012), 1344–1354.
3. Simpson, E.L., Bieber, T., Eckert, L., et al. Patient burden of moderate-to-severe atopic dermatitis: insights from a phase 2b clinical trial of dupilumab in adults. J Am Acad Dermatol 74 (2016), 491–498.
4. Fivenson, D., Arnold, R.J., Kaniecki, D.J., et al. The effect of atopic dermatitis on total burden of illness and quality of life on adults and children in a large managed care organization. J Manag Care Pharm 8 (2002), 333–342.
5. Barbeau, M., Lalonde, H., Burden of atopic dermatitis in Canada. Int J Dermatol 45 (2006), 31–36.
6. Chamlin, S.L., The psychosocial burden of childhood atopic dermatitis. Dermatol Ther 19 (2006), 104–107.
7. Dalgard, F.J., Gieler, U., Tomas-Aragones, L., et al. The psychological burden of skin diseases: a cross-sectional multicenter study among dermatological out-patients in 13 European countries. J Invest Dermatol 135 (2015), 984–991.
8. Bender, B.G., Leung, S.B., Leung, D.Y., Actigraphy assessment of sleep disturbance in patients with atopic dermatitis: an objective life quality measure. J Allergy Clin Immunol 111 (2003), 598–602.
9. Wittkowski, A., Richards, H.L., Griffiths, C.E., et al. Illness perception in individuals with atopic dermatitis. Psychol Health Med 12 (2007), 433–444.
10. Yano, C., Saeki, H., Ishiji, T., et al. Impact of disease severity on sleep quality in Japanese patients with atopic dermatitis. J Dermatol Sci 72 (2013), 195–197.
11. Yano, C., Saeki, H., Ishiji, T., et al. Impact of disease severity on work productivity and activity impairment in Japanese patients with atopic dermatitis. J Dermatol 40 (2013), 736–739.
12. Beck, L.A., Thaçi, D., Hamilton, J.D., et al. Dupilumab for the treatment of adults with moderate-to-severe atopic dermatitis. N Engl J Med 371 (2014), 130–139.
13. Thaçi, D., Simpson, E.L., Beck, L.A., et al. Efficacy and safety of dupilumab in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments: a randomized, placebo controlled, dose-ranging phase 2b trial. Lancet 387 (2015), 40–52.
14. US Department of Health and Human Services Food and Drug Administration. Guidance for industry. Patient-reported outcome measures: use in medical product development to support labeling claims. December 2009. Available at: http://www.fda.gov/downloads/Drugs/./Guidances/UCM193282.pdf. Accessed April 10, 2016.
15. Calvert, M., Blazeby, J., Altman, D.G., et al. Reporting of patient-reported outcomes in randomized trials: the CONSORT PRO extension. JAMA 309 (2013), 814–822.
16. Schachner, L.A., Lamerson, C., Sheehan, M.P., et al. Tacrolimus ointment 0.03% is safe and effective for the treatment of mild to moderate atopic dermatitis in pediatric patients: results from a randomized, double-blind, vehicle-controlled study. Pediatrics 116 (2005), e334–e342.
17. Eichenfield, L.F., Consensus guidelines in diagnosis and treatment of atopic dermatitis. Allergy 59:Suppl (2004), 86–92.
18. Hanifin, J.M., Thurston, M., Omoto, M., et al. The Eczema Area and Severity Index (EASI): assessment of reliability in atopic dermatitis. EASI Evaluator Group. Exp Dermatol 10 (2001), 11–18.
19. Phan, N.Q., Blome, C., Fritz, F., et al. Assessment of pruritus intensity: prospective study on validity and reliability of the visual analogue scale, numerical rating scale and verbal rating scale in 471 patients with chronic pruritus. Acta Derm Venereol 92 (2012), 502–507.
20. Kunz, B., Oranje, A.P., Labreze, L., et al. Clinical validation and guidelines for the SCORAD index: consensus report of the European Task Force on Atopic Dermatitis. Dermatology 195 (1997), 10–19.
21. Charman, C.R., Venn, A.J., Williams, H.C., The Patient-Oriented Eczema Measure: development and initial validation of a new tool for measuring atopic eczema severity from the patients' perspective. Arch Dermatol 140 (2004), 1513–1519.
22. Finlay, A.Y., Khan, G.K., Dermatology Life Quality Index (DLQI)–a simple practical measure for routine clinical use. Clin Exp Dermatol 19 (1994), 210–216.
23. Zigmond, A.S., Snaith, R.P., The Hospital Anxiety and Depression Scale. Acta Psychiatr Scand Suppl 67 (1983), 361–370.
24. The EuroQol Group. EuroQol–a new facility for the measurement of health-related quality of life. The EuroQol Group. Health Policy 16 (1990), 199–208.
25. Dolan, P., Modeling valuations for EuroQol health states. Med Care 35 (1997), 1095–1108.
26. Schram, M.E., Spuls, P.I., Leeflang, M.M., et al. EASI, (objective) SCORAD and POEM for atopic eczema: responsiveness and minimal clinically important difference. Allergy 67 (2012), 99–106.
27. Khilji, F.A., Gonzalez, M., Finlay, A.Y., Clinical meaning of change in Dermatology Life Quality Index scores. [abstract] Br J Dermatol, 147(Suppl s62), 2002, 50.
28. Walters, S.J., Brazier, J.E., Comparison of the minimally important difference for two health state utility measures: EQ-5D and SF-6D. Qual Life Res 14 (2005), 1523–1532.
29. Simpson E, Beck LA, Wu R, et al. Correlation between clinical and patient-reported outcomes in patients with moderate-to-severe atopic dermatitis in a phase 2 clinical trial of dupilumab. Poster presented at: 23rd World Congress of Dermatology; June 8-13, 2015; Vancouver, British Columbia, Canada.
30. Rumble, M.E., White, K.H., Benca, R.M., Sleep disturbances in mood disorders. Psychiatr Clin North Am 38 (2015), 743–759.
31. Zachariae, R., Zachariae, C., Ibsen, H.H., et al. Psychological symptoms and quality of life of dermatology outpatients and hospitalized dermatology patients. Acta Derm Venereol 84 (2004), 205–212.
32. Dieris-Hirche, J., Gieler, U., Kupfer, J.P., et al. Suicidal ideation, anxiety and depression in adult patients with atopic dermatitis. [in German] Hautarzt 60 (2009), 641–646.
33. Kimata, H., Prevalence of suicidal ideation in patients with atopic dermatitis. Suicide Life Threat Behav 36 (2006), 120–124.
34. Yaghmaie, P., Koudelka, C.W., Simpson, E.L., Mental health comorbidity in patients with atopic dermatitis. J Allergy Clin Immunol 131 (2013), 428–433.
35. Tyring, S., Gottlieb, A., Papp, K., et al. Etanercept and clinical outcomes, fatigue, and depression in psoriasis: double-blind placebo-controlled randomized phase III trial. Lancet 367 (2006), 29–35.
36. Krishnadas, R., Nicol, A., Sassarini, J., et al. Circulating tumor necrosis factor is highly correlated with brainstem serotonin transporter availability in humans. Brain Behav Immun 51 (2016), 29–38.
37. Ben-Gashir, M.A., Seed, P.T., Hay, R.J., Quality of life and disease severity are correlated in children with atopic dermatitis. Br J Dermatol 150 (2004), 284–290.
38. Kim, D.H., Li, K., Seo, S.J., et al. Quality of life and disease severity are correlated in patients with atopic dermatitis. J Korean Med Sci 27 (2012), 1327–1332.
39. Haeck, I.M., ten Berge, O., van Velsen, S.G., et al. Moderate correlation between quality of life and disease activity in adult patients with atopic dermatitis. J Eur Acad Dermatol Venereol 26 (2012), 236–241.