Top

Health and Quality of Life Outcomes

Published in:

Open Access 01-12-2013 | Research

Improvements in patient-reported outcomes with apremilast, an oral phosphodiesterase 4 inhibitor, in the treatment of moderate to severe psoriasis: results from a phase IIb randomized, controlled study

Authors: Vibeke Strand, David Fiorentino, ChiaChi Hu, Robert M Day, Randall M Stevens, Kim A Papp

Published in: Health and Quality of Life Outcomes | Issue 1/2013

Abstract

Background

Apremilast, a specific inhibitor of phosphodiesterase 4, modulates pro-inflammatory and anti-inflammatory cytokine production.

Objectives

Apremilast’s effect on patient-reported outcomes (PROs) in patients with moderate to severe psoriasis was evaluated in a phase IIb randomized, controlled trial (NCT00773734).

Methods

In this 16-week, placebo-controlled study, 352 patients with moderate to severe plaque psoriasis received placebo or apremilast (10, 20, or 30 mg BID). PROs included Dermatology Life Quality Index (DLQI), pruritus visual analog scale (VAS), and Short-Form Health Survey (SF-36) to assess health-related quality of life (HRQOL). Changes from baseline and patients reporting improvements ≥minimum clinically important differences (MCID) were analyzed. Correlations between changes across various PRO instruments were explored.

Results

Baseline DLQI (>10 points) and SF-36 MCS and domain scores indicated impairments in HRQOL. At 16 weeks, greater improvements from baseline in DLQI scores were reported with apremilast 20 (−5.9) and 30 mg BID (−4.4) compared with placebo (1.9; P≤0.005 for both), and a greater proportion of patients reported improvements ≥MCID (20 mg BID, 49.4%, 30 mg BID, 44.3%) versus placebo (25.0%; P<0.04). Greater improvements from baseline in pruritus VAS scores were reported with apremilast 20 (−35.5%) and 30 mg BID (−43.7%) versus placebo (−6.1%; P≤0.005). Significant and clinically meaningful improvements in SF-36 mental component summary scores (P≤0.008) and Bodily Pain, Mental Health, and Role-Emotional domains were reported with all apremilast doses (P<0.05), and Social Functioning with 20 and 30 mg BID (P<0.05) and Physical Functioning with 20 mg BID (P<0.03). Correlations between SF-36 scores and DLQI were moderate (r>0.30 and ≤0.60) and low between SF-36 and pruritus VAS (r≤0.30), indicating they measure different aspects of the disease.

Conclusions

Apremilast treatment resulted in improved HRQOL, including DLQI and pruritus VAS over 16 weeks of treatment, in patients with moderate to severe psoriasis.

Available only for authorised users

Kurd SK, Gelfand JM: The prevalence of previously diagnosed and undiagnosed psoriasis in US adults: results from NHANES 2003–2004. J Am Acad Dermatol 2009, 60: 218–224. 10.1016/j.jaad.2008.09.022PubMedCrossRef

Augustin M, Reich K, Glaeske G, Schaefer I, Radtke M: Co-morbidity and age-related prevalence of psoriasis: analysis of health insurance data in Germany. Acta Derm Venereol 2010, 90: 147–151. 10.2340/00015555-0770PubMedCrossRef

Kimball AB, Jacobson C, Weiss S, Vreeland MG, Wu Y: The psychosocial burden of psoriasis. Am J Clin Dermatol 2005, 6: 383–392. 10.2165/00128071-200506060-00005PubMedCrossRef

Reich A, Hrehorow E, Szepietowski JC: Pruritus is an important factor negatively influencing the well-being of psoriatic patients. Acta Derm Venereol 2010, 90: 257–263.PubMedCrossRef

Meyer N, Paul C, Feneron D, Bardoulat I, Thiriet C, Camara C, Sid-Mohand D, Le Pen C, Ortonne JP: Psoriasis: an epidemiological evaluation of disease burden in 590 patients. J Eur Acad Dermatol Venereol 2010, 24: 1075–1082.PubMed

Kurd SK, Troxel AB, Crits-Christoph P, Gelfand JM: The risk of depression, anxiety, and suicidality in patients with psoriasis: a population-based cohort study. Arch Dermatol 2010, 146: 891–895. 10.1001/archdermatol.2010.186PubMedCentralPubMed

Strand V, Sharp V, Koenig AS, Park G, Shi Y, Wang B, Zack DJ, Fiorentino D: Comparison of health-related quality of life in rheumatoid arthritis, psoriatic arthritis and psoriasis and effects of etanercept treatment. Ann Rheum Dis 2012, 17: 1143–1150.CrossRef

Krueger GG, Langley RG, Finlay AY, Griffiths CE, Woolley JM, Lalla D, Jahreis A: Patient-reported outcomes of psoriasis improvement with etanercept therapy: results of a randomized phase III trial. Br J Dermatol 2005, 153: 1192–1199. 10.1111/j.1365-2133.2005.06948.xPubMedCrossRef

Lebwohl M, Papp K, Han C, Schenkel B, Yeilding N, Wang Y, Krueger GG: Ustekinumab improves health-related quality of life in patients with moderate-to-severe psoriasis: results from the PHOENIX 1 trial. Br J Dermatol 2010, 162: 137–146. 10.1111/j.1365-2133.2009.09491.xPubMedCrossRef

10.

Reich K, Nestle FO, Papp K, Ortonne JP, Evans R, Guzzo C, Li S, Dooley LT, Griffiths CE: Infliximab induction and maintenance therapy for moderate-to-severe psoriasis: a phase III, multicentre, double-blind trial. Lancet 2005, 366: 1367–1374. 10.1016/S0140-6736(05)67566-6PubMedCrossRef

11.

Saurat JH, Guerin A, Yu AP, Latremouille-Viau D, Wu EQ, Gupta SR, Bao Y, Mulani PM: High prevalence of potential drug-drug interactions for psoriasis patients prescribed methotrexate or cyclosporine for psoriasis: associated clinical and economic outcomes in real-world practice. Dermatology 2010, 220: 128–137. 10.1159/000275198PubMedCrossRef

12.

Ravindran V, Scott DL, Choy EH: A systematic review and meta-analysis of efficacy and toxicity of disease modifying anti-rheumatic drugs and biological agents for psoriatic arthritis. Ann Rheum Dis 2008, 67: 855–859. 10.1136/ard.2007.072652PubMedCrossRef

13.

Richards HL, Fortune DG, Griffiths CE: Adherence to treatment in patients with psoriasis. J Eur Acad Dermatol Venereol 2006, 20: 370–379. 10.1111/j.1468-3083.2006.01565.xPubMedCrossRef

14.

Serezani CH, Ballinger MN, Aronoff DM, Peters-Golden M: Cyclic AMP: master regulator of innate immune cell function. Am J Respir Cell Mol Biol 2008, 39: 127–132. 10.1165/rcmb.2008-0091TRPubMedCentralPubMedCrossRef

15.

Tasken K, Aandahl EM: Localized effects of cAMP mediated by distinct routes of protein kinase A. Physiol Rev 2004, 84: 137–167. 10.1152/physrev.00021.2003PubMedCrossRef

16.

Houslay MD, Schafer P, Zhang KY: Keynote review: phosphodiesterase-4 as a therapeutic target. Drug Discov Today 2005, 10: 1503–1519. 10.1016/S1359-6446(05)03622-6PubMedCrossRef

17.

Baumer W, Hoppmann J, Rundfeldt C, Kietzmann M: Highly selective phosphodiesterase 4 inhibitors for the treatment of allergic skin diseases and psoriasis. Inflamm Allergy Drug Targets 2007, 6: 17–26. 10.2174/187152807780077318PubMedCrossRef

18.

Schafer PH, Parton A, Gandhi AK, Capone L, Adams M, Wu L, Bartlett JB, Loveland MA, Gilhar A, Cheung Y-F, Baillie GS, Houslay MD, Man H-W, Muller GW, Stirling DI: Apremilast, a cAMP phosphodiesterase-4 inhibitor, demonstrates anti-inflammatory activity in vitro and in a model of psoriasis. Br J Pharmacol 2010, 159: 842–855. 10.1111/j.1476-5381.2009.00559.xPubMedCentralPubMedCrossRef

19.

Salari P, Abdollahi M: Phosphodiesterase inhibitors in inflammatory bowel disease. Expert Opin Investig Drugs 2012, 21: 261–264. 10.1517/13543784.2012.658915PubMedCrossRef

20.

Papp K, Cather J, Rosoph L, Sofen H, Langley RG, Matheson RT, Hu A, Day RM: The efficacy of apremilast, a phosphodiesterase-4 inhibitor, in the treatment of moderate to severe psoriasis: results of a phase 2 randomised study. Lancet 2012, 380: 738–746. 10.1016/S0140-6736(12)60642-4PubMedCrossRef

21.

Schett G, Wollenhaupt J, Papp K, Joos R, DeVlam KL, Rodrigues JF, Vessey A, Hu CC, Stevens R: Oral apremilast in the treatment of active psoriatic arthritis: results of a multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum 2012, 64: 3156–3167. 10.1002/art.34627PubMedCrossRef

22.

Gottlieb AB, Strober B, Krueger JG, Rohane P, Zeldis JB, Hu CC, Kipnis C: An open-label, single-arm pilot study in patients with severe plaque-type psoriasis treated with an oral anti-inflammatory agent, apremilast. Curr Med Res Opin 2008, 24: 1529–1538. 10.1185/030079908X301866PubMedCrossRef

23.

Basra MK, Fenech R, Gatt RM, Salek MS, Finlay AY: The Dermatology Life Quality Index 1994–2007: a comprehensive review of validation data and clinical results. Br J Dermatol 2008, 159: 997–1035.PubMed

24.

Strand V, Bombardier C, Maetzel A, Scott D, Crawford B: Use of minimum clinically important differences (MCID) in evaluating patient responses to treatment of rheumatoid arthtitis (RA) [abstract 810]. Arthritis Rheum 2001,44(suppl 9):S187.

25.

Strand V, Scott DL, Emery P, Kalden JR, Smolen JS, Cannon GW, Tugwell P, Crawford B: Physical function and health related quality of life: analysis of 2-year data from randomized, controlled studies of leflunomide, sulfasalazine, or methotrexate in patients with active rheumatoid arthritis. J Rheumatol 2005, 32: 590–601.PubMed

26.

Hazes JM, Taylor P, Strand V, Purcaru O, Coteur G, Mease P: Physical function improvements and relief from fatigue and pain are associated with increased productivity at work and at home in rheumatoid arthritis patients treated with certolizumab pegol. Rheumatology (Oxford) 2010, 49: 1900–1910. 10.1093/rheumatology/keq109CrossRef

27.

Tugwell P, Wells G, Strand V, Maetzel A, Bombardier C, Crawford B, Dorrier C, Thompson A: Clinical improvement as reflected in measures of function and health-related quality of life following treatment with leflunomide compared with methotrexate in patients with rheumatoid arthritis: sensitivity and relative efficiency to detect a treatment effect in a twelve-month, placebo-controlled trial. Leflunomide Rheumatoid Arthritis Investigators Group. Arthritis Rheum 2000, 43: 506–514. 10.1002/1529-0131(200003)43:3<506::AID-ANR5>3.0.CO;2-UPubMedCrossRef

28.

Hongbo Y, Thomas CL, Harrison MA, Salek MS, Finlay AY: Translating the science of quality of life into practice: What do dermatology life quality index scores mean? J Invest Dermatol 2005, 125: 659–664. 10.1111/j.0022-202X.2005.23621.xPubMedCrossRef

29.

Strand V, Crawford B, Singh J, Choy E, Smolen JS, Khanna D: Use of “spydergrams” to present and interpret SF-36 health-related quality of life data across rheumatic diseases. Ann Rheum Dis 2009, 68: 1800–1804. 10.1136/ard.2009.115550PubMedCentralPubMedCrossRef

30.

Ara R, Brazier J: Deriving an algorithm to convert the eight mean SF-36 dimension scores into a mean EQ-5D preference-based score from published studies (where patient level data are not available). Value Health 2008, 11: 1131–1143. 10.1111/j.1524-4733.2008.00352.xPubMedCrossRef

31.

Ara R, Brazier J: Predicting the short form-6D preference-based index using the eight mean short form-36 health dimension scores: estimating preference-based health-related utilities when patient level data are not available. Value Health 2009, 12: 346–353. 10.1111/j.1524-4733.2008.00428.xPubMedCrossRef

32.

Ware J, Kosinski M, Dewey JE: How to Score Version 2 of the SF-36 Health Survey. Lincoln, RI: QualityMetric Inc.; 2000.

33.

Cohen J: Statistical Power Analysis for the Behavioral Sciences. 2nd edition. Hillsdale, NJ: Lawrence Erlbaum Associates, Inc.; 1988.

34.

National Psoriasis Foundation: Report on the Psycho-Social Impacts of Psoriasis. [http://www.psoriasis.org/Document.DOC?id=619]

35.

Devrimci-Ozguven H, Kundakci TN, Kumbasar H, Boyvat A: The depression, anxiety, life satisfaction and affective expression levels in psoriasis patients. J Eur Acad Dermatol Venereol 2000, 14: 267–271. 10.1046/j.1468-3083.2000.00085.xPubMedCrossRef

36.

Kimball AB, Gladman D, Gelfand JM, Gordon K, Horn EJ, Korman NJ, Korver G, Krueger GG, Strober BE, Lebwohl MG: National Psoriasis Foundation clinical consensus on psoriasis comorbidities and recommendations for screening. J Am Acad Dermatol 2008, 58: 1031–1042. 10.1016/j.jaad.2008.01.006PubMedCentralPubMedCrossRef

37.

Kimball AB, Bensimon AG, Guerin A, Yu AP, Wu EQ, Okun MM, Bao Y, Gupta SR, Mulani PM: Efficacy and safety of adalimumab among patients with moderate to severe psoriasis with co-morbidities: Subanalysis of results from a randomized, double-blind, placebo-controlled, phase III trial. Am J Clin Dermatol 2011, 12: 51–62. 10.2165/11530640-000000000-00000PubMedCrossRef

38.

Flytstrom I, Stenberg B, Svensson A, Bergbrant IM: Methotrexate vs. ciclosporin in psoriasis: effectiveness, quality of life and safety. A randomized controlled trial. Br J Dermatol 2008, 158: 116–121.PubMed

39.

Reich K: Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate to severe psoriasis: 16-week results of a phase 3, randomized, controlled trial (ESTEEM 1) [oral presentation]. Miami, FL: Presented at: the 71st Annual Meeting of the American Academy of Dermatology; 2013.

Title: Improvements in patient-reported outcomes with apremilast, an oral phosphodiesterase 4 inhibitor, in the treatment of moderate to severe psoriasis: results from a phase IIb randomized, controlled study
Authors: Vibeke Strand
David Fiorentino
ChiaChi Hu
Robert M Day
Randall M Stevens
Kim A Papp
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: Health and Quality of Life Outcomes / Issue 1/2013
Electronic ISSN: 1477-7525
DOI: https://doi.org/10.1186/1477-7525-11-82

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Improvements in patient-reported outcomes with apremilast, an oral phosphodiesterase 4 inhibitor, in the treatment of moderate to severe psoriasis: results from a phase IIb randomized, controlled study

Abstract

Background

Objectives

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Objectives

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2013

Promising insights into the health related quality of life for children with severe obesity

Development of the Adult PedsQL™ Neurofibromatosis Type 1 Module: Initial Feasibility, Reliability and Validity

Cross-cultural adaptation and psychometric properties of the Brazilian version of the scale of oral health outcomes for 5-year-old children (SOHO-5)

Health-related quality of life and survival in Chinese patients with chronic liver disease

Cross-cultural French adaptation and validation of the Impact On Family Scale (IOFS)

Development and validation of the living with pulmonary hypertension questionnaire in pulmonary arterial hypertension patients