Importance
Therapies that reduce psoriasis symptoms may improve work productivity.
Objective
To assess the effect of ixekizumab therapy on work productivity, measured by the Work Productivity and Activity Impairment–Psoriasis (WPAI-PSO).
Design, Setting, and Participants
Three multicenter, randomized double-blind phase 3 trials conducted during the following periods: December 2011 through August 2014 (UNCOVER-1), May 2012 through April 2015 (UNCOVER-2), and August 2012 through July 2014 (UNCOVER-3). Adult outpatients with moderate-to-severe chronic plaque psoriasis were included.
Interventions
In UNCOVER-1, patients were randomized 1:1:1 to subcutaneous placebo or 80 mg ixekizumab every 2 weeks (Q2W) or every 4 weeks (Q4W) for 12 weeks; UNCOVER-2 and UNCOVER-3 also had an etanercept arm (50 mg twice weekly). Maintenance of initial ixekizumab response was evaluated in UNCOVER-1 and UNCOVER-2 during a randomized withdrawal period following week 12 through week 60. The WPAI-PSO questionnaire was administered at baseline and week 12 for all patients and at weeks 24, 36, 52, and 60 for patients in UNCOVER-1 and UNCOVER-2.
Main Outcomes and Measures
Change in work productivity from baseline as measured by WPAI-PSO scores.
Results
Across trials, 5101 patients consented; 3866 were randomized (mean [SD] age, UNCOVER-1, 45.7 [12.9] y, 68.1% male; UNCOVER-2: 45.0 [13.0] y, 67.1% male; UNCOVER-3: 45.8 [13.1] y, 68.2% male). At week 12 in UNCOVER-1, the ixekizumab Q4W and ixekizumab Q2W groups showed significantly greater improvements in WPAI-PSO scores (least squares mean change from baseline [SE]) relative to placebo: absenteeism (–3.5 [0.87], P < .001; –2.6 [0.84], P = .003, respectively, vs 0.2 [0.88]), presenteeism (–18.8 [1.28], P < .001; –18.3 [1.24], P < .001, vs 0.5 [1.30]), work productivity loss (–20.6 [1.38], P < .001; –19.8 [1.33], P < .001, vs –0.8 [1.40]), and activity impairment (–24.5 [1.18], P < .001; –25.2 [1.15], P < .001, vs 0.8 [1.18]). Similar results were obtained for UNCOVER-2 and UNCOVER-3, with the exception of absenteeism with ixekizumab Q4W in UNCOVER-2. Additionally, ixekizumab-treated patients showed significantly greater improvements in WPAI-PSO scores vs etanercept-treated patients: UNCOVER-2: presenteeism, work productivity loss, activity impairment (P < .001 both doses), UNCOVER-3: activity impairment (ie, regular activities outside of work) (ixekizumab Q2W; P = .009). Improvements in WPAI-PSO scores at week 12 were sustained to at least week 60.
Conclusions and Relevance
Ixekizumab-treated patients reported short- and long-term improvements in work productivity, which could lead to reduced productivity-related cost burden in patients with psoriasis.
Trial Registration
clinicaltrials.gov Identifiers: NCT01474512, NCT01597245, NCT01646177
Psoriasis is a systemic, long-term inflammatory condition primarily affecting the skin, nails, and joints. It is associated with substantial comorbidities and can be both disfiguring and disabling.1-6 In addition to causing physical discomfort, the symptoms of psoriasis affect work-related activities, social relationships, and mental health, leading to poor quality of life in people with psoriasis.7-11 Because of the complexity of the condition, treatment of patients with moderate-to-severe psoriasis involves assessment and management of both skin symptoms and health-related quality of life.2,12
Work-related activities (paid and unpaid) are an important component of patient well-being; however, the effect of dermatologic conditions on work-related activities is rarely assessed. Global psoriasis prevalence peaks in ages ranging from 20 to 60 years, during adults’ working years.13 Missed time from work or reduced productivity at work can have substantial economic ramifications for the patient, family, employer, and society. Psoriasis symptoms can limit the type of work that an individual performs at a job and can also affect activities of daily living. Patients with psoriasis report missed work and reduced productivity while at work due to their skin condition.9,14-23 In addition to the cost of treatment, there are costs associated with loss of productivity and wages.16-18,21,24-26
Impairment of paid and unpaid work activities can be quantitated by the Work Productivity and Activity Impairment (WPAI) instrument.27 The validated, self-reported WPAI instrument can be used to measure work-related impairment due to general health, a specific health problem, or specific to a particular condition. In the 3 randomized clinical trials reported in this analysis, WPAI-Psoriasis (WPAI-PSO) scores were assessed.
Ixekizumab is an anti–interleukin 17A IgG4 monoclonal antibody with high binding affinity to the soluble cytokine interleukin 17A.28,29 Interleukin 17A is recognized as a key cytokine in the development and persistence of psoriasis.30 Ixekizumab has been studied in 3 multinational, placebo-controlled, randomized, double-blind clinical trials (UNCOVER-1, UNCOVER-2, UNCOVER-3).31,32 Coprimary objectives were to assess superiority of ixekizumab to placebo (UNCOVER-1) or placebo and etanercept (UNCOVER-2, UNCOVER-3) in treatment of moderate-to-severe psoriasis, as measured at week 12 by (1) a static Physician’s Global Assessment (sPGA) score of clear or minimal (0 or 1) and (2) a Psoriasis Area and Severity Index (PASI) reduction of at least 75% (PASI 75).31,32 Secondary objectives of UNCOVER-1, UNCOVER-2, and UNCOVER-3 included assessing changes from baseline in several patient-reported outcomes. Herein we report the effect of ixekizumab therapy on work productivity in UNCOVER-1, UNCOVER-2, and UNCOVER-3 as measured by the WPAI-PSO questionnaire.
Box Section Ref IDKey Points
Question Do patient Work Productivity and Activity Impairment–Psoriasis (WPAI-PSO) levels improve with ixekizumab treatment, compared with etanercept and placebo over 12 weeks, and are improvements with ixekizumab sustained through 60 weeks?
Findings Across 3 phase 3 clinical trials, ixekizumab treatment resulted in significantly improved WPAI-PSO outcomes compared with placebo and etanercept. At week 60, ixekizumab responders who continued ixekizumab treatment sustained their week-12 improvements and reported significantly better WPAI-PSO outcomes than ixekizumab responders switched to placebo.
Meaning Treatment with ixekizumab sustainably reduces the negative effect of psoriasis on patients’ work productivity and engagement in activities outside work.
Eligibility criteria for UNCOVER-1 (NCT01474512), UNCOVER-2 (NCT01597245), and UNCOVER-3 (NCT01646177) included age at least 18 years with a confirmed diagnosis of chronic plaque psoriasis at least 6 months prior to randomization, at least 10% body surface area involvement at screening and baseline visits, an sPGA score at least 3 and PASI score at least 12 at screening and baseline visits, and candidacy for phototherapy and/or systemic therapy.31,32 Protocols and consent forms were approved by an investigational review board at each site. All patients signed an informed consent form before initiation of study procedures. Additional details on inclusion and exclusion criteria, study sites, and investigators are described elsewhere.31,32
Study Design and Treatment
UNCOVER-1, UNCOVER-2, and UNCOVER-3 are multicenter, randomized, double-blind, placebo-controlled, parallel-group phase 3 studies. UNCOVER-2 and UNCOVER-3 had an active comparator (etanercept). Details of these studies including blinding have been presented elsewhere.31,32
During the UNCOVER-1 induction period, patients were randomized 1:1:1 to receive ixekizumab 80 mg every 2 weeks (Q2W), ixekizumab 80 mg every 4 weeks (Q4W) (each with a starting dose of 160 mg), or placebo.32 Double-blind investigational product was assigned to each patient by a computer-generated random sequence using an interactive voice response system. The 12-week induction period was followed by a randomized withdrawal period (weeks 12-60). At week 12, ixekizumab responders (sPGA score of 0 or 1) were rerandomized 1:1:1 to ixekizumab 80 mg Q4W or ixekizumab 80 mg every 12 weeks or placebo.
During the UNCOVER-2 and UNCOVER-3 induction periods, patients were randomized 2:2:2:1 to receive ixekizumab 80 mg Q2W, ixekizumab 80 mg Q4W (each with a 160-mg starting dose), etanercept 50 mg twice weekly, or placebo.31 The 12-week induction period of UNCOVER-2 was followed by a randomized withdrawal period identical to UNCOVER-1, and the maintenance data from the placebo arm and the ixekizumab 80-mg Q4W arm of these 2 trials were used for this analysis. UNCOVER-3 did not have a randomized withdrawal phase, but an open-label follow-up after the 12-week induction phase and data from its follow-up period were not included in this analysis.
Measurement of change from baseline of WPAI-PSO scores in ixekizumab-treated patients relative to comparator was a prespecified secondary end point in all 3 studies. The WPAI-PSO questionnaire consists of 6 questions that assess current employment status (yes/no), psoriasis-related missed time from work (hours), missed time from work for other reasons (hours), time actually worked (hours), effect of psoriasis on work while working (0-10 point scale), and impact of psoriasis on daily activities (0-10 point scale) in the 7 days prior to completing the questionnaire.27,33 From these questions, 4 scores capturing the impact on productivity due to patients’ psoriasis are derived: percent absenteeism (work time missed), percent presenteeism (impairment at work/reduced on-the-job effectiveness), percent work productivity loss (overall work impairment associated with absenteeism and presenteeism), and percent activity impairment (activities performed outside of work). Higher scores indicate greater impairment. For example, a patient with scores of 4, 23, 24, and 31 in absenteeism, presenteeism, work productivity loss, and activity impairment, respectively, has reported 4% work time missed, 23% impairment while working, 24% overall work impairment, and 31% activity impairment due to psoriasis. Patients provided employment status data (eg, employed vs unemployed, part vs full time) at baseline via an investigator’s case report form, so the unemployment rate due to psoriasis was from a predefined question and was patient reported.
The WPAI-PSO questionnaire was administered at baseline and week 12 for all patients in all studies and at weeks 24, 36, 52, and 60 for patients in UNCOVER-1 and UNCOVER-2. Only patients working for pay were included in analyses of absenteeism, presenteeism, and overall work impairment. Any patient could answer the overall activity impairment question. In all studies, treatment group comparisons of mean score change from baseline were analyzed using an analysis of covariance (ANCOVA) model after imputing the missing values using the last observation carried forward (LOCF) method.
Between December 6, 2011, and April 25, 2013, 1296 patients were randomized in UNCOVER-1; between May 30, 2012, and December 30, 2013, 1224 patients were randomized in UNCOVER-2; and between August 11, 2012, and February 27, 2014, 1346 patients were randomized in UNCOVER-3 (eFigures 1-3 in the Supplement). The follow-up dates were August 7, 2014, for UNCOVER-1; April 15, 2015, for UNCOVER-2; and July 14, 2014, for UNCOVER-3. The intent-to-treat population comprised 3866 patients across all 3 studies (Table 1 and eFigures 1-3 in the Supplement). Table 1 presents baseline demographic characteristics, and Table 2 provides baseline WPAI-PSO scores. The patient-reported full-time employment (working for pay) rate ranged from 54.3% to 68.2% and the part-time employment rate ranged from 8.3% to 14.6%. The patient-reported unemployment rate due to psoriasis ranged from 0.8% to 6.1%. As reported previously,31 ixekizumab therapy demonstrated efficacy superior to placebo and etanercept as measured by the proportion of patients achieving an sPGA score of 0 or 1 (sPGA 0,1) and at least a 75% improvement in the PASI (PASI-75) at week 12 (eTable 1 in the Supplement). Ixekizumab therapy also demonstrated efficacy superior to that of placebo in those patients treated with ixekizumab during the first 12 weeks who were rerandomized to ixekizumab treatment in the maintenance phase, as measured by the proportion of patients achieving sPGA 0,1 and PASI-75 responses at week 60 (eTable 1 in the Supplement).
WPAI-PSO Scores From Baseline to Week 12
At week 12 in UNCOVER-1, patients treated with ixekizumab 80 mg Q4W and ixekizumab 80 mg Q2W showed significantly greater improvement compared with placebo in all WPAI-PSO scores (absenteeism, P < .001 and P = .003, respectively; presenteeism, P < .001 for both doses; work productivity loss, P < .001 for both doses; and activity impairment, P < .001 for both doses) (eTable 2 in the Supplement, Figure 1, and eFigures 4-6 in the Supplement).
At week 12 in UNCOVER-2, patients treated with ixekizumab 80 mg Q4W and ixekizumab 80 mg Q2W showed significantly greater improvement compared with both placebo and etanercept in presenteeism, work productivity loss, and activity impairment scores (P < .001 for all comparisons in all scores) (eTable 2 in the Supplement, Figure 1, and eFigures 4-6 in the Supplement). In addition, patients treated with ixekizumab 80 mg Q2W showed significantly greater improvement compared with placebo in the absenteeism score (P = .02).
In UNCOVER-3, by week 12, improvements in productivity impairment in the ixekizumab 80 mg Q4W and ixekizumab 80 mg Q2W groups were statistically significant compared with placebo in all WPAI-PSO scores (absenteeism, P = .045 and P = .01, respectively; presenteeism, P < .001 for both doses; work productivity loss, P < .001 for both doses; and activity impairment, P < .001 for both doses) (eTable 2 in the Supplement, Figure 1, and eFigures 4-6 in the Supplement). In addition, patients treated with ixekizumab 80 mg Q2W showed significantly greater improvement in activity impairment scores compared with those treated with etanercept (P = .009); the differences between the ixekizumab Q4W group vs etanercept were numerically greater but not statistically significant (−23.3 vs −21.1; P = .08).
WPAI-PSO Scores to Week 60
eTable 2 in the Supplement and Figures 2 and 3 show WPAI-PSO response of ixekizumab/ixekizumab 80 mg Q4W vs ixekizumab/placebo during the maintenance phase to week 60 for patients who reached the status of sPGA-defined responders at week 12. The WPAI-PSO scores for patients treated with ixekizumab 80 mg Q4W in the maintenance phase showed improvement from baseline to week 24 in both studies. The improvement in each of the 4 WPAI-PSO scores was maintained from weeks 24 to 60 in both studies. In contrast, the responders at week 12 who were treated with placebo in the maintenance phase showed worsening of the 4 WPAI-PSO scores after week 24 in both studies.
In UNCOVER 1, there were significantly greater improvements from baseline with ixekizumab/ixekizumab Q4W vs ixekizumab/placebo at week 60, as well as at weeks 24, 36, and 52 for presenteeism, work productivity loss, and activity impairment scores; however, significant improvement with ixekizumab/ixekizumab Q4W vs ixekizumab/placebo was only achieved at week 52 for absenteeism (Figure 2).
In UNCOVER-2, the ixekizumab/ixekizumab Q4W group experienced significantly greater improvements from baseline than the ixekizumab/placebo group in presenteeism and activity impairment at all measured time points except presenteeism at week 24, and work productivity loss score at weeks 52 and 60 (Figure 3). However, there were no statistically significant differences at any time point for absenteeism.
Impairment in work productivity is an important patient-centered issue.9,16-25 However, it is rarely studied in dermatology using validated outcome measures. In a study by the National Psoriasis Foundation with surveys taken from 2003 through 2009 and 2011, 12% of respondents with psoriasis were unemployed and, of these, 92% cited psoriasis and/or psoriatic arthritis as the only reason for unemployment; among working respondents, 49% missed work because of psoriasis.22 Other studies performed across several countries using various methodologies have reported that patients with psoriasis lose between 1.4 and 49 work days annually and many patients with psoriasis (11%-65%) report reduced productivity at work.9,14-21 Some patients with psoriasis have reported early retirement solely due to their condition34 or can only work part-time. In addition, psoriasis can interfere with nonpaid work activities such as household and yard chores, shopping, exercise, and recreational activities. Missed time from work and reduced productivity while at work is associated with considerable economic consequences for the patient and his/her family, employers, and society.35 A recent systematic review estimated the annual indirect economic burden of psoriasis in the United States to be $23.9 to $35.4 billion (2013 US dollars) from productivity losses due to absenteeism and presenteeism.36
This study uses validated outcome measures for work activity and examined how novel therapies affect work activities in a systematic and controlled fashion. Specifically, this study comprehensively reports the effects of ixekizumab treatment on work-related activities using the WPAI-PSO questionnaire. This was a prespecified secondary analysis of 3 international, multicenter, placebo-controlled, randomized, double-blind, phase 3 trials involving more than 3800 patients, of which approximately 2300 patients were ixekizumab treated.31,32 Two of the trials used etanercept treatment as an active-control arm.31
During the first 12 weeks of treatment, patients with psoriasis treated with ixekizumab 80 mg Q2W and ixekizumab 80 mg QW4 experienced an overall increase in work productivity and improvement in their abilities to perform daily activities relative to placebo-treated patients. The ixekizumab 80 mg Q2W group was significantly better in reducing activity impairment vs etanercept in both active comparator studies. In UNCOVER-2, ixekizumab-treated patients also experienced improved presenteeism and work productivity loss scores relative to etanercept-treated patients. A post hoc analysis was performed to evaluate the relationship between WPAI-PSO and clinical score (ie, PASI) improvements by examining the differences in WPAI-PSO score improvements observed in various PASI score improvement groups. Greater WPAI score improvements were seen in those with greater PASI score improvement (eFigure 7 in the Supplement). For example, patients with PASI score improvements of greater than 50% consistently had significantly greater WPAI-PSO score improvements than those with PASI score improvements of less than 50%.
This study also showed that continued treatment with ixekizumab 80 mg Q4W in responders (ixekizumab/ixekizumab Q4W group) led to sustained improvement in WPAI-PSO scores through week 60. In contrast, UNCOVER-1 and UNCOVER-2 responders who were withdrawn from ixekizumab therapy at week 12 (ixekizumab/placebo group) had numerical deterioration in their WPAI-PSO scores. In addition, those withdrawn from treatment in UNCOVER-1 experienced significant deterioration in their absenteeism WPAI-PSO scores (within treatment group change from baseline comparisons). The worsening of WPAI-PSO scores in patients who were switched to placebo in the maintenance period suggests the importance of continuing therapy.
To estimate the impact on indirect costs, we can consider the example of reduction in work productivity loss seen in the ixekizumab 80 mg Q2W UNCOVER-2 group of 17.5 percentage points relative to placebo at week 12. If we assume that the effect is maintained for 1 year multiplied by the mean US yearly salary in 2014 of $47 230,37 the savings in indirect costs is $8265 per patient per year. The indirect cost savings relative to etanercept is $2739 (5.8% × $47 230) per patient per year.
The strengths of this study include the randomized, double-blind trial design, the use of rerandomization followed by a maintenance period to study sustained treatment effects, and the large number of patients who were exposed to ixekizumab therapy. As with any clinical study, the generalizability of results in broader populations of adults with moderate-to-severe plaque psoriasis is limited. The maintenance data analyses were limited to those patients who were initial (ie, week 12) responders and therefore were more likely to experience greater long-term WPAI-PSO score improvements relative to placebo than those who were not initial responders. Finally, the psychometric properties of the WPAI-PSO questionnaire have not been published in the moderate-to-severe psoriasis population.
Ixekizumab-treated patients reported less impairment in work productivity than placebo-treated patients; and with some scores, less impairment than etanercept-treated patients, as measured by the WPAI-PSO, and this improvement was sustained to at least 60 weeks. The positive effects of ixekizumab treatment on WPAI-PSO scores that are reported here are consistent with other biologic agents.38-42 Although not directly tested here, it is expected that less impairment in work productivity would be associated with a reduction in the productivity-related cost burden to the patient, the patient’s family, and to society.
Accepted for Publication: January 30, 2016.
Corresponding Author: April W. Armstrong, MD, MPH, Keck School of Medicine at USC, Dermatology, University of Southern California, KAM 510, Office of the Dean, 1975 Zonal Ave, Los Angeles, CA 90089 (aprilarmstrong@post.harvard.edu).
Published Online: March 7, 2016. doi:10.1001/jamadermatol.2016.0269.
Author Contributions: Dr Armstrong and Ms Edson-Heredia had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Armstrong, Ståhle, Edson-Heredia, Zhu.
Acquisition, analysis, or interpretation of data: Armstrong, Lynde, McBride, Edson-Heredia, Zhu, Amato, Nikaï, Yang, Gordon.
Drafting of the manuscript: Armstrong, Lynde, Zhu, Amato, Nikaï, Gordon.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Armstrong, Zhu, Yang.
Obtained funding: Armstrong.
Administrative, technical, or material support: Armstrong, Amato.
Study supervision: Armstrong, Lynde.
Conflict of Interest Disclosures: Dr Armstrong has been a consultant for and received honoraria from Abbvie, Amgen, Janssen, Merck, Eli Lilly and Company, Novartis, and Pfizer and has received grant support from Abbvie, Janssen, and Eli Lilly and Company. Dr Lynde has been an investigator in clinical trials sponsored by Abbvie, Amgen, Boehringer Ingelheim, Celgene, Coherus, Dermira, Galderma, Innovaderm, Janssen, Eli Lilly and Company, Leo Pharma, Merck, MSD, Medimmune, Novartis, Pfizer, Regeneron, Takeda, and Xoma and has acted as a paid advisor or speaker or received travel support from Abbvie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly and Company, Janssen, Leo Pharma, Merck Serono, MSD, Novartis, Pfizer, Sandoz, and Valeant. Dr McBride has served as a consultant to Abbvie, Janssen, and Pfizer and has received speaker’s fees from Abbvie, Janssen, and Amgen, and grants from Abbvie. Dr Ståhle has received honoraria from AbbVie, Novartis, Eli Lilly and Company, Pfizer, Janssen, and Amgen and has received grant support from Pfizer, Abbvie, and Janssen. Ms Edson-Heredia, Drs Zhu and Amato, Ms Nikaï, and Dr Yang are employees and stockholders of Eli Lilly and Company. Dr Gordon has served as a consultant for and received honoraria from Abbvie, Amgen, Celgene, Eli Lilly and Company, Janssen, Pfizer, and Novartis and has received grant support from Abbvie, Amgen, Celgene, Eli Lilly and Company, Janssen, and Merck. No other disclosures are reported.
Funding/Support: This study was supported by Eli Lilly and Company.
Role of the Funder/Sponsor: Eli Lilly and Company participated in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Previous Presentation: This study was presented at the American Academy of Dermatology annual meeting; March 7, 2016; Washington, DC. The WPAI-PSO results at week 12 for the UNCOVER-1 study only were presented as a poster at the 2015 European Academy of Dermatology and Venereology annual congress; October 7-11, 2015; Copenhagen, Denmark.
Additional Contributions: We are indebted to the patients and study personnel who participated in UNCOVER-1, UNCOVER-2, and UNCOVER-3. We are also indebted to Lori Kornberg, PhD, and Rosemary Procko, BA, both of INC Research, Raleigh, North Carolina, who provided writing and editorial support, respectively, on behalf of Eli Lilly and Company. We also thank Grace Song, MS, of MacroStat, Shanghai, China, who assisted with the data analysis. They were not compensated beyond their salary for their contribution to the study.
1.Edson-Heredia
E, Zhu
B, Lefevre
C,
et al. Prevalence and incidence rates of cardiovascular, autoimmune, and other diseases in patients with psoriatic or psoriatic arthritis: a retrospective study using Clinical Practice Research Datalink.
J Eur Acad Dermatol Venereol. 2015;29(5):955-963.
PubMedGoogle ScholarCrossref 2.Menter
A, Gottlieb
A, Feldman
SR,
et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 1. overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics.
J Am Acad Dermatol. 2008;58(5):826-850.
PubMedGoogle ScholarCrossref 3.Sommer
DM, Jenisch
S, Suchan
M, Christophers
E, Weichenthal
M. Increased prevalence of the metabolic syndrome in patients with moderate to severe psoriasis.
Arch Dermatol Res. 2006;298(7):321-328.
PubMedGoogle ScholarCrossref 4.Wu
JJ, Choi
YM, Bebchuk
JD. Risk of myocardial infarction in psoriasis patients: a retrospective cohort study.
J Dermatolog Treat. 2015;26(3):230-234.
PubMedGoogle ScholarCrossref 5.Wu
JJ, Nguyen
TU, Poon
KY, Herrinton
LJ. The association of psoriasis with autoimmune diseases.
J Am Acad Dermatol. 2012;67(5):924-930.
PubMedGoogle ScholarCrossref 6.Armstrong
AW, Schupp
C, Bebo
B. Psoriasis comorbidities: results from the National Psoriasis Foundation surveys 2003 to 2011.
Dermatology. 2012;225(2):121-126.
PubMedGoogle ScholarCrossref 7.Fried
RG, Friedman
S, Paradis
C,
et al. Trivial or terrible? the psychosocial impact of psoriasis.
Int J Dermatol. 1995;34(2):101-105.
PubMedGoogle ScholarCrossref 8.Kimball
AB, Jacobson
C, Weiss
S, Vreeland
MG, Wu
Y. The psychosocial burden of psoriasis.
Am J Clin Dermatol. 2005;6(6):383-392.
PubMedGoogle ScholarCrossref 9.Lewis-Beck
C, Abouzaid
S, Xie
L, Baser
O, Kim
E. Analysis of the relationship between psoriasis symptom severity and quality of life, work productivity, and activity impairment among patients with moderate-to-severe psoriasis using structural equation modeling.
Patient Prefer Adherence. 2013;7:199-205.
PubMedGoogle Scholar 10.Rapp
SR, Feldman
SR, Exum
ML, Fleischer
AB
Jr, Reboussin
DM. Psoriasis causes as much disability as other major medical diseases.
J Am Acad Dermatol. 1999;41(3, pt 1):401-407.
PubMedGoogle ScholarCrossref 11.Sampogna
F, Tabolli
S, Abeni
D; IDI Multipurpose Psoriasis Research on Vital Experiences (IMPROVE) investigators. Living with psoriasis: prevalence of shame, anger, worry, and problems in daily activities and social life.
Acta Derm Venereol. 2012;92(3):299-303.
PubMedGoogle ScholarCrossref 13.Parisi
R, Symmons
DP, Griffiths
CE, Ashcroft
DM; Identification and Management of Psoriasis and Associated Comorbidity (IMPACT) project team. Global epidemiology of psoriasis: a systematic review of incidence and prevalence.
J Invest Dermatol. 2013;133(2):377-385.
PubMedGoogle ScholarCrossref 14.Allen
H, Bunn
WB
III, Naim
AB. The self-reported health and productivity burden of autoimmune disorders at a major self-insured employer.
J Occup Environ Med. 2012;54(9):1049-1063.
PubMedGoogle ScholarCrossref 15.Augustin
M, Glaeske
G, Schäfer
I, Rustenbach
SJ, Hoer
A, Radtke
MA. Processes of psoriasis health care in Germany—long-term analysis of data from the statutory health insurances.
J Dtsch Dermatol Ges. 2012;10(9):648-655.
PubMedGoogle Scholar 16.Berger
K, Ehlken
B, Kugland
B, Augustin
M. Cost-of-illness in patients with moderate and severe chronic psoriasis vulgaris in Germany.
J Dtsch Dermatol Ges. 2005;3(7):511-518.
PubMedGoogle ScholarCrossref 17.Carrascosa
JM, Pujol
R, Daudén
E,
et al. A prospective evaluation of the cost of psoriasis in Spain (EPIDERMA project: phase II).
J Eur Acad Dermatol Venereol. 2006;20(7):840-845.
PubMedGoogle Scholar 18.Chan
B, Hales
B, Shear
N,
et al. Work-related lost productivity and its economic impact on Canadian patients with moderate to severe psoriasis.
J Cutan Med Surg. 2009;13(4):192-197.
PubMedGoogle ScholarCrossref 19.Langenbruch
AK, Radtke
MA, Augustin
M. Quality of psoriasis care from the patients’ perspective—results of the national health care study PsoReal.
Eur J Dermatol. 2012;22(4):518-524.
PubMedGoogle Scholar 20.Meyer
N, Paul
C, Feneron
D,
et al. Psoriasis: an epidemiological evaluation of disease burden in 590 patients.
J Eur Acad Dermatol Venereol. 2010;24(9):1075-1082.
PubMedGoogle Scholar 21.Schöffski
O, Augustin
M, Prinz
J,
et al. Costs and quality of life in patients with moderate to severe plaque-type psoriasis in Germany: a multi-center study.
J Dtsch Dermatol Ges. 2007;5(3):209-218.
PubMedGoogle ScholarCrossref 22.Armstrong
AW, Schupp
C, Wu
J, Bebo
B. Quality of life and work productivity impairment among psoriasis patients: findings from the National Psoriasis Foundation survey data 2003-2011.
PLoS One. 2012;7(12):e52935.
PubMedGoogle ScholarCrossref 23.Pearce
DJ, Singh
S, Balkrishnan
R, Kulkarni
A, Fleischer
AB, Feldman
SR. The negative impact of psoriasis on the workplace.
J Dermatolog Treat. 2006;17(1):24-28.
PubMedGoogle ScholarCrossref 24.Fowler
JF, Duh
MS, Rovba
L,
et al. The impact of psoriasis on health care costs and patient work loss.
J Am Acad Dermatol. 2008;59(5):772-780.
PubMedGoogle ScholarCrossref 25.Levy
AR, Davie
AM, Brazier
NC,
et al. Economic burden of moderate to severe plaque psoriasis in Canada.
Int J Dermatol. 2012;51(12):1432-1440.
PubMedGoogle ScholarCrossref 26.Schmitt
JM, Ford
DE. Work limitations and productivity loss are associated with health-related quality of life but not with clinical severity in patients with psoriasis.
Dermatology. 2006;213(2):102-110.
PubMedGoogle ScholarCrossref 27.Reilly
MC, Zbrozek
AS, Dukes
EM. The validity and reproducibility of a work productivity and activity impairment instrument.
Pharmacoeconomics. 1993;4(5):353-365.
PubMedGoogle ScholarCrossref 28.Genovese
MC, Van den Bosch
F, Roberson
SA,
et al. LY2439821, a humanized anti-interleukin-17 monoclonal antibody, in the treatment of patients with rheumatoid arthritis: a phase I randomized, double-blind, placebo-controlled, proof-of-concept study.
Arthritis Rheum. 2010;62(4):929-939.
PubMedGoogle ScholarCrossref 29.Leonardi
C, Matheson
R, Zachariae
C,
et al. Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis.
N Engl J Med. 2012;366(13):1190-1199.
PubMedGoogle ScholarCrossref 31.Griffiths
CE, Reich
K, Lebwohl
M,
et al; UNCOVER-2 and UNCOVER-3 investigators. Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials.
Lancet. 2015;386(9993):541-551.
PubMedGoogle ScholarCrossref 34.Mattila
K, Leino
M, Mustonen
A, Koulu
L, Tuominen
R. Influence of psoriasis on work.
Eur J Dermatol. 2013;23(2):208-211.
PubMedGoogle Scholar 35.Jacobs
P, Bissonnette
R, Guenther
LC. Socioeconomic burden of immune-mediated inflammatory diseases—focusing on work productivity and disability.
J Rheumatol Suppl. 2011;88:55-61.
PubMedGoogle ScholarCrossref 36.Brezinski
EA, Dhillon
JS, Armstrong
AW. Economic burden of psoriasis in the United States: a systematic review.
JAMA Dermatol. 2015;151(6):651-658.
PubMedGoogle ScholarCrossref 38.Kimball
AB, Yu
AP, Signorovitch
J,
et al. The effects of adalimumab treatment and psoriasis severity on self-reported work productivity and activity impairment for patients with moderate to severe psoriasis.
J Am Acad Dermatol. 2012;66(2):e67-e76.
PubMedGoogle ScholarCrossref 39.Papp
KA, Signorovitch
J, Ramakrishnan
K,
et al. Effects of adalimumab versus placebo on risk of symptom worsening in psoriasis and subsequent impacts on health-related quality-of-life: analysis of pooled data from two randomized, double-blind, placebo-controlled, multicentre clinical trials.
Clin Drug Investig. 2011;31(1):51-60.
PubMedGoogle ScholarCrossref 40.Reich
K, Schenkel
B, Zhao
N,
et al. Ustekinumab decreases work limitations, improves work productivity, and reduces work days missed in patients with moderate-to-severe psoriasis: results from PHOENIX 2.
J Dermatolog Treat. 2011;22(6):337-347.
PubMedGoogle ScholarCrossref 41.Revicki
DA, Willian
MK, Menter
A,
et al. Impact of adalimumab treatment on patient-reported outcomes: results from a ehase III clinical trial in patients with moderate to severe plaque psoriasis.
J Dermatolog Treat. 2007;18(6):341-350.
PubMedGoogle ScholarCrossref 42.Vender
R, Lynde
C, Ho
V, Chau
D, Poulin-Costello
M. Work productivity and healthcare resource utilization outcomes for patients on etanercept for moderate-to-severe plaque psoriasis: results from a 1-year, multicentre, open-label, single-arm study in a clinical setting.
Appl Health Econ Health Policy. 2012;10(5):343-353.
PubMedGoogle ScholarCrossref