The effects of adalimumab treatment and psoriasis severity on self-reported work productivity and activity impairment for patients with moderate to severe psoriasis

The effects of adalimumab treatment and psoriasis severity on self-reported work productivity and activity impairment for patients with moderate to severe psoriasis Alexa Boer Kimball, MD, MPH,a Andrew P. Yu, PhD,b James Signorovitch, PhD,b Jipan Xie, MD, PhD,b Magda Tsaneva, BA,b Shiraz R. Gupta, PharmD, MPH,c Yanjun Bao, PhD,c and Parvez M. Mulani, PhDc Boston, Massachusetts, and Abbott Park, Illinois Background: Psoriasis significantly impairs work productivity and daily activities. Objectives: We sought to examine the effects of adalimumab on psoriasis-related work productivity and activity impairment and associations between the impairment and psoriasis severity in patients with moderate to severe psoriasis. Methods: Data were from the first 16 weeks of the Randomized controlled EValuation of adalimumab Every other week dosing in moderate to severe psoriasis TriAL (REVEAL). Outcomes as measured by the Work Productivity and Activity Impairment Questionnaire for Psoriasis (WPAI-Psoriasis) included employment status, total work productivity impairment, and total activity impairment. Logistic regression and analyses of covariance were used to assess the effects of adalimumab and treatment response ( $ 75% improvement in Psoriasis Area and Severity Index responders) on WPAI-Psoriasis outcomes. Longitudinal generalized estimating equations and Pearson correlation coefficients were used to assess associations between WPAI outcomes and psoriasis severity. Results: Greater improvements in total work productivity impairment and total activity impairment were observed with adalimumab treatment versus placebo (15.5 and 11.1 percentage points, respectively; P \ .001). Unemployment rate, total work productivity impairment, and total activity impairment were significantly associated with greater baseline psoriasis severity. Changes in WPAI outcomes were significantly correlated with greater psoriasis severity. The Dermatology Life Quality Index had stronger associations with changes in WPAI outcomes compared with clinical severity measures (Psoriasis Area and Severity Index and Physician Global Assessment). Limitations: REVEAL only included WPAI data for 16 weeks. Therefore, long-term impact of adalimumab treatment on productivity outcomes could not be assessed. In addition, information on occupational job title or industry was not collected and data were not adjusted for psoriatic arthritis. Conclusions: Adalimumab reduced psoriasis-related work productivity and activity impairment in patients with moderate to severe psoriasis. ( J Am Acad Dermatol 2012;66:e67-76.) Key words: adalimumab; biologic therapy; cost savings; disease severity; psoriasis; work productivity and activity impairment. From Harvard Medical School, Bostona; Analysis Group Inc, Bostonb; and Abbott Laboratories, Abbott Park.c Funding for manuscript development was provided by Abbott Laboratories. Medical writing services were provided by Teresa R. Brtva, PhD, and Cathryn M. Carter, MS, of Arbor Communications Inc, Ann Arbor, MI, and were funded by Abbott Laboratories. Disclosure: Dr Kimball is an investigator and consultant for Amgen, Centocor, and Abbott Laboratories and has received fellowship grants from Centocor. Drs Yu, Signorovitch, and Xie, and Ms Tsaneva are employees of Analysis Group Inc, which is under contract with Abbott Laboratories. Drs Gupta, Bao, and Mulani

are employees of Abbott Laboratories and hold stock in Abbott Laboratories. Accepted for publication October 3, 2010. Reprints not available from the authors. Correspondence to: Alexa Boer Kimball, MD, MPH, Harvard Medical School, 50 Staniford St, #246, Boston, MA 02114. E-mail: [email protected]. Published online May 26, 2011. 0190-9622/$36.00 ª 2010 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2010.10.020

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Psoriasis is a chronic, immune-mediated skin the impact of various diseases on patients’ ability to disease that affects 1% to 3% of the population in work and perform daily activities.12 It can be used to 1,2 the United States. Symptoms of psoriasis generally assess the work productivity and activity impairment include pain and pruritus of affected skin in different related to a variety of diseases by replacing ‘‘problem’’ parts of the body and may vary over time.3 Psoriasis in the original questionnaire with the name of the can be disfiguring and disabling and often leads to disease. A comprehensive review of instruments impairment in physical and emotional well-being measuring health-related work productivity considand social interactions of ered it to be the most psychopatients.4,5 The debilitating metrically validated and CAPSULE SUMMARY effects of psoriasis are espefrequently used instrument.13 cially prominent in patients Unlike most work productivThis study used the Work Productivity with moderate to severe psoity instruments, the design of and Activity Impairment Questionnaire riasis, which have been rethe WPAI-SHP makes it easily for Psoriasis to quantify the effects of a ported to represent 21% to adaptable across a multitude psoriasis treatment (adalimumab) on 33% of the total psoriasis of diseases and it has been work productivity and activity population.6,7 validated in a number of impairment. Psoriasis also poses a sigdisease areas, including Adalimumab therapy led to nificant economic burden on immune-mediated and derimprovements in work productivity and patients, health care systems, matologic conditions.13-17 It nonwork activities compared with and society, with estimated has also been widely used in placebo, and these improvements were annual direct medical costs different populations to assess significantly associated with reductions exceeding $1 billion in the the burden of psoriasis on in psoriasis severity. United States in 2004.6 In work productivity and daily addition to direct health activities.18-20 Furthermore, care costs, psoriasis may the WPAI-SHP not only captures work-related impaircause substantial indirect costs owing to a high rate ment, but it also measures impairment in nonwork of work loss in this patient population.8-10 Up to activities. The WPAI-SHP, therefore, is a most appro15.5% work productivity impairment and 23.7% total priate patient-reported outcome measure to assess activity impairment (TAI) have been reported to be disease-related work productivity and activity associated with psoriasis.8,9 Combining absenteeism impairment. (ie, missed work) and presenteeism (ie, productivity The Randomized controlled EValuation of adaliloss at work), the estimated annual indirect costs mumab Every other week dosing in moderate to associated with psoriasis were greater than $16 severe psoriasis triAL (REVEAL) included the WPAI billion, far exceeding the estimated direct costs.8 for Psoriasis (WPAI-Psoriasis) as an outcome meaAlthough these studies have shown that psoriasis sure in the treatment of psoriasis. Several published significantly impairs work productivity and daily studies based on REVEAL have demonstrated that activities, there have been no studies published on adalimumab significantly reduces psoriasis severity the use of a validated instrument to directly assess the and improves health-related quality of life.21,22 impact of a treatment on work productivity, includThe inclusion of the WPAI-Psoriasis in REVEAL ing both presenteeism and absenteeism, in psoriasis. presented an opportunity to directly estimate the The recent development of biologic therapies, such effect of a psoriasis treatment on work productivity. as adalimumab, etanercept, and infliximab, has draTherefore, the primary aim of the current study was matically changed the treatment of patients with to examine the effect of adalimumab treatment on moderate to severe psoriasis. Although it is important psoriasis-related work productivity and activity imto demonstrate that these treatments are efficacious pairment among patients with moderate to severe and well tolerated from a clinical perspective, it is psoriasis using data from the randomized controlled also important to understand their impact on work clinical trial, REVEAL. Our hypotheses were that productivity and activities, given the substantial adalimumab treatment could reduce work producindirect costs associated with psoriasis. To date, the tivity and activity impairment and that the pathway to study closest to this type of evaluation examined the achieve reductions in work productivity and activity effect of infliximab on general productivity using a impairment was through the reduction of psoriasis visual analog scale.11 severity. To test the second hypothesis, the current The Work Productivity and Activity Impairment study also assessed the associations between the Questionnaire
Specific Health Problem (WPAI-SHP) WPAI outcomes and psoriasis severity as well as is a validated instrument that has been used to study treatment response. d

d

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Abbreviations used: DLQI: PASI: PGA: REVEAL:

Dermatology Life Quality Index Psoriasis Area and Severity Index Physician Global Assessment randomized controlled evaluation of adalimumab every other week dosing in moderate to severe psoriasis trial TAI: total activity impairment TWPI: total work productivity impairment WPAI: Work Productivity and Activity Impairment Questionnaire WPAI-Psoriasis: Work Productivity and Activity Impairment Questionnaire for Psoriasis WPAI-SHP: Work Productivity and Activity Impairment Questionnaire
Specific Health Problem

METHODS Data and sample Data were obtained from the phase III clinical trial, REVEAL, which evaluated the efficacy and safety of adalimumab in patients with moderate to severe psoriasis. In this trial, patients were followed during 3 treatment periods for a maximum of 52 weeks. The current study used data from the first 16 weeks of REVEAL, during which patients were randomized to receive adalimumab or placebo in a double-blind fashion. Adult patients with moderate to severe psoriasis defined by affected body surface area, Psoriasis Area and Severity Index (PASI) score, and Physician Global Assessment (PGA) were included in the study. A detailed description of the study design has been reported elsewhere.23 Data from all patients enrolled in REVEAL were used to examine TAI and employment status. A subsample of all patients employed at both baseline and at week 16 was used to examine work productivity impairment. Measures WPAI-Psoriasis. The questionnaire was adapted from the WPAI-SHP version 2.0 (available at http:// www.reillyassociates.net/WPAI_SHP.html). All 6 questions in the WPAI were included to measure work productivity and activity impairment related to skin psoriasis. Following the standard methodology,24 the following measures were constructed from the questions: (1) current employment status; (2) absenteeism, defined as the percentage of time missed from work as a result of the disease; (3) presenteeism, defined as the percentage reduced productivity while working; (4) TAI, defined as the percentage impairment in regular daily activities other than work; and (5) total work productivity

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impairment (TWPI), representing the total percentage of work impairment associated with psoriasis from both absenteeism and presenteeism. The percentage of impairment associated with psoriasis was self-attributed by each patient. In REVEAL, WPAI-Psoriasis scores were collected at baseline and week 16. Psoriasis severity measures. To assess the relationship between WPAI outcomes and severity of psoriasis, 3 different severity indexes were used: PASI, PGA, and the Dermatology Life Quality Index (DLQI). These instruments take into consideration clinical severity of psoriasis symptoms and patients’ subjective assessments of severity. PASI is the most widely used composite score, assessing both the extent of body surface area involvement and the severity of the psoriatic lesions by location.25 PASI is a continuous score, ranging from 0 to 72, in which a larger number indicates greater psoriasis severity. In this study, both continuous PASI and categorical PASI scores (\10, 10-20, and $ 20) were used to assess severity.26 PGA is a qualitative measure of psoriasis severity, which classifies the disease state into several categories: clear, minimal, mild, moderate, severe, and very severe.27 It has been extensively used in clinical trials. In the current study, we reclassified PGA into 4 categories: clear, mild (including the original minimal and mild), moderate, and severe (including severe and very severe). The DLQI is based on a questionnaire that assesses symptoms, feelings, and limitations that the disease poses on patients’ daily activities.28,29 The DLQI score ranges from 0 to 30, where a lower score denotes better quality of life. As with PASI, both continuous and categorical DLQI scores (\10, 10-20, and $ 20) were used in the analyses.30 Psoriasis is considered severe if the patient’s PASI score and DLQI score are 10 or greater.31 Treatment response. Patients who responded to treatment (responders) were defined as those achieving an improvement in PASI score of 75% or more at week 16 compared with the baseline score, the primary efficacy end point in numerous clinical trials23,32-35; otherwise, the patient was classified as a nonresponder. Statistical analyses Effects of adalimumab on WPAI outcomes. The WPAI outcomes were examined at baseline and at week 16 for the two treatment groups (adalimumab and placebo). Changes in WPAI outcomes were assessed in each treatment group and compared between the two groups. McNemar tests were used to test the differences in employment rates between

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baseline and week 16 within each treatment group, and a logistic regression was used to examine the effects of adalimumab on employment at week 16, adjusting for treatment groups and baseline employment status. For continuous outcomes, such as TAI, TWPI, presenteeism, and absenteeism, paired Student t tests were used to test differences between baseline and week 16 within each treatment group, and analyses of covariance were used to assess effects of adalimumab on changes in the outcomes, adjusting for treatment group and the corresponding baseline score. The method has been used previously to assess the effects of adalimumab on patientreported outcomes.21 Association between WPAI outcomes and psoriasis severity. The associations between WPAI outcomes and psoriasis severity were first assessed using categorical PASI, PGA, and DLQI measures. Logistic regression was used to estimate the adjusted odds ratios of being employed among patients in different psoriasis severity categories. Longitudinal generalized estimating equation models were used to assess the association between the continuous WPAI measures (ie, TAI, TWPI, presenteeism, and absenteeism) and the severity of psoriasis, adjusting for baseline characteristics (age, sex, race, ethnicity, and psoriasis duration). In addition, the associations between improvements in WPAI outcomes and psoriasis clinical symptomatic relief (measured using changes in PASI and DLQI) from baseline to week 16 were assessed using Pearson correlation coefficients. Effects of treatment response on WPAI outcomes. The WPAI outcomes were examined both at baseline and at week 16 for the responder and nonresponder groups. Changes in the WPAI outcomes were then assessed within each group and compared between the responders and nonresponders. The statistical analyses were similar to those used to assess the effects of adalimumab on WPAI outcomes, except that the logistic regression and the analyses of covariance controlled for responder status in the models instead of treatment groups. Missing observations. Observations with missing values for WPAI outcomes were excluded from the analyses. Missing values for psoriasis severity (PASI, PGA, and DLQI) were imputed using last observation carried forward in all analyses except for the analysis of association between work productivity loss and psoriasis severity, in which observations with missing severity values were excluded. In sensitivity analyses, only observed data (ie, observations with missing values for either WPAI outcomes or psoriasis severity measures were excluded from the sensitivity analyses) were used.

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Table I. Baseline characteristics for employed patients with psoriasis Characteristic

Age, y, mean 6 SD Male, n (%) White, n (%) Psoriasis history Duration of psoriasis, y, mean 6 SD Prior systemic psoriasis therapy,y n (%) History of psoriatic arthritis, n (%) Psoriasis baseline assessments, mean 6 SD BSA % affected by psoriasis PASI score PGA, n (%) Moderate Severe Very severe Work productivity, mean 6 SD TWPI, % Presenteeism, % Absenteeism, %

Placebo (N = 270)

Adalimumab P (N = 557) value*

44.0 6 11.9 42.4 6 11.4 .0233 197 (73.0) 388 (69.7) .3274 243 (90.0) 503 (90.3) .8899 18.4 6 11.3 18.1 6 11.2 .3846 85 (31.5)

177 (31.8)

.9317

66 (24.4)

137 (24.6)

.9621

24.7 6 14.1 25.7 6 15.0 .2221 18.7 6 6.9

18.8 6 6.8 .3449

145 (53.7) 108 (40.0) 16 (5.9)

287 (51.5) 234 (42.0) 36 (6.5)

.8088

17.9 6 23.6 18.5 6 23.8 .3117 16.8 6 22.1 17.8 6 22.8 .2535 2.6 6 10.6 3.3 6 13.0 .3517

BSA, Body surface area; PASI, Psoriasis Area Severity Index; PGA, Physician Global Assessment; TWPI, total work productivity impairment. *x 2 Test for categorical variables; Student t test for continuous variables. y Biologic and nonbiologic systemic therapies in past 12 months.

RESULTS Baseline characteristics Baseline characteristics of patients randomized to receive adalimumab and placebo in REVEAL were similar between treatment groups and have been reported elsewhere.21,23 Among all patients enrolled in the trial, 73.3% of the patients in the adalimumab group and 74.4% in the placebo group were employed at baseline. Among the 827 patients employed both at baseline and at week 16, baseline characteristics were not significantly different between the adalimumab- and placebo-treated patients, except for the mean age (Table I). Among all patients in REVEAL, the average TAI at baseline was 26.6% in the adalimumab group (n = 785) and 27.1% in the placebo group (n = 374). Effects of adalimumab on WPAI outcomes Over the 16-week treatment period, both adalimumab- and placebo-treated patients experienced

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Table II. Change in work productivity loss over 16 weeks among patients with psoriasis in Randomized controlled EValuation of adalimumab Every other week dosing in moderate to severe psoriasis triAL (REVEAL)* P values Work productivity measures

Employment Adalimumab, n (%) Placebo, n (%) TWPI, %y Adalimumab, mean 6 SD Placebo, mean 6 SD Impairment caused by disease-related absenteeism, %z Adalimumab, mean 6 SD Placebo, mean 6 SD Impairment while working owing to presenteeism, %x Adalimumab, mean 6 SD Placebo, mean 6 SD TAI, %k Adalimumab, mean 6 SD Placebo, mean 6 SD

N

Baseline

Wk 16

Change

Wk 16 vs baseline{

15 (1.9) 3 (0.8)

.0874 .5900

.6284

Adalimumab vs placebo#

797 380

588 (73.8) 284 (74.7)

603 (75.7) 287 (75.5)

494 246

18.3 6 23.8 17.9 6 23.7

4.9 6 13.2 15.6 6 22.6

e13.4 6 23.8 e2.3 6 19.7

\.0001 .0708

\.0001

518 255

3.1 6 12.5 2.7 6 10.8

1.2 6 8.7 2.7 6 13.6

e1.9 6 14.3 e0.05 6 14.2

.0027 .9575

.0607

526 256

17.7 6 22.8 16.8 6 22.0

4.8 6 12.9 15.3 6 22.1

e12.9 6 22.7 e1.5 6 20.6

\.0001 .2380

\.0001

785 374

26.7 6 27.2 26.5 6 28.9

7.9 6 17.5 23.2 6 27.6

e18.8 6 26.8 e3.3 6 25.1

\.0001 .0109

\.0001

Total of 1212 patients (814 adalimumab and 398 placebo) were enrolled in trial. Only patients with nonmissing values for employment at both baseline and wk 16 were included in analysis. There were 35 patients with missing employment information at either baseline or wk 16. TAI, Total activity impairment; TWPI, total work productivity impairment. *For Work Productivity and Activity Impairment Questionnaire outcomes, sample was restricted to patients with baseline and at least one follow-up measurement for outcome specified. Missing values were imputed using last observation carried forward. y Calculated as [{hours absent from work due to psoriasis/(hours absent from work due to psoriasis 1 hours actually worked)} 1 {1
hours absent from work due to psoriasis/(hours absent from work due to psoriasis 1 hours actually worked)} 3 (percentage reduced productivity at work)] 3 100%. Among 827 patients who were employed at both baseline and wk 16, there were 87 patients with missing TWPI information at either baseline or wk 16. z Calculated as [hours absent from work owing to psoriasis/(hours absent from work owing to psoriasis 1 hours actually worked)] 3 100%. Among 827 patients who were employed at both baseline and wk 16, there were 54 patients with missing absenteeism information at either baseline or wk 16. x Calculated using visual analog scale as percentage reduced productivity while working. Among 827 patients who were employed at both baseline and wk 16, there were 45 patients with missing presenteeism information at either baseline or wk 16. k Calculated using visual analog scale as percent impairment in regular daily activities other than working at job. Among 1212 patients enrolled in trial, there were 53 patients with missing TAI information at either baseline or wk 16. { Paired Student t tests used for continuous variables. McNemar test used for categorical variable. # P values for continuous variables are based on analysis of covariance model. P values for categorical variable are estimated using logistic model. Both models were adjusted for baseline score and treatment.

modest but nonsignificant increases in their employment rates (Table II). For patients who were employed both at baseline and at week 16, significant decreases between baseline and week 16 were observed for TWPI, absenteeism, and presenteeism (13.4, 1.9, and 12.9 percentage points, respectively; all P \.010) in the adalimumab group, whereas the corresponding changes were small and nonsignificant in the placebo group. Adalimumab-treated patients also had significantly greater improvements in TWPI and presenteeism (by 11.1 and 11.4 percentage points, respectively), compared with those who received placebo (both P \ .001). Among all patients in REVEAL, TAI score decreased by 18.8 percentage points from baseline to week 16 in the adalimumab group, which was 15.5 percentage

points greater than the reduction in the placebo group (P \.001) (Table II). Association between psoriasis severity and WPAI outcomes The results from the generalized estimating equation models showed that all WPAI measures were positively and significantly associated with psoriasis severity. In general, patients with more severe disease were less likely to be employed (Table III). Among employed patients, increased psoriasis severity was associated with greater impairment in total work productivity, presenteeism, and absenteeism. Greater differences in TWPI and presenteeism were observed among the 3 severity groups based on DLQI, compared with the severity groups defined by

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Table III. Associations between severity of psoriasis and work productivity: longitudinal models using Randomized controlled EValuation of adalimumab Every other week dosing in moderate to severe psoriasis triAL (REVEAL) data PASI (reference = 0e10) Work productivity measures

$ 10 and \20

$ 20

DLQI (reference = 0e10) $ 10 and \20

$ 20

PGA (reference = clear) Mild

Moderate

Severe

Employment* (N = 2389) Odds ratio 0.89 0.77 0.83 0.63 1.12 0.99 0.80 95% CI (0.78-1.02) (0.63-0.93) (0.70-0.97) (0.46-0.86) (0.83-1.51) (0.85-1.16) (0.67-0.96) P value .0844 .0086 .0187 .0037 .4635 .9258 .0180 TWPIy (N = 1682) Coefficient 11.73 19.90 19.78 46.41 4.35 13.42 19.11 95% CI (9.97-13.49) (16.64-23.17) (17.38-22.18) (40.73-52.08) (1.64-7.06) (11.39-15.45) (16.61-21.61) P value \.0001 \.0001 \.0001 \.0001 .0016 \.0001 \.0001 Presenteeismz (N = 1735) Coefficient 11.82 19.19 19.26 44.59 3.30 12.97 18.75 95% CI (10.20-13.43) (16.18-22.19) (16.97-21.55) (39.34-49.85) (1.08-5.51) (11.14-14.80) (16.36-21.15) P value \.0001 \.0001 \.0001 \.0001 .0035 \.0001 \.0001 Absenteeismx (N = 1725) Coefficient 2.29 3.65 4.38 14.05 1.78 2.16 4.43 95% CI (1.19-3.38) (1.87-5.43) (2.77-6.00) (8.94-19.17) (e0.54 to 4.11) (1.13-3.19) (3.00-5.86) P value \.0001 \.0001 \.0001 \.0001 .1326 \.0001 \.0001 TAIk (N = 2371) Coefficient 17.25 27.41 28.61 54.20 6.15 19.48 27.24 95% CI (15.55-18.94) (24.61-30.21) (26.40-30.81) (50.12-58.28) (3.50-8.80) (17.61-21.34) (24.94-29.55) P value \.0001 \.0001 \.0001 \.0001 \.0001 \.0001 \.0001 N indicates number of observations. Because longitudinal models were used, multiple observations per patient were possible. Generalized estimating equation models were used to estimate coefficients, adjusting for baseline characteristics (ie, age, sex, race, ethnicity, and psoriasis duration). CI, Confidence interval; DLQI, Dermatology Life Quality Index; PASI, Psoriasis Area Severity Index; PGA, Physician Global Assessment; TAI, total activity impairment; TWPI, total work productivity impairment. *Baseline employment rate was 73.9%. Number of missing observations for employment was 35. y TWPI calculated as [{hours absent from work due to psoriasis/(hours absent from work due to psoriasis 1 hours actually worked)} 1 {1
hours absent from work due to psoriasis/(hours absent from work due to psoriasis 1 hours actually worked)} 3 (percentage reduced productivity at work)] 3 100%. Number of missing observations for TWPI was 80. z Presenteeism calculated using visual analog scale as percentage reduced productivity while working. Number of missing observations for presenteeism was 27. x Absenteeism calculated as [hours absent from work owing to psoriasis/(hours absent from work owing to psoriasis 1 hours actually worked)] 3 100%. Number of missing observations for absenteeism was 37. k TAI calculated using visual analog scale as percentage impairment in regular daily activities other than working at job. Number of missing observations for TAI was 53.

PASI or PGA (Table III). Compared with the differences in TWPI and presenteeism, the differences in impairment caused by absenteeism were much smaller among the different severity groups (Table III). Results for TAI in the total patient sample were similar to those for TWPI (Table III). In assessing the associations between changes in WPAI outcomes and changes in psoriasis severity, Pearson correlation coefficients showed that changes in PASI score from baseline to week 16 were significantly and positively correlated with changes in TAI, TWPI, presenteeism, and absenteeism (correlation coefficients = 0.29, 0.33, 0.39, and 0.12, respectively).

Compared with change in PASI score, change in DLQI score showed a higher degree of correlation with WPAI outcomes (correlation coefficients = 0.57, 0.58, 0.66, and 0.28 for TAI, TWPI, presenteeism, and absenteeism, respectively). Effects of treatment response on WPAI outcomes Compared with nonresponders, responders had significant greater improvements in WPAI outcomes during the 16-week period, except for employment rate (Table IV). For responders, the improvements in TWPI, presenteeism, and absenteeism were 13.0,

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Table IV. Changes in work productivity over 16 weeks for 75% or more improvement in Psoriasis Area Severity Index responders versus nonresponders in Randomized controlled EValuation of adalimumab Every other week dosing in moderate to severe psoriasis triAL (REVEAL)* P values{ Work productivity measures

Employment Responder, n (%) Nonresponder, n (%) TWPI, %y Responder, mean 6 SD Nonresponder, mean 6 Presenteeism, %z Responder, mean 6 SD Nonresponder, mean 6 Absenteeism, %x Responder, mean 6 SD Nonresponder, mean 6 TAI, %k Responder, mean 6 SD Nonresponder, mean 6

N

Baseline

Wk 16

Change

Wk 16 vs baseline

Responder vs nonresponder

17 (2.6) 1 (0.2)

.0533 1.0000

.0666

652 525

490 (75.2) 382 (72.8)

507 (77.8) 383 (73.0)

410 330

17.6 6 23.3 18.7 6 24.3

2.2 6 7.8 16.3 6 22.7

e15.5 6 23.0 e2.5 6 21.1

\.0001 .0333

\.0001

SD

436 346

17.3 6 22.5 17.5 6 22.7

2.0 6 6.9 16.2 6 22.3

e15.3 6 21.8 e1.4 6 21.4

\.0001 .2374

\.0001

SD

429 344

3.0 6 12.1 3.0 6 11.7

0.4 6 4.2 3.4 6 15.0

e2.6 6 12.0 0.4 6 16.6

\.0001 .6496

\.0001

SD

643 516

26.6 6 27.0 26.7 6 28.7

4.2 6 11.8 23.5 6 27.4

e22.4 6 25.6 e3.2 6 25.4

\.0001 .0050

\.0001

SD

Total of 1212 patients (814 adalimumab and 398 placebo) were enrolled in trial. There were 35 patients with missing employment information at either baseline or wk 16. TAI, Total activity impairment; TWPI, total work productivity impairment. *Responder was defined as achieving $ 75% improvement in Psoriasis Area Severity Index at any follow-up visit; otherwise, patient was classified as nonresponder. Missing values were imputed using last observation carried forward. y TWPI calculated as [{hours absent from work due to psoriasis/(hours absent from work due to psoriasis 1 hours actually worked)} 1 {1
hours absent from work due to psoriasis/(hours absent from work due to psoriasis 1 hours actually worked)} 3 (percentage reduced productivity at work)] 3 100%. Among 827 patients who were employed at both baseline and wk 16, there were 87 patients with missing TWPI information at either baseline or wk 16. z Presenteeism calculated using visual analog scale as percentage reduced productivity while working. Among 827 patients who were employed at both baseline and wk 16, there were 45 patients with missing presenteeism information at either baseline or wk 16. x Absenteeism calculated as [hours absent from work owing to psoriasis/(hours absent from work owing to psoriasis 1 hours actually worked)] 3 100%. Among 827 patients who were employed at both baseline and wk 16, there were 54 patients with missing absenteeism information at either baseline or wk 16. k TAI calculated using visual analog scale as percentage impairment in regular daily activities other than working at job. Among 1212 patients enrolled in trial, there were 53 patients with missing absenteeism information at either baseline or wk 16. { Paired Student t tests used to compare baseline and wk-16 scores within each group; analysis of covariance models used to compare differences between responders and nonresponders, except for employment rate, for which logistic regression was used to compare probability of being employed at wk 16 between responders and nonresponders.

13.9, and 3.0 percentage points greater, respectively, compared with the corresponding improvements in the nonresponder group (all P \ .001) (Table IV). The improvement in TAI was 19.2 percentage points greater in the responder group compared with the nonresponder group (P \.001) (Table IV). Sensitivity analyses Results from the sensitivity analyses using the observed values yielded similar results (not shown) compared with those presented above that used last observation carried forward.

DISCUSSION Using data from REVEAL, the current study examined the effect of a treatment on work productivity

and activity impairment in patients with psoriasis using the WPAI-Psoriasis. The WPAI is a wellvalidated, self-reported instrument measuring work productivity and activity impairment related to general health or, as in this case, a specific disease. Unlike employer reports, which can also be used to measure both work productivity and activity impairment, the WPAI also captures information on productivity losses that are not recorded by employers, such as reduced productivity at work and short durations of missed work (eg, a couple of hours). Therefore, the goal of the current study was to comprehensively quantify the treatment effects of adalimumab on work productivity and other daily activities. The results indicate that adalimumab can substantially reduce psoriasis-related work productivity and

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activity impairment among patients with moderate to severe psoriasis. The mean improvements in TWPI, presenteeism, and TAI in the adalimumab group all exceeded the minimum clinically important differences, as defined by a half SD from the baseline score.36 Based on TWPI, the change in overall work productivity loss from baseline to week 16 can be translated into approximately a 60% reduction in psoriasis-related work productivity impairment. The majority of the reduction was attributed to the improvement in presenteeism. The 16 weeks of adalimumab treatment led to improvements of 11.1 and 15.5 percentage points in TWPI and TAI, respectively, compared with placebo. For a full-time employee working 40 hours per week, the improvement in work productivity associated with adalimumab treatment would be equivalent to an additional 4.4 hours of work productivity at week 16 compared with baseline (based on the calculation of percentage of total work productivity improvement 3 40 hr/wk). Assuming that the benefit of adalimumab on work productivity would persist for 1 year, the annualized indirect cost savings for employers were estimated to be $4515 per full-time employed patient based on the 2007 average annual salary for full-time employees in the United States (11.1% 3 $40,690 = $4515).37 The indirect costs estimated using this methodology are higher than those previously reported,8,10 possibly because the current study included both absenteeism and presenteeism in its calculation of cost and included more patients given the diagnosis of severe psoriasis. Our findings on the association between work productivity and disease severity are largely consistent with previous literature.8,9,38 Schmitt and Ford8 found positive associations between work productivity loss and PASI or DLQI. Pearce et al9 showed that patients with mild psoriasis as measured by PGA had less work productivity impairment than those with moderate or severe disease. Horn et al38 reported that patients with severe psoriasis as defined by body surface area were more likely to have lower incomes and to report psoriasis as the reason for not being employed than were those with mild psoriasis. Taken together, these studies demonstrated that the detrimental effects of psoriasis on work productivity and nonwork activities may generally be associated with increasing psoriasis severity. The improvements in work productivity and activity impairment observed among adalimumabtreated patients in this study parallel the reductions in disease severity demonstrated in this population in previous studies.21-23,34 In REVEAL, the study on which these analyses were based, 71% adalimumabtreated patients achieved 75% or more improvement

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in PASI score at week 1623 and 55% of patients achieved a DLQI score of 0 or 1 at week 16, indicating that psoriasis did not affect a patient’s life at all (Abbott Laboratories; data on file). Given these findings, it is likely that the impact of adalimumab on work productivity and TAI could be largely attributable to its impact on disease severity. There are some limitations of the current study. First, because the data used were from a clinical trial that selected only patients with psoriasis who met certain inclusion or exclusion criteria and were restricted to certain concomitant medications, the study population may not be fully representative of the psoriasis population in a routine practice setting. Therefore, the generalizability of the study findings may be limited. However, the randomization of patients in REVEAL improved the internal validity of the current analysis. Second, the WPAI-Psoriasis was measured only at baseline and week 16 in REVEAL and therefore the study was unable to assess the long-term effects of adalimumab on work productivity and activity impairment. As a lifelong, chronic illness causing substantial psychosocial impairment,4,5 psoriasis may impact career development and prevent individuals from achieving their full economic potential. This could be a major source of indirect costs associated with psoriasis and warrants further investigation. Future studies will need to focus on the long-term effects of adalimumab on WPAI outcomes. Third, approximately 25% of the study population had concurrent psoriatic arthritis, and it is possible that improvements in work productivity and activity impairment for this subgroup could be attributed in part to improved joint function. In REVEAL, neither clinical nor patient-reported assessments of joint function were collected; therefore, the association between improvements in WPAI outcomes and improvements in joint function could not be evaluated. Nevertheless, the WPAI-Psoriasis was designed to assess work productivity and activity impairment related to skin psoriasis only; thus, the impairment observed in this study was attributed to psoriasis. Future studies that collect both clinical and patient-reported assessments of joint function are needed to fully evaluate the association between work productivity and improved joint function in patients with moderate to severe psoriasis. Lastly, although the WPAI has been validated, like any tool that requires self-reporting, it may be subject to some biases. In summary, adalimumab treatment effectively reduced psoriasis-related work productivity and activity impairment in patients with moderate to severe psoriasis. Based on the strong association between WPAI outcomes and disease severity identified in this

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study, it may be concluded that the positive effects of adalimumab on work productivity are likely partially a result of its impact in reducing disease severity. Given the vastly greater indirect costs ($16 billion) incurred by patients with psoriasis compared with direct medical costs,8 indirect costs savings resulting from effective treatments are important to include in modeling analyses to elucidate the benefits of treatment. REFERENCES 1. 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;60:218-24. 2. Adams PF, Hendershot GE, Marano MA. Current estimates from the national health interview survey, 1996. Vital Health Stat 10 1999;200:1-203. 3. Greaves MW, Weinstein GD. Treatment of psoriasis. N Engl J Med 1995;332:581-8. 4. Kimball AB, Jacobson C, Weiss S, Vreeland MG, Wu Y. The psychosocial burden of psoriasis. Am J Clin Dermatol 2005;6: 383-92. 5. Menter A, Gottlieb A, Feldman SR, Van Voorhees AS, Leonardi CL, Gordon KB, 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;58:826-50. 6. The Society for Investigative Dermatology and the American Academy of Dermatology Association. The burden of skin diseases 2004. Available from: URL:http://www.sidnet.org/ pdfs/Burden%20of%20Skin%20Diseases%202004.pdf. Accessed April 13, 2009. 7. National Psoriasis Foundation. Benchmark survey on psoriasis and psoriatic arthritis: summary of top line results. Available from: URL:http://www.psoriasis.org/files/pdfs/press/npfsurvey. pdf. Accessed April 13, 2009. 8. 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; 213:102-10. 9. Pearce DJ, Singh S, Balkrishnan R, Kulkarni A, Fleischer AB, Feldman SR. The negative impact of psoriasis on the workplace. J Dermatolog Treat 2006;17:24-8. 10. Fowler JF, Duh MS, Rovba L, Buteau S, Pinheiro L, Lobo F, et al. The impact of psoriasis on health care costs and patient work loss. J Am Acad Dermatol 2008;59:772-80. 11. Reich K, Nestle FO, Wu Y, Bala M, Eisenberg D, Guzzo C, et al. Infliximab treatment improves productivity among patients with moderate-to-severe psoriasis. Eur J Dermatol 2007;17: 381-6. 12. Reilly MC, Zbrozek AS, Dukes EM. The validity and reproducibility of a work productivity and activity impairment instrument. Pharmacoeconomics 1993;4:353-65. 13. Prasad M, Wahlqvist P, Shikiar R, Shih YC. A review of self-report instruments measuring health-related work productivity: a patient-reported outcomes perspective. Pharmacoeconomics 2004;22:225-44. 14. Reilly MC, Lavin PT, Kahler KH, Pariser DM. Validation of the Dermatology Life Quality Index and the Work Productivity and Activity Impairment-Chronic Hand Dermatitis questionnaire in chronic hand dermatitis. J Am Acad Dermatol 2003;48: 128-30.

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35. Saurat JH, Stingl G, Dubertret L, Papp K, Langley RG, Ortonne JP, et al. Efficacy and safety results from the randomized controlled comparative study of adalimumab vs methotrexate vs placebo in patients with psoriasis (CHAMPION). Br J Dermatol 2008;158:558-66. 36. Norman GR, Sloan JA, Wyrwich KW. Interpretation of changes in health-related quality of life: the remarkable universality of half a standard deviation. Med Care 2003;41:582-92. 37. US Department of Labor, Bureau of Labor Statistics. National occupational employment and wage estimates. 2007. Available from: URL:http://www.bls.gov/oes/current/oes_nat.htm# b00-0000. Accessed April 13, 2009. 38. Horn EJ, Fox KM, Patel V, Chiou CF, Dann F, Lebwohl M. Association of patient-reported psoriasis severity with income and employment. J Am Acad Dermatol 2007;57:963-71.