Journal of Crohn's and Colitis (2014) 8, 1362–1377

Available online at www.sciencedirect.com

ScienceDirect

REVIEW ARTICLE

Sick leave and disability pension in inflammatory bowel disease: A systematic review Katharina Büsch a,⁎, Simone A. da Silva b , Michelle Holton c , Fabiana M. Rabacow b , Hamed Khalili d , Jonas F. Ludvigsson e,f a

Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden Department of Preventive Medicine, University of São Paulo, São Paulo, Brazil c Lorimer Enterprises Inc., Red Deer, Alberta, Canada d Digestive Healthcare Center, Massachusetts General Hospital, Boston, MA, USA e Department of Pediatrics, Örebro University Hospital, Örebro, Sweden f Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Sweden b

Received 31 March 2014; received in revised form 16 May 2014; accepted 17 June 2014 KEYWORDS Work outcomes; Crohn's disease; Ulcerative colitis; Review

Abstract Background & aims: Inflammatory bowel disease has considerable effects on work-related outcomes and leads to high societal costs due to sick leave and disability pension. The aims of this study were to systematically review evidence on work-related outcomes that are relevant to productivity losses and to evaluate whether medical or surgical interventions have a positive impact on patients' work ability. Methods: A systematic literature search in PubMed was conducted in June 2013. Abstracts were screened by two independent reviewers, and full-text articles describing the frequency of work-related outcomes were retrieved. Two independent reviewers extracted data according to the PRISMA Statement for Reporting Systematic Reviews and Meta-Analyses. Findings were organized by study design (non-interventional/interventional). Non-interventional studies were structured according to whether they presented data in comparison to control groups or not and interventional studies were summarized according to type of intervention.

Abbreviations: A, absenteeism; ADA, adalimumab; CD, Crohn's disease; CPC, conventional proctocolectomy and Brooke ileostomy; CZP, certolizumab pegol; HPWAW, hours per week actually worked; HPWFP, productivity and hours per week fully productive; IBD, inflammatory bowel disease; IC, indeterminate colitis; IFX, infliximab; IPAA, ileal J-pouch–anal anastomosis; OP, operation; P, presenteeism; RCP, restorative proctocolectomy; RCT, randomized controlled trials; SIA, social insurance agency; TAI, total activity impairment; TWPI, total work productivity impairment; UC, ulcerative colitis; WP, work productivity; WPAI, Work Productivity and Activity Impairment. ⁎ Corresponding author at: Clinical Epidemiology Unit, Dept of Medicine (Solna), Karolinska Institutet, SE-171 76 Stockholm, Sweden. Tel.: + 46 70 168 08 33. E-mail addresses: [email protected], [email protected] (K. Büsch).

http://dx.doi.org/10.1016/j.crohns.2014.06.006 1873-9946/© 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

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Results: This review included 30 non-interventional (15 with comparison groups and 15 without comparison group) and 17 interventional studies (9 surgical and 8 medical). The majority of the studies reported a high burden of work-related outcomes among inflammatory bowel disease patients regardless of the methodology used. While biologic agents showed positive effect on work absenteeism and presenteeism in randomized clinical trials, the impact of surgical interventions needs further evaluation. Conclusions: Inflammatory bowel disease patients experience a high burden in work-related outcomes. Additional data on productivity losses and the long-term impact of interventions is needed to help inform decision-makers about treatment options and their benefits in reducing productivity losses in inflammatory bowel disease patients. © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Contents 1. 2.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1. Literature search and data synthesis . . . . . . . . . . . 3. Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1. Non-interventional studies . . . . . . . . . . . . . . . . . 3.1.1. Employment status . . . . . . . . . . . . . . . . 3.1.2. Sick leave . . . . . . . . . . . . . . . . . . . . . 3.1.3. Work disability . . . . . . . . . . . . . . . . . . . 3.1.4. Early retirement . . . . . . . . . . . . . . . . . . 3.1.5. Unemployment . . . . . . . . . . . . . . . . . . . 3.2. Interventional studies . . . . . . . . . . . . . . . . . . . 3.2.1. Surgical interventions for IBD . . . . . . . . . . 3.2.2. Medical treatment for IBD . . . . . . . . . . . . 4. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1. Strengths and limitations . . . . . . . . . . . . . . . . . 4.1.1. Methodological challenges with studies included 5. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Author contributions . . . . . . . . . . . . . . . . . . . . . . . . . . Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . Grant funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1. Introduction Immune-mediated inflammatory disorders including Crohn's disease (CD) and ulcerative colitis (UC) have considerable effects on employment outcomes.1 Many patients develop inflammatory bowel disease (IBD) at an early age which can result in high societal costs due to sick leave and disability pension.2 To date, studies conducted on IBD and work outcome have primarily examined the occupational and socioeconomic distribution of the disease and productivity changes as a result of IBD. Little is known about the impact of interventions on labor force participation. However, increased knowledge about productivity losses could inform patients about prognosis and facilitate decisions about treatments. This is especially relevant as IBD is a chronic disorder and therefore social

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1363 1365 1365 1368 1368 1368 1368 1368 1368 1372 1372 1372 1374 1374 1374 1375 1375 1375 1375 1375 . . 1375

support is of paramount importance for patients to continue active labor force participation. Previous reviews have been limited in that they only included work-related outcomes as part of an overall summary of the disease burden,1–8 provided information for specific countries and/or included IBD as part of a review on the burden of immune-mediated inflammatory diseases.1,3,6,7 In the current review burden is defined as the cumulative consequence of IBD compared to the state in a healthy person. One review9 focusing solely on the education and employment behavior in IBD was not systematic and did not include recently published reports.10–29 Furthermore, studies investigating the effect of specific interventions on work outcomes have not yet been summarized.30–46 The aim of this study was to perform a systematic review of published studies on domains of work participation that are relevant for the quantification of productivity

Non-interventional studies in IBD, UC and/or CD patients versus matched comparator groups.

Study

Number of patients

Reference/control group

Inflammatory bowel disease (IBD) 680 IBD 715 age- & sexBoonen et al.60 patients a matched controls

Crohn's disease (CD) Sorensen et al.61 106 CD patients

Working/ employed, %

Sick leave, %

Employed b: IBD: 65% Controls: 68%

All-cause: IBD: 62% Controls: 53% Disease specific: IBD: 40%

Work disability c: IBD: 28% Controls: 10%

Employed: CD: 65% Controls: 64%

Sick leave d,e: CD: 72% Controls: 69%

Disabled: CD: 3% Controls: 0%

Employed b: CD: 62% Controls (IBD): 68%

All-cause: CD: 69% Controls (IBD): 53% Disease specific: CD: 41% Absenteeism: CD: 88% Controls: 88%

Work disability c: CD: 32% Controls (IBD): 10%

282 CD patients

Gibson et al.15

6569 CD patients

Propensity score matched controls

Employed: CD: 37%

Employed UC: 71% Controls: 73%

Sick leave d: UC: 69% Controls: 73%

Employed b: UC: 69% Controls (IBD): 68% Employed: UC: 41%

All-cause: UC: 59% Controls (IBD): 53% Disease specific: UC: 29% Absenteeism: UC: 86% Controls: 84% Sick leave f: UC: 21% Controls: 13%

Ulcerative colitis (UC) Hendriksen et al.10 122 UC patients

Boonen et al.60

359 UC patients

83 age- & sex-matched patients with acute condition from same area with duration b 14 days 715 age- & sexmatched controls

Gibson et al.15

8970 UC patients

Propensity score matched controls

Neovius et al.46

19557 UC patients

97785 -matched controls by age, sex, education and county of residence

Disability pension, %

Early retirement, %

Unemployment, %

Unemployed: CD: 6% Controls: 7% Early retirement: CD: 0% Controls (IBD): 3%

Unemployed: CD: 2% Controls (IBD): 3%

Short-term disability: CD: 20% Controls: 7%

Full work capacity: UC: 84% Controls: 86%

Disabled: UC: 2% Controls: 0%

Work disability c: UC: 24% Controls (IBD): 10%

Short-term disability: UC: 15% Controls: 6% Disability pension g: UC: 15% Controls: 11%

Unemployed: UC: 2% Controls: 4%

Early retirement: UC: 3% Controls (IBD): 3%

Unemployed: UC: 3% Controls (IBD): 3%

K. Büsch et al.

Boonen et al.60

75 age- & sex-matched patients admitted to hospital for acute conditions b 28 days 715 age- & sex-matched controls

Working capacity, %

1364

Table 1

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Figure 1 Flowchart of study selection and inclusion. *Articles only counted in one of the exclusion groups, even though articles could be excluded for N 1 reason; IBD = inflammatory bowel disease. Two studies of the 45 included manuscripts were included in both – the non-interventional and interventional – sections as they reported results for IBD patients alone or in comparison to matched controls and results for surgical interventions.38,46

losses in adults with IBD. A secondary aim was to systematically summarize the evidence regarding the impact of medical or surgical interventions on work-outcomes in IBD patients.

2. Methods 2.1. Literature search and data synthesis A systematic search was conducted in PubMed MEDLINE and EMBASE47 in June 2011 and was updated in June 2013 (KB, MH). Search terms included combinations of ‘Crohn's disease’, ‘ulcerative colitis’, ‘inflammatory bowel disease’ and ‘(un-) employment’, ‘sick leave’, ‘absenteeism’, ‘work loss’, ‘productivity loss’, ‘disability pension’ or ‘early retirement’ (detailed search strategy is available upon request from the

corresponding author). Besides the requirement to include full-text articles published in English, no further restrictions were applied. For the initial screening, abstracts were screened by two independent reviewers (KB and SAdS). Full-text articles were retrieved if abstracts included information on work-related outcomes such as employment status, work capacity, sick leave, disability pension or early retirement in adults and if publications were reviews, comments or editorials. Exclusion criteria included non-IBD related research or animal research, pediatric populations, no reported work-related outcomes, case reports, study protocols or interventions not of interest (e.g. nursing interventions). To complement the database search, the reference lists of included studies and review articles were screened to identify additional studies using publication titles (KB).

Notes to Table 1: a b c d e f g

The IBD group includes patients with indeterminate colitis (IC); no separate results presented for the IC group. Defined as full and/or part-time employed. Defined as full or part-time work disability. Defined as sick leave b11 days. Data reported for 75 patients and 50 controls. Defined as sick leave N 14 days paid by the Social Insurance Agency (SIA). Defined as limited or permanent and at least 25% reduction of work capacity expected to remain for at least 1 year as recorded by the SIA.

Non-interventional studies in IBD, UC and/or CD patients versus comparator groups (not matched).

Study

Number of Reference/ patients control group

Inflammatory bowel disease (IBD) 2474 IBD 14,177 general Bernstein et al. patients b population (study A)62 a controls 80 IBD 26,082 controls Bernstein et al. patients (study B)62 187 IBD 10,704 persons Longobardi patients without selfet al.65 reported IBD Longobardi et al.64

105 IBD w 23,462 persons symptoms without self82 IBD w/o reported IBD symptoms

Bernklev et al.12

495 IBD patients

General population

Vergara et al.24

106 IBD patients

24 healthy controls

Hoivik et al.16

501 IBD patients

Background population

Gunnarsson et al.17

200 IBD patients

89,846 persons without selfreported IBD

Mayberry et al.63

58 CD patients

Sick leave, %

Employed: IBD: 59% Controls: 69% Labor force c: IBD: 71% Controls: 79% Labor force d: IBD: 71% Controls: 82%

Working capacity, %

Disability pension, % Disabled: IBD: 1% Controls: 4%

Unemployed: IBD: 11% Controls: 4%

Disability pension: IBD: 8% Controls: 9%

Labor force non-participation e: IBD: 29% Controls: 19% Labor force non-participation: IBD w symptoms: 31% IBD w/o symptoms: 18% Controls: 15% Unemployed: IBD: 12% Controls: 4%

Labor force f: IBD w symptoms: 69% IBD w/o symptoms: 82% Controls: 85%

Employed h: IBD: 81% Controls: 100%

General population

50 controls Employed: (23 buddy & 27 CD: 79% community controls) Controls: 90%

All-cause g: IBD: 49% Controls: not presented Disease specific: IBD: 19% Sick leave i: IBD: 16% Controls: not presented

Early Unemployment, retirement, % %

Unemployed: IBD: 5% Controls: not presented Disability pension: IBD: 19% Controls: 10% Disease specific: IBD: 11%

Missing workdays j: IBD: 72% Controls: 59% Disabled k: CD: 12–20% Controls: 4% Unemployed l: CD: 50% Controls: 24%

K. Büsch et al.

Crohn's disease (CD) Binder et al.18 185 CD patients

Working/employed, %

1366

Table 2

1232 CD patients

Bernklev et al.12

161 CD patients

14,177 general Employed: population controls CD: 56% Controls: 69% General population

Stjernman et al.11 505 CD patients

General population

Hoivik et al.16

Background population

160 CD patients

Ulcerative colitis (UC) Bernstein et al. 1242 UC (study A)62 a patients

14,177 general population controls

Bernklev et al.12

334 UC patients

General population

Hoivik et al.16

341 UC patients

Background population

All-cause g: CD: 53% Disease specific: CD: 23%

Labor force m: CD: 66% Controls: 81%

Reduced capacity n: CD: 27% Controls: 11% Disease specific o: CD: 13%

Employed: UC: 62% Controls: 69% All-cause g: UC: 47% Disease specific: UC: 18%

Disabled: CD: 2% Controls: 4% Disability pension: CD:15% Controls: 9%

Unemployed: CD: 12% Controls: 4% Unemployed: CD: 9% Controls: 4%

Disability pension p: CD: 16% Controls: 7% Disease specific o: CD: 7% Disability pension: CD: 19% Controls: 10% Disease specific: CD: 16%

Unemployed: CD: 4% Controls: 4%

Disabled: UC: 1% Controls: 4% Disability pension: UC: 5% Controls: 9%

Unemployed: UC: 11% Controls: 4% Unemployed: UC: 13% Controls: 4%

Productivity in Inflammatory Bowel Disease

Bernstein et al. (study A)62 a

Disability pension: UC: 18% Controls: 10% Disease specific: UC: 9%

1367

a The two different Bernstein et al. studies (A and B) are reported separately. b Estimates presented are based on the age-adjusted results for the IBD, UC and CD groups in 1995–1996 vs the Manitoba population in 1996. c Individuals unemployed but actively seeking work were considered to be part of the labor force. d Defined as worked for pay or profit at any time in the past 12 months. e Defined as not working during the past 12 months. f Defined as worked during the past 12 months. g Defined as sick leave during the previous 6 months due to any reason (all-cause) or due to IBD, UC or CD (disease specific). h Defined as actively working plus persons on temporal sick leave. i Defined as temporary or permanent sick leave. j Defined as missed work due to illness among working adults between 18 and 64 years. k Defined as disabled after 5 years of disease. l Defined as being unemployed ≥ 6 weeks. m Defined as partial or full-time employed or unemployed, but able to work (20–64 years). n Numbers provided for 402 patients (25–64 years). o Estimation based on the information provided in the publication. p Numbers provided for 433 patients (20–64 years).

1368 A flowchart describing the article search process is depicted in Fig. 1. Data extraction was performed by at least two independent reviewers (KB and SAdS; in case of questions review by MH and/or FMR) taking the PRISMA Statement for Reporting Systematic Reviews and Meta-Analyses into account.48 Outcomes included employment status, work capacity, sick leave, disability pension, early retirement and the Work Productivity and Activity Impairment: Crohn's Disease (WPAI: CD). The WPAI is a validated, self-administered questionnaire assessing the impact of CD on the patient's ability to work and/or perform non-work activities.49 Results of the WPAI are expressed as a percentage of impairment, with higher percentages indicating greater impairment and less productivity. The results include four scores: percentage of time work missed (absenteeism), percentage of impairment while working (presenteeism), percentage of activity impairment (total work productivity impairment; TWPI), and an overall percentage work impairment score (total activity impairment; TAI). Original studies describing the frequency of work-related outcomes in patients with CD, UC or IBD were included. Papers which did not report outcome frequencies or reported incomplete/insufficient denominator information were excluded.50–59 The findings were organized by study design (noninterventional/interventional). Non-interventional studies were then structured according to whether they presented data in comparison to control groups or not and interventional studies were structured according to type of intervention. Whenever possible, a comparison of outcomes was made between two groups (IBD patients and controls) or two time points (before and after intervention). Direct comparisons and pooling of effect estimates by use of meta-analysis was not attempted due to heterogeneity between studies. The main reasons for variations between studies were differences in definitions used for CD/UC (e.g. based on ICD codes, case history or endoscopy results, Lennard–Jones criteria for CD) and outcome measures such as employment or working status, sick leave and/or disability pension. Additionally there were differences between populations investigated (e.g. socioeconomic status), differences in the observation period, and variations in assessment of both exposure and work-related outcomes (e.g. register excerpts versus interviews). Therefore only narrative summaries are provided.

3. Results A total of 112 studies were identified after the electronic search. Based on information in the abstracts 44 studies were excluded. Sixty-eight articles were then selected for full-text review and their reference lists were screened for additional articles using publication titles (Fig. 1). Hand searching by title led to the identification and review of 32 additional articles. Of those, 9 were included while 23 were excluded. In total, 30 non-interventional and 17 interventional studies formed the basis of this review.

3.1. Non-interventional studies Thirty non-interventional studies provided information on ≥ 1 work-related outcome of interest. Fifteen studies compared

K. Büsch et al. work-related outcomes in the patient population(s) to matched (Table 1) or unmatched controls (Table 2). Another 15 studies described work outcomes in IBD only (Table 3). All non-interventional studies were categorized according to outcome investigated. 3.1.1. Employment status Three studies provided information on the number of patients being employed in the IBD, UC or CD groups compared to their matched controls (Table 1).10,60,61 When compared to ageand sex-matched controls, employment was lower in patients compared to controls.60 However, when the comparison was made to age- and sex-matched controls, who had been admitted to a hospital for acute conditions, similar employment frequencies were observed (65% of CD patients versus 64% of controls61 and 71% of UC patients versus 73% of controls were employed).10 All studies involving unmatched comparator groups reported a lower number of IBD patients being employed or part of the labor force compared to the comparator groups (Table 2).24,62,63,11,62,64,65 The difference became more evident in IBD patients with symptoms when compared to IBD patients without symptoms or controls. Overall, the IBD population with symptoms was more than two times as likely as the non-IBD population to be out of the labor force (OR = 2.14).64 Similar to the studies that included comparator groups, the papers solely describing IBD, UC or CD patients showed high, but varying frequencies in employment (65%–73% in IBD, 48%–73% in CD and 61%–79% in UC; Table 3).13,25,28,38,66 3.1.2. Sick leave While in two studies sick leave which was defined as b 11 days was similar between CD or UC patients and their matched controls,10,61 a register based study showed that a significantly higher proportion of UC patients had a documented sick leave of N 14 days paid by the Social Insurance Agency (SIA) when compared to matched controls (Table 1).46 Studies without comparison groups showed similar and also lower values for the frequency of sick leave in IBD patient populations (10%–51% for CD and 8%–40% for UC; Table 3).23,25,38 3.1.3. Work disability All studies using a matched control design, reported a higher frequency of work disability in IBD, UC or CD patients compared to the matched comparator groups (Table 1).46,60,15 Those findings are supported by the majority of studies compared to non-matched comparators, who showed that more IBD, UC or CD patients were disabled or receive pension (Table 2).11,16,18 Nevertheless, one study reported a lower frequency of patients being disabled or on disability pension compared to the general population.62 3.1.4. Early retirement Only one study compared patients to age- and sex-matched controls and reported that 0% of CD and 3% of UC patients versus 3% of controls were on early retirement (Table 1).60 Two additional studies evaluated early retirement in IBD patients only and reported that 4% of CD and 5% of UC patients25 and 7% of IBD28 patients were retired or had early retirements (Table 3).

Non-interventional studies in IBD, UC and/or CD patients only.

Study

Number of patients

Inflammatory bowel disease (IBD) 170/144 IBD patients a Wyke et al.38

Working/ employed, %

Sick leave, %

Employed b: IBD: 68%/65%

Sick leave c: IBD: 41%/46%

Ghosh & Mitchell29

5636 IBD patients d

Nurmi et al.28

556 IBD patients d

Employed: IBD: 73%

Absenteeism f: IBD: 19% of all; 27% of employed

Viazis et al.27

1181 IBD patients

Employed h: IBD: 71%

Time off work i: IBD: 57%

Crohn's disease (CD) Gazzard et al.19

85 CD patients

Wyke et al.38

95/83 CD patients a

Ferguson et al.66

50 CD patients

Juan et al.13

635 CD patients

Feagan et al. (international)14

573 CD patients

Feagan et al. (Europe)14 o

146 CD patients

Stark et al.20

241 CD patients

Working capacity, %

Disability pension, %

Early retirement, %

Unemployment, %

Unemployed: IBD: 1%/5% Reduced ability to perform work e: IBD: 69% Pension g: IBD: 27% all-cause IBD: 7% diseaserelated Reduced work capability: IBD: 40%

Productivity in Inflammatory Bowel Disease

Table 3

Unemployed: IBD: 11%

Benefits j: 5% Sick leave c: CD: 45%/51% Employed: CD: 72% Employed: CD: 48% Employed n: CD: 61% Part-time employed: CD: 11% Employed n: CD: 63%

Days of work k: CD: 36%

Short term leave p: CD: 14%

Disabled l: CD: 15% Disability compensation: CD: 25% Disability compensation: CD: 34%

Unemployed: CD: 8% Unemployed m: CD: 37% Unemployed: CD: 39% Unemployed: CD: 45% Unemployed: CD: 3% (Continued on next page)

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Table 3 (continued) Study

Number of patients

Working/ employed, %

Sick leave, %

Working capacity, %

Disability pension, %

Early retirement, %

Unemployment, %

Long-term disability: CD: 19% 3025 CD patients

Ananthakrishnan et al.21

737 CD patients

Vergara et al.23

108 CD patients

Nurmi et al.28

153 CD patients

Hoivik et al.26

98 CD patients

Viazis et al.27

642 CD patients

Van der Valk et al.

1315 CD patients

Siebert et al.67

699 CD patients

Ulcerative colitis (UC) Hendriksen et al.22

512 UC patients

Wyke et al.38

75/61 UC patients a

Ferguson et al.66

20 UC patients

Stark et al.20

242 UC patients

Ghosh & Mitchell29

2333 UC patients

Reduced ability to perform work e: CD: 72% Disability compensation q: CD: 5% Working r: CD: 90% Employed: CD: 73% Working t: CD: 72% Employed h: CD: 69% Employed: CD: 54%

Sick leave s: CD: 10% Absenteeism f: CD: 22% of all; 31% of employed Sick leave u: CD: 16% Unemployed: CD: 12% Sick leave v: CD: 10% of all; 18% of employed

Disabled w: CD: 23%

Employed y: CD: 53%

Disability pension z: CD: 8%

Full work capacity aa: UC: 90%

Retired x: CD: 4% Unemployed y: CD: 24%

Disability pension ab: UC: b 5%

Sick leave c: UC: 36%/40% Employed: UC: 79% Employed n: UC: 67%

Short term leave p: UC: 15%

Long-term disability: UC: 7% Reduced ability to perform work e: UC: 66%

Unemployed: UC: 11% Unemployed: UC: 3%

K. Büsch et al.

Ghosh & Mitchell29

365 UC & proctitis patients

Employed: UC: 74%

Viazis et al.27

539 UC patients

Van der Valk et al.25

937 UC patients

Employed h: UC: 73% Employed: UC: 61%

Siebert et al.67

488 UC patients

Absenteeism f: UC: 18% of all; 25% of employed Unemployed: UC: 10% Sick leave v: UC: 8% of all; 13% of employed

Employed y: UC: 56%

a Number of patients included in initial/follow-up survey. aa Fully capable defined as less than 1 month lost during the year. ab Defined as all-cause disability pension. b Defined as full-, part-time and self-employed. c Defined as absence during the year preceding the survey. d The IBD group includes patients with indeterminate colitis (IC). e Defined as symptoms that affected patients' ability to work. f Defined as absence from work during the previous 12 months due to IBD. g Defined as full- or part-time pension. h Defined as part- and full-time employment. i Defined as need of outpatient visits due to problems related to IBD. j Defined as need for social security benefits or special invalid benefits. k Defined as work days lost due to disease. l Defined as totally or partially disabled due to disease complications. m Defined as unemployed and/or housekeeping. n Defined as part- or full-time employed. o Europe incl. Belgium, France, Germany, Italy, Netherlands, Norway, Spain, Sweden and the UK. p Defined as sick leave and medical appointments. q Defined as ever received permanent work disability compensation related to CD. r Defined as “actively working”. s Defined as temporarily sick leave. t Working includes students and pupils. u Defined as sick leave in the last 6 months. v Defined as sick leave during the previous 3 months. w Defined as partially or fully work disabled. x Defined as (early) retired. y Provided in written correspondence. z Defined as temporary and permanent work disabilities as a result of IBD.

Disabled w: UC: 13% Disability pension z: UC: 3%

Retired x: UC: 5% Unemployed y: UC: 18%

Productivity in Inflammatory Bowel Disease

Ulcerative colitis (UC) Nurmi et al.28

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K. Büsch et al.

3.1.5. Unemployment While studies comparing unemployment rates in IBD, UC or CD patients compared to matched controls found no or minor differences between the groups (Table 1),61,10,60 studies which reported unemployment compared to the general population found greater differences (4% of the general population versus 11%–12% of IBD, 4%–12% of CD, and 11%– 13% of UC patients).11,12,62 Especially, IBD patients experiencing symptoms were at higher risk of not being part of the labor force compared to patients without symptoms (Table 2).64 Higher frequencies of unemployment were reported in two CD specific studies which reported up to 45% of CD patients being unemployed (Table 3).13,14

biologic treatment on work outcomes in IBD patients (Table 5).30–37 3.2.1. Surgical interventions for IBD Of nine studies describing work-related outcomes in patients with IBD-related surgery, six studies examined outcomes after surgery only.38–42,45 Three studies investigated normal work capacity, disability or retirement before and after surgical intervention (Table 4).43,44,46

3.2. Interventional studies

3.2.1.1. Employment status. No information on employment status before surgery was provided. Employment after UC surgery seems to vary between 80%43 and 95%.42 Daly et al. included housewives in their estimate,42 while Damgaard et al. defined being employed as full or part-time employment only.43

Of 17 studies, nine reviewed surgical interventions (Table 4),38–46 while eight investigated the impact of

3.2.1.2. Working capacity. Damgaard et al. investigated the proportion of subjects with normal and reduced work capacity

Table 4

Interventional studies (surgical interventions).

Study

Disease Number of Intervention patients

Outcomes

Wyke et al.38

IBD

120

Martinsson et al.39 IBD

53

No change Had to change Modified work/hours Retrained Premature retirement Lighter work Change not due to health Normal work capacity post-OP

CD UC

16 37

Nordgren et al.40

CD

136 a

Watts et al.41

UC

131 b

Daly et al.42

UC

100

Damgaard et al.43 UC

49

Mikkola et al.44

UC

119 121

Johnson et al.45

UC

58

Neovius et al.46

UC

807

Surgery

Main results

44% (53/120) 10% (12/120) 13% (15/120) 2% (2/120) 4% (5/120) 3% (4/120) 24% (29/120) Ileostomy IBD: 77% (41/53); CD: 69% (11/16); UC: 81% (30/37) Change in job (e.g. work hours) IBD: 13% (7/53) Retrained IBD: 4% (2/53) Full disability/early retirement pension IBD: 6% (3/53) Primary excisional Normal work capacity post-OP 73% (78/107) surgery (proctocolectomy Reduced work capacity 14% (15/107) or ileorectal anastomosis) Temporary sick leave for CD 6% (6/107) Disability pension (DP) 7% (8/107) Primary surgical Returned to pre-OP work 88% (105/119) treatment Seek for lighter work 8% (10/119) Not returned to work 3% (4/119) Total excision of the Employed (incl. housewives) 95% (95/100) large intestine, Retired after OP 3% (3/100) and ileostomy Incapable of working 1% (1/100) Mucosal proctectomy Employed (full-/part-time) post-OP 80% (39/49) and IPAA Normal work capacity pre-OP 12% (6/49) Normal work capacity post-OP 94% (46/49) Conventional Retired before OP CPC: 10% (12/119); proctocolectomy (CPC) RCP: 4% (5/121) Restorative Retired after OP CPC: 10% (11/107); proctocolectomy (RCP) RCP: 3% (3/116) Restorative Reduced workload 9% (5/58) proctocolectomy Disability pension (DP) 5% (3/58) Colectomy Fully disabled 3 years before colectomy 5.9% (48/807) Fully disabled 3 years after colectomy 12.4% (100/807)

IBD = inflammatory bowel disease; UC = ulcerative colitis; CD = Crohn's disease; IPAA = ileal J-pouch–anal anastomosis; CPC = conventional proctocolectomy and Brooke ileostomy; RCP = restorative proctocolectomy; OP = operation. a 107 patients in working age. b Results were only provided for 119 patients with an ileostomy.

Interventional studies (medical interventions).

Study

Disease Number of Setting; time horizon Intervention patients

UC Reinisch et al.30 a CD Lichtenstein et al.31 Feagan et al.32 CD

728 573

Feagan et al.33 CD

168 b; 79

RCT; WELCOME 26 weeks

Lichtiger et al.34

CD

673; 300

RCT; CHOICE 24 weeks

Panaccione et al.35

CD

304; 271

RCT; ACCESS 24 weeks

Louis et al.36

CD

945; 785

RCT; CARE 20 weeks

Binion et al.37

CD

1202 employed patients

Meta-analysis of data from ACCESS, CARE, CHOICE, EXTEND 26 weeks

215 b

RCTs; ACT 1 & ACT 2 30 weeks RCT; ACCENT I 54 weeks RCT; PRECiSE 2 26 weeks

Method

Employed, % (n)

Infliximab (IFX)

As observed

65% (470/728)

IFX

As observed

62% (353/573)

Certolizumab pegol (CZP) c

Intention to treat (ITT): last observation carried forward (LOCF)

64% (138/215)

Mean WPAI Mean WPAI Mean change scores, scores, end in WP outcome baseline

A: 22 P: 43 TWPI: 50 TAI: 51 CZP after IFX As observed; no imputation 55% (92/168) A: 23 failure c of missing data P: 43 TWPI: 46 TAI: 64 Adalimumab (ADA) As observed 63% (423/673) A: 15 after IFX failure P: 44 TWPI: 49 TAI: 58 ADA Intention to treat (ITT): Baseline: 64% (195/304) A: 16 last observation carried P: 50 End: 69% (187/271) TWPI: 57 forward (LOCF) TAI: 63 ADA As observed; non-responder 57% (542/945) A: 23 imputation (NRI) P: 45 TWPI: 52 TAI: 57 ADA

A: 12 P: 26 TWPI: 30 TAI: 36 A: 9 P: 25 TWPI: 28 TAI: 34 A: 9 e P: 25 e TWPI: 29 TAI: 33

A: − 12 P: − 18 TWPI: − 21 TAI: − 19 A: − 15 d P: − 15 TWPI: − 20 TAI: − 28 A: − 7 P: − 18 TWPI: − 19 TAI: − 24 A: − 7 e P: − 26 e TWPI: − 29 e TAI: − 31 e A: − 10 P: − 20 TWPI: − 21 TAI: − 26 A: − 9 P: − 24 TWPI: − 27 TAI: NA

1373

IBD = inflammatory bowel disease; UC = ulcerative colitis; CD = Crohn's disease; RCT = randomized clinical trial; CZP = certolizumab pegol; ADA = adalimumab; IFX = infliximab; WP = work productivity; WPAI = work productivity and activity impairment; A = absenteeism; P = presenteeism; TWPI = total work productivity impairment; TAI = total activity impairment. a Reinisch et al. and Lichtenstein et al. did only provide information on subgroups of IBD patients in remission vs not in remission (overall IBD data not provided when contacting authors thus no data presented in table). b Responding patients. c Approved US label; EMEA refused marketing authorization for CZP. d Estimated mean change based on figure in publication. e Provided by the authors in written correspondence.

Productivity in Inflammatory Bowel Disease

Table 5

1374 before and after mucosal proctectomy and ileal J-pouch–anal anastomosis in 49 UC patients (median follow-up time after surgery was 42 months). The proportion of subjects with normal capacity to work increased from 12% pre-operatively to 94% post-operatively.43 Two Swedish studies came to the conclusion that 81% of UC subjects and 69%–73% of CD subjects reported normal work capacity after surgery.39,40 3.2.1.3. Retirement/disability pension. Between 4% and 6% of IBD patients retired prematurely or were fully disabled after surgery.38,39 The percentage was slightly higher in a study in CD patients (7% were on disability pension after primary excisional surgery)40 compared to a study in UC patients (5% of UC patients were on disability pension after restorative proctocolectomy).45 Two studies evaluated the impact of surgery on retirement and disability pension in UC patients. One found a 50% increase in the proportion of patients being fully disabled after colectomy.46 The other reported similar number of patients being retired before and after surgery, but noted a higher number of patients retiring after conventional proctocolectomy when compared to restorative proctocolectomy.44 3.2.1.4. Other work-related outcomes. Temporary sick leave due to CD during the follow-up period after surgery was reported by 5% of patients.40 A change in job was reported in 10% to 13% of IBD patients38,39 and 13% had to modify their work/hours.38 Lighter work was sought for by 3% of IBD patients.38 3.2.2. Medical treatment for IBD Eight studies investigated work-related outcomes in UC30 and CD31–37 patients with biologic treatment. All studies used self-reported outcome measures with six using the WPAI:CD questionnaire (Table 5).32–37 3.2.2.1. Employment status. Most studies reported only baseline data regarding employment status, with the number of employed patients varying between 55% and 65%.30–36 One of the eight studies reported a positive effect on employment status after 24 weeks of treatment (64% of UC patients employed at baseline versus 69% at the end of study).35 Lichtenstein et al. provided employment information by remission status for 162 CD patients who were unemployed at baseline and had data at week 54. Of the 58 patients in remission 31% were employed at week 54 compared to 16% among the 104 CD patients not in remission.31 3.2.2.2. WPAI scores. Six studies reported significant changes in WPAI scores from baseline to end of study.32–37 Reduction in the mean absenteeism score ranged from − 7 to − 15, in the mean presenteeism score from − 15 to − 20 and in the mean TWPI score from − 19 to − 21 in the employed patient population. All five RCTs reported also significant improvements in mean TAI score from baseline (mean change from − 19 to − 28).32–36 3.2.2.3. Work outcomes. Reinisch et al. calculated hours per week actually worked (HPWAW), productivity and hours per week fully productive (HPWFP) to evaluate work and productivity of UC patients. HPWFP was calculated as HPWAW × productivity score / 100. At week 30, greater improvements

K. Büsch et al. were seen for all three outcomes in patients in remission compared with those UC patients not in remission.30

4. Discussion This systematic review of published articles quantifies the frequency of work-related outcomes in IBD (and specifically in UC and CD), and summarizes the effect of surgical and medical interventions on work-related outcomes. Compared with the review by Marri et al. published in 2005,9 which investigated education and employment behavior in IBD patients, the current systematic review included 13 studies that were not identified10,13,18,19,22,31,39–45 and 24 studies published after 2005.11,12,14–17,20,21,23–30,32–37,46,67 In addition, all studies that investigated the effect of surgical or medical interventions on work outcomes were summarized.30–46 Similar to Marri et al.9 this review found that the majority of studies report an increased frequency of sick leave, disability pension and unemployment in IBD. Furthermore, it was found that medical treatment, defined as biologic agents, seems to have a positive effect on absenteeism and presenteeism in randomized clinical trials.32–37 However, the impact of medical interventions over a longer follow-up and other outcomes such as employment and disability pension as well as the impact of surgical interventions need further evaluation.

4.1. Strengths and limitations This is the first paper systematically summarizing information regarding frequency of employment status, sick leave, working capacity, disability pension and early retirement in IBD, UC and CD patients including medical and surgical interventions and their effect on different work-related outcomes. Our extensive literature review enabled us to identify a number of areas where additional research is needed. These include interventions and their impact on work-related outcomes and risk factors impacting workrelated outcomes in patients with IBD. Evidence of an impact of medical and surgical intervention on work-related outcomes in IBD patients is limited. Medical interventions have so far only been evaluated in specifically defined patient groups included in clinical trials with a short duration (20–54 weeks)31,36 not allowing for extrapolation. Most papers reviewing surgical interventions are small in size (49–136 participants)40,43 and are based on self-reported information potentially affected by both non-response and recall bias. The resulting imprecision in estimates and uncertainty of the generalizability of the findings is therefore substantial. Additional robust data is needed to better understand whether medical treatment could restore work ability to the level of the general population, or in case of surgical intervention even to pre-surgery levels. In addition, a better understanding of risk factors interacting to create work limitations and work loss is required to better guide early interventions for individual patients to prevent or at least postpone work disability and job loss. Several limitations are acknowledged including the fact that pooling of effect estimates was not possible due to great heterogeneity between studies regarding definition of IBD, definition of outcomes, study population, study design and outcome measurement. Those differences in study design and

Productivity in Inflammatory Bowel Disease methods could explain parts of the observed variation in results. Additional reasons, which could have influenced work outcomes and therefore results reported, could be differences and changes in legislations, labor market flexibilities at the time of the study or different social security systems influencing patient work motivation.68,69 For instance, the official unemployment rate in the Netherlands (Eurostat, accessed Jan 8, 2014) at the time of the Boonen et al.60 study was 2–3%, as compared with above 8% in 1984. It is therefore important that data on IBD cases and controls are obtained simultaneously. Cyclical and structural changes in the labor market will otherwise bias the results, and natural changes may also explain the differences in e.g. unemployment rates over time within and between countries. 4.1.1. Methodological challenges with studies included As mentioned above, it is important to consider a number of factors when reviewing studies of work-related outcomes. For example, one issue mentioned is the limiting comparability concerning the study populations. While some studies reported work-related outcomes for those in working age (19–64 years),11,46 others restricted the analysis to those being employed.37 In addition, some studies selected subgroups to report different outcomes (e.g. results on sick leave and presenteeism were reported for those employed or in working age),28,32–37,46 while measures on employment status were often reported for the total group. Another issue is the differences in comparator groups impacting comparability of results (some studies matched for age and sex,10,60,61 others for propensity score15). In the studies using unmatched comparator groups, the comparison was made with the general population or general population controls as well as with unmatched non-IBD, healthy, buddy or community controls.11,12,16–18,24,62–65 Comparability of results is also limited by different definitions of IBD. Some papers used self-reported information,64,65 while others used case history and endoscopic result or ICD codes to classify patients.10,40,46,60,62 Other papers did not provide a definition of IBD or their outcome. Others used a wide range of methods and definitions (eg. registers from social insurance agencies,46,60 self-composed questionnaires or validated instruments such as the WPAI)32–37 thus comparability remains limited. Finally, most studies used different definitions to describe work-related outcomes. For example, definition of work status ranged from working (including also students),26 labor force participation (considered all individuals who were unemployed,11 all unemployed individuals who were actively seeking work62 or all having worked for pay or profit at any time in the past 12 months),64,65 being employed (defined as full-time, part-time20,27,60 and/or self-employment)38 to working actively (defined as being employed and not being on sick leave).23,24 The resulting significant heterogeneity between studies made an interpretation of results difficult. Therefore, to enhance comparability between studies, consensus on outcome instruments and on how to conduct and report studies on work-related outcomes is needed.68 However, an unequivocal definition of those outcomes is difficult and measurements may not be sufficient to capture the real burden.7,62 For example, employment as an outcome variable would not be sufficient as a higher percentage of IBD patients are at home and not actively in the labor

1375 force.62 In addition, sick leave is restricted to labor force participants. This will lead to selection bias, as the sickest and most vulnerable individuals never enter the labor market and never run the risk of sick leave.69

5. Conclusion The majority of studies have found that patients with IBD experience a high burden in work-related outcomes regardless of the methodology used to measure and quantify these outcomes. While biologic agents showed positive effect on absenteeism and presenteeism in randomized clinical trials, the impact of surgical interventions needs further evaluation. In conclusion, additional data on productivity losses and long-term impact of interventions is needed to help inform decisions about treatment options and their benefits in reducing loss of economic productivity and work disability.

Author contributions Guarantor of the article: Katharina Büsch Study concept and design: Büsch K., da Silva S.A. Analysis: Büsch K., da Silva S.A., Holton M., Rabacow F.M. Drafting of the manuscript: Büsch K. Critical revision of the manuscript for important intellectual content: Büsch K., da Silva S.A., Holton M., Khalili H., Ludvigsson J.F., Rabacow F.M. Obtained funding: NA Study supervision: Khalili H., Ludvigsson J.F.

Conflict of interest JFL is a professor in clinical epidemiology at Karolinska Institutet and a pediatrician at the Örebro University Hospital. HK is an instructor in medicine at Harvard Medical School and a physician at the Massachusetts General Hospital. FMR is a registered PhD-student at the University of São Paulo. MH is an employee of Lorimer Enterprises Inc. and has served previously as a consultant for AbbVie and Abbott. SAdS is doing post-doctoral research at the University of São Paulo. KB is a registered PhD-student at Karolinska Institutet, and an employee of AbbVie AB. KB holds stocks in AbbVie AB.

Grant funding HK is supported by a career development award from the American Gastroenterological Association (AGA) and by the National Institute of Diabetes and Digestive and Kidney Diseases (K23 DK099681). JFL has received funding from the Karolinska Institutet Strategic Research Program in Epidemiology. No funding or writing assistance was provided for this project.

References 1. Jacobs P, Bissonnette R, Guenther LC. Socioeconomic burden of immune-mediated inflammatory diseases–focusing on work productivity and disability. J Rheumatol Suppl 2011 Nov;88: 55–61.

1376 2. Cohen RD. The pharmacoeconomics of biologic therapy for IBD. Nat Rev Gastroenterol Hepatol 2010 Feb;7(2):103–9. 3. Fedorak RN, Wong K, Bridges R. Canadian Digestive Health Foundation Public Impact Series. Inflammatory bowel disease in Canada: Incidence, prevalence, and direct and indirect economic impact. Can J Gastroenterol 2010 Nov;24(11): 651–5. 4. Bodger K. Cost of illness of Crohn's disease. Pharmacoeconomics 2002;20(10):639–52. 5. Ward FM, Bodger K, Daly MJ, Heatley RV. Clinical economics review: medical management of inflammatory bowel disease. Aliment Pharmacol Ther 1999 Jan;13(1):15–25. 6. Luces C, Bodger K. Economic burden of inflammatory bowel disease: a UK perspective. Expert Rev Pharmacoecon Outcomes Res 2006 Aug;6(4):471–82. 7. Burisch J, Jess T, Martinato M, Lakatos PL, EpiCom E. The burden of inflammatory bowel disease in Europe. J Crohns Colitis 2013 May;7(4):322–37. 8. Calkins BM. Mendeloff AI. Epidemiology of inflammatory bowel disease. Epidemiol Rev 1986;8:60–91. 9. Marri SR, Buchman AL. The education and employment status of patients with inflammatory bowel diseases. Inflamm Bowel Dis 2005 Feb;11(2):171–7. 10. Hendriksen C, Binder V. Social prognosis in patients with ulcerative colitis. Br Med J 1980 Aug 30;281(6240):581–3. 11. Stjernman H, Tysk C, Almer S, Strom M, Hjortswang H. Unfavourable outcome for women in a study of health-related quality of life, social factors and work disability in Crohn's disease. Eur J Gastroenterol Hepatol 2011 Aug;23(8):671–9. 12. Bernklev T, Jahnsen J, Henriksen M, Lygren I, Aadland E, Sauar J, et al. Relationship between sick leave, unemployment, disability, and health-related quality of life in patients with inflammatory bowel disease. Inflamm Bowel Dis 2006 May;12(5):402–12. 13. Juan J, Estiarte R, Colome E, Artes M, Jimenez FJ, Alonso J. Burden of illness of Crohn's disease in Spain. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 2003 Dec;35(12):853–61. 14. Feagan BG, Bala M, Yan S, Olson A, Hanauer S. Unemployment and disability in patients with moderately to severely active Crohn's disease. J Clin Gastroenterol 2005 May-Jun;39(5): 390–5. 15. Gibson TB, Ng E, Ozminkowski RJ, Wang S, Burton WN, Goetzel RZ, et al. The direct and indirect cost burden of Crohn's disease and ulcerative colitis. J Occup Environ Med 2008 Nov;50(11): 1261–72. 16. Hoivik ML, Moum B, Solberg IC, Henriksen M, Cvancarova M, Bernklev T, et al. Work disability in inflammatory bowel disease patients 10 years after disease onset: results from the IBSEN Study. Gut 2013 Mar;62(3):368–75. 17. Gunnarsson C, Chen J, Rizzo JA, Ladapo JA, Naim A, Lofland JH. The employee absenteeism costs of inflammatory bowel disease: evidence from US National Survey Data. J Occup Environ Med 2013 Apr;55(4):393–401. 18. Binder V, Hendriksen C, Kreiner S. Prognosis in Crohn's disease– based on results from a regional patient group from the county of Copenhagen. Gut 1985 Feb;26(2):146–50. 19. Gazzard BG, Price HL, Libby GW, Dawson AM. The social toll of Crohn's disease. Br Med J 1978 Oct 21;2(6145):1117–9. 20. Stark R, Konig HH, Leidl R. Costs of inflammatory bowel disease in Germany. Pharmacoeconomics 2006;24(8):797–814. 21. Ananthakrishnan AN, Weber LR, Knox JF, Skaros S, Emmons J, Lundeen S, et al. Permanent work disability in Crohn's disease. Am J Gastroenterol 2008 Jan;103(1):154–61. 22. Hendriksen C, Kreiner S, Binder V. Long term prognosis in ulcerative colitis–based on results from a regional patient group from the county of Copenhagen. Gut 1985 Feb;26(2):158–63.

K. Büsch et al. 23. Vergara M, Montserrat A, Casellas F, Gallardo O, Suarez D, Motos J, et al. Development and validation of the Crohn's disease perceived work disability questionnaire. Inflamm Bowel Dis 2011 Nov;17(11):2350–7. 24. Vergara M, Montserrat A, Casellas F, Maudsley M, Gallardo O, Ricart E, et al. Validation of the Spanish Work Productivity and Activity impairment questionnaire: Crohn's disease version. Eur J Gastroenterol Hepatol 2009 Jul;21(7):809–15. 25. van der Valk ME, Mangen MJ, Leenders M, Dijkstra G, van Bodegraven AA, Fidder HH, et al. Healthcare costs of inflammatory bowel disease have shifted from hospitalisation and surgery towards anti-TNFalpha therapy: results from the COIN study. Gut 2012 Nov 7. 26. Hoivik ML, Bernklev T, Solberg IC, Cvancarova M, Lygren I, Jahnsen J, et al. Patients with Crohn's disease experience reduced general health and vitality in the chronic stage: ten-year results from the IBSEN study. J Crohns Colitis 2012 May;6(4):441–53. 27. Viazis NMG, Karmiris K, Polymeros D, Kouklakis G, Maris T, Karagiannis J, Karamanolis DG. Inflammatory bowel disease: Greek patients’ perspective on quality of life, information on the disease, work productivity and family support. Annals of Gastroenterology 2013;26:52–8. 28. Nurmi E, Haapamaki J, Paavilainen E, Rantanen A, Hillila M, Arkkila P. The burden of inflammatory bowel disease on health care utilization and quality of life. Scand J Gastroenterol 2013 Jan;48(1):51–7. 29. Ghosh S, Mitchell R. Impact of inflammatory bowel disease on quality of life: Results of the European Federation of Crohn's and Ulcerative Colitis Associations (EFCCA) patient survey. J Crohns Colitis 2007 Sep;1(1):10–20. 30. Reinisch W, Sandborn WJ, Bala M, Yan S, Feagan BG, Rutgeerts P, et al. Response and remission are associated with improved quality of life, employment and disability status, hours worked, and productivity of patients with ulcerative colitis. Inflamm Bowel Dis 2007 Sep;13(9):1135–40. 31. Lichtenstein GR, Yan S, Bala M, Hanauer S. Remission in patients with Crohn's disease is associated with improvement in employment and quality of life and a decrease in hospitalizations and surgeries. Am J Gastroenterol 2004 Jan;99(1):91–6. 32. Feagan BG, Reilly MC, Gerlier L, Brabant Y, Brown M, Schreiber S. Clinical trial: the effects of certolizumab pegol therapy on work productivity in patients with moderate-to-severe Crohn's disease in the PRECiSE 2 study. Aliment Pharmacol Ther 2010 Jun;31(12):1276–85. 33. Feagan BG, Sandborn WJ, Wolf DC, Coteur G, Purcaru O, Brabant Y, et al. Randomised clinical trial: improvement in health outcomes with certolizumab pegol in patients with active Crohn's disease with prior loss of response to infliximab. Aliment Pharmacol Ther 2011 Mar;33(5):541–50. 34. Lichtiger S, Binion DG, Wolf DC, Present DH, Bensimon AG, Wu E, et al. The CHOICE trial: adalimumab demonstrates safety, fistula healing, improved quality of life and increased work productivity in patients with Crohn's disease who failed prior infliximab therapy. Aliment Pharmacol Ther 2010 Nov;32(10): 1228–39. 35. Panaccione R, Loftus Jr EV, Binion D, McHugh K, Alam S, Chen N, et al. Efficacy and safety of adalimumab in Canadian patients with moderate to severe Crohn's disease: results of the Adalimumab in Canadian SubjeCts with ModErate to Severe Crohn's DiseaSe (ACCESS) trial. Can J Gastroenterol 2011 Aug;25(8):419–25. 36. Louis E, Lofberg R, Reinisch W, Camez A, Yang M, Pollack PF, et al. Adalimumab improves patient-reported outcomes and reduces indirect costs in patients with moderate to severe Crohn's disease: results from the CARE trial. J Crohns Colitis 2013 Feb;7(1):34–43. 37. Binion DG, Louis E, Oldenburg B, Mulani P, Bensimon AG, Yang M, et al. Effect of adalimumab on work productivity and

Productivity in Inflammatory Bowel Disease

38.

39.

40.

41.

42. 43.

44.

45.

46.

47. 48.

49.

50.

51.

52.

53.

54.

indirect costs in moderate to severe Crohn's disease: a meta-analysis. Can J Gastroenterol 2011 Sep;25(9):492–6. Wyke RJ, Edwards FC, Allan RN. Employment problems and prospects for patients with inflammatory bowel disease. Gut 1988 Sep;29(9):1229–35. Martinsson ES, Josefsson M, Ek AC. Working capacity and quality of life after undergoing an ileostomy. J Adv Nurs 1991 Sep;16(9):1035–41. Nordgren SR, Fasth SB, Oresland TO, Hulten LA. Long-term follow-up in Crohn's disease. Mortality, morbidity, and functional status. Scand J Gastroenterol 1994 Dec;29(12):1122–8. Watts JM, de Dombal FT, Goligher JC. Long-term complications and prognosis following major surgery for ulcerative colitis. Br J Surg 1966 Dec;53(12):1014–23. Daly DW, Brooke BN. Ileostomy and excision of the large intestine for ulcerative colitis. Lancet 1967 Jul 8;2(7506):62–4. Damgaard B, Wettergren A, Kirkegaard P. Social and sexual function following ileal pouch-anal anastomosis. Dis Colon Rectum 1995 Mar;38(3):286–9. Mikkola K, Luukkonen P, Jarvinen HJ. Restorative compared with conventional proctocolectomy for the treatment of ulcerative colitis. Eur J Surg 1996 Apr;162(4):315–9. Johnson E, Carlsen E, Nazir M, Nygaard K. Morbidity and functional outcome after restorative proctocolectomy for ulcerative colitis. Eur J Surg 2001 Jan;167(1):40–5. Neovius M, Arkema EV, Blomqvist P, Ekbom A, Smedby KE. Patients with ulcerative colitis miss more days of work than the general population, even following colectomy. Gastroenterology 2013 Mar;144(3):536–43. Dunikowski LG. EMBASE and MEDLINE searches. Can Fam Physician 2005 Sep;51:1191. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med 2009 Aug 18;151(4):W65–94. Reilly MC, Gerlier L, Brabant Y, Validity Brown M. reliability, and responsiveness of the work productivity and activity impairment questionnaire in Crohn's disease. Clinical therapeutics 2008 Feb;30(2):393–404. Allen H, Bunn 3rd WB, Naim AB. The self-reported health and productivity burden of autoimmune disorders at a major self-insured employer. J Occup Environ Med 2012 Sep;54(9): 1049–63. Bassi A, Dodd S, Williamson P, Bodger K. Cost of illness of inflammatory bowel disease in the UK: a single centre retrospective study. Gut 2004 Oct;53(10):1471–8. Duepree HJ, Senagore AJ, Delaney CP, Brady KM, Fazio VW. Advantages of laparoscopic resection for ileocecal Crohn's disease. Dis Colon Rectum 2002 May;45(5):605–10. Eckardt VF, Lesshafft C, Kanzler G, Bernhard G. Disability and health care use in patients with Crohn's disease: a spouse control study. Am J Gastroenterol 1994 Dec;89(12):2157–62. Reichel C, Streit J, Wunsch S. Linking Crohn's disease health status measurements with International Classification of Functioning, Disability and Health and vocational rehabilitation outcomes. J Rehabil Med 2010 Jan;42(1):74–80.

1377 55. Scarpa M, Ruffolo C, Bassi D, Boetto R, D'Inca R, Buda A, et al. Intestinal surgery for Crohn's disease: predictors of recovery, quality of life, and costs. J Gastrointest Surg 2009 Dec;13(12): 2128–35. 56. Sonnenberg A. Disability and need for rehabilitation among patients with inflammatory bowel disease. Digestion 1992;51(3): 168–78. 57. Sonnenberg A. Disability from inflammatory bowel disease among employees in West Germany. Gut 1989 Mar;30(3): 367–70. 58. Sonnenberg A. Occupational distribution of inflammatory bowel disease among German employees. Gut 1990 Sep;31(9): 1037–40. 59. Straus WL, Eisen GM, Sandler RS, Murray SC, Sessions JT. Crohn's disease: does race matter? The Mid-Atlantic Crohn's Disease Study Group. Am J Gastroenterol 2000 Feb;95(2):479–83. 60. Boonen A, Dagnelie PC, Feleus A, Hesselink MA, Muris JW, Stockbrugger RW, et al. The impact of inflammatory bowel disease on labor force participation: results of a population sampled case-control study. Inflamm Bowel Dis 2002 Nov;8(6): 382–9. 61. Sorensen VZ, Olsen BG, Binder V. Life prospects and quality of life in patients with Crohn's disease. Gut 1987 Apr;28(4):382–5. 62. Bernstein CN, Kraut A, Blanchard JF, Rawsthorne P, Yu N, Walld R. The relationship between inflammatory bowel disease and socioeconomic variables. Am J Gastroenterol 2001 Jul;96(7): 2117–25. 63. Mayberry MK, Probert C, Srivastava E, Rhodes J, Mayberry JF. Perceived discrimination in education and employment by people with Crohn's disease: a case control study of educational achievement and employment. Gut 1992 Mar;33(3):312–4. 64. Longobardi T, Jacobs P, Bernstein CN. Work losses related to inflammatory bowel disease in the United States: results from the National Health Interview Survey. Am J Gastroenterol 2003 May;98(5):1064–72. 65. Longobardi T, Jacobs P, Wu L, Bernstein CN. Work losses related to inflammatory bowel disease in Canada: results from a National Population Health Survey. Am J Gastroenterol 2003 Apr;98(4):844–9. 66. Ferguson A, Sedgwick DM, Drummond J. Morbidity of juvenile onset inflammatory bowel disease: effects on education and employment in early adult life. Gut 1994 May;35(5):665–8. 67. Siebert U, Wurm J, Gothe RM, Arvandi M, Vavricka SR, von Kanel R, et al. Predictors of temporary and permanent work disability in patients with inflammatory bowel disease: results of the swiss inflammatory bowel disease cohort study. Inflamm Bowel Dis 2013 Mar-Apr;19(4):847–55. 68. ter Wee MM, Lems WF, Usan H, Gulpen A, Boonen A. The effect of biological agents on work participation in rheumatoid arthritis patients: a systematic review. Ann Rheum Dis 2012 Feb;71(2):161–71. 69. Neovius K, Johansson K, Kark M, Neovius M. Obesity status and sick leave: a systematic review. Obesity reviews : an official journal of the International Association for the Study of Obesity 2009 Jan;10(1):17–27.

Sick leave and disability pension in inflammatory bowel disease: a systematic review.

Inflammatory bowel disease has considerable effects on work-related outcomes and leads to high societal costs due to sick leave and disability pension...
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