Abstract

Objective. To answer the question ‘does TNF blockade therapy enable people with severe AS to return to work or work more productively?’.

Methods. All patients with AS currently receiving anti-TNF therapy at two UK Hospitals were asked to complete a questionnaire. This asked about occupational history, type of work, degree of job-related physical activity, working hours and sickness absence from work both currently (on anti-TNF treatment) and pre-treatment.

Results. Sixty-five patients (72.3% male), aged 29–64 (mean 46.1) yrs, whose duration of anti-TNF treatment ranged from 3 to 56 (mean 19.1) months were studied. Twenty-four (36.9%) patients were receiving infliximab, 21 (32.3%) etanercept and 20 (30.8%) adalimumab. Pre-treatment, 46 (70.8%) were in employment (1 was a student); 38 (58.5%) were working full-time and 8 (12.3%) part-time; 19 (29.2%) were not working. On treatment, 50 (76.9%) patients were working, 44 (67.7%) full-time and 6 (9.2%) part-time. Two individuals who worked part-time pre-treatment had returned to work full-time. Thus, on treatment, 4 of the 19 patients who were previously unable to work returned to employment, and 2 others increased their work from part-time to full-time. Patients rated the effect of AS on work capacity as 7.05/10 pre-treatment and 2.92/10 post-treatment. Those who were working lost, on average, 15 days from work due to sick leave in the 12 months pre-treatment and 0.91 days in the first 12 months on treatment.

Conclusions. Treatment of active AS with TNF blockade appears to be associated with improved capacity for work.

Background

The physical features and symptoms of AS are well-recognized. More subtle effects, however, especially fatigue, poor sleep, reduced independence and work disability, receive less attention and the effects of treatment on these is unclear. One-third of patients with AS give up work before normal retirement age and another 15% reduce or change their work because of AS [1]. The impact of work disability has, however, only recently drawn attention [2, 3]. In a Dutch study, overall participation in the labour force was 54.2% for the AS cohort, a significant reduction of 11% compared with the general population of the same working age [4]. In the middle decades of life, the work capacity of people with AS is similar to that of people with RA [5]. Work disability is associated with being older, longer duration of disease, lower educational standards, comorbidity, hip surgery, greater physical impairment, pain, fatigue, stiffness, anxious and depressed mood, smoking and lower self-esteem [6, 7]. More than three-quarters of patients with AS who had stopped working were officially recognized as work disabled.

Being unable to work has important consequences for the individual and his/her family through both loss of earnings and the loss of self-esteem that a career and income provide. It is also associated with substantial societal costs through social and income support and the loss of skills from the labour force [8, 9]. These societal costs are difficult to measure and vary from one country to another depending on the social support structure. Nonetheless, costs are substantial for those with severe disease and are compounded by added medical costs associated with need for joint surgery, hospital treatment and costs associated with comorbidities such as osteoporosis. Functional disability is the most important indicator of high total costs and direct costs among these patients [9]. The risks of having high total costs (>$10 000/yr) increased by a factor of 3 with each one point increase in the HAQ-S score. The authors concluded that interventions that reduce functional disability would be anticipated to be the most effective means of decreasing the costs of AS.

Biological therapy with each of the three currently licensed TNF-α blocking drugs has revolutionized the treatment of this hitherto poorly managed condition and effects on the symptoms of AS [10–13] and health-related quality of life (QoL) are well recognized [14–16]. However, treatment is expensive, has substantial potential for toxicity [17] and conclusive evidence of a disease-modifying effect—in terms of preventing ankylosis—is lacking. Impressive, if incomplete, reductions in bone oedema suggest reduction and, in some cases, resolution of spinal inflammation, which may be expected to diminish further progression to ankylosis [18, 19]. Similarly, short-term radiographic studies suggest small benefits in terms of reduced radiographic progression although some progression occurs even during treatment [20].

In spite of these uncertainties, judgements have to be made about where the balance point lies between benefits of biologic treatment of AS and the costs, including toxicity [21]. It may be considered that, for some, symptomatic benefit alone justifies the high cost and risks. But there are cogent arguments that the substantial costs and potential risks can only be justified by more fundamental and lasting benefits [22]. In this context, lasting changes in work capacity, lifestyle and socioeconomic circumstances might well be tantamount to disease modification, and evidence of these should be taken into account in assessing the place of biologic therapy. Irrespective of the effects on ankylosis, failure of treatment to reverse the devastating employment effects for people with AS would indicate a poor functional benefit whilst even a modest recovery of work capacity would have a major effect on personal independence and health-related and societal costs.

Some preliminary evidence of improved work capacity amongst AS sufferers associated with TNF blockade therapy has been presented [23] though major impact factors such as return to work have not been reported. This study has therefore addressed the issue of return to work and related aspects in people with AS on anti-TNF treatment by means of structured questionnaires combined with standard measures of disease activity, function and response to treatment.

Methods

All patients with AS attending rheumatology clinics at Northwick Park and Norfolk and Norwich Hospitals, who were aged 18–65 yrs and currently receiving anti-TNF therapy, were asked to complete a questionnaire delivered by one of us (A.K.G.). All fulfilled current British Society for Rheumatology criteria for initiation and continuation of TNF blockade treatment [24]. Patient demographics, duration of disease, the TNF blocker used and duration of treatment were noted. Measures of disease activity (Bath Ankylosing Spondylitis Disease Activity Index—BASDAI [25]), function (Bath Ankylosing Spondylitis Functional Index—BASFI [26]) spinal mobility (Bath Ankylosing Spondylitis Metrology Index—BASMI [27, 28]) and health-related QoL (ASQoL [29]) were recorded and analysed both pre-treatment and at the survey point. The questionnaire asked details about occupational history, including type of work, degree of job-related physical activity, duration of work and sickness absence from work both currently (on anti-TNF treatment) and pre-treatment. For the purposes of this study a working week of 35 h or over was considered ‘full-time’ work, with <35 h/week being recorded as ‘part-time’.

Those participants who were working were asked to describe their work as predominantly sedentary, standing, physical or heavy manual and to rank on a 0–10 linear scale how much they considered that AS had affected their ability to work pre- and post-anti-TNF therapy (where 0 is not affected at all and 10 is severely affected). All study participants gave informed consent. Approval from the local ethics committees was obtained for carrying out this study. Statistical analysis was not undertaken in view of the small numbers of patients studied.

Results

Seventy-eight patients with AS of working age and recorded as currently receiving anti-TNF therapy were invited to participate in the study. Sixty-five (72.3% male) aged 29–64 (mean 46.1) yrs consented to take part and provided complete data sets. Six individuals were no longer receiving anti-TNF treatment, three were not contactable and four returned incomplete data. In the 65 evaluated patients, the duration of disease prior to anti-TNF treatment ranged from 1 to 50 (mean 14.06) yrs. The duration of anti-TNF treatment at the time of study ranged from 3 to 56 (mean 19.14) months. Twenty-four (36.92%) patients were receiving infliximab, 21 (32.31%) etanercept and 20 (30.77%) adalimumab.

The mean scores, pre-treatment, for disease activity (BASDAI), functional state (BASFI) and ASQoL were 6.45, 5.89 and 11.11, respectively. After 3 months of treatment, BASDAI, BASFI and ASQoL scores had fallen to 2.88, 3.21, 4.55, respectively, and at the time of survey, after a mean of 19.4 (3–56) months to 1.43, 3.07 and 5.08, respectively (Fig. 1).

Fig. 1.

Response to anti-TNF treatment of 65 patients with AS in terms of disease activity (BASDAI), function (BASDAI) and health-related QoL (ASQoL). Data from all patients were available pre-treatment at 3 months and after 3–56 months (mean 19.1 months—‘now’) for BASDAI and BASFI. Data for ASQoL was obtained for 41 patients pre-treatment, 26 at 3 months and 66 at the latest assessment (‘now’).

Fig. 1.

Response to anti-TNF treatment of 65 patients with AS in terms of disease activity (BASDAI), function (BASDAI) and health-related QoL (ASQoL). Data from all patients were available pre-treatment at 3 months and after 3–56 months (mean 19.1 months—‘now’) for BASDAI and BASFI. Data for ASQoL was obtained for 41 patients pre-treatment, 26 at 3 months and 66 at the latest assessment (‘now’).

Before receiving anti-TNF treatment, 46 (70.8%) were in employment (one was a student): 38 (58.5%) were in full-time and 8 (12.3%) in part-time work. Three were self-employed. Nineteen (29.2%) were not working. Six of those not working (9.2% of the whole group) were unable to work outside of the home due to AS, two were temporarily disabled and 11 had retired on health grounds. Thirty-three individuals, of whom 21 were employed, had received anti-TNF treatment for 12 months or more. In the year prior to starting anti-TNF treatment, these 21 individuals lost, on average, 15 days from work due to sick leave (Table 1). Four individuals required more than 12 weeks of leave.

Table 1.

Employment status and type of work of 65 people with AS before and on anti-TNF treatment

 Pre-treatment On treatment 
Full-time employment, n (%) 38 (58.5) 44 (67.7) 
Part-time employment, n (%) 8 (12.3) 6 (9.2) 
Sedentary, n (%) 24 (52.17) 27 (54) 
Standing, n (%) 5 (10.8) 4 (8) 
Physical, n (%) 12 (26.1) 14 (28) 
Heavy manual, n (%) 5 (10.8) 5 (10) 
Average hours worked (per week) 37.8 39.3 
Not in work, n (%) 19 (29.2) 15 (23.1) 
Temporarily disabled (receiving benefit), n (%) 2 (3.1) 0 (0.0) 
Retired on health grounds, n (%) 11 (16.9) 11 (16.9) 
Unable to work outside of the home due to AS, n (%) 6 (9.2) 4 (6.1) 
Mean days of sick leave over 12 months (n = 36) 15 (n = 21) 0.91 (n = 24) 
 Pre-treatment On treatment 
Full-time employment, n (%) 38 (58.5) 44 (67.7) 
Part-time employment, n (%) 8 (12.3) 6 (9.2) 
Sedentary, n (%) 24 (52.17) 27 (54) 
Standing, n (%) 5 (10.8) 4 (8) 
Physical, n (%) 12 (26.1) 14 (28) 
Heavy manual, n (%) 5 (10.8) 5 (10) 
Average hours worked (per week) 37.8 39.3 
Not in work, n (%) 19 (29.2) 15 (23.1) 
Temporarily disabled (receiving benefit), n (%) 2 (3.1) 0 (0.0) 
Retired on health grounds, n (%) 11 (16.9) 11 (16.9) 
Unable to work outside of the home due to AS, n (%) 6 (9.2) 4 (6.1) 
Mean days of sick leave over 12 months (n = 36) 15 (n = 21) 0.91 (n = 24) 

At the survey time point, on treatment, 50 (76.9%) patients were working: 44 (67.7%) full-time and 6 (9.2%) part-time. Two individuals who worked part-time pre-treatment had returned to work full-time. Two of the six individuals who were previously unable to work out of the home and the two who were temporarily disabled and receiving benefit returned to work. Thus, on treatment, 4 of the 19 previously unable to work returned to employment, a fall in unemployment of 21.1%, and two others increased their work from part-time to full-time. The nature of the work, the degree of physical activity required and the approximate number of hours worked by these 46 individuals are also presented in Table 1.

During their first 12 months of treatment, 24 of the 33 individuals who had received anti-TNF treatment for 12 months or more were employed and took a mean of 0.91 days of sick leave, compared with 15 days in the previous year (Table 1).

The perceptions of the 46 patients who were working prior to starting anti-TNF treatment recorded the degree to which AS impacted adversely on their capacity for work as 7.05 pre-treatment and 2.92 post-treatment.

Discussion

This study was designed primarily to answer the question ‘does TNF blockade therapy enable people with severe AS to return to work or work more productively?’. Although the data at this stage of a continuing investigation are from a relatively small number of patients, the findings are striking. In keeping with other published experience, nearly one-third of the study population were unable to work because of AS in spite of being of ‘working age’. Of these, one in four returned to work within 18 months of starting treatment. Overall, the time spent at work increased slightly but sick leave was dramatically reduced and may reduce further once hospital monitoring is reduced to less-obtrusive levels. Moreover, patients’ perception of the impact of AS on their work capacity had been radically improved.

These findings are in line with the findings of van der Heijde et al. [23] that patients treated with infliximab had significant reductions in limitations of work and daily activity and became significantly more productive at work.

The limited scope and short duration of this study leave many important questions unanswered. Particularly, larger studies are needed to tell us: can those who returned to work stay at work? Would earlier treatment stop people falling out of work? How do the economics actually work out—do the cost savings resulting from resumption of gainful employment actually outweigh the cost of treatment? However, whatever the fine detail, if one in four of the one-third of the patients with AS who give up work before normal retirement age could be prevented from doing so or returned to work with less time lost due to sickness there would be substantial societal as well as personal benefits. If other well-recognized benefits of anti-TNF treatment, notably improved energy and well-being, are added the effect on work and on life-modification may be greater.

Conclusions

TNF blockade therapy for people with severe AS in the UK was associated with improved capacity for work, increased gainful employment and reduced time off work. Although small sample size precluded meaningful statistical analysis, all measures favoured an association between biologic treatment and improved work capacity. Recruitment to this cohort continues.

graphic

Acknowledgements

We are grateful to Schering-Plough for making A.K.G. available as an independent research assistant.

Funding: The department is in receipt of research funding from Wyeth, Abbott and Schering-Plough.

Disclosure statement: A.K.G. is an employee of Schering-Plough. K.G. has been an advisory board member for Wyeth, Abbott and Schering-Plough. A.C.K. has received honoraria for attending ad hoc boards and speaking at meetings from Schering-Plough, Abbott and Wyeth. All other authors have declared no conflicts of interest.

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