Socioeconomic Impact and Prognosis

Introduction

Patients with ankylosing spondylitis/axial spondyloarthritis (AS/axSpA) have their disease onset at young age, which increases the lifetime impact of their disease-associated reduced vitality and quality of life. Physical consequences associated with disease have a direct relationship with a patient’s ability to work. Many patients cannot maintain the level of employment that they had before the onset of their disease as they experience progressive functional impairment over time, resulting in decreased work productivity, progressive disability and possible job loss compared to the general population. A greater impact of the disease on work productivity has been observed in patients living in rural areas as compared with urban dwellers. Patients with extra-spinal disease manifestations, such as involvement of hip, shoulder and peripheral joints, inflammatory bowel disease, psoriasis and uveitis substantially contribute to morbidity.

Patients with physically demanding jobs are much more likely to change their type of work, decrease their work hours, or experience temporary or permanent work disability in contrast to patients who have jobs that are less physically demanding. Early cessation of employment for patients with ankylosing spondylitis (AS) is also associated with low level of education, complete ossification of the spine, hip joint involvement, acute anterior uveitis (AAU), female gender and the coexistence of nonrheumatic diseases. They leave the labor force at a 2- to 3-fold higher rate than the general population, and report similar pain and functional disability as those with rheumatoid arthritis (RA). Moreover, AS usually begins at the prime of one’s life, so these patients must deal with the illness for a longer time. All of this has a tremendous impact on patients and on society at large in terms of economic costs, both direct and indirect. Estimation of the lifetime cost of AS would require cost data from an inception cohort as well as mortality rates but no such data are currently available.

Socioeconomic refers to society-related economic factors that relate to and influence one another. For example, one’s employment will dictate the income, and the income level often correlates to the level of education and the level of education helps to dictate one’s employment. Socioeconomic status defined as level of education is associated with functional outcomes in several rheumatic diseases and low level of education is an independent predictor of radiographic progression that is associated with poorer functional outcomes in long-standing AS. A similar effect is observed among smokers and blue-collar (manual) workers.

Individual-level and country-level health inequalities exist also among patients with spondyloarthritis (SpA). Women and lower educated persons had worse disease activity and somewhat worse physical function. While patients in less socioeconomically developed countries had higher disease activity, they reported similar physical function. Data from the cross-sectional, multinational (22 countries worldwide) COMOSPA (COMOrbidities in SpA) study found that women and lower educated patients had worse disease activity and somewhat worse physical function. A study of Chinese patients with AS found low socioeconomic status, lack of health insurance and fatigue contributed to depression that may require a psychological care approach that is different from those of other countries.

The socioeconomic impact of diseases refers to the effect of the illness on the ability to perform paid or unpaid work and on the effect on health resources. Direct healthcare costs alone do not describe the total costs associated with AS, and the productivity losses associated with this disease are considerable. Cost of illness studies classically analyze the direct healthcare and non-healthcare costs, productivity costs, and intangible costs. Functional disability is usually the most important predictor of high total costs. Table 18-1 compares the cost of AS per patient per year in the United States and Europe in studies published in 2002/2003. There are remarkable differences in work status and productivity costs between the three European countries. This has implications for the generalizability of health economic studies, and there are limitations of comparability of cost of illness studies that have been published.

But, overall, the AS-related costs of illness are substantial and the high costs of formal or informal help and work disability reflect the impact of the disease on physical functioning. Figure 18-1 shows two hypotheses proposed by Ramiro and colleagues to explain the interaction of factors influencing the relationship between disease activity (as measured with the Ankylosing Spondylitis Disease Activity Score (ASDAS)) and radiographic progression (as measured with the 2-year modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) progression) and impact of gender, smoking and low socioeconomic status (measured with education, personal income and family income).

A systematic review of only the indirect costs related to absenteeism and presenteeism associated with AS reported that the average annual indirect cost per patient varies from US$660.95 to $45,953.87, expressed in 2013 prices (US dollars) using the consumer price index and purchasing power parity. The mean annual indirect cost per patient equaled US$6,454.76. Most of the factors associated with higher cost were related to greater disease activity and functional disability. Therefore, early appropriate treatment is crucial, and interventions that maintain or improve patients’ functional ability will likely have the greatest potential to decrease the costs of AS.

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Economic Evaluation of Biologic Therapy

Tumor necrosis factor inhibitors (TNFis) are highly effective in AS in alleviating pain and reducing clinical disease activity in both axial and peripheral arthritis, reducing or ameliorating extraarticular manifestations, improving quality of life and maintaining long-term efficacy out to 15 years. The clinical response is greater in patients with earlier stages of disease and less damage. Several pharmaceutically funded randomized controlled trials showed positive influence of TNFis on secondary work-related outcomes among the axSpA patients participating in those trials. Observational data from the British Society for Rheumatology Biologics Register (BSRBR)-AS alone or pooled in a meta-analysis with the data from other observational studies support a positive effect of biologic drugs on work impairment and activity in patients with axSpA. Importantly, despite the consistent improvements in work impairment observed with biological therapy in these studies, there remains a significant loss in work productivity, which is associated with poor patient-reported disease outcome measures.

Full economic evaluations, including cost-effectiveness of the TNFis for the treatment of AS have been published. However, robust estimates of the longer-term clinical cost-effectiveness of TNFis for AS is needed. Incremental cost-effectiveness ratios of adalimumab vs conventional therapy in the United Kingdom (UK) were estimated to improve with longer time horizons (48 weeks to 5 and 30 years). The central estimate was that over 30 years of adalimumab therapy yielded 1.03 more quality-adjusted life-years per patient initiating therapy. This analysis indicates that adalimumab, when used according to UK treatment guidelines, is cost effective compared to conventional therapy for treating AS patients. The short-term (12-month) model showed that the large front-loading of costs makes none of the TNFis appear cost effective at the currently acceptable threshold, with infliximab yielding much poorer economic results.

Corbett and co-workers have reported that TNFis are approximately equally effective, and their effectiveness appears to be maintained over time, with around 50% of patients still responding at 2 years. Evidence for an effect of TNFis delaying disease progression was limited. Sequential treatment with TNFis can be worthwhile but the drug survival response rates and benefits get reduced with second and third TNFi. The de novo model, which addressed many of the issues of earlier evaluations, generated incremental cost-effectiveness ratios ranging from £19,240 to £66,529 depending on the TNFi and modeling assumptions.

In addition to the patient’s physical limitations, work productivity is also influenced by lifestyle, emotional, social, cultural and occupational factors and understanding these potential risk factors may further contribute to the development of preventive strategies to maintain patient participation in the labor force. This consideration, together with the convincing evidence that effective but expensive treatment with TNFis which sustain improvements in work outcomes, has resulted in greater interest in the socioeconomic consequences in patients with AS. A recent budget impact analysis comparing treatment with secukinumab (150 mg) or adalimumab (40 mg) showed that secukinumab is a cost-saving treatment option compared with adalimumab in the treatment of patients with AS in Finland and in Korea.

There is a need to inculcate in AS patients, as in those with other chronic rheumatic diseases, a direct/positive and reappraisal type of coping response for dealing with health and daily-life stressors that they may face because it results in better outcomes than evasive/negative and avoidant/emotional responses that reflect poor adjustment to disease. Patients using positive coping mechanisms generally have good social as well as family relationships, good educational level and stable jobs. The negative type of coping is generally associated with low educational level, poor health outcomes and the individual’s independent social role; and it results in low health status, high level of pain, low adherence to treatment and long-term risk behavior.

Prognosis

There is, in general, a gradual progression of the disease over the years, leading to worsening physical function. A predictable pattern of AS emerges within the first 10 years of the disease, and thus if the hip joints were normal after 10 years of the disease will subsequently remain unaffected. Poor response or intolerance to treatment, and the presence of severe extraarticular complications, and other factors discussed above worsen the prognosis. The stage of AS at diagnosis and initiation of appropriate therapy, the severity of early stages of the disease, the quality of medical management and the degree of patient compliance with the suggested treatment also influence the prognosis. Functional disability progresses more rapidly in older patients and smokers and less rapidly in those who have better social support and who can perform back exercises regularly.

A small proportion of axSpA patients experience inadequate treatment response despite the use of novel potent therapeutics such as biologic and targeted synthetic DMARDs (b/tsDMARDs). By an analogy to “difficult to treat rheumatoid arthritis” (D2T RA) defined by the EULAR task force, an extrapolated definition for “D2T axSpA” has been proposed for patients who have failed to respond to multiple bDMARDs and tsDMARDs. Comorbidities like depression and fibromyalgia which are more common in D2T-axSpA patients can complicate assessment of disease activity in such patients. A 2023 study demonstrated that nosiplastic pain and neuropathic pain components may also contribute to residual symptoms in AS treated with bDMARDs.

Previous reports had reported increased mortality in AS, possibly resulting from cardiopulmonary diseases, comorbidities, smoking, spinal fractures due to physical trauma, GI bleeding, alcohol-related injury and miscellaneous conditions (such as amyloidosis, and complications of spinal irradiation (excess malignancies, especially a 5-fold increase in leukemias). Subsequent studies have confirmed previous reports of increased mortality in AS, and the most recent study, comprising patients from Sweden, Norway and Denmark, also confirms increased mortality in AS. It found increased mortality for both men (age-adjusted HR = 1.53, 95% CI 1.36-1.72) and women (age-adjusted HR = 1.83, 95% CI 1.50-2.22). Within the AS cohort, statistically significant predictors for death were a lower level of education, general comorbidities (diabetes, infections, cardiovascular (CV), pulmonary and malignant diseases) and previous hip replacement surgery. A recent meta-analysis showed that comorbidities are common in axSpA patients, with most of them being more than in control populations. This study identified hypertension (22.3%), any infection (18.3%), hyperlipidemia (17.1%), obesity (13.5%) and any CV disease (CVD, 12.3%) as the top five most prevalent comorbidities. Overall comorbidity burden, and many individual conditions, were associated worse disease severity, work productivity and mortality.

An earlier smaller study from Norway reported that parameters associated with reduced survival include the duration and intensity of inflammation, and the factors independently associated with reduced survival were diagnostic delay (OR 1.05), increasing levels of CRP (OR 2.68), work disability (OR 3.65), and not using any NSAIDs (OR 4.35). Thus, there is a need for early disease detection and effective anti-inflammatory treatment, as well as management and prevention of comorbidities. It is hoped that survival of patients with milder disease, diagnosed early and managed with more effective therapy will be comparable to the general population.

The most recent study of the life expectancy of a Swiss cohort of patients with AS vs the general population during 35 years of longitudinal follow up reported that AS patients have a significantly shortened life expectancy, but not among those with nr-axSpA. Possession of HLA-B27 by the patients did not influence their life expectancy.