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Rheumatoid arthritis (RA), psoriasis, and inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), are among the most common autoimmune diseases. Collectively, they affect about 10 million patients in the United States. They are chronic conditions characterized by immune-mediated inflammation of unknown etiology and for which there is no cure. Substantial morbidity, shortened survival, and diminished health-related quality of life (HR-QOL) are associated with these diseases during the many decades that patients cope with them.
The chief goal of therapy is to suppress disease flares and extend periods of remission if remission is attainable. Biologics are the mainstay of treatment for severe disease, and the extent to which they are used reflects the disease burden associated with autoimmune diseases.
Three of the top six best-selling prescription drugs in 2015 were biologics used to treat autoimmune disorders. In 2015, spending on drugs for autoimmune disorders accounted for 20% of all specialty drug spending.
Diminished HR-QOL and the inability to work at full productivity are among the negative consequences of moderate to severe autoimmune disease. A survey of a major self-insured employer (Navistar) found self-reported prevalence of RA, psoriasis, and IBD in 2009 was 4.2%, 3%, and 1.2%, respectively (Allen 2012). An important finding in this study was that if mild autoimmune disease stayed mild, the productivity of employees remained comparable to that of employees without autoimmune disease.
About 1.2 million Americans have IBD (Table 1). The age of onset for IBD occurs in two peaks, the first between ages 15 and 30 and a second peak between 60 and 80 years. The signs and symptoms of IBD are severe diarrhea, abdominal pain, blood in the stool, fatigue, and weight loss. They are similar to the signs and symptoms of other diseases, so clinicians sometimes have difficulty diagnosing IBD. When IBD is diagnosed, in about 15% of cases it is not possible to further classify the disease as CD or UC. Such cases are known as indeterminate colitis (Friedman 2015). As time goes by, it eventually becomes clear whether indeterminate colitis is CD or UC. In mild to moderate disease of either kind, some of the treatments are the same.
| Table 1 |
Differences between the major inflammatory bowel diseases
|Crohn’s disease||Ulcerative colitis|
|US prevalence, estimated||565,000||593,000|
|Commercially insured pediatric||58 per 100,000||34 per 100,000|
|Commercially insured adult||241 per 100,000||243 per 100,000|
|Anatomical regions typically involved||Any part of the intestine, usually ileum and colon||Rectum and part or all (pancolitis) of colon|
|Typical extent of inflammation||Transmural||Mucosal only|
|Presence of granulomas, strictures, fistulas||Typical||Atypical|
|Risk associated with cigarette smoking||Increased risk, increased severity||Decreased risk (increased risk in former smokers and nonsmokers)|
|Genetic factors||More prominent||Less prominent|
|Involvement of autophagy gene ATG16L1 in pathogenesis||Yes||No|
|Involvement of genes regulating interleukin 23-Th17 pathway||Yes||Yes|
|Sources: Abraham 2009, Friedman 2015, Kappelman 2013|
About a third of IBD patients have one or more extraintestinal manifestations of their disease. These complications may involve the skin (e.g., erythema nodosum, pyoderma gangrenosum), bone and joints (e.g., peripheral arthritis, ankylosing spondylitis, low bone mass), eyes (e.g., conjunctivitis, uveitis), liver (e.g., fatty liver, gallstones), genitourinary system (e.g., calculi, ureteral obstruction), and cardiovascular system (e.g., venous and arterial thrombosis).
In addition to taking drugs to control their disease and the comorbid conditions associated with it, patients with IBD may take drugs to manage comorbid conditions that are common in the general population. An analysis of insurance claim records for 150 million individuals showed that many comorbidities were much more prevalent among patients with IBD than matched members in the general population, such as deficiency anemias (21.2% vs 6.7%), fluid and electrolyte disorders (12.5% vs 3.5%), weight loss (6.4% vs 1.2%), liver disease (4.6% vs 1.3%), and RA (4.1% vs 1.3%) (Buckley 2013). With all this comorbidity, as well as their disease, it’s not surprising that patients with IBD had more prescriptions than matched members: 38% of patients with IBD had 10–19 prescriptions compared with 22.5% of matched members, and 16.3% of IBD patients had 20 or more prescriptions compared with 5.5% of matched members (Buckley 2013). Polypharmacy of this magnitude puts people at risk for becoming nonadherent to their drug regimens as well as for experiencing drug interactions.
An analysis of data from the Medical Expenditure Panel Surveys showed that insurers’ expenditures for patients with UC and CD are 64% and 124% higher, respectively, than for patients without the conditions (Figure 1). The same analysis also showed that aggregate incremental per-patient costs for UC and CD are comparable to those for major chronic conditions (Figure 2).
These expenditures, for adults with health insurance, were calculated from respondent-reported data between 1996 and 2009 in the Household Component of the Medical Expenditure Panel Survey (MEPS). The MEPS database was developed by the Agency for Healthcare Research and Quality.
Source: Gunnarsson 2012
The common pattern with milder forms of IBD is occasional periods of relapse amid longer periods of relatively normal health, so many patients with IBD can work full-time, even if their productivity is somewhat impaired compared with workers without IBD. During disease flares, however, patients with IBD are twice as likely as people without IBD to be out of the labor force (Jacobs 2011).
CD=Crohn’s disease, CHD=coronary heart disease, COPD=chronic obstructive pulmonary disease, UC=ulcerative colitis.
*Aggregate means all the health expenditures for the patient with the disease, and incremental refers to expenditures beyond those incurred by patients without IBD in a reference group, so the dollar amounts reflect additional expenditures, not total expenditures. Aggregate incremental per-patient expenditures for CD and UC are comparable to those for major chronic conditions, although total expenditures for CD and UC are much less because of the substantially lower prevalence of IBD.
Source: Gunnarsson 2012
Estimates of psoriasis prevalence range from 0.95% to 3.2%. Prevalence in the middle of this range—2.2%—translates into an estimate of about 5.3 million Americans having psoriasis in 2013 (Vanderpuye-Orgle 2015). There are several subtypes of psoriasis, the most common of which is plaque psoriasis. Plaque psoriasis is characterized by plaques—elevated, inflamed areas of the skin—that are often itchy and painful. They tend to stay roughly the same size and appear on the scalp, knees, elbows, lower back, palms, and soles.
The National Psoriasis Foundation defines psoriasis severity in terms of percentage of the body surface area (BSA) covered: mild, <3%; moderate, 3–10%; severe, >10%. (NPF 2016). A more complicated measure commonly used in clinical research but not in clinical practice is the Psoriasis Area and Severity Index [PASI], in which scores ≤10 indicate mild disease; 11–20, moderate; and >20, severe. In the United States, comparative rates of psoriasis severity are 83%, 11%, and 5% for mild, moderate, and severe disease, respectively (Vanderpuye-Orgle 2015). Treatments are determined by disease severity, with topical treatments and phototherapy usually used for mild localized psoriasis and systemic medications for moderate to severe disease, especially if it is resistant to other treatments. Systemic medications may also be used if the disease is substantially impairing the patient’s quality of life (e.g., psoriasis that affects the soles or palms).
Common comorbidities among patients with psoriasis are psoriatic arthritis, which develops in up to 30% of patients with psoriasis, and metabolic syndrome, which in turn is associated with increased risk for cardiovascular disease, stroke, and diabetes. In an analysis of a large managed care database (Kimball 2011), the psoriasis-associated comorbidities with the highest average incremental six-month costs were cerebrovascular disease, peripheral vascular disease, cardiovascular disease, depression, and diabetes. The three most costly comorbidities were also the ones with the highest rates of inpatient care or emergency care. For the comorbidities of cardiovascular, cerebrovascular, and peripheral vascular disease, the inpatient incidence rate ratios (IRR) compared with psoriasis patients without the comorbidity were 4.19, 3.74, and 3.22, respectively; for emergency care (the combination of inpatient and emergency department services), the IRRs for the same three comorbidities were 3.06, 3.21, and 2.67, respectively. Depression was the comorbidity resulting in the highest IRR for outpatient care, 1.82.
In a study that compared the effect of psoriasis on productivity with the effect of other costly diseases (atrial fibrillation, neck or lower back pain, and stroke), mean work impairment costs for patients with psoriasis were comparable to those for the other conditions (Table 2). Presenteeism accounted for most of the productivity costs associated with psoriasis (Carter 2011). Among patients with psoriatic arthritis, lost productivity because of absenteeism and presenteeism was substantially higher, such that only neck or lower back pain resulted in a greater productivity burden. In a Finnish study enrolling only patients with moderate to severe psoriasis, absenteeism and presenteeism accounted for 38% of costs attributed to lost productivity, with the remaining 62% of productivity loss attributed to other medical issues (Mustonen 2015).
| Table 2 |
Productivity burden among patients with psoriasis, psoriatic arthritis, and other costly conditions (in dollars)
|Absenteeism||Presenteeism||Overall work impairment|
|Neck/lower back pain (n=504)||6,755||13,181||19,935|
|Psoriatic arthritis (n=347)||5,748||11,665||17,413|
|Atrial fibrillation (n=319)||3,358||5,915||9,273|
|Source: Carter 2011|
In the United States, the total annual cost of psoriasis has been estimated at $35 billion (Figure 3), including $12 billion in direct costs and $23 billion in indirect costs (Vanderpuye-Orgle 2015). As in other studies, presenteeism was a greater contributor to lost productivity than was absenteeism.
HR-QOL=health-related quality of life.
Total costs of psoriasis, in billions of 2013 dollars. Green shades represent direct costs, orange shades represent indirect costs associated with productivity, and pink represents indirect costs attributed to HR-QOL.
Source: Vanderpuye-Orgle 2015
About 1.5 million U.S. adults are living with RA (NIAMSD 2014). The disease affects peripheral joints in a symmetrical fashion, usually beginning with inflammation of synovial tissue in the small joints of the hands and feet. RA often is accompanied by extreme unremitting fatigue, depression, and cognitive dysfunction. The clinical course of RA is highly variable. Up to 10% of patients who meet the diagnostic criteria for RA will experience spontaneous remission within six months, but most patients will develop progressive disease whose intensity varies over time. Other patients experience recurring cycles of very active disease and minimally active disease (Shah 2015).
The goal of contemporary treatment is to halt or slow the progression of RA before joint damage occurs. Prior to the biologic era, a highly aggressive form of RA led to severe joint destruction. Treatment with disease-modifying antirheumatic drugs (DMARDs), especially the biologic DMARDs, in the early stages of RA has made this outcome less common. Not all patients respond to DMARDs, either the conventional or biologic variety. Although there is no cure for RA, early diagnosis followed by effective treatment lets many patients pursue usual activities because their disease activity has been minimized.
Compared with the general population, patients with RA have twice the mortality rate, with median life expectancy reduced by seven and three years in men and women, respectively (Shah 2015). Compared with the general population, patients with RA are at twice the risk of CVD, partly due to the prevalence of multiple common CVD risk factors and possibly because of the interaction of systemic inflammation with CVD risk factors (Cutolo 2014). The increased risk for myocardial infarction among people with RA is similar to the increased risk among those with diabetes.
Other comorbidities include osteoporosis (prevalence 20% to 30%), often as a consequence of prolonged use of prednisone and subsequent hip fracture; infection; subcutaneous nodules, once found in up to 40% of patients, especially those with very active disease; Sjögren’s syndrome (characterized by dry eyes or dry mouth), occurring in about 10% of patients with RA; lung disorders (e.g., pleuritis, interstitial lung disease, lung nodules); and lymphoma, which occurs two to four times as often in people with RA as in the general population (Shah 2015).
If left untreated or poorly controlled, RA limits the ability of patients to function well in domestic or vocational settings. Research has shown that up to half of such patients leave the workforce less than 10 years after disease onset and up to 90% have stopped working prior to age 65 (Birnbaum 2010). From a societal perspective, the total cost of RA in the U.S. has been estimated at $39 billion in 2005 dollars (Birnbaum 2010). About half of the total was attributed to intangible costs—diminished QOL ($10 billion) and premature mortality ($10 billion)—and half to direct ($9 billion) and indirect costs ($10 billion). Direct medical costs were evenly divided between employer-provided health insurance and Medicare and Medicaid (Figure 4).
Direct costs of RA, in hundreds of millions of 2005 dollars. Total direct costs were about $9 billion. Green shades indicate spending related to employer-sponsored health care insurance; blue shades, government-sponsored. Employers’ expenditures were estimated from claims records from 1999 to 2005 in the Ingenix Employer Database, which covers 6 million beneficiaries employed by 37 large US companies. Government costs were estimated from Medicare and Florida Medicaid databases for the same range of years.
Source: Birnbaum 2010
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Allen H, Bunn WB 3rd, Naim AB. The self-reported health and productivity burden of autoimmune disorders at a major self-insured employer. J Occup Environ Med. 2012;54(9):1049–1063.
Birnbaum H, Pike C, Kaufman R, et al. Societal cost of rheumatoid arthritis patients in the US. Curr Med Res Opin. 2010;26(1):77–90.
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Kimball AB, Guérin A, Tsaneva M, et al. Economic burden of comorbidities in patients with psoriasis is substantial. J Eur Acad Dermatol Venereol. 2011;25(2):157–163.
Mustonen A, Mattila K, Leino M, et al. How much of the productivity losses among psoriasis patients are due to psoriasis. BMC Health Serv Res. 2015;15:87.
NIAMSD (National Institute of Arthritis and Musculoskeletal and Skin Diseases). Handout on health: rheumatoid arthritis. August 2014. http://www.niams.nih.gov/health_info/rheumatic_disease/#1. Accessed June 9, 2016.
NPF (National Psoriasis Foundation). About psoriasis. 2016. https://www.psoriasis.org/about-psoriasis. Accessed June 9, 2016.
Shah A, St Clair EW. Rheumatoid arthritis. In: Kasper DL, Fauci AS, Hauser SL, et al, eds. Harrison’s Principles of Internal Medicine, vol 2. 19th edition. New York, NY: McGraw Hill Medical; 2015:2136–2149.
Vanderpuye-Orgle J, Zhao Y, Lu J, et al. Evaluating the economic burden of psoriasis in the United States. J Am Acad Dermatol. 2015;72(6):961–967.e5.
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