Increasing healthcare costs in inflammatory bowel disease 2007-2020 in Sweden.

BACKGROUND: Inflammatory bowel disease has been linked to increasing healthcare costs, but longitudinal data on other societal costs are scarce. AIM: To assess costs, including productivity losses, in patients with prevalent Crohn's disease (CD) or ulcerative colitis (UC) in Sweden between 2007 and 2020. METHODS: We linked data from national registers on all patients with CD or UC and a matched (sex, birthyear, healthcare region and education) reference population. We assessed mean costs/year in Euros, inflation-adjusted to 2020, for hospitalisations, out-patient visits, medications, sick leave and disability pension. We defined excess costs as the mean difference between patients and matched comparators. RESULTS: Between 2007 and 2020, absolute mean annual societal costs in working-age (18-64 years) individuals decreased by 17% in CD (-24% in the comparators) and by 20% in UC (-27% in comparators), due to decreasing costs from sick leave and disability, a consequence of stricter sick leave regulations. Excess costs in 2007 were dominated by productivity losses. In 2020, excess costs were mostly healthcare costs. Absolute and excess costs increased in paediatric and elderly patients. Overall, costs for TNF inhibitors/targeted therapies increased by 274% in CD and 638% in UC, and the proportion treated increased from 5% to 26% in CD, and from 1% to 10% in UC. CONCLUSION: Between 2007 and 2020, excess costs shifted from productivity losses to direct healthcare costs; that is, the patients' compensation for sickness absence decreased, while society increased its spending on medications. Medication costs were driven both by expanding use of TNF inhibitors and by high costs for newer targeted therapies.

Women's Earnings are more Affected by Inflammatory Bowel Disease than Men's: A Register-Based Swedish Cohort Study.

BACKGROUND AND AIMS: Patients with inflammatory bowel disease [IBD] are subject to more work disability than the general population. We aimed to estimate the monetary cost of IBD for the individual through assessment of earnings in relation to diagnosis. METHODS: Through linkage of national registers, we identified patients aged 30-55 years at first IBD diagnosis in Sweden in 2002-2011, and same-sex IBD-free siblings. We estimated taxable earnings and disposable income from 5 years before to 5 years after diagnosis. RESULTS: The 5961 patients [27% Crohn's disease, 68% ulcerative colitis, 4.3% IBD unclassified] had similar taxable earnings to their 7810 siblings until the year of diagnosis, when earnings decreased and remained lower than for siblings during follow-up. The adjusted difference in earnings over the entire 5-year period after diagnosis was -5% [-8212€; 95% confidence interval: -11 458 to -4967€]. The difference was greater in women than in men, and greater in Crohn's disease than in ulcerative colitis. When stratifying for sex and IBD subtype and comparing earnings during each year of follow-up, median annual earnings were lower in women with Crohn's disease and ulcerative colitis than in their sisters during all years of follow-up, whereas the men had similar annual taxable earnings to their brothers. Disposable income was similar between patients and siblings during the investigated time period. CONCLUSION: From the year of diagnosis and at least 5 years onwards, patients with IBD had 5% lower earnings than siblings, mainly explained by differences between women with IBD and their sisters. However, there were no differences in disposable income.

Healthcare use, work loss and total costs in incident and prevalent Crohn's disease and ulcerative colitis: results from a nationwide study in Sweden.

BACKGROUND: There are limited data on population-wide assessment of cost in Crohn's disease (CD) and ulcerative colitis (UC). AIM: To estimate the societal cost of actively treated CD and UC in Sweden. METHODS: We identified 10 117 prevalent CD and 19 762 prevalent UC patients, aged ≥18 years on 1 January 2014 and 4028 adult incident CD cases and 8659 adult incident UC cases (2010-2013) from Swedish Patient Register. Each case was matched to five population comparators. Healthcare costs were calculated from medications, outpatient visits, hospitalisations and surgery. Cost of productivity losses was derived from disability pension and sick leave. RESULTS: The mean annual societal costs per working-age patient (18-64 years) with CD and UC were $22 813 (vs $7533 per comparator) and $14 136 (vs $7351 per comparator), respectively. In patients aged ≥65 years, the mean annual costs of CD and UC were $9726 and $8072 vs $3875 and $4016 per comparator, respectively. The majority of cost for both CD (56%) and UC (59%) patients originated from productivity losses. Higher societal cost of working-age CD patients as compared to UC patients was related to greater utilisation of anti-TNF (22.2% vs 7.4%) and increased annual disability pension (44 days vs 25 days). Among incident CD and UC patients, the mean total cost over the first year per patient was over three times higher than comparators. CONCLUSION: In Sweden, the societal cost of incident and prevalent CD and UC patients was consistently two to three times higher than the general population.

Impact of discordance between patient's and evaluator's global assessment on treatment outcomes in 14 868 patients with spondyloarthritis.

OBJECTIVES: To assess the impact of 'patient's minus evaluator's global assessment of disease activity' (ΔPEG) at treatment initiation on retention and remission rates of TNF inhibitors (TNFi) in psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) patients across Europe. METHODS: Real-life data from PsA and axSpA patients starting their first TNFi from 11 countries in the European Spondyloarthritis Research Collaboration Network were pooled. Retention rates were compared by Kaplan-Meier analyses with log-rank test and by Cox regression, and remission rates by χ2 test and by logistic regression across quartiles of baseline ΔPEG, separately in female and male PsA and axSpA patients. RESULTS: We included 14 868 spondyloarthritis (5855 PsA, 9013 axSpA) patients. Baseline ΔPEG was negatively associated with 6/12/24-months' TNFi retention rates in female and male PsA and axSpA patients (P <0.001), with 6/12/24-months' BASDAI < 2 (P ≤0.002) and ASDAS < 1.3 (P ≤0.005) in axSpA patients, and with DAS28CRP(4)<2.6 (P ≤0.04) and DAPSA28 ≤ 4 (P ≤0.01), but not DAS28CRP(3)<2.6 (P ≥0.13) in PsA patients, with few exceptions on remission rates. Retention and remission rates were overall lower in female than male patients. CONCLUSION: High baseline patient's compared with evaluator's global assessment was associated with lower 6/12/24-months' remission as well as retention rates of first TNFi in both PsA and axSpA patients. These results highlight the importance of discordance between patient's and evaluator's perspective on disease outcomes.

Sick Leave and Disability Pension in Prevalent Patients With Crohn's Disease.

BACKGROUND AND AIMS: Crohn's disease may affect the ability to work and lead to permanent disability. We aimed to investigate work loss in prevalent patients. METHODS: We identified patients with Crohn's disease and general population comparators matched by sex, birth year, healthcare region and education. We assessed days of sick leave and disability pension retrieved from the Swedish Social Insurance Agency and estimated the absolute and relative risk of receiving disability pension [minimum 25% work impairment]. RESULTS: In 2014, the 20638 Crohn's disease patients [median age 44 years] had more than twice as many mean lost workdays [disability pension: 44; sick leave: 19] as the 102038 comparators [disability pension: 20; sick leave: 8], mean difference 35 days [95% confidence interval 33-37]. However, the majority had no lost workdays [68% of patients and 85% of comparators]. The proportion of patients receiving disability pension was 15% (6.5% in the comparators, risk ratio 2.34 [2.25-2.43]) and was higher in all subgroups, especially in female patients [28% vs 13% in the comparators], in those with ≤9 years of education [41% vs 23%] and in ages 60-64 years [46% vs 25%]. The relative risk of disability pension within the patient cohort [adjusted for age, sex, region and education] was higher in patients with complicated disease behaviour, extraintestinal manifestations, need of surgery or treatment with biologics. The differences between patients and comparators remained when comparing other calendar years [2006-2013]. CONCLUSION: Work loss was found in approximately one-third of patients. The mean number of lost workdays was twice as high as in the comparators.

Patient global assessment in measuring disease activity in rheumatoid arthritis: a review of the literature.

Patient-reported outcomes (PROs) reflect the patient's perspective and are used in rheumatoid arthritis (RA) routine clinical practice. Patient global assessment (PGA) is one of the most widely used PROs in RA practice and research and is included in several composite scores such as the 28-joint Disease Activity Score (DAS28). PGA is often assessed by a single question with a 0-10 or 0-100 response. The content can vary and relates either to global health (e.g., how is your health overall) or to disease activity (e.g., how active is your arthritis). The wordings used as anchors, i.e., for the score of 0, 10, or 100 according to the scale used, and the timing (i.e., this day or this week) also vary. The different possible ways of measuring PGA translate into variations in its interpretation and reporting and may impact on measures of disease activity and consequently achievement of treat-to-target goals. Furthermore, although PGA is associated with objective measures of disease activity, it is also associated with other aspects of health, such as psychological distress or comorbidities, which leads to situations of discordance between objective RA assessments and PGA. Focusing on the role of PGA, its use and interpretation in RA, this review explores its validity and correlations with other disease measures and its overall value for research and routine clinical practice.

Sarcoidosis incidence and prevalence: a nationwide register-based assessment in Sweden.

Our objective was to estimate the contemporary incidence and prevalence of sarcoidosis using Swedish population-based register data.Adults with any sarcoidosis-coded visit were identified from the National Patient Register (hospitalisations 1964-2013 and outpatient care 2001-2013). Demographic and medication dispensing data were retrieved from national registers. We estimated the prevalence of sarcoidosis in 2013 overall and by county of residence. The incidence of sarcoidosis during 2003-2012 was estimated by sex, age, education level and year of diagnosis. Case definitions were varied to test their robustness.More than 16 000 individuals had a history of sarcoidosis in 2013. When defined as two or more sarcoidosis-coded visits, the prevalence was 160 per 100 000. Using different definitions, the prevalence ranged from 152 (requiring a specialist visit) to 215 per 100 000 (only one visit required). The highest prevalence was observed in northern less densely populated counties. The incidence was 11.5 per 100 000 per year and varied by -10% to +30% depending on case definition. The incidence peaked in males aged 30-50 years and in females aged 50-60 years, but did not differ by education level and was stable over time.This study represents the largest epidemiological investigation of sarcoidosis using population-based individual-level data. Age at diagnosis in men was 10 years younger than in women and geographical variation was observed.

Does disease activity at start of biologic therapy influence work-loss in RA patients?

OBJECTIVE: To compare work-loss in RA patients starting their first biologic with high vs moderate disease activity. METHODS: We identified all RA patients aged 20-63 years in the Swedish Biologics Register who started their first biologic 2007-09 with high disease activity (DAS28 >5.1; n = 868) or moderate disease activity (DAS28 3.2-5.1; n = 854). Work days lost, defined as sick leave and disability pension days from the Swedish Social Insurance Agency, were assessed over 5 years after first bio-start. We estimated between-group mean differences adjusted for age, sex, calendar year, education level, disease duration, comorbidities and work-loss the month before bio-start. RESULTS: During 5 years after anti-TNF start, mean monthly work days lost declined from 16.0 to 9.2 (42%; P < 0.001) in patients with high disease activity at baseline and from 12.0 to 7.2 (40%; P < 0.001) in patients with moderate disease activity, with no between-group difference (adjusted mean difference 0.81; 95% CI - 0.44, 2.05). Accumulated 5-year work-loss was, however, higher in the high activity group (724 vs 548 days; adjusted mean difference 70; 95% CI 20, 120), but after stratification on baseline disability pension status, no differences in accumulated work-loss were detected. CONCLUSION: Substantial work-loss was seen in both patients with high and patients with moderate disease activity at anti-TNF start, with a 5-year decline in mean monthly work days lost by ∼40% in both groups and no between-group difference. Accumulated work-loss over 5 years was higher in the high-activity group, which may be explained by differences in baseline disability pension status.

Does disease activity at the start of biologic therapy influence health care costs in patients with RA?

OBJECTIVE: To investigate whether disease activity at baseline influences health care costs in patients with RA initiating biologic treatment. METHODS: In the Swedish Biologics Register, we identified patients with RA with baseline 28-joint DAS (DAS28) recorded and starting their first biologic in 2007-11 [n = 1638 with moderate disease activity (DAS28 3.2-5.1) and n = 1870 with high disease activity (DAS28 > 5.1)]. Data on inpatient and outpatient care and prescription drugs were retrieved from nationwide registers. Mean cost differences were estimated adjusted for age, sex and costs the year before treatment start. RESULTS: Patients with high (vs moderate) disease activity were older (60 vs 56 years; P < 0.001), but did not differ in sex distribution (75 vs 74% women; P = 0.99) or disease duration (10 vs 10 years; P = 0.13). The year after initiation of biologics, patients with high (vs moderate) baseline disease activity accumulated 9% higher health care costs, but the difference was not statistically significant after adjustment [€19,333 vs €17,810; adjusted difference €870 (95% CI -2, 1742)]. In the subgroup of patients with up to 4 years of follow-up data, decreasing costs were observed over the follow-up time, but no difference was found between patients with high compared with moderate baseline disease activity [€13,704 vs €12,349; adjusted difference 878 (95% CI -364, 2120)]. Irrespective of baseline disease activity, health care costs were approximately three times higher the year after initiation of biologics than the year before due to increased drug costs. CONCLUSION: Over up to 4 years of follow-up, no difference in health care costs was found after adjustment in patients starting their first biologic treatment with high vs moderate baseline disease activity.

The EULAR Study Group for Registers and Observational Drug Studies: comparability of the patient case mix in the European biologic disease modifying anti-rheumatic drug registers.

OBJECTIVE: Under the auspices of the European League Against Rheumatism (EULAR), a study group of investigators representing European biologic DMARD (bDMARD) registers was convened. The purpose of this initial assessment was to collect and compare a cross section of patient characteristics and collate information on the availability of potential confounders within these registers. METHODS: Baseline characteristics of patients starting their first bDMARD in an arbitrary year (2008) for the treatment of RA, including demographic and disease characteristics, bDMARD drug details and co-morbidities, were collected and compared across 14 European bDMARD registers. RESULTS: A total of 5320 patients were included. Half the registers had restricted recruitment to certain bDMARDs during the study year. All registers` collected data on age, gender, disease duration, seropositivity for IgM-RF and 28-joint DAS (DAS28). The mean DAS28 ranged from 4.2 to 6.6 and the mean HAQ from 0.8 to 1.9. Current smoking ranged from 9% to 34%. Nine registers reported co-morbidities with varying prevalence. CONCLUSION: In addition to demonstrating European-wide collaboration across rheumatology bDMARD registers, this assessment identified differences in prescribing patterns, recruitment strategies and data items collected. These differences need to be considered when applying strategies for combined analysis. The lack of a common data model across Europe calls for further work to harmonize data collection across registers.

Costs for hospital care, drugs and lost work days in incident and prevalent rheumatoid arthritis: how large, and how are they distributed?

OBJECTIVE: To estimate the costs related to hospital care, drug use and work loss in prevalent and incident patients with rheumatoid arthritis (RA), and to describe their distribution. METHODS: A cohort of prevalent patients with RA ≥18 years on Jan 1, 2010, was identified from the Swedish National Patient Register (requiring ≥2 visits listing RA) and the Swedish Rheumatology Quality Register, and followed until 31 December 2010. From the same registers, patients with the 1st visit listing RA in 2009, with a 2nd visit within 1 year, were identified to the incident cohort, and were followed for 1 year. Five sex-matched, age-matched, education-matched and county-matched general population comparators were sampled per patient with RA. Costs were retrieved from national registers. RESULTS: The mean annual cost, including productivity losses per patients with RA (n=49 829) aged 18-64 years was €23 147 versus €8364 (median €15 059 vs €277) per comparator. In patients with RA ≥65 years, the mean healthcare cost was €6438 versus €2773 (median €2458 vs €677) per comparator. 13% of the patients accounted for 50% of the cost. For the incident patients with RA (n=2695), the mean monthly cost increased from a level close to the comparators 1 year before register identification (18-64 years: €736 vs €644; ≥65 years: €192 vs €178), peaked the month following the identification date, and decreased to twice the cost of the comparators 1 year after diagnosis (18-64 years: €1252 vs €628; ≥65 years: €487 vs €230). CONCLUSIONS: The mean annual cost in patients with established RA, and mean monthly cost in newly diagnosed patients with RA, were 2-3 times higher than in the general population.

Incidence of rheumatoid arthritis in Sweden: a nationwide population-based assessment of incidence, its determinants, and treatment penetration.

OBJECTIVE: To estimate the nationwide incidence of rheumatoid arthritis (RA) in Sweden, including its variation across age, sex, geography, and demography, and to describe the sensitivity of register-based incidence estimates to different RA case definitions. METHODS: Incident RA patients were identified using the Swedish National Patient Register. In the base case, incident RA was defined as first-ever inpatient or nonprimary outpatient care visit listing an RA diagnosis in 2006-2008, with a second visit listing RA within 1 year. Patients prescribed disease-modifying antirheumatic drugs more than 6 months prior to the first visit listing RA were not regarded as incident. The robustness of this definition was evaluated by more liberal and strict criteria, and by penetration of antirheumatic treatment. RESULTS: Between 2006 and 2008, 8,826 individuals were identified as incident RA patients. The overall incidence was 41 per 100,000 (56 for women, 25 for men). The incidence increased with age and peaked in the 70-79 years age group for both women and men. The age- and sex-standardized incidences were lower in densely populated areas and in individuals with high educational level. No geographic trends were noted. More liberal and strict definitions of RA only altered the observed incidence by approximately 14%. CONCLUSION: The overall nationwide register-based incidence of RA was robust across different case definitions. In a country with universal access to care, RA displayed demographic and socioeconomic, but no geographic, variations in incidence, and peaks at an older age than most commonly reported, with no difference in peak age at RA onset between sexes.

How large are the productivity losses in contemporary patients with RA, and how soon in relation to diagnosis do they develop?

OBJECTIVE: To estimate the sick leave and disability pension trajectory in patients diagnosed with early rheumatoid arthritis (RA) 1999-2007, and in prevalent patients in 2007. METHODS: Individuals aged 19-59 years diagnosed with early RA were identified in the Swedish Rheumatology Quality Register (1999-2007; n=3029; 47 years; 73% women). Additionally, prevalent patients in 2007 were identified in the National Patient Register (n=25,922; 52 years; 73% women). For each patient, five age-, sex-, education- and county-matched general population comparators were sampled. Sick leave and disability pension days were retrieved from national registers. RESULTS: Sick leave and disability pension increased from a mean 43 to 77 days/year from 2 to 1 years before RA diagnosis. A further increase to 147 days/year was observed the next year, followed by a rebound to 116 days/year 4 years after diagnosis. During the 4 years following diagnosis, sick leave decreased from a mean 118 to 35 and disability pension increased from 29 to 81 days/year. In the prevalent RA population, patients had a mean 158 annual days of sick leave and disability pension compared to 71 in comparators. Large variations existed across age, sex and education level, but RA patients had consistently higher levels. In 2007, the costs associated with sick leave and disability pension were €16,000 per patient with €9,000 attributable to RA. CONCLUSION: Despite better drugs and improved treatment strategies, data from contemporary patients with early and established RA continue to indicate large unmet needs.

Does cancer that occurs during or after anti-tumor necrosis factor therapy have a worse prognosis? A national assessment of overall and site-specific cancer survival in rheumatoid arthritis patients treated with biologic agents.

OBJECTIVE: Tumor necrosis factor (TNF) may affect tumor development and spreading. While data on the incidence of cancer following anti-TNF therapy have been published, the purpose of this study was to examine the clinical presentation and outcome of cancers that develop during or after anti-TNF therapy. METHODS: By linking data from Swedish clinical registries of rheumatoid arthritis (RA) patients, including Anti-Rheumatic Therapy in Sweden (ARTIS), the Swedish Biologics Register, with nationwide data on hospitalizations and outpatient visits for RA, we assembled a cohort of 78,483 RA patients who were alive in 1999 or who entered the cohort thereafter. Of these, 8,562 patients started therapy with a biologic agent (98% started an anti-TNF) during the period from January 1, 1999 to December 31, 2007. Linkage to the Swedish Cancer Register and other registers identified first primary cancers occurring during 1999-2007 as well as post-cancer survival through March 31, 2009. Through this linkage, we identified 314 cancers in patients who were undergoing, or had a history of, treatment with biologic agents and 4,650 cancers in patients who were biologics-naive at the time of cancer diagnosis. The distributions of tumor stage among the biologics-exposed and the biologics-naive patients were compared. The relative risk of death among the biologics-exposed versus the 586 matched biologics-naive cancer cases were assessed by Cox regression analyses. Through chart review in a defined subset, we gathered additional clinical information and validated the diagnoses. RESULTS: For all cancers combined, the distribution of cancer stages at the time of cancer diagnosis was largely similar between those in the biologics-exposed and the matched biologics-naive groups. Based on the total of 113 deaths among those with cancer in the biologics-exposed group versus the 256 deaths among those with cancer in the biologics-naive group, the relative risk of death following cancer associated with exposure to anti-TNF was 1.1 (95% confidence interval 0.8-1.6). CONCLUSION: During routine care, cancers that occur following anti-TNF therapy are not characterized by any markedly altered stage at presentation or by altered post-cancer survival rates.

Infections requiring hospitalization in the abatacept clinical development program: an epidemiological assessment.

INTRODUCTION: Patients with rheumatoid arthritis (RA) have an increased risk of infection and this risk appears to be higher with anti-TNF (tumor necrosis factor) agents. We pooled data from the cumulative abatacept RA clinical development program, both double-blind and open-label periods, to estimate the incidence rates (IRs) of infections requiring hospitalization including pneumonia and opportunistic infections, in comparison with RA patients treated with non-biologic disease-modifying antirheumatic drugs (DMARDs) from several reference cohorts. METHODS: Infections reported in seven abatacept clinical trials of RA patients (double-blind and open-label periods) were tabulated. Comparisons were made between the observed IRs in abatacept-treated patients and those in over 133,000 patients exposed to non-biologic DMARDs in six reference RA cohorts. Age- and sex-adjusted IRs of infections requiring hospitalization, including pneumonia (most frequent hospital infection), were used to estimate the expected IRs with abatacept by the method of indirect adjustment. Standardized incidence ratios (SIR) and 95% CI were calculated comparing incidence in the cumulative abatacept experience with incidence in each RA cohort. RESULTS: A total of 1,955 (double-blind period) and 4,134 (double-blind + open-label periods with a cumulative exposure of 8,392 person-years) abatacept-treated RA patients were analyzed. Observed IRs for infections requiring hospitalization during the double-blind period were 3.05 per 100-patient years for abatacept-treated patients and 2.15 per 100 patient years for placebo. In the cumulative population, observed IR for infections requiring hospitalization was 2.72 per 100-patient years. Rates for abatacept were similar to expected IRs based on other RA non-biologic DMARD cohorts. CONCLUSIONS: IRs of infections requiring hospitalization and pneumonia in abatacept trials are consistent with expected IRs based on reference RA DMARD cohorts. RA patients are at higher risk of infection compared with the general population, making the RA DMARD cohorts an appropriate reference group. The safety of abatacept, including incidence of infections requiring hospitalization, will continue to be monitored in a post-marketing surveillance program.