Burden of idiopathic inflammatory rheumatic diseases in occupational healthcare: increased absenteeism and healthcare resource utilization.

OBJECTIVES: Patients with idiopathic inflammatory rheumatic diseases (IIRD) often have decreased working capacity resulting in indirect costs. However, data on patients' short-term sick leave has been limited. This retrospective cohort study evaluated the number and length of sick leave, including short-term leave, and occupational healthcare resource utilization (HCRU) of the working-aged patients with IIRD compared to controls. METHODS: The data on sick leave and occupational HCRU were gathered from the electronic medical records of the largest occupational healthcare provider in Finland from January 2012 to December 2019. Employed patients with an IIRD (including rheumatoid arthritis, spondyloarthritis, psoriatic and enteropathic arthritis, juvenile arthritis, and reactive arthritis) with at least a 12-months follow-up were identified and compared to age-, sex-, and follow-up matched controls without IIRD. RESULTS: Altogether 5405 patients with IIRD were identified and compared with an equal number of controls. The patients incurred approximately 2.5 times more sick leave than controls: 21.7 versus 8.5 days per patient year, respectively. Short-term sick leave was common: 83% of sickness absence periods of the patients lasted 1-9 days and represented 30% of the total absenteeism. Loss of productivity due to lost workdays was on average €4572 (95% confidence interval €4352-4804) per patient year. Occupational HCRU was approximately 1.8 times higher among IIRD patients than controls. CONCLUSIONS: Workers with an IIRD incur considerably more sick leave and use more occupational healthcare services than controls. Short sick leave not registered in national insurance registers constitute a significant portion of days off work among patients with IIRD.

Patients with rheumatoid arthritis facing sick leave or work disability meet varying regulations: a study among rheumatologists and patients from 44 European countries.

OBJECTIVES: To describe and explore differences in formal regulations around sick leave and work disability (WD) for patients with rheumatoid arthritis (RA), as well as perceptions by rheumatologists and patients on the system's performance, across European countries. METHODS: We conducted three cross-sectional surveys in 50 European countries: one on work (re-)integration and social security (SS) system arrangements in case of sick leave and long-term WD due to RA (one rheumatologist per country), and two among approximately 15 rheumatologists and 15 patients per country on perceptions regarding SS arrangements on work participation. Differences in regulations and perceptions were compared across categories defined by gross domestic product (GDP), type of social welfare regime, European Union (EU) membership and country RA WD rates. RESULTS: Forty-four (88%) countries provided data on regulations, 33 (75%) on perceptions of rheumatologists (n=539) and 34 (77%) on perceptions of patients (n=719). While large variation was observed across all regulations across countries, no relationship was found between most of regulations or income compensation and GDP, type of SS system or rates of WD. Regarding perceptions, rheumatologists in high GDP and EU-member countries felt less confident in their role in the decision process towards WD (ß=-0.5 (95% CI -0.9 to -0.2) and ß=-0.5 (95% CI -1.0 to -0.1), respectively). The Scandinavian and Bismarckian system scored best on patients' and rheumatologists' perceptions of regulations and system performance. CONCLUSIONS: There is large heterogeneity in rules and regulations of SS systems across Europe in relation to WD of patients with RA, and it cannot be explained by existing welfare regimes, EU membership or country's wealth.

Cost-effectiveness of abatacept, tocilizumab and TNF-inhibitors compared with rituximab as second-line biologic drug in rheumatoid arthritis.

OBJECTIVES: The objective of this study was to evaluate the cost-effectiveness of abatacept, tocilizumab, and tumor necrosis factor (TNF) inhibitors as compared with rituximab in Finnish rheumatoid arthritis patients, who have previously been treated with TNF inhibitors. METHODS: A patient-level simulation model was developed to predict costs and outcomes associated with four biological drugs (abatacept, tocilizumab, rituximab and TNF inhibitors) in the treatment of rheumatoid arthritis. Following lack of efficacy or adverse events, the patients were switched to another biological drug until all four options were exhausted. After that, the patients were assumed to receive a 6th line treatment until death. The patients' baseline characteristics and regression models used in the simulation were based on observational data from the National Register for Biological Treatments in Finland. Direct costs comprised drug costs, administration costs, costs of switching, and outpatient and inpatient care, while indirect costs included disability pension and sick leaves due to rheumatoid arthritis. Several subgroup and deterministic sensitivity analyses were conducted. RESULTS: Drug costs were the lowest for rituximab, but when administration costs and costs of switching were included, drug costs were the lowest for TNF inhibitors. Abatacept was associated with the highest drug costs, whereas rituximab was associated with the highest healthcare costs. In total, TNF inhibitors had the lowest direct costs, while rituximab had the highest direct costs. The amount of quality-adjusted life years (QALY) gained ranged from 9.405 for rituximab to 9.661 for TNF inhibitors. TNF inhibitors, abatacept, and tocilizumab were dominant in comparison to RTX. CONCLUSIONS: TNF inhibitors, abatacept, and tocilizumab had lower costs and higher QALYs than rituximab, and therefore, they were dominant in comparison to rituximab. As TNF inhibitors had the lowest costs and highest QALYs, they were the most cost-effective treatment option.

Cost-effectiveness of secukinumab compared to other biologics in the treatment of ankylosing spondylitis in Finland.

AIM: This study assesses the cost-effectiveness of secukinumab vs currently licensed biologics for the treatment of ankylosing spondylitis (AS) from the Finnish health care system perspective. METHODS: A semi-Markov model compared secukinumab with adalimumab, adalimumab biosimilar, certolizumab pegol, etanercept, etanercept biosimilar, golimumab, and infliximab in a biologic-naïve population over a lifetime horizon. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was used to assess the treatment response. Efficacy inputs were obtained from the network meta-analysis, and other model inputs were obtained from the published literature and Finnish sources. Main study outcomes included quality-adjusted life years (QALYs) gained and incremental cost-effectiveness ratio in terms of cost per QALY gained. Robustness of results was confirmed by sensitivity analyses and alternative scenario analyses. RESULTS: Secukinumab achieved highest QALYs (13.1) at lowest expected lifetime cost (€279,872) vs other comparators in biologic-naïve AS patients in the base case analysis, thus it dominated other biologics. Golimumab had a second highest QALYs (12.9) at the total cost of €309,551. Results were sensitive to variation in BASDAI 50 response for secukinumab, baseline Bath Ankylosing Spondylitis Functional Index (BASFI) score across all drugs, change in BASDAI and BASFI scores, and discount rates as observed in the one-way sensitivity analyses. Secukinumab was either dominant or cost-effective treatment in different alternative scenarios. CONCLUSION: Secukinumab presented itself to be the dominant (ie, less costly and more effective) treatment vs other comparators for the biologic-naïve patients with AS in Finland.

Budget impact analysis of secukinumab versus adalimumab in the treatment of ankylosing spondylitis.

BACKGROUND: Biologic treatments have enhanced the treatment outcomes of patients with active ankylosing spondylitis (AS). Until recently, TNF-alpha-inhibitors have been the only biologics approved for the treatment of active AS. The objective of this study was to assess the potential financial impact of the first non-TNF-alpha biologic secukinumab (fully human IL-17A-inhibitor) vs adalimumab (TNF-alpha-inhibitor) in the treatment of AS in Finland. MATERIALS AND METHODS: In this model-based budget impact analysis, patients were treated either with secukinumab (150 mg) or adalimumab (40 mg). The number of patients and market share of different biologics were based on national reimbursement registry data. Adalimumab was the most commonly used biologic treatment for AS, and in the base case analysis all adalimumab patients are assumed to switch to secukinumab. Response rates were based on a matching-adjusted indirect comparison between secukinumab and adalimumab. Patients not achieving response were switched to another biologic treatment. RESULTS: Treating AS patients with secukinumab instead of adalimumab leads to potential savings of 18.2 million euros within a 5-year time period. The total costs within the follow-up time were 59.5 million euros and 77.7 million euros with and without secukinumab, respectively. According to sensitivity analyses, a higher adoption rate of secukinumab corresponds to higher potential savings. CONCLUSIONS: Secukinumab is a cost-saving treatment option compared with adalimumab in the treatment of AS in Finland. More patients could be treated with a biologic by allocating resources more efficiently.

Increasing incidence and shifting profile of idiopathic inflammatory rheumatic diseases in adults during this millennium.

To explore the trends in the incidence of idiopathic inflammatory rheumatic diseases (IIRDs) after the turn of the millennium. From a nationwide register maintained by the Social Insurance Institution of Finland, we collected all adult patients with IIRDs granted a new special reimbursement for anti-rheumatic drugs between 2000 and 2014. Temporal trends in the incidences of various IIRDs were estimated in three 5-year intervals. A total of 58,405 adult patients were identified. Between 2000-2004 and 2010-2014, the age-adjusted incidence rate of IIRDs increased from 114 to 116/100000 [incidence rate ratio (IRR) 1.03 (95% CI 1.01 to 1.06)] in women and from 67 to 69/100,000 [IRR 1.10 (95% CI 1.06-1.14)] in men. The incidence of seropositive rheumatoid arthritis (RA) remained stable while that of seronegative RA decreased. For other diagnoses, the incidences either increased (unspecified arthritis, psoriatic arthritis, spondyloarthritis), remained stable (reactive arthritis), or decreased (SLE and the group of diseases with the ICD-10 code M35). The gender difference in spondyloarthritis leveled as the incidence in women increased at a higher rate than in men. Mean age at IIRD diagnosis decreased among women. The total age-adjusted incidence of IIRDs has gradually increased, due to the increase in unspecified arthritis, psoriatic arthritis, and spondyloarthritis. This, in addition to the ascending number of individuals at risk in the population, translates into a growing burden to the health care system.

Cost-effectiveness analysis of secukinumab versus other biologics and apremilast in the treatment of active Psoriatic arthritis: a Finnish perspective.

OBJECTIVE: To study cost-effectiveness of an interleukin (IL)-17A inhibitor secukinumab, with other biologics and apremilast in patients with Psoriatic arthritis (PsA) from payer perspective in Finland. METHODS: In this semi-Markov model, subcutaneous (SC) secukinumab was compared with SC treatments etanercept and its biosimilar, certolizumab pegol, adalimumab and its biosimilar, golimumab, ustekinumab, intravenous (IV) treatment infliximab, as well as oral non-biologic apremilast. Patients without prior exposure (naïve) to biologics and without moderate to severe psoriasis were considered for secukinumab 150 mg group. Secukinumab 300 mg group included naïve patients with moderate to severe psoriasis and all patients with prior biologic exposure. The PsA Response Criteria (PsARC) at 12-week was primary criteria for treatment response. Other clinical as well as cost related model inputs were derived from relevant clinical trials as well as Finnish publications. The key model outcomes were quality-adjusted life years and incremental cost-effectiveness ratio. An annual 3% discount rate was applied to all future costs and benefits. Model input variations were assessed through sensitivity analyses and alternative scenario analyses. RESULTS: For a lifetime horizon (60 years), secukinumab 150 mg dominated all branded SC biologics and apremilast with highest QALY of 8.01 and lowest lifetime cost of €187,776, while it was cost-effective against IV infliximab among biologic-naïve patients without moderate to severe psoriasis. Secukinumab 300 mg was cost-effective against all branded SC biologics and apremilast and dominated IV infliximab among biologic-naïve patients with moderate to severe psoriasis, while it was cost-effective in biologic experienced patients. With the one-way sensitivity analysis, PsARC response, drug acquisition cost, and health assessment questionnaire score were the most important parameters affecting the outcomes. Across all treatment groups, patients on secukinumab were most likely to achieve highest net monetary benefit than other competitors in probabilistic sensitivity analysis. With alternative scenario analysis, results largely remained unchanged. CONCLUSIONS: Secukinumab is a cost-effective treatment for PsA patients from a Finnish payer's perspective.

Modeled Health Economic Impact of a Hypothetical Certolizumab Pegol Risk-Sharing Scheme for Patients with Moderate-to-Severe Rheumatoid Arthritis in Finland.

PURPOSE: To model the American College of Rheumatology (ACR) outcomes, cost-effectiveness, and budget impact of certolizumab pegol (CZP) (with and without a hypothetical risk-sharing scheme at treatment initiation for biologic-naïve patients) versus the current mix of reimbursed biologics for treatment of moderate-to-severe rheumatoid arthritis (RA) in Finland. METHODS: A probabilistic model with 12-week cycles and a societal approach was developed for the years 2015-2019, accounting for differences in ACR responses (meta-analysis), mortality, and persistence. The risk-sharing scheme included a treatment switch and refund of the costs associated with CZP acquisition if patients failed to achieve ACR20 response at week 12. For the current treatment mix, ACR20 at week 24 determined treatment continuation. Quality-adjusted life years were derived on the basis of the Health Utilities Index. RESULTS: In the Finnish target population, CZP treatment with a risk-sharing scheme led to a estimated annual net expenditure decrease ranging from 1.7% in 2015 to 5.6% in 2019 compared with the current treatment mix. Per patient over the 5 years, CZP risk sharing was estimated to decrease the time without ACR response by 5%-units, decrease work absenteeism by 24 days, and increase the time with ACR20, ACR50, and ACR70 responses by 5%-, 6%-, and 1%-units, respectively, with a gain of 0.03 quality-adjusted life years. The modeled risk-sharing scheme showed reduced costs of €7866 per patient, with a more than 95% probability of cost-effectiveness when compared with the current treatment mix. CONCLUSION: The present analysis estimated that CZP, with or without the risk-sharing scheme, is a cost-effective alternative treatment for RA patients in Finland. The surplus provided by the CZP risk-sharing scheme could fund treatment for 6% more Finnish RA patients. FUNDING: UCB Pharma.

Longterm Work Productivity Costs Due to Absenteeism and Permanent Work Disability in Patients with Early Rheumatoid Arthritis: A Nationwide Register Study of 7831 Patients.

OBJECTIVE: To estimate the development and potential disproportional distribution of longterm productivity costs (PC) and their determinants leading to work absenteeism and permanent work disability in working-aged patients with early rheumatoid arthritis (RA). METHODS: A cohort of subjects with early RA was created by identifying the new cases of RA from the national drug reimbursement register that had been granted a special reimbursement for their antirheumatic medications for RA from 2000-2007. The dataset was enriched by cross-linking with other national registries detailing work absenteeism days and permanent disability pensions. In the base case, the human capital approach was applied to estimate PC based on subjects' annual number of absenteeism days and incomes. Hurdle regression analysis was applied to study the determinants of PC. RESULTS: Among the 7831 subjects with early RA, the mean (bootstrapped 95% CI) annual PC per person-observation year was €4800 (4547-5070). The annual PC declined after the first year of RA diagnosis, but increased significantly in subsequent years. In addition, the PC was heavily disproportionally concentrated in a small fraction of patients with RA, because only around 20% of patients accounted for the majority of total annual PC. The initiation of active drug treatment during the first 3 months after RA diagnosis significantly reduced the cumulative PC when compared with no drug treatment. CONCLUSION: The longterm PC increased significantly in parallel with years elapsing after RA diagnosis. Further, the majority of these PC are incurred by a small proportion of patients.

Cost-effectiveness of biologic compared with conventional synthetic disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis: a Register study.

OBJECTIVE: The aim of this study was to explore the cost-effectiveness of biological DMARDs (bDMARDs) compared with conventional synthetic DMARDs (csDMARDs) for RA using real-world data from Finnish registers. METHODS: RA patients starting their first bDMARD and comparator patients using csDMARDs during 2007-11 were obtained from the National register of biologic treatments in Finland and the Jyväskylä Central Hospital patient records. Propensity score matching was applied to adjust for differences between bDMARD and csDMARD users. Effectiveness was measured in quality-adjusted life years (QALY) and based on the register of biologic treatments in Finland and Jyväskylä Central Hospital patient records, whereas the direct costs were obtained from relevant Finnish national registers. Patients were followed up for 2 years, and both costs and effectiveness for the second year were discounted at 3%. The incremental cost-effectiveness ratio (ICER) with 95% CI was calculated based on bootstrapped mean costs and effectiveness. RESULTS: Of 1581 RA patients meeting study inclusion criteria, 552 bDMARD and 220 csDMARD users were included in analyses after matching. Mean costs for bDMARDs and csDMARDs were €55 371 and €24 879, while mean effectiveness was 1.23 and 1.20 QALYs, respectively. Consequent ICER was €902 210/QALY. Results were confirmed in sensitivity analyses. CONCLUSION: The high incremental cost and the small, non-significant difference in effectiveness resulted in high ICER, suggesting that bDMARDs are not cost-effective. Regardless of matching, latent confounders may introduce bias to the results.

A survey on the medication adherence to methotrexate among rheumatoid arthritis patients treated with self-administered biologic drugs.

OBJECTIVES: Methotrexate (MTX) is the most widely used co-therapy among rheumatoid arthritis (RA) patients using biological disease-modifying anti-rheumatic drugs (bDMARDs). However, adherence to MTX treatment remains a concern with estimates of adherence ranging from 59 to 63%. The objective of this study was to assess the self-reported use and adherence to MTX among RA patients treated with self-administered bDMARDs. METHODS: An electronic questionnaire survey was conducted in 68 community pharmacies in Finland. To be included in the present study patients had to be at least 18 years old, be currently using a self-administered bDMARD and be diagnosed with RA. The results are presented as medians with their respective interquartile ranges (IQR) or percentages. RESULTS: Of the 158 pharmacy customers asked to participate, 135 (85%) consented to complete the questionnaire. The included respondents were predominantly female (72%) with a median age of 55 (IQR 44-65) and rheumatic activity of 3 out of 10 (IQR 2-6.5). The majority (91%) of the included respondents were using TNF-inhibitors and 27% of all patients were on biologic monotherapy. MTX was currently used by 45% of the respondents while 50% were past users. Of the current MTX users, 6.8% identified themselves moderately non-adherent to the treatment. MTX-related adverse events were important factors associated with nonadherence and discontinuation of the treatment. CONCLUSIONS: Only 45% of the respondents were currently using MTX co-therapy, but the ones who did were adherent to their treatment. Self-reported adherence may however be subject to social desirability bias and recall bias.

Cost-effectiveness of routine measuring of serum drug concentrations and anti-drug antibodies in treatment of rheumatoid arthritis patients with TNF-α blockers.

Monitoring of anti-drug antibodies (ADAbs) or serum concentrations of biologicals in treatment of rheumatoid arthritis could provide an explanation for a loss of efficacy and help in the choice of subsequent medication. Current clinical practices do not generally include such monitoring of tumor necrosis factor (TNF)-α blockers on a routine basis. The main aims of this study were to estimate the probabilities of optimal and nonoptimal treatment decisions if infliximab or adalimumab drug trough level (DL) and ADAbs are tested or not in rheumatoid arthritis, and to model cost-effectiveness of performing such monitoring on a routine basis. Data on DLs and ADAbs concentrations were obtained in Finland from clinically requested monitoring analyses of 486 and 1,137 samples from patients on adalimumab and infliximab, respectively. DL was within the target range in 42% of samples from adalimumab- and 50.4% of infliximab-treated patients. ADAbs were detected in approximately 20% and 13.5% of samples from adalimumab- and infliximab-treated patients, respectively. ADAbs were found in 52.3% and 41.3% of those with low adalimumab or infliximab DLs, respectively. The monitoring data were incorporated into probabilities for making the optimal treatment decision. Economic impact of clinical decision-making was modeled in a short-term (3-6 months) scenario with 100 hypothetical patients. In the model, the combined measurement of DLs and ADAbs was cost-saving compared to the nontesting scenario when the monitoring results affected the treatment decision in at least 2-5 of 100 patients, a proportion which is easily exceeded in real-life clinical practice. This study indicates that routine monitoring of drug level and ADAbs is cost-beneficial in clinical practice, thereby improving the decision-making process in using TNF-α blockers.

Improving data collection processes for routine evaluation of treatment cost-effectiveness.

The healthcare system in Finland has begun routine collection of health-related quality of life (HRQoL) information for patients in hospitals to support more systematic cost-effectiveness analysis (CEA). This article describes the systematic collection of HRQoL survey data, and addresses challenges in the implementation of patient surveys and acquisition of cost data in the case hospital. Challenges include problems with incomplete data and undefined management processes. In order to support CEA of hospital treatments, improvements are sought from the process management literature and in the observation of healthcare professionals. The article has been written from an information system and process management perspective, concluding that process ownership, automation of data collection and better staff training are keys to generating more reliable data.

Cost-utility of different treatment strategies after the failure of tumour necrosis factor inhibitor in rheumatoid arthritis in the Finnish setting.

OBJECTIVE: To evaluate the cost-utility of different treatment strategies in severe RA after TNF-inhibitor failure. METHODS: The cost-effectiveness of treatment strategies was compared in a group of hypothetical Finnish RA patients. Initially, the patients received either best supportive care (BSC) or one of the following treatments before BSC: adalimumab (ADAL), abatacept (ABAT), etanercept (ETAN), infliximab (INFL) or rituximab (RTX). Further treatments were added to the most cost-effective strategy in a stepwise manner. The analysis was performed on an Excel-based Markov state transition model using the probabilistic approach. The clinical outcomes related to treatments were estimated from published clinical trials. The gained quality-adjusted life-years (QALYs) were estimated based on Health Utilities Index (HUI-3) and disease severity scores (HAQ). The resource use and costs were obtained from the Finnish treatment practice, one published study, the Finnish Unit Cost list and Finnish Medicine Tariffs. RESULTS: Treatment with RTX was more effective and less costly than treatment with ADAL, ABAT or ETAN after TNF-inhibitor failure. An additional QALY gained with RTX costs 30,248 euros compared with BSC. The incremental cost-effectiveness ratios (ICERs) are 50,941, 50,372, 36,121 and 67,003 euros per QALY gained for adding ADAL, ETAN, INFL and ABAT to the RTX strategy, respectively. According to the cost-effectiveness acceptability frontier (CEAF), only BSC or treatments with RTX or RTX followed by INFL should be considered after TNF-inhibitor failure, if willingness to pay is between 0 and 50,000 euros per QALY gained. CONCLUSIONS: Treatment with RTX is a cost-effective treatment strategy in RA patients in Finland.

Impact of initial aggressive drug treatment with a combination of disease-modifying antirheumatic drugs on the development of work disability in early rheumatoid arthritis: a five-year randomized followup trial.

OBJECTIVE: To compare the efficacy of therapy with a combination of disease-modifying antirheumatic drugs (DMARDs) versus therapy with a single DMARD in the prevention of work disability in patients with early rheumatoid arthritis (RA). METHODS: In the Finnish Rheumatoid Arthritis Combination Therapy trial, 195 patients with recent-onset RA were randomly assigned to receive either combination therapy with DMARDs (sulfasalazine, methotrexate, hydroxychloroquine) plus prednisolone or single therapy with a DMARD with or without prednisolone. After 2 years, the drug treatment strategy was no longer restricted. At baseline, 162 patients (80 in the combination-treatment group and 82 in the single-treatment group) were still working or at least available for work. After 5 years of followup, data on all sick leave and retirement were obtained from social insurance registers or case records. The main outcome for each patient was the cumulative duration of all sick leaves and RA-related disability pensions, divided by the observation period during which the patient was not retired because of another disease or because of age. RESULTS: The cumulative duration of work disability per patient-observation year was significantly lower in those randomized to combination therapy than in those randomized to single therapy: median 12.4 days (interquartile range [IQR] 0-54) versus 32.2 days (IQR 6-293) (P = 0.008, sex- and age-adjusted P = 0.009). This was mainly due to the difference in sick leaves (i.e., work disability periods