Potential Cost Implications of Mandatory Non-Medical Switching Policies for Biologics for Rheumatic Conditions and Inflammatory Bowel Disease in Canada.

In 2018, TNFα inhibitors were the highest cost drug class for Canadian public drug programs. In 2019, two Canadian provinces announced mandatory nonmedical switching policies in an attempt to reduce their costs by increasing biosimilar uptake. The national impact of similar policies across Canada is unknown. We conducted a cross-sectional analysis of monthly publicly funded prescription claims for infliximab, etanercept, and adalimumab between June 2015 and December 2019. We reported the market share of biosimilars for infliximab and etanercept in 2019 for each province and estimated the cost savings that public payers could have realized in 2019 if mandatory switching policies had been implemented across Canada, including a sensitivity analysis, which assumed that governments receive a 25% rebate on all biologics. Provincial drug programs spent CAD $991.84 million on infliximab, etanercept, and adalimumab in 2019, and, when biosimilars were available, they constituted only 15.5% of national utilization of these drugs. In British Columbia, the implementation of a mandatory switching policy for patients with rheumatic conditions increased the biosimilar market share of infliximab and etanercept by 299% (from 19.7% to 78.5%). If applied nationwide to all three biologics for all indications, we estimate such policies could lead to annual savings of between CAD $179.71 million and CAD $425.64 million nationally. The overall market share of biosimilars remains low in all provinces where mandatory switching policies have not been introduced. The cost implications of successfully increasing biosimilar uptake would be substantial, particularly as more biosimilars reach the Canadian market.

Are There Benefits and Risks to Biosimilars from a Patient Perspective?

Biosimilars are copies of biologic medications, which no longer are protected by patent, that are intended to be marketed at lower prices than their reference products to increase patient access to treatment. Because a biosimilar must have equivalent pharmacokinetic parameters and efficacy and comparable safety and immunogenicity with its reference product, the only significant difference between the two should be cost. Lower-priced biosimilars are intended to introduce market competition. The availability of biosimilars should yield savings for the health care system and improve treatment outcomes by expanding patient access to effective medications. However, patients should partake of these cost savings.

Guidelines for management of rheumatic diseases in developing countries from basics to real-world situation: relevance, need, and processes for development.

Guidelines or recommendations help to provide uniform standards in medical practice. The development of guidelines requires adherence to pre-defined norms prescribed by different international organizations such as the European League against Rheumatism (EULAR). We searched Pubmed and LILACS to identify published papers in five major rheumatic diseases (rheumatoid arthritis, systemic lupus erythematosus, spondyloarthropathies, osteoarthritis, and scleroderma) from different countries based on their economic prosperity and could find a lack of published literature from most economically weaker regions. Similarly, published guidelines in these rheumatic diseases were sparse from Asia and Africa, which are economically developed to a lesser extent than other regions of the world. Considering differing economic realities driving patient care in different regions of the world, unique challenges in certain geographic areas such as musculoskeletal manifestations of infectious diseases like leprosy and tuberculosis, as well as distinct risk of malignancies and other comorbid conditions, National Rheumatology societies should work towards developing more guidelines for rheumatic diseases from regions such as Asia and Africa, while following strictly the prescribed norms for the same. With a paucity of guidelines for such regions currently, an alternative (although less preferable) suggestion would be that major international societies, whose guidelines are widely read and followed the world over, should consider inputs from experts from diverse regions of the world while developing these guidelines.

Second-line treatment persistence and costs among patients with immune-mediated rheumatic diseases treated with subcutaneous TNF-alpha inhibitors.

The objective of this study was to describe treatment persistence with second-line subcutaneous tumor necrosis factor-alpha inhibitors (SC-TNFis) in patients with immune-mediated rheumatic diseases (IMRDs) in Sweden, and the impact of non-persistence on healthcare costs. This retrospective observational study was based on Swedish national health register data. Adults were identified through filled prescriptions for adalimumab (ADA), etanercept (ETA), certolizumab pegol (CZP) and golimumab (GLM). Persistence was estimated over 3 years for propensity score-matched (PSM) cohorts using non-parametric survival analysis. Unadjusted comparisons of costs comprised specialized outpatient care, inpatient care, and medication. In total, N = 845 patients were identified and three PSM cohorts were generated (GLM vs. ADA, ETA, and CZP, respectively). GLM exhibited higher persistence than ADA over the study period (p = 0.040), and numerically higher persistence than ETA and CZP for 36 and 30 months, respectively. Persistent and non-persistent patients had similar mean total cost at 12 month pre-treatment ($5185 vs. $5064, p = 0.750). During the 12 month post-treatment initiation, persistent patients had lower mean total costs ($4377 vs. $6605), corresponding to a cost difference of $2228 (p < 0.001). In second-line treatment with SC-TNFis for IMRDs in Sweden, GLM exhibited significantly higher persistence than ADA over the course of the study. Similarly, GLM showed numerically higher persistence than ETA and CZP, which is concurrent with results observed in first-line SC-TNFi treatment. Considering the lower healthcare costs for persistent patients, the choice of second-line SC-TNFi among eligible patients may merit careful consideration given its impact on patients and payers.

Filling the gaps in SARDs research: collection and linkage of administrative health data and self-reported survey data for a general population-based cohort of individuals with and without diagnoses of systemic autoimmune rheumatic disease (SARDs) from British Columbia, Canada.

PURPOSE: Systemic autoimmune rheumatic diseases (SARDs) are a group of debilitating autoimmune diseases, including systemic lupus erythematosus and related disorders. Assessing the healthcare and economic burden of SARDs has been challenging: while administrative databases can be used to determine healthcare utilisation and costs with minimal selection and recall bias, other health, sociodemographic and economic data have typically been sourced from highly selected, clinic-based cohorts. To address these gaps, we are collecting self-reported survey data from a general population-based cohort of individuals with and without SARDs and linking it to their longitudinal administrative health data. PARTICIPANTS: Using administrative data from the province of British Columbia (BC), Canada, we established a population-based cohort of all BC adults receiving care for SARDs during 1996-2010 (n=20 729) and non-SARD individuals randomly selected from the general population. BC Ministry of Health granted us contact information for 12 000 SARD and non-SARD individuals, who were recruited to complete the surveys by mail or online. FINDINGS TO DATE: Four hundred individuals were initially invited to participate, with 135 (34%) consenting and 127 (94%) submitting the first survey (72% completed online). Sixty-three (49.6%) reported ≥1 SARD diagnosis. The non-SARDs group (n=64) was 92% female with mean age 57.0±11.6 years. The SARDs group (n=63) was 94% female with mean age 56.5±13.1 years. Forty-eight per cent of those with SARDs were current-or-former smokers (mean 10.6±16.2 pack-years), and 33% were overweight or obese (mean body mass index of 24.4±5.3). FUTURE PLANS: Health and productivity data collected from the surveys will be linked to participants' administrative health data from the years 1990-2013, allowing us to determine the healthcare and lost productivity costs of SARDs, and assess the impact of patient-reported variables on utilisation, costs, disability and clinical outcomes. Findings will be disseminated through scientific conferences and peer-reviewed journals.

Impact of Chronic Diseases and Multimorbidity on Health and Health Care Costs: The Additional Role of Musculoskeletal Disorders.

OBJECTIVE: Chronic diseases are increasingly prevalent and often occur as multimorbidity. This study compares the impact of musculoskeletal disorders (MSKDs) on health and health care costs with other chronic diseases, and assesses the additional impact of MSKDs on these outcomes when occurring as part of multimorbidity. METHODS: A household survey in a random Dutch population sample (n = 8,904) yielded information on sociodemographics, presence of 9 physician-confirmed chronic diseases (i.e., musculoskeletal, migraine, diabetes mellitus, cardiovascular, cancer, respiratory, skin, mental, and gastrointestinal), physical component summary (PCS) and mental component summary (MCS) scores of the Short Form 12 health survey, and health care utilization. The independent influence of different diseases and the role of MSKDs with increasing number of morbidities on PCS/MCS and 3-month societal health care costs were explored through multivariable linear and zero-inflated negative binomial regressions, respectively. RESULTS: Twenty percent of all subjects and 56% of those with multimorbidity had an MSKD. MSKDs had the largest impact on PCS (ß = -8.37 [95% confidence interval (95% CI) -8.84, -7.89]) but no significant impact on MCS. When MSKDs occurred as part of multimorbidity, an amplification of the adverse effect on PCS but not on MCS was seen, irrespective of the number of comorbidities. MSKDs were responsible for a 2-fold increase in costs (Exp [ß] = 2.27 [95% CI 2.08, 2.51]), which was the second highest cost increase of all diseases (after cancer). Significant amplification of costs was seen when MSKDs co-occurred with mental diseases. CONCLUSION: MSKDs often co-occur with other chronic diseases. In the context of multimorbidity, presence of an MSKD amplifies the impact on physical health, and to a lesser extent on health care costs, but not on mental health.

Treatment persistence among patients with immune-mediated rheumatic disease newly treated with subcutaneous TNF-alpha inhibitors and costs associated with non-persistence.

The main objective of this study was to describe real-world treatment persistence with subcutaneous tumor necrosis factor-alpha inhibitors (SC-TNFi) in patients with ankylosing spondylitis, psoriatic arthritis, or rheumatoid arthritis [collectively immune-mediated rheumatic disease, (IMRD)] in Sweden. A secondary objective was to describe potential effects on health care resource utilization (HCRU) cost from non-persistence. Patients were identified through filled prescriptions for adalimumab (ADA), etanercept (ETA), certolizumab pegol (CZP), and golimumab (GLM) between 5/6/2010 and 12/31/2012 from the Swedish Prescribed Drug Register. Persistence was estimated using survival analysis. Costs were derived from HCRU and comprised specialized outpatient care, inpatient care and non-disease-modifying antirheumatic drug medications. A total of 4903 patients were identified (ADA: 1823, ETA: 1704, CZP: 622, GLM: 754). Comparisons over 3 years showed that GLM had significantly higher persistence than ADA (p = 0.022) and ETA (p = 0.004). The mean difference in non-biologic HCRU costs between persistent and non-persistent patients was higher after compared to before the start of biologic therapy. SC-TNFi-naïve IMRD patients initiating treatment with GLM had significantly higher persistence rates than patients initiating treatment with ADA or ETA in Sweden. Furthermore, persistence rates observed in the study were lower than those observed in clinical trials, highlighting the need for an all-party (provider-patient-payer-drug manufacturer) engagement and development of programs to increase persistence rates in clinical practice, thus leading to improved clinical outcomes. In addition, the results of this study indicate that persistence to treatment with SC-TNFi may be associated with cost offsets in terms of non-biologic costs.

[Evolution of biologicals in inflammation medicine--biosimilars in gastroenterology, rheumatology and dermatology]. / Evolution der Biologika in der Entzündungsmedizin--Biosimilars in Gastroenterologie, Rheumatologie und Dermatologie.

Biologicals revolutionized the therapy of chronic inflammatory diseases in gastroenterology, rheumatology and dermatology in the last decade. The first generation biologicals mainly targeted against the pro-inflammatory cytokine TNF-α. The evolution of these therapies in the last years led to the development of new antibodies and to the admission of first generation "generic" biologics - the biosimilars. Biosimilars are not a fundamental new pharmacological development for existing substances, however they have the potential to lead to enormous cost savings in healthcare without reducing the level of care for patients. Biosimilars are not identical with the originator, but in an extensive biosimilarity exercise including analytical, preclinical and comparative clinical studies it was shown that the biosimilars could demonstrate comparability in all relevant aspects with the originator.In September 2013, the Infliximab biosimilars (Inflectra(®), Remsina(®)) were the first biosimilars for monoclonal antibodies to be authorized by the EMA for use in the European Union. By demonstrating the therapeutic similarity only in one indication (rheumatoid arthritis) the EMA agreed with an extrapolation also to all approved indications of the originator. This could be a relevant problem in clinical practice. Therefore, comparative studies with the originator are required in all approved indications.After expiration of the national patent protection in beginning of 2015, the infliximab biosimilars will be launched on the market in Germany and will be part of the therapeutic arsenal in gastroenterology, rheumatology and dermatology. Interchangeability (Switching) of biosimilars with the originator will be subject of an important discussion with the health care providers. Regardless of the biosimilars EMA-approval, several potential problems (efficacy, extrapolation, switching, long-term safety) should be the topic of intensive long-term registries in the future.

Costs of pain in rheumatology.

Chronic pain has been identified as an important issue related to various rheumatic diseases. At the time of a major government spending review, it is appropriate to discuss the pain characterising rheumatic diseases and its related costs. It is clearly essential for healthcare authorities to rationalise their policies on the basis of the increasing expectations of the users of healthcare services while simultaneously balancing their books. There are few published studies concerning the costs of pain of any kind, and the same is true of the costs of the chronic pain associated with diseases such as rheumatoid arthritis, osteoarthritis, and fibromyalgia.

Embitterment in patients with a rheumatic disease after a disability pension examination: occurrence and potential determinants.

OBJECTIVES: Health care and vocational professionals regularly encounter patients with rheumatic diseases who are embittered after a disability pension examination. People who are embittered typically feel victimised, experience resentment and injustice, resist help, and have difficulty coping. Our objective was to examine the occurrence of embitterment in patients with rheumatic diseases after a disability pension examination and the association of embitterment with its possible determinants helplessness and illness invalidation at work. METHODS: The Illness Cognition Questionnaire (ICQ), Illness Invalidation Inventory (3*I), and Bern Embitterment Inventory were completed by patients who had 9 to 12 weeks earlier received the result of a disability pension examination. Diagnoses were fibromyalgia (n=103), rheumatoid arthritis (n=46), osteoarthritis (n=158), another rheumatic disease (n=62), and more than one rheumatic disease (n=187). Scores were compared to scores of reference groups. Hierarchical regression analyses were conducted. RESULTS: Eighteen to 27 percent of patients had high levels of embitterment with no differences between diagnostic groups (p=0.71). Helplessness (p<0.001), the two invalidation dimensions discounting and lack of understanding (p<0.001), and the combination of helplessness with these invalidation dimensions (p<0.01), were predictive of more embitterment. CONCLUSIONS: Our results suggest that, after a disability pension examination, embitterment is present in about one out of five patients with a rheumatic disease. This is problematic insofar as embitterment limits well-being, functioning, and the potential to reintegrate to work. To the extent that helplessness and invalidation at work are causal determinants of embitterment, interventions targeting these aspects may be key to reduce embitterment.

[Trends of work force participation of patients with rheumatic diseases : results from German social insurance data and the national database of the German collaborative arthritis centers]. / Trends der Erwerbstätigkeit von Rheumakranken : Ergebnisse aus Sozialversicherungsdaten und Kerndokumentation der Rheumazentren in Deutschland.

Positive therapeutic effects on the work force participation derived from international clinical trials may not be directly transferable to the community based care in Germany. Therefore recent changes of data regarding sick leave (SL), work disability pension (WDP) and employment from the social insurance and from the national database of the German collaborative arthritis centers were analyzed covering a time period of at least 10 years. Health insurance data showed a steeper decline in the average duration of SL caused by rheumatoid arthritis (RA), ankylosing spondylitis (AS) and systemic lupus erythematosus (SLE) compared with all other diseases. In RA patients from the collaborative arthritis centers the mean duration of SL was much more reduced than the average duration of SL for members of the compulsory health insurance. The proportion of gainfully employed RA patients in collaborative arthritis centers has particularly increased in women. According to data from the pension insurance fund less incident cases of WDP due to RA, AS, and SLE have been observed than WDP caused by all other diseases. Thus different nationwide data show positive changes of the work force participation of individuals suffering from inflammatory rheumatic diseases in Germany.

Biologic agents in rheumatology: unmet issues after 200 trials and $200 billion sales.

Anti-TNF agents and other biologic therapies are widely prescribed for a variety of indications, with total sales that exceed $200 billion to date. In rheumatic diseases, biologic agents have now been studied in more than 200 randomized clinical trials and over 100 subsequent meta-analyses; however, the information obtained does not always meet the needs of patients and clinicians. In this Review, we discuss the current issues concerning the evidence derived from such studies: potential biases favouring positive results; a paucity of head-to-head comparisons between biologically active agents; overwhelming involvement of manufacturer sponsors in trials and in the synthesis of the evidence; the preference for trials with limited follow-up; and the potential for spurious findings on adverse events, leading to endless debates about malignancy risk. We debate the responsibilities of regulatory authorities, the pharmaceutical industry and academia in attempting to solve these shortcomings and challenges. We propose that improvements in the evidence regarding biologic treatments that are continually being added to the therapeutic armamentarium for rheumatic diseases might require revisiting the design and conduct of studies. For example, trials with long-term follow-up that are independent of the pharmaceutical industry, head-to-head comparisons of therapeutic agents and the use of rigorous clinical outcomes should be considered, and public availability of raw data endorsed.

Injectable tumor necrosis factor α inhibitors and outpatient antimicrobial use in children with rheumatic diseases: analyses of prescription claims from a pharmacy benefit manager database.

OBJECTIVE: To estimate the incidence and rate of outpatient antibiotic and antiviral medication use among children receiving methotrexate and/or an injectable tumor necrosis factor α (iTNFα) inhibitor (etanercept and/or adalimumab)and to compare these rates with those of a control population. METHODS: Data were obtained from a pharmacy benefit manager (PBM) database. Children were included if they had >1 prescription claim for an iTNFα inhibitor or methotrexate prescribed by a pediatric or adult rheumatologist between 2008 and 2010 and if they were age <18 years at the time of the claim. A control cohort of randomly selected children was generated from the PBM database. Poisson regression was used to compare antimicrobial rate ratios (RRs). Incidence rates and RRs were adjusted for age, sex, and prednisone exposure. RESULTS: In total, 4,312 children were included. The adjusted RRs for antibiotic prescriptions among children receiving methotrexate monotherapy or iTNFα inhibitor and methotrexate combination therapy compared with the control cohort were 2.18 (95% confidence interval [95% CI] 1.92­2.47) and 2.12 (95% CI 1.79­2.50), respectively. The adjusted RRs for antiviral prescriptions among children receiving methotrexate monotherapy or iTNFα inhibitor and methotrexate combination therapy compared with the control cohort were 3.67 (95% CI 1.98­6.78) and 4.34 (95% CI 1.86­10.14), respectively. The RRs for the iTNFα inhibitor group were similar in magnitude. There was no significant difference in RRs between the medication exposure categories for either antibiotic or antiviral prescriptions. CONCLUSION: Children receiving methotrexate and/or an iTNFα inhibitor had higher rates of antibiotic and antiviral use compared with the control cohort. Data sets with additional patient-level and disease-specific data are required to assess this association in more detail.

Capturing all of the costs in NICE appraisals: the impact of inflammatory rheumatic diseases on productivity.

Inflammatory rheumatic diseases are common. It is estimated that ∼2.1% of the population has an inflammatory rheumatic disease (Andrianakos A, Trontzas P, Christoyannis F et al. Prevalence of rheumatic diseases in Greece: a cross-sectional population based epidemiological study. The ESORDIG Study. J Rheumatol 2003;30:1589-601). For diseases such as RA, PsA and AS, onset is most frequent between the ages of 30 and 50 years. The impact of inflammatory rheumatic diseases on physical functioning can be significant. Patients can suffer from swollen joints that cause pain and disability. This can reduce sufferers' ability to lead fully productive lives. This has major financial consequences for sufferers and their families and there is an economic impact on society. The National Institute for Health and Clinical Excellence (NICE) technology appraisal process has typically ignored any improvements in productivity that may result from treatment. There have been calls to extend the perspective of economic evaluations to include productivity costs as one aspect of wider social effects. However, there are a number of issues that must be resolved before productivity costs can become a routine input into the calculation of cost-effectiveness of treatments. First, there is limited agreement regarding the practical details and appropriate methods for their inclusion in economic evaluation. Second, there are issues that must be addressed regarding society's preference for equity. This issue arises when considering individual's economic productivity, that is to say, how we weigh individuals who are more productive (e.g. those in employment) against those who are less so (e.g. the unemployed). Finally, it is important to consider cross-budgetary effects, since productivity has cost and benefit implications outside of health.

[Profile of use of anti tumor necrosis factor in Colombian patients]. / Perfil de utilización de los anti-factor de necrosis tumoral en pacientes de Colombia.

INTRODUCTION: Tumor necrosis factor-alpha antagonists (anti-TNFα) have shown an increasing consumption and generate a significant economic burden on health systems. OBJECTIVES: The prescribing patterns of tumor necrosis factor-alpha antagonists were determined in a patient population associated with the Sistema General de Seguridad Social en Salud in Colombia. MATERIALS AND METHODS: A descriptive observational study was conducted in 316 patients with respect to use of tumor necrosis factor-alpha antagonists during a treatment period from January 2008 to June 2009. The database examined contained indications of use, inclusion criteria to medication, duration of illness, co-morbidities and adverse reactions. The data were retrieved from the clinical histories. Student's t test was used for the comparison of quantitative variables, and the chi-square test was used to establish associations between categorical variables and multivariate analysis were used. RESULTS: Mean age was 44.613.9 years; 63.9% of participants were female. Of the 316 patients, 17.1% received monotherapy. The order of prescription drugs was as follows: adalimumab (37.3%), infliximab (37.3%) and etanercept (25.4%), all were prescribed in appropriately defined daily doses. Co-medication drugs most frequently prescribed were: disease-modifying anti-rheumatic (82.9%), NSAIDs (29.1%), omeprazole (22.5%), antihypertensives (21.2%), folic acid (19.9%) calcium plus vitamin D (9.8%), calcitriol (6.0%). 10.4% of patients had a record of some adverse drug reaction. The average cost of therapy per patient per year was US$23,464. CONCLUSIONS: Anti-TNFα are being used at recommended doses, particularly in rheumatoid arthritis and in combination with other anti-rheumatic drugs. The direct cost of therapy was high for the country's health system.

Autoantibody detection with indirect immunofluorescence on HEp-2 cells: starting serum dilutions for systemic rheumatic diseases.

Antinuclear antibodies (ANA) are determined, among other reasons, to identify samples which need a second test to detect the associated specificities. Our aim was to evaluate the clinical and economic impact generated by using an initial dilution for ANA of 1:160. We analyzed all samples for which ANA, anti-ENA and anti-dsDNA were requested over a 1-year period. ANA were detected by indirect immunofluorescence. Anti-ENA were analyzed with a combination of techniques. Anti-dsDNA were detected by radioimmunoassay. Cost analysis was performed by calculating the difference between two cut-offs (ANA 1:40 and 1:160). A total of 13,233 samples were processed for ANA, of which 59.9% were positive with the 1:40 cut-off and 39.2% with the 1:160 cut-off. At ANA titer 1:40, 0.2% of the samples were anti-ENA-positive and 2.2% were anti-dsDNA positive. Only ANA dilutions of 1:160 and higher showed significantly increased positive predictive value for anti-ENA (1.5 versus 0.2, p=0.029) and anti-dsDNA (8.3 versus 2.2, p<0.001) compared to the 1:40 titer. With the 1:160 cut-off, 16.6% fewer ANA tests, 41.8% fewer anti-ENA determinations and 36.4% fewer anti-dsDNA tests would have been needed. The average saving was 0.87 cost-units per sample (1 unit=2.06euro). We conclude that setting the starting dilution for ANA at 1:160 avoids unnecessary studies, increases the positive predictive values of ANA for anti-ENA and anti-dsDNA, and generates clinical and economic benefits.

[The G-DRG System 2009--relevant changes for rheumatology]. / Das G-DRG-System 2010--Relevantes für die Rheumatologie.

The following article presents the major general and specific changes in the G-DRG system, in the classification systems for diagnoses and procedures as well as for the billing process for 2010. Since the G-DRG system is primarily a tool for the redistribution of resources, every hospital needs to analyze the economic effects of the changes by applying the G-DRG transition-grouper to its own cases. Depending on their clinical focus, rheumatological departments may experience positive or negative consequences from the adjustments. In addition, relevant current case law is considered.

[Rheumatic diseases and work: Patient activity versus disease activity]. / Doenças reumáticas e trabalho: a actividade do doente versus a actividade da doença.

Rheumatic diseases have a substantial impact on the patient but also on the work status and on a social-economical context. In Europe 25% of the cost of disease is related with rheumatic diseases. We are focusing more on disease activity as a clinical challenge but we have to consider that patient occupational activity is a main issue as a strategic gold for patient management. Rheumatologists have to prove on a daily basis their positive impact on the socio-economical impact of these diseases. The search for practical solutions to empower patients in their work status must be based not only on disease activity management but also in facilitating the work station adaptation to the unique characteristics and ability of each patient.