Eficacia y seguridad del calcipotriol y el dipropionato de betametasona en pacientes adultos con psoriasis vulgar en placas moderada o severa, no respondedores a la terapia tópica y sistémica convencional, y no tributarios a terapia biológica / Efficacy and safety of calcipotriol and betamethasone dipropionate in adult patients with moderate or severe plaque psoriasis vulgaris, unresponsive to conventional topical and systemic therapy, and not amenable to biological therapy

ANTECEDENTES: En el marco de la metodología ad hoc para evaluar solicitudes de tecnologías sanitarias, aprobada mediante Resolución de Institución de Evaluación de Tecnologías en Salud e Investigación N° 111-IETSI-ESSALUD-2021, se ha elaborado el presente dictamen que expone la evaluación de la eficacia y seguridad del calcipotriol y dipropionato de betametasona (DB) en pacientes adultos con psoriasis vulgar en placas moderada o severa, no respondedores a la terapia tópica y sistémica convencional, y no tributarios a terapia biológica. Así, la médico dermatóloga, Dra. Lorraine Lía Málaga Medina del Servicio de Dermatología del Hospital Nacional Carlos Seguin Escobedo, siguiendo la Directiva N.° 003-IETSI-ESSALUD-2016, envió al Instituto de Evaluación de Tecnologías en Salud e Investigación - IETSI la solicitud de uso por fuera del petitorio farmacológico de EsSalud el producto farmacéutico calcipotriol en combinación con el (DB), para el tratamiento de los pacientes adultos con psoriasis vulgar en placas moderada o severa, no respondedores a la terapia tópica y sistémica convencional, y no tributarios a terapia biológica. ASPECTOS GENERALES: La psoriasis vulgar en placas es una enfermedad crónica de la piel que se presenta como placas eritematosas y escamosas que aparecen, mayoritariamente, en el cuero cabelludo, el tronco, los glúteos, y los miembros inferiores y superiores (de Rie et al., 2004). Esta enfermedad es considerada como un problema de salud pública por su alta prevalencia, alto riesgo de morbilidad y porque deteriora la calidad de vida y salud mental en los pacientes que la padecen (Boehncke & Schón, 2015). La psoriasis afecta del 1 % al 3 % de la población mundial; y la psoriasis vulgar en placas representa hasta el 90 % de todas las manifestaciones de la psoriasis (Augustin et al., 2010). Además, la presencia de esta enfermedad se asocia a mayor riesgo de sufrir artritis psoriásica, enfermedades cardiovasculares, diabetes mellitus, obesidad, enfermedad del hígado graso no alcohólico y enfermedades inflamatorias del intestino (Gisondi et al., 2020). Asimismo, el 75 % de estos pacientes percibe un deterioro en su calidad de vida y cerca del 10 % ha tenido ideación suicida (Bhosle et al., 2006). METODOLOGÍA: Se llevó a cabo una búsqueda bibliográfica exhaustiva con el objetivo de identificar la mejor evidencia disponible sobre la eficacia y seguridad del CAL-DB, en comparación con mejor terapia de soporte, en pacientes adultos con psoriasis vulgar en placas moderada o severa no respondedores a la terapia tópica y sistémica convencional y no tributarios a terapia biológica. La búsqueda se realizó en las bases de datos bibliográfica de PubMed, The Cochrane Library y LILACS. Asimismo, se realizó una búsqueda manual dentro de las páginas web pertenecientes a grupos que realizan evaluación de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC) incluyendo el National Institute for Health and Care Excellence (NICE), la Agency for Healthcare Research and Quality's (AHRQ), la Scottish I ntercollegiate Guidelines Network (SIGN), la New Zealand Guidelines Group (NZGG), la National Health and Medical Research Council (NHMRC), el Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI), el Centro Nacional de Excelencia Tecnológica en Salud (CENETEC), la Canadian Agency for Drugs and Technologies in Health (CADTH), el Institute for Quality and Efficiency in Health Care (IQWIG), el Scottish Medicines Consortium (SMC), la Comissáo Nacional de I ncorpornáo de Tecnologías no Sistema Único de Saúde (CONITEC), el Instituto de Evaluación Tecnológica en Salud (IETS) y el Instituto de Efectividad Clínica y Sanitaria (IECS). Finalmente, se realizó una búsqueda adicional en la página web de registro de ensayos clínicos (EC) www.clinicaltrials.gov, para identificar EC en curso o aún no publicados. RESULTADOS: Tras ampliar los criterios de selección de documentos, se incluyó una GPC publicada por el NICE (2012) que realiza recomendaciones sobre la evaluación y el tratamiento de pacientes con psoriasis vulgar de severidad moderada o severa. Además, se incluyeron dos ETS publicadas por la CONITEC (2012), y la HAS (2019) que tuvieron como objetivo evaluar la evidencia disponible acerca de la eficacia y seguridad del uso del Cal-DB en pacientes adultos con psoriasis vulgar en placas e incluyeron, en su cuerpo de evidencia, ECA donde participaron pacientes con psoriasis vulgar de severidad moderada a severa. También, se incluyó el estudio pivotal citado en la ficha técnica del Daivobet ® aprobada por DIGEMID (2018), el cual es un ECA de fase II que comparó la eficacia y seguridad del uso del CAL-DB versus el calcipotriol en monoterapia, el DB en monoterapia y placebo, en pacientes con psoriasis vulgar de cualquier severidad de enfermedad (Fleming et al., 2010). Por último, se incluyó un estudio observacional que comparó el uso de la fototerapia y el CAL-DB en pacientes con severidad de enfermedad de moderada a severa (Polanska et al., 2019). ONCLUSIÓN: Por lo expuesto, el Instituto de Evaluación de Tecnologías en Salud e Investigación no aprueba el uso combinado del calcipotriol y el dipropionato de betametasona en pacientes adultos con psoriasis vulgar moderada o severa, no respondedores a la terapia tópica y sistémica convencional y no tributarios a terapia biológica, como producto farmacéutico no incluido en el Petitorio Farmacológico de EsSalud.

Clinical and economic burden of severe asthma among US patients treated with biologic therapies.

BACKGROUND: Patients with severe asthma may remain uncontrolled despite biologic therapy in addition to standard therapy, but this disease burden has not been quantified. OBJECTIVE: To estimate the clinical and economic burden in a US national sample. METHODS: Patients who have severe asthma with indicated biologic treatment (earliest use = index date) were selected from the MarketScan database between January 1, 2013, and June 30, 2018. Inclusion criteria were continuous enrollment for 12 months postindex with a minimum of 2 biologic fills, greater than or equal to 12 years of age, evidence of medium- to high-dose inhaled corticosteroids and long-acting ß-agonist combination before the index, and absence of other respiratory diagnoses and malignancies. Disease exacerbations (used to classify asthma control), health care costs, and treatment characteristics were reported during the 12-month postindex period. RESULTS: The sample included 3262 biologic patients; 88% with anti-immunoglobulin E therapy (omalizumab) and 12% non-anti-immunoglobulin E (reslizumab, mepolizumab, benralizumab). The mean age was 49 (±15) years; 64% were women. Prescriptions included inhaled corticosteroids and long-acting ß-agonist (82%), systemic corticosteroids (76%), and leukotriene receptor antagonists (68%). Notably, 63% of patients presented greater than or equal to 1 asthma exacerbation (mean 1.3 per patient/year). Furthermore, 35% of patients were categorized as having controlled asthma, whereas 28% were suboptimally controlled and 29% were uncontrolled. Patients with uncontrolled disease had higher all-cause and asthma-related costs ($69,206 and $45,693, respectively) than patients with suboptimally controlled ($59,407 and $40,793, respectively) or controlled disease ($53,083 and $38,393, respectively). Furthermore, 62% of newly treated patients were persistent with their index biologic. CONCLUSION: Biologic therapies are effective in reducing exacerbations, but a substantial proportion of patients with severe asthma treated with current biologics continue to experience uncontrolled disease, highlighting a remaining unmet need for patients with severe uncontrolled asthma.

One-year direct costs of biological therapy in rheumatoid arthritis and its predictive factors: data from the Moroccan RBSMR registry.

The aim of the study was to estimate the annual direct costs of biological therapies in rheumatoid arthritis (RA), and to establish possible factors associated with those costs. The main data source was the Moroccan registry of biological therapies in rheumatic diseases (RBSMR Registry). We included patients with available 1-year data. Variables related to socio-economic status, disease and biological therapy were collected. Direct costs included prices of biologics, costs of infusions, and subcutaneous injections. Differences in costs across groups were tested by Mann-Whitney and Kruskal-Wallis tests. Correlations analysis was performed in search of factors associated with high costs. We included 197 rheumatoid arthritis patients. The mean age was 52.3 ± 11 years, with female predominance 86.8%. Receiving one of the following therapies: rituximab (n = 132), tocilizumab (n = 37), or TNF-blockers (n = 28). Median one-year direct costs per patient were €1665 [€1472-€9879]. The total annual direct costs were € 978,494. Rituximab, constituted 25.7% of the total annual budget. TNF-blockers and tocilizumab represented 27.3% and 47% of this overall budget, respectively. Although the costs were not significantly different in terms of gender or level of study, the insurance type significantly affected the cost estimation. A positive correlation was found between the annual direct cost and body mass index (r = 0.15, p = 0.04). In Morocco, a developing country, the annual direct costs of biological therapy are high. Our results may contribute to the development of strategies for better governance of these costs.

Empirical Investigation of Ethical Challenges Related to the Use of Biological Therapies.

The aim of this study was to investigate the ethical dilemma of prioritising financial resources to expensive biological therapies. For this purpose, the four principles of biomedical ethics formulated by ethicists Tom Beauchamp and James Childress were used as a theoretical framework. Based on arguments of justice, Beauchamp and Childress advocate for a health care system organised in line with the Danish system. Notably, our study was carried out in a Danish setting.

Biologic Therapy for Ulcerative Colitis.

Five biologics are approved for the treatment of ulcerative colitis (UC): infliximab, adalimumab, golimumab, vedolizumab, and ustekinumab. These drugs have varying levels of efficacy and are recommended as first-line treatment of moderate to severe UC. There has been only 1 head-to-head trial comparing the efficacy of the biologics, adalimumab and vedolizumab, which has important implications for management. Therapeutic drug monitoring of biologics, especially anti-TNF alpha agents, may improve the long-term efficacy of these agents. The future of treatment may include personalization of medications, based on patient-specific and disease-specific characteristics as well as biomarkers, along with appropriate therapeutic drug monitoring.

A Critical Look at the Efficacy and Costs of Biologic Therapy for Chronic Rhinosinusitis with Nasal Polyposis.

PURPOSE OF REVIEW: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly prevalent disease that results in significant healthcare-related costs as well as costs to society with lost productivity and time. Unfortunately, a significant percentage of patients who suffer with this disease will not find relief from current standard of care medications and surgery. With ongoing efforts to understand the pathophysiology of CRSwNP has come the introduction of monoclonal antibodies, or "biologics," targeting specific elements of the inflammatory pathway in CRSwNP. Despite efficacy, these come at significant cost and, to date, no studies on the cost-efficacy of these biologics in CRSwNP have been published. RECENT FINDINGS: Multiple studies have now demonstrated efficacy for biologics in the treatment of CRSwNP as a primary indication. However, the gains in quality of life and objective measures, while consistent, are small and, arguably, the clinical significance is still unclear. In addition, the high cost of these medications may be hard to justify when evaluated in cost-efficacy studies against standard of care therapy in CRSwNP. Furthermore, while the current literature is most robust in showing the benefit of the biologics in asthma, it does not fully support cost-efficacy for biologics. This review evaluates the current literature regarding efficacy of monoclonal antibodies for the treatment of CRSwNP and considers this efficacy in light of the cost implications to individuals and society.

Systematic Literature Review of Economic Evaluations of Biological Treatment Sequences for Patients with Moderate to Severe Rheumatoid Arthritis Previously Treated with Disease-Modifying Anti-rheumatic Drugs.

OBJECTIVE: This systematic literature review (SLR) had two objectives: to analyse published economic evaluations of biological disease-modifying anti-rheumatic drugs (bDMARDs) for patients with moderate to severe rheumatoid arthritis (RA) previously treated with DMARDs and to assess the quality of those that included sequences of treatments. METHODS: We performed an SLR on PubMed, Central, Cochrane, and French databases from January 2000 to December 2018. The search focused on cost-effectiveness/utility/benefit analyses. We extracted data on treatment sequences, outcomes (e.g. quality-adjusted life year) and choices of economic evaluation methods (e.g. model type, type of analysis, and method of utility estimation). We analysed the improvement of methods by comparing two sub-periods (2000-2009 and 2010-2018). The quality of reporting and the quality of the methods were assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) and a set of eight key aspects for a reference case for economic evaluation of bDMARDs based on the Outcome Measures in Rheumatology (OMERACT) and Drummond checklists. Data extraction and study assessment were performed independently by two health economists. RESULTS: From the 824 records identified in the initial search, 51 publications were selected. Of these, 31 included sequences. Individual models such as discrete-event simulations were used in over two-fifths (22/51, 43%) of the selected studies. Few studies (7/51, 14%) used utility scores based on generic instruments (e.g. EQ-5D). Estimation of hospitalization costs was described in only approximately one-third of studies (19/51). Loss of quality of life (QoL) related to adverse events such as tuberculosis and pneumonia was included in one-tenth (5/51, 10%) of the studies. It was difficult to compare the results of the economic evaluations (i.e. incremental cost-effectiveness ratios) due to the high heterogeneity of studies in terms of disease stage, data sources, inputs, and methods of health outcome assessment used. For identified studies including sequences, the CHEERS assessment of reporting quality showed insufficient reporting of uncertainty analyses and utility weights in more than a third of the studies (11/31, 35%; 9/25, 36%). An in-depth assessment of the quality of the studies revealed that only seven, mostly conducted during the sub-period 2010-2018, addressed the majority of methodological quality assessment issues such as the simulation of patient sequence pathways, the use of systematic reviews and meta-analyses of comparative effectiveness, the choice of treatment sequence, and rules for switching. CONCLUSION: Our SLR identified a lack of high-quality evaluations assessing bDMARD sequences, although some improvements were made in the reporting and modelling of patients' pathways in studies published after 2010. In order to improve economic evaluations of RA, clear health technology assessment guidance on RA health-related QoL instruments must be provided, and data including long-term disease progression must be made available.

Cost-utility analysis of de-escalating biological disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis.

OBJECTIVE: Recent guideline updates have suggested de-escalating DMARDs when patients with rheumatoid arthritis achieve remission or low disease activity. We aim to evaluate whether it is cost-effective to de-escalate the biological form of DMARDs (bDMARDs). METHODS: Using a Markov model, we performed a cost-utility analysis for RA patients on bDMARD treatment. We compared continuing treatment (standard care) to a tapering approach (i.e., an immediate 50% dose reduction), withdrawal (i.e., an immediate 100% dose reduction) and tapering followed by withdrawal of bDMARDs. The parametrization is based on a comprehensive literature review. Results were computed for 30 years with a cycle length of three months. We applied the payer's perspective for Germany and conducted deterministic and probabilistic sensitivity analyses. RESULTS: Tapering or withdrawing bDMARD treatment resulted in ICERs of €526,254 (incr. costs -78,845, incr. QALYs -0.1498) or €216,879 (incr. costs -€121,691, incr. QALYs -0.5611) compared to standard care. Tapering followed by withdrawal resulted in a loss of 0.4354 QALYs and savings of €107,969 per patient, with an ICER of €247,987. Deterministic sensitivity analysis revealed that our results remained largely unaffected by parameter changes. Probabilistic sensitivity analysis suggests that tapering, withdrawal and tapering followed by withdrawal were dominant in 39.8%, 28.2% and 29.0% of 10,000 iterations. CONCLUSION: Our findings suggest that de-escalating bDMARDs in patients with RA may result in high cost savings but also a decrease in quality of life compared to standard care. If decision makers choose to implement de-escalation in daily practice, our results suggest the tapering approach.

Early Surgery Versus Biologic Therapy in Limited Nonstricturing Ileocecal Crohn's Disease-A Decision-making Analysis.

BACKGROUND: Surgery is the preferred option for patients with symptomatic localized fibrostenotic ileocecal Crohn's disease (CD) but not for those with predominantly active inflammation without obstruction. The benefit of early surgery in patients with a limited nonstricturing ileocecal CD over biologic treatment is still a debate. OBJECTIVE: Our objective is to formulate a decision analysis model based on recently published data to explore whether early surgery in patients with limited nonstricturing CD is preferred over biologic treatment. METHODS: We constructed a Markov model comparing 2 strategies of treatment: (1) early surgery vs (2) biologic treatment. To estimate the quality-adjusted life years (QALYs) and the costs in each strategy, we simulated 10,000 virtual patients with the Markov model using a Monte Carlo simulation 100 times. Sensitivity analyses were performed to evaluate the robustness of the model and address uncertainties in the estimation of model parameters. RESULTS: The costs were $29,457 ± $407 and $50,382 ± $525 (mean ± SD) for early surgery strategy and biologic treatment strategy, respectively. The QALY was 6.24 ± 0.01 and 5.81 ± 0.01 for early surgery strategy and biologic treatment strategy, respectively. CONCLUSION: The strategy of early surgery dominates (higher QALY value [efficacy] and less cost) compared with the strategy of biologic treatment in patients with limited ileocecal CD.

Predicting response to anti-TNFα therapy among patients with axial spondyloarthritis (axSpA): results from BSRBR-AS.

OBJECTIVES: While many axSpA patients, eligible to receive anti-TNFα therapy, derive benefit when prescribed them, some patients do not. The current study aims to identify modifiable targets to improve outcome as well as non-modifiable targets that identify groups less likely to derive benefit. METHODS: The BSRBR-AS is a prospective cohort study of axSpA patients who, at recruitment, were naïve to biologic therapy. Those in the 'biologic' sub-cohort commenced their first anti-TNFα therapy at recruitment or during follow-up. Prior to commencement, information was collected on socio-economic, clinical and patient-reported factors. Outcome was assessed according to ASAS20, ASAS40, ASDAS reduction and achieving a moderate/inactive ASDAS disease state. RESULTS: 335 participants commenced their first anti-TNFα therapy and were followed up at a median of 14 (inter-quartile range 12-17) weeks. Response varied between 33% and 52% according to criteria used. Adverse socio-economic factors, fewer years in education predicted lower likelihood of response across outcome measures as did not working full-time. Co-morbidities and poor mental health were clinical and patient-reported factors, respectively, associated with lack of response. The models, particularly those using ASDAS, were good at predicting those who did not respond (negative predictive value (NPV) 77%). CONCLUSION: Some factors predicting non-response (such as mental health) are modifiable but many (such as social/economic factors) are not modifiable in clinic. They do, however, identify patients who are unlikely to benefit from biologic therapy alone. Priority should focus on how these patients receive the benefits that many derive from such therapies.

A call for cost-effectiveness analysis for biologic therapies in chronic rhinosinusitis with nasal polyps.

OBJECTIVE: To identify the need for cost-effectiveness analysis of biologic therapies in the treatment of chronic rhinosinusitis (CRS). DATA SOURCES: Clinical trials of monoclonal antibodies (omalizumab, benralizumab, mepolizumab and dupilumab) for nasal polyposis or chronic rhinosinusitis published on PubMed. STUDY SELECTIONS: Clinical trials of biologic therapies in CRS and nasal polyposis. RESULTS: No cost-effectiveness analyses of biologic therapies in CRS have been performed. CONCLUSION: As more clinical trials of biologic therapies for CRS are conducted, there is a need for cost-effectiveness analysis. Future analyses should consider these therapies as part of medical therapeutic options compared with surgery. To increase generalizability, analyses should include samples from allergy and primary care clinics rather than only otolaryngology clinics.

Biological therapy in the treatment of psoriatic arthritis: economic and epidemiological considerations.

Background: Biological therapies have a significant economic and clinical burden but, in general, lose their effectiveness over time. This study evaluated the medication persistence and costs associated to use of anti-TNF agents for psoriatic arthritis (PsA) treatment. Methods: A historical cohort composed of individuals in Brazil with PsA diagnosis was developed during the period between 2010 and 2015. The difference among the anti-TNF agents was verified by the log-rank test. The predictors of medication non-persistence were identified by Cox regression. The costs were compared by variance analysis with Bonferroni correction. Results: 11,008 patients were analyzed. Adalimumab (51%) was the most used anti-TNF agent. Individuals using adalimumab presented higher medication persistence as compared to etanercept and infliximab. The costs with anti-TNF agents corresponded to 90% of the total costs and were similar among anti-TNF agents. The non-persistence predictors were female sex, younger patients, to live in the Northeastern and Northern regions of Brazil, to use infliximab and etanercept, and have more comorbidities. Conclusion: The direct costs with anti-TNF agents were the main component of total costs. Outpatient and inpatient costs increase when medication persistence decreases. A considerable price reduction of anti-TNF agents has been observed over the years.

Providing cost-effective care for food allergy.

OBJECTIVE: To review the cost-effectiveness of food allergy management strategies. DATA SOURCES AND STUDY SELECTIONS: A narrative review and synthesis of literature identified using a PubMed search of relevant articles describing cost-effectiveness evaluations of food allergy management. RESULTS: Screening at-risk infants for peanut allergy carries risk of overdiagnosis and is not cost-effective. Evidence suggests that cost-effective care could be better optimized by minimizing delay in oral food challenges for eligible patients, clarifying the role of precautionary allergen labeling, incorporating patient-preference sensitive care in activation of emergency medical services for resolved allergic reactions, and considering value-based pricing and school-supply models for epinephrine. Finally, the annual value-based cost (willingness to pay [WTP] $100,000/quality-adjusted life years [QALY]) of peanut immunotherapy has been estimated to be between $1568 and $6568 for epicutaneous immunotherapy (EPIT) and between $1235 and $5235 for probiotic with peanut oil immunotherapy (POIT), with each therapy showing more favorable cost-effectiveness with greater improvements in health utility, particularly if sustained unresponsiveness can be achieved. CONCLUSION: Many aspects of food allergy management are not cost-effective, and recent evaluations suggest a greater role for incorporating patient and family preferences into guideline-based and traditionally reflexive management decisions. Caregiver understanding of food allergy screening tradeoffs is critical, given that screening children before allergen exposure has significant costs and results in overdiagnosis, especially when oral food challenges are omitted from diagnostic algorithms. Cost-effectiveness analysis can help to identify important decision levers in patient management across a wide range of topics. Further research is needed to better understand health state utilities of specific patient populations.

The Cost-effectiveness of Biological Therapy Cycles in the Management of Crohn's Disease.

OBJECTIVES: To examine the cost-effectiveness of continued treatment for patients with moderate-severe Crohn's disease in clinical remission, with a combination of anti-tumour necrosis factor alpha [anti-TNFα] [infliximab] and immunomodulator therapy compared with two different withdrawal strategies: [1] withdrawal of the anti-TNFα therapy; and [2] withdrawal of the immunomodulator therapy, respectively. METHODS: A decision-tree model was constructed mimicking three treatment arms: [1] continued combination therapy with infliximab and immunomodulator; [2] withdrawal of infliximab; or [3] withdrawal of the immunomodulator. Relapses in each arm are managed with treatment intensification and re-institution of the de-escalated drug according to a prespecified algorithm. State-dependent relapse risks, remission probabilities, and quality of life weights were collected from previous published studies. RESULTS: Combination therapy was less costly and more efficient than the withdrawal of the immunomodulator, and more costly and more efficient than withdrawal of infliximab. Whether or not combination therapy is cost-effective, compared with the alternatives, depends primarily on current pharmaceutical prices and the willingness-to-pay per additional quality-adjusted life-year [QALY]. CONCLUSIONS: Combination therapy using a combination of anti-TNFα [infliximab] and an immunomodulator is cost-effective in the treatment of Crohn's disease compared with treatment cycles in which the immunomodulator is withdrawn. Combination treatment is cost-effective compared with treatment cycles in which infliximab is withdrawn, at prices of infliximab below€192/100 mg, given a willingness-to-pay threshold at€49 020 [Sweden] per additional QALY.

Advanced therapy medicinal products and health technology assessment principles and practices for value-based and sustainable healthcare.

BACKGROUND: Advanced therapy medicinal products (ATMPs) are beginning to reach European markets, and questions are being asked about their value for patients and how healthcare systems should pay for them. OBJECTIVES: To identify and discuss potential challenges of ATMPs in view of current health technology assessment (HTA) methodology-specifically economic evaluation methods-in Europe as it relates to ATMPs, and to suggest potential solutions to these challenges. METHODS: An Expert Panel reviewed current HTA principles and practices in relation to the specific characteristics of ATMPs. RESULTS: Three key topics were identified and prioritised for discussion-uncertainty, discounting, and health outcomes and value. The panel discussed that evidence challenges linked to increased uncertainty may be mitigated by collection of follow-on data, use of value of information analysis, and/or outcomes-based contracts. For discount rates, an international, multi-disciplinary forum should be established to consider the economic, social and ethical implications of the choice of rate. Finally, consideration of the feasibility of assessing the value of ATMPs beyond health gain may also be key for decision-making. CONCLUSIONS: ATMPs face a challenge in demonstrating their value within current HTA frameworks. Consideration of current HTA principles and practices with regards to the specific characteristics of ATMPs and continued dialogue will be key to ensuring appropriate market access. CLASSIFICATION CODE: I.

Persistence rates and medical costs of biological therapies for psoriasis treatment in Japan: a real-world data study using a claims database.

BACKGROUND: Biological therapies (BTs) including infliximab (IFX), adalimumab (ADL), secukinumab (SCK) and ustekinumab (UST) are approved in Japan for the treatment of psoriasis. Although the persistence rates and medical costs of BTs treatment have been investigated in multiple foreign studies in recent years, few such studies have been conducted in Japan and the differences between patients who adhered to treatment and those who did not have not been reported. This study is aimed at investigating the persistence rates and medical costs of BTs in the treatment of psoriasis in Japan, using the real-world data from a large-scale claims database. METHODS: Claims data from the JMDC database (August 2009 to December 2016) were used for this analysis. Patient data were extracted using the ICD10 code for psoriasis and claims records of BT injections. Twelve-month and 24-month persistence rates of BTs were estimated by Kaplan-Meier methodology, and 12-month-medical costs before and after BT initiation were compared between persistent and non-persistent patient groups at 12 months. RESULTS: A total of 205 psoriasis patients treated with BTs (BT-naïve patients: 177) were identified. The 12-month/24-month persistence rates for ADL, IFX, SCK, and UST in BT-naïve patients were 46.8% ± 16.6%/46.8 ± 16.6%, 53.0% ± 14.9%/41.0% ± 15.5%, 55.4%/55.4% (95% CI not available) and 79.4% ± 9.9%/71.9% ± 12.2%, respectively. Statistically significant differences in persistence were found among different BT treatments, and UST was found to have the highest persistence rate. The total medical costs during the 12 months after BT initiation in BT-naïve patients were (in 1000 Japanese Yen): 2218 for ADL, 3409 for IFX, 465 for SCK, 2824 for UST (average: 2828). Compared with the 12-month persistent patient group, the total medical costs in the persistent group was higher (Δ:+ 118), but for some medications such as IFX or UST cost increases were lower for persistent patients. CONCLUSIONS: UST was found to have the highest persistence rate among all BTs for psoriasis treatment in Japan. The 12-month medical costs after BT initiation in the persistent patient group may not have increased as much as in the non-persistent patient group for some medications.

Effectiveness, Complications, and Costs of Rheumatoid Arthritis Treatment with Biologics in Alberta: Experience of Indigenous and Non-indigenous Patients.

OBJECTIVE: To examine clinical effectiveness, treatment complications, and healthcare costs for indigenous and non-indigenous Albertans with rheumatoid arthritis (RA) participating in the Alberta Biologics Pharmacosurveillance program. METHODS: Patients initiating biologic therapy in Alberta (2004-2012) were characterized for disease severity and treatment response. Provincial hospitalization separations, physician claims, outpatient department data, and emergency department data were used to estimate treatment complication event rates and healthcare costs. RESULTS: Indigenous patients (n = 90) presented with higher disease activity [mean 28-joint count Disease Activity Score (DAS28) 6.11] than non-indigenous patients (n = 1400, mean DAS28 5.19, p < 0.0001). Improvements in DAS28, function, swollen joint count, CRP, and patient and physician global evaluation scores were comparable to non-indigenous patients, but indigenous patients did not have a significant improvement in erythrocyte sedimentation rate (-0.31 per month, 95% CI -0.79 to 0.16, p = 0.199). At the end of study followup, 13% (12/90) of indigenous and 33% (455/1400) of non-indigenous patients were in DAS28 remission (p < 0.001). Indigenous patients had a 40% increased risk of all-cause hospitalization [adjusted incidence rate ratio (IRR) 1.4, 95% CI 1.1-1.8, p = 0.01] and a 4-fold increase in serious infection rate (adjusted IRR 4.0, 95% CI 2.3-7.0, p < 0.001). Non-indigenous patients incurred higher costs for RA-related hospitalizations (difference $896, 95% CI 520-1273, p < 0.001), and outpatient department visits (difference $128, 95% CI 2-255, p = 0.047). CONCLUSION: We identified disparities in treatment outcomes, safety profiles, and patient-experienced effects of RA for the indigenous population in Alberta. These disparities are critical to address to facilitate and achieve desired RA outcomes from individual and population perspectives.

Cost-Effectiveness of Biological Asthma Treatments: A Systematic Review and Recommendations for Future Economic Evaluations.

BACKGROUND: Recently developed asthma biological therapies have been shown to provide relief for severe asthma patients not controlled by inhaled treatment. Given the relatively high costs of biological therapies, cost-effectiveness analyses (CEAs) may be required as a prerequisite for coverage and reimbursement. OBJECTIVE: We aimed to systematically review published literature on the economic impact of biological asthma therapies and to identify key drivers that impact cost-effectiveness in order to provide recommendations for future economic evaluations. METHODS: We conducted a systematic literature search in PubMed and Google Scholar. We included studies that assessed the cost-effectiveness of asthma biologics and were published in English between 2000 and 2018. The Quality of Health Economic Studies (QHES) instrument was used to evaluate quality. RESULTS: Twenty asthma biological CEAs were identified. Nineteen studies analyzed the cost-effectiveness of omalizumab, and one study analyzed mepolizumab. Ten studies concluded that omalizumab was cost-effective in base-case scenarios, four studies concluded omalizumab was not cost-effective, and the remaining studies concluded omalizumab or mepolizumab was cost-effective only when targeted to specific severe subgroups or given considerable price discounts. Key drivers of cost-effectiveness included day-to-day health-related quality of life (HRQoL), asthma-related mortality, acquisition price of the biological therapy, and time horizon. CONCLUSIONS: Most studies recommended carefully targeting biological therapy to specific populations such as responders or discounting acquisition price in order to further improve value. The quality of the studies was generally satisfactory, but improved evidence is needed linking HRQoL to utilities as well as understanding interventions' impact on asthma-related mortality. Key recommendations from this review may allow for greater comparability across future cost-effectiveness studies.