Inibidor da C1 esterase derivado de plasma via subcutânea para profilaxia de crises de angioedema hereditário / Plasma-derived C1 esterase inhibitor subcutaneously for prophylaxis of hereditary angioedema crises

INTRODUÇÃO: O angioedema hereditário (AEH) é uma imunodeficiência primária do sistema complemento, e foi classificado como um erro inato da imunidade em decorrência da deficiência de inibidor de C1 esterase, proteína que controla as vias de ativação do complemento. Trata-se de doença com herança autossômica dominante, heterogeneidade de lócus e expressividade variável. A classificação mais atualizada do AEH agrupa os pacientes naqueles com deficiência do inibidor da C1- esterase (C1-INH), codificado pelo gene SERPING1 e naqueles C1-INH normal (anteriormente denominado de tipo III). O diagnóstico é realizado através do exame clínico (anamnese, exame físico e quadro clínico) e laboratorial (dosagem de C4 e de C1-INH), além de teste genético (presença de mutação patogênica em SERPING1) para confirmação. Embora AEH não tenha cura, há tratamento para a profilaxia e controle das crises. Atualmente, para o tratamento de profilaxia, o Protocolo Clínico e Diretrizes Terapêuticas (PCDT) do angioedema associado a deficiência de C1 esterase (C1-INH) do Ministério da Saúde, recomenda o uso de andrógenos atenuados, sendo o mais utilizado o danazol, e plasma fresco congelado para o tratamento de crises. PERGUNTA 1: O inibidor de C1 esterase via subcutânea é uma alternativa na

Qualitative assessment of healthy volunteer experience receiving subcutaneous infusions of high-dose benzathine penicillin G (SCIP) provides insights into design of late phase clinical studies.

INTRODUCTION: Secondary prophylaxis to prevent rheumatic heart disease (RHD) progression, in the form of four-weekly intramuscular benzathine benzylpenicillin G (BPG) injections, has remained unchanged since 1955. Qualitative investigations into patient preference have highlighted the need for long-acting penicillins to be delivered less frequently, ideally with reduced pain. We describe the experience of healthy volunteers participating in a phase-I safety, tolerability and pharmacokinetic trial of subcutaneous infusions of high-dose benzathine penicillin G (BPG)-the SCIP study (Australian New Zealand Clinical Trials Registry ACTRN12622000916741). METHODS: Participants (n = 24) received between 6.9 mL to 20.7 mL (3-9 times the standard dose) of BPG as a single infusion into the abdominal subcutaneous tissues via a spring-driven syringe pump over approximately 20 minutes. Semi-structured interviews at four time points were recorded, transcribed verbatim and thematically analysed. Tolerability and specific descriptors of the experience were explored, alongside thoughts on how the intervention could be improved for future trials in children and young adults receiving monthly BPG intramuscular injections for RHD. RESULTS: Participants tolerated the infusion well and were able describe their experiences throughout. Most reported minimal pain, substantiated via quantitative pain scores. Abdominal bruising at the infusion site did not concern participants nor impair normal activities. Insight into how SCIP could be improved for children included the use of topical analgesia, distractions via television or personal devices, a drawn-out infusion time with reduced delivery speed, and alternative infusion sites. Trust in the trial team was high. CONCLUSION: Qualitative research is an important adjunct for early-phase clinical trials, particularly when adherence to the planned intervention is a key driver of success. These results will inform later-phase SCIP trials in people living with RHD and other indications.

Sistema de infusión continua de insulina con sensor de glucemia en pacientes con Diabetes / Continuous insulin infusion system with blood glucose sensor in patients with Diabetes

INTRODUCCIÓN: La diabetes mellitus es un problema de salud de gran prevalencia y representa una alta carga de enfermedad. La prevalencia mundial estimada de diabetes mellitus casi se ha duplicado (del 4,7% al 8,5%) en la población adulta en los últimos 20 años. La diabetes mellitus tipo 1 representa del 5 al 10% del total de las personas con diabetes mellitus, siendo su incidencia en Argentina de 9 cada 100.000 habitantes, manifestándose especialmente en el grupo etario menores a 15 años (niños y adolescentes) y en menor medida en el grupo de adolescentes y jóvenes de 15 a 30 años. El manejo de los pacientes con diabetes mellitus tipo 1 con requerimiento de insulina presenta diferentes alternativas tecnológicas, tanto en nuevas formulaciones de insulina, dispositivos de automonitoreo, esquemas de administración optimizados y distintos sistemas de infusión subcutánea de insulina que pueden incluso combinar estos avances, con sugerencias de beneficios particulares sobre variables de resultado clínico en poblaciones de pacientes específicas. OBJETIVO: El objetivo general del presente informe es evaluar la eficacia y seguridad de los sistemas de Infusión continua subcutánea de insulina con sensor de glucemia en pacientes con diabetes mellitus tipo 1 hasta los 18 años de edad y en pacientes embarazadas, así como su impacto en los presupuestos sanitarios, en la equidad y en la salud pública. METODOLOGÍA: Para ello se realizó una búsqueda bibliográfica en las principales bases de datos, como así también en sociedades científicas, agencias reguladoras, financiadores de salud y agencias de evaluación de tecnologías sanitarias. Previo a la evaluación de la calidad de la evidencia, dos pares de investigadores evaluaron la confianza global de las revisiones sistemáticas mediante la herramienta Amstar-2 y el riesgo de sesgo de los ECAs incluidos se evaluaron previamente con la herramienta ROBCochrane. Las posibles divergencias fueron resueltas por un quinto investigador. Para la evaluación de la calidad de la evidencia incluida, se utilizó la metodología GRADE por medio de la aplicación GRADEpro. Para estimar el impacto de los costos en el sistema de salud de llevó a cabo un análisis de impacto presupuestario simulando escenarios de introducción de estas tecnologías en el cuidado de la población de pacientes diabetes mellitus tipo 1 objetivo. RESULTADOS: Con respecto al uso de sistemas de infusión continua de insulina con sensor en comparación con esquemas optimizados de múltiples inyecciones diarias (estándar de tratamiento) en niños y adolescentes con diabetes mellitus tipo 1, se concluyó que existe incertidumbre sobre el efecto de la intervención sobre la prevención de episodios de cetoacidosis, la incidencia de episodios de hipoglucemia severa, la calidad de vida en niños de 12 a 16 años y podría asociarse con una disminución marginal en la media de HbA1C. En el análisis de subgrupo relacionado con sistemas de infusión continua de insulina con monitoreo continuo de glucemia (CGM o tipo híbrido) frente a múltiples dosis de insulina en relación a otros dispositivos con sensor de tipo no híbrido mostraron que podría asociarse con una disminución marginal de la HbA1C. Con respecto a los dispositivos de infusión continua de insulina subcutánea comparado con múltiples inyecciones diarias en pacientes embarazadas con diabetes mellitus tipo 1, se concluyó que existe incertidumbre sobre el efecto de la intervención en la mortalidad perinatal, incidencia de parto pretérmino en la ganancia de peso materna en el embarazo mino (<37 semanas), en el promedio de HbA1C en el tercer trimestre, en la incidencia de macrosomía fetal, y en la incidencia de recién nacido de alto peso para la edad gestacional. El resultado del análisis de impacto presupuestario de inclusión de esta tecnología aún en escenarios conservadores de inserción tiene como repercusión un importante incremento en el gasto, superando las estimaciones presupuestarias para inversión anual en innovación tecnológica. CONCLUSIÓN: Completando el análisis del marco de valor, el uso sistemas infusores de insulina con sensor continuo de glucemia tendría un impacto probablemente negativo sobre la equidad y para la salud pública. Por lo tanto, en el contexto actual y ante las condiciones evaluadas en el marco de valor y los parámetros de costos analizados, se recomienda no cubrir la tecnología en evaluación.(AU)

Economic evaluation of subcutaneous versus intravenous immunoglobulin therapy in chronic inflammatory demyelinating polyneuropathy: a real-life study.

OBJECTIVES: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired peripheral neuropathy of immunological origin with a clinical presentation and course that are extremely variable. The therapeutic approach generally includes corticosteroid drugs, intravenous immunoglobulins (IVIGs) or plasmapheresis alone or in combination as first line therapy, and immunosuppressants. In 2014 the Italian regulatory agency included subcutaneous immunoglobulins (SCIGs) in the list of off-label drugs reimbursed by the national health service. Our aim is to compare costs and outcomes of IVIG versus SCIG therapy. METHODS: Patients medical records and therapeutic plans were retrospectively analysed to collect data on IVIG treatments 1 year before the switch to SCIG, and after 1 year of treatment with SCIG. A budget impact analysis was conducted through resource identification and quantification, and healthcare and non-health care costs evaluation. RESULTS: 13 of 34 patients affected by CIDP who were referred to our neurophysiopathological unit and treated with IVIG were switched to home-based SCIG. After 1 year of receiving SCIG, 12 patients remained neurologically stable and reported good outcomes. Considering the cost of IVIG (€30.97/g) and adding to this the direct and indirect healthcare costs, the total cost of IVIG treatment for the 12 patients in a year was €371 417.06, compared with the cost of SCIG (€51.57/g) for a total annual cost of €631 745.16, not including indirect costs. CONCLUSIONS: We observe a higher cost for SCIG treatment versus IVIG, which is not in line with data in the literature. However, SCIGs offer some important safety benefits and improvements in patient quality of life.

Efficacy and quality of life assessment in the use of subcutaneous immunoglobulin treatment for children with primary immunodeficiency disorder.

Summary: Introduction. Most patients with primary and secondary immunodeficiencies need regular Intravenous Immunoglobulin (IVIG) or Subcutaneous Immunoglobulin (SCIG) treatment. This study aimed to evaluate the serum IgG trough levels, frequency of mild and severe infections, frequency and duration of hospitalization, duration of absence of school, and quality of life in patients switching their IVIG therapy to SCIG administration. Materials. Twenty-nine patients with immunodeficiency on regular IVIG treatment and who agreed to receive SCIG treatment were included. Seven patients discontinued treatment after the first SCIG administration. We collected data regarding serum IgG levels, annual numbers of infections, hospital admissions, and adverse events prior to and following SCIG initiation. PedsQL tests such as Scale Total Score (STS), Physical Health Total Score (PHTS), Psychosocial Health Total Score (PsyHTS), emotional functionality, social functionality, school/work problems score were calculated separately for all patients and their parents. Results. In twenty-two cases who were diagnosed as primary immunodeficiency, the most common indication for initiation of SCIG treatment was the long transfusion period of IVIG treatments and the difficulty of access to the hospital. No systemic side effects were noted except local redness, pain, and swelling on the injection site. The median IgG value was 588.9 mg/dl during IVIG treatment and 872 mg/dl one year after SCIG treatment. Annual frequency of infections and absence to school/work decreased significantly in the SCIG group while the annual number of hospitalizations and hospital stay time did not change significantly. There was a significant increase in the "quality of life" scores of the patients and their families. Conclusions. SCIG treatment provides ideal and protective immunoglobulin levels and offers the comfort of treatment in their home environment, thus increasing the patient's satisfaction and quality of life.

Home-based subcutaneous immunoglobulin for chronic inflammatory demyelinating polyneuropathy patients: A Swiss cost-minimization analysis.

PURPOSE: To compare the cost of two patient management strategies with similar efficacies for chronic inflammatory demyelinating polyneuropathy (CIDP) patients in the chronic phase: hospital-based IV immunoglobulin G (IVIg) and home-based subcutaneous immunoglobulin G (SCIg) associated with an interprofessional drug therapy management programme (initial training and follow-up). METHODS: A 48-week model-based cost-minimization analysis from a societal perspective was performed. Resources included immunoglobulin (IVIg: 1 g/kg/3 weeks; SCIg: 0.4 g/kg/week initially and 0.2 g/kg/week in the maintenance phase), hospital charges, time of professionals, infusion material, transport and losses of productivity for patients. Costs were expressed in Swiss francs (CHF) (1 CHF = 0.93€ = US$1.10, www.xe.com, 2020/10/28). RESULTS: The total costs of IVIg were higher than those of SCIg for health insurance and other payers: 114,747 CHF versus 86,558 CHF and 8,762 CHF versus 2,401 CHF, respectively. The results were sensitive to the immunoglobulin doses, as this was the main cost driver. The SCIg daily cost in the initial phase was higher for health insurance than hospital-based IVIg was, but the additional costs were compensated during the maintenance phase (from week 28). The professional costs associated with the switch were not fully covered by the insurance and were borne by the pharmacist and the nurse. CONCLUSIONS: SCIg for CIDP patients reinforced by an interprofessional drug therapy management programme may be a cost-effective and sustainable alternative to IVIg in the Swiss system context. From an economic perspective, this therapy alternative should be more widely supported by healthcare systems and proposed to eligible patients by professionals.

Primary immunodeficiency disease: a cost-utility analysis comparing intravenous vs subcutaneous immunoglobulin replacement therapy in Australia.

BACKGROUND: Hospital-based intravenous immunoglobulin (IVIg) treatment has been the standard treatment mode for patients with primary immunodeficiency disease (PID). With the newer home-based subcutaneous immunoglobulin (SCIg) becoming approved for use in most countries, the question arises as to whether SCIg is a cost-effective treatment mode compared to IVIg in Australia. MATERIALS AND METHODS: We developed a Markov cohort simulation model with six health states: PID without infection, PID with infection treated at home or hospital, bronchiectasis without infection, bronchiectasis with infection treated at home or hospital, bronchiectasis with chronic Pseudomonas aeruginosa infection, and death, from an Australian healthcare system perspective. A 10-year time horizon with weekly cycles was chosen, and the expected costs and quality-adjusted life-years (QALYs) of the two treatment options estimated. RESULTS: The cumulative 10-year cost per patient was 297,547 Australian dollars (A$) with IVIg and A$ 251,713 for SCIg. IVIg resulted in 5.55 QALYs and SCIg 5.57 QALYs. Thus, SCIg appears to be a cost-saving option and possibly improves QALY from the Australian healthcare system perspective (i.e., the dominant treatment option). A probabilistic sensitivity analysis showed that the SCIg option is preferred in 93.2% of simulations given willingness to pay of A$ 50,000 per QALY gained. DISCUSSION: The results suggest that home-based SCIg is a cost-effective treatment option for patients with PID in Queensland, Australia.

Managing cost of care and healthcare utilization in patients using immunoglobulin agents.

The introduction of human immunoglobulin (Ig) therapies 40 years ago reduced the risk of often life-threatening infections for individuals with one of several immune-related conditions known as primary immunodeficiencies. Since then, the use of Ig has expanded to numerous other conditions. However, even though less than 1% of covered lives under Medicare or commercial insurers require Ig, it is in the top 5 drug categories in terms of annual spending. The cost of Ig is directly related to the type of delivery method used and the site of care. Numerous studies attest to the efficacy and cost savings of shifting Ig to the home setting, as well as shifting patients from intravenous Ig (IVIG) to subcutaneous Ig (SCIG). In addition, surveys find that patients with primary immunodeficiencies prefer home delivery, with patient evaluations also finding a preference for SCIG. Payers have numerous options to ensure Ig is used appropriately for the right patient in the right setting. These include formulary management, site-of-care programs, education for providers and patients on the possibility of switching from IVIG to SCIG, preauthorization policies that restrict the use of Ig to certain specialties for specific indications, implementation of evidence-based coverage criteria, and shifting coverage from the medical to the pharmacy benefit.

Subcutaneous furosemide for the treatment of heart failure: a state-of-the art review.

The prevalence of heart failure (HF) is on the rise. By 2030, over eight million Americans (46% increase from current prevalence) will have heart failure. In the USA, approximately 30 billion dollars is spent annually on heart failure and this number will likely double in 2030. Thus, HF represents a significant economic burden. Acute decompensated heart failure (ADHF) is a clinical spectrum, which refers to increasing symptoms and signs of heart failure prompting an emergency room visit or hospitalization. In ADHF, inpatient administration of intravenous diuretic is the standard of care due to the variability in the absorption of oral diuretics. Within 30 days, 25-30% of these patients are readmitted with recurrent ADHF. Recent efforts have focused in reducing HF readmission, and thereby decreasing costs; hence, innovative outpatient treatment options have emerged. Subcutaneous furosemide use will potentially overcome the need to place intravenous lines, reduce associated expenses, and enable management of ADHF at home. This review presents data on the pharmacodynamics and pharmacokinetics of subcutaneous furosemide, scientific evidence on the use of this therapy in the palliative and hospice population, and its experimental use as an outpatient therapy and/or as a bridge from inpatient to home.

Hyaluronidase-Assisted Resuscitation in Kenya for Severely Dehydrated Children.

BACKGROUND: Dehydration, mainly due to diarrheal illnesses, is a leading cause of childhood mortality worldwide. Intravenous (IV) therapy is the standard of care for patients who were unable to tolerate oral rehydration; however, placing IVs in fragile, dehydrated veins can be challenging. Studies in resource-rich settings comparing hyaluronidase-assisted subcutaneous rehydration with standard IV rehydration in children have demonstrated several benefits of subcutaneous rehydration, including time and success of line placement, ease of use, satisfaction, and cost-effectiveness. METHODS: A single-arm trial assessing the feasibility of hyaluronidase-assisted subcutaneous resuscitation for the treatment of moderately to severely dehydrated individuals in western Kenya was conducted. Children aged 2 months or older who presented with moderately to severely dehydration clinically warranting parenteral rehydration and had at least 2 failed IV attempts were eligible. Study staff received training on standard dehydration management and hyaluronidase infusion processes. Children received all other standards of care. They were monitored from presentation and through discharge, with a 1-week phone follow-up. Predischarge surveys were completed by caregivers, and semistructured interviews with providers were performed. RESULTS: A total of 51 children were enrolled (median age, 13.0 months; interquartile range of 18 months). Fifty-one patients (100%) had severe dehydration. The median length of subcutaneous infusion was 3.0 hours (interquartile range [IQR], 2.95). The median total subcutaneous infusion was 700.0 mL (IQR, 420 mL). Median time to resolution of moderate to severe dehydration symptoms was 3.0 hours (IQR, 2.95 hours). There were no significant complications. CONCLUSIONS: Hyaluronidase-assisted subcutaneous resuscitation is a feasible alternative to IV hydration in moderately to severely dehydrated children with difficult to obtain IV access in resource-limited areas.

Potential cost savings owing to the route of administration of oncology drugs: a microcosting study of intravenous and subcutaneous administration of trastuzumab and rituximab in the Netherlands.

There is little evidence on the costs associated with the route of administration of oncology drugs. We investigated time and resource use for hospitals and patients and compared healthcare and societal costs for intravenous (IV) and subcutaneous (SC) administration of trastuzumab and rituximab. Data for the preparation and administration of both drugs were collected at the hospital pharmacy and at the oncology day care unit. Patients completed a questionnaire for obtaining information on societal costs (productivity losses, informal care and traveling expenses). A total of 126 patients were recruited in six hospitals; 82 received trastuzumab (37 IV and 45 SC) and 44 received rituximab (23 IV and 21 SC). The costs per administration (including societal cost but excluding drug costs) were &OV0556;167 and &OV0556;264 for IV and &OV0556;76 and &OV0556;146 for SC trastuzumab and rituximab, respectively. The costs for SC administration were lower in all categories. The largest cost component was related to time spent at the day care unit (overhead costs). This resulted in savings of &OV0556;47 for SC trastuzumab and &OV0556;69 for SC rituximab. The costs related to time of healthcare professionals was &OV0556;9 lower for both drugs. The costs for consumables resulted in another &OV0556;12 savings. Societal costs were &OV0556;22 lower for SC trastuzumab and &OV0556;28 lower for SC rituximab. Although administration costs are relatively a small part of the total costs, important savings can be generated by switching to an SC route of administration especially because a large number of patients receive oncology drugs and patients receive more than one administration.

Cost-effectiveness of sensor-augmented pump therapy in two different patient populations with type 1 diabetes in Italy.

BACKGROUND AND AIMS: Sensor-augmented pump therapy (SAP) combines real time continuous glucose monitoring (CGM) with Continuous Subcutaneous Insulin Infusion (CSII) and provides additional benefits beyond those provided by CSII alone. SAP with automated insulin suspension provides early warning of the onset of hyperglycemia and hypoglycemia and has the functionality to suspend insulin delivery if sensor glucose levels are predicted to fall below a predefined threshold. Aim of this study was to assess the cost-effectiveness of SAP with automated insulin suspension versus CSII alone in type 1 diabetes. METHODS AND RESULTS: Cost-effectiveness analysis was performed using the CORE Diabetes Model. The analysis was performed in two different cohorts: one with high baseline HbA1c and one at elevated risk for hypoglycemic events. Clinical input data were sourced from published data. The analysis was conducted from a societal perspective over a lifetime time horizon; costs and clinical outcomes were discounted at 3% per year. In patients with poor glycemic control, SAP with automated insulin suspension resulted in improved discounted quality-adjusted life expectancy (QALY) versus CSII (12.44 QALYs vs. 10.99 QALYs) but higher mean total lifetime costs (€324,991 vs. €259,852), resulting in an incremental cost effectiveness ratio (ICER) of €44,982 per QALY gained. In patients at elevated risk for hypoglycemia, the ICER was €33,692 per QALY gained for SAP versus CSII. CONCLUSION: In Italy, the use of SAP with automated insulin suspension is associated with projected improvements in outcomes as compared to CSII. These benefits translate into an ICER usually considered as good value for money, particularly in patients at elevated risk of hypoglycemia.

Continuous Glucose Monitoring Use in Type 1 Diabetes: Longitudinal Analysis Demonstrates Meaningful Improvements in HbA1c and Reductions in Health Care Utilization.

BACKGROUND: Real-time continuous glucose monitoring (rtCGM) improves glycemic control in type 1 diabetes (T1D) patients treated with continuous subcutaneous insulin infusion (CSII). However, the benefits of rtCGM in T1D patients treated with multiple daily insulin injection (MDI) therapy has not been well studied. We explored the effects of rtCGM versus self-monitoring of blood glucose (SMBG) on clinical outcomes within a large T1D population treated with either CSII or MDI therapy. METHODS: This retrospective, longitudinal analysis utilized datasets from T1D patients enrolled in a commercial health plan to assess changes in HbA1c in 187 naïve to rtCGM users and 6260 SMBG users. Propensity score modeling was used to assess inpatient admissions, emergency room (ER) visits in 1130 patients (565 rtCGM, 565 SMBG). Differences in HbA1c reduction (rtCGM+MDI vs rtCGM+CSII) were evaluated. RESULTS: Larger, clinically meaningful HbA1c reductions were seen among rtCGM versus SMBG users: -0.5% ( P = .004) versus -0.2% ( P < .0001); 0.3% diff in diff, P = .03. All-cause inpatient admissions were lower for rtCGM users: -42%, P = .013. Emergency room visits coded for diabetic ketoacidosis (DKA) were four times higher for SMBG patients than rtCGM patients: 17 versus 4, P = .0318. HbA1c reductions were most notable with rtCGM+MDI versus rtCGM+CSII treatment: -0.6% ( P = .01) versus -0.3% ( P = .16). CONCLUSIONS: Use of rtCGM in T1D patients facilitates greater HbA1c improvements and reduced health care system utilization compared with traditional SMBG use regardless of insulin administration method. Treatment with rtCGM in conjunction with MDI confers similar or greater glycemic benefits without the additional costs associated with CSII therapy.

Budget impact of continuous subcutaneous insulin infusion therapy in patients with type 1 diabetes who experience severe recurrent hypoglycemic episodes in Spain. / Impacto presupuestario de la infusión subcutánea continua de insulina en el tratamiento de pacientes con diabetes tipo 1 que presentan episodios de hipoglucemia grave recurrente en España.

OBJECTIVE: Hypoglycemia is one of the most common complications to achieve a good metabolic control, and has been listed by several scientific associations as a common indication to start treatment with continuous subcutaneous insulin infusion (CSII). Use of CSII is still residual in Spain as compared to neighbouring countries, and cost of acquisition cost is one of the main reasons. This study estimates the budget impact of treatment with CSII, as compared to multiple daily insulin injections, of patients with type 1 diabetes mellitus who experience recurrent severe hypoglycemia episodes from the National Healthcare System perspective. METHODS: Budget impact was based on a retrospective, observational study evaluating the efficacy of CSII in patients with type 1 diabetes mellitus conducted at Hospital Clínic i Universitari in Barcelona, where one of the main indications for switching to CSII were recurrent severe hypoglycemia episodes. The mean number of annual episodes was 1.33 in the two years prior to CSII start and 0.08 in the last two years of follow up (p=0.003). Costs of treatment and major hypoglycemic events over a four-year period were considered. Costs were taken from different Spanish data sources and expressed in € of 2016. RESULTS: Treatment with CSII increased costs by €9,509 per patient as compared to multiple daily insulin injections (€11,902-€2,393). Cost associated to severe hypoglycemic events decreased by €19,330 per patient treated with CSIII (€1,371-€20,701). Results suggest mean total savings of €9,821 per patient during the four-year study period. CONCLUSION: The higher costs associated to CSII therapy may be totally offset by the severe hypoglycemic events prevented.

Subcutaneous immunoglobulin treatment in CIDP and MMN. Efficacy, treatment satisfaction and costs.

Subcutaneous administration of immunoglobulin (SCIG) in chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN) has been reported in several case reports and in a few randomized trials during the last decade. In this review we present the studies on SCIG in CIDP and MMN with special focus on the clinical effects. Moreover, the effect on quality of life, side effects to SCIG and the health economic perspectives are reviewed. Nine case studies, three randomized trials and six long-term, follow-up studies were identified. Most of the studies are conducted in patients switched from regular IVIG to SCIG treatment; one study involves treatment-naïve patients. The review shows that none of the studies have been powered to demonstrate an effect on disability. SCIG can maintain muscle strength for a period of 1 to 2years and ability seems preserved for a similar period. Quality of life is generally unchanged or improved after switch to SCIG and generalized side-effects seem fewer, whereas local reactions at the injection site occur. Health economic analyses favour SCIG at the doses used in the reviewed studies.

The Effect of a Subcutaneous Infusion of GLP-1, OXM, and PYY on Energy Intake and Expenditure in Obese Volunteers.

Background: Roux-en-Y gastric bypass (RYGB) surgery is currently the most effective treatment of obesity, although limited by availability and operative risk. The gut hormones Glucagon-like peptide-1 (GLP-1), Peptide YY (PYY), and Oxyntomodulin (OXM) are elevated postprandially after RYGB, which has been postulated to contribute to its metabolic benefits. Objective: We hypothesized that infusion of the three gut hormones to achieve levels similar to those encountered postprandially in RYGB patients might be effective in suppressing appetite. The aim of this study was to investigate the effect of a continuous infusion of GLP-1, OXM, and PYY (GOP) on energy intake and expenditure in obese volunteers. Methods: Obese volunteers were randomized to receive an infusion of GOP or placebo in a single-blinded, randomized, placebo-controlled crossover study for 10.5 hours a day. This was delivered subcutaneously using a pump device, allowing volunteers to remain ambulatory. Ad libitum food intake studies were performed during the infusion, and energy expenditure was measured using a ventilated hood calorimeter. Results: Postprandial levels of GLP-1, OXM, and PYY seen post RYGB were successfully matched using 4 pmol/kg/min, 4 pmol/kg/min, and 0.4 pmol/kg/min, respectively. This dose led to a mean reduction of 32% in food intake. No significant effects on resting energy expenditure were observed. Conclusion: This is, to our knowledge, the first time that an acute continuous subcutaneous infusion of GOP, replicating the postprandial levels observed after RYGB, is shown to be safe and effective in reducing food intake. This data suggests that triple hormone therapy might be a useful tool against obesity.

Non-adherence to subcutaneous biological medication in patients with rheumatoid arthritis: a multicentre, non-interventional study.

OBJECTIVES: To evaluate non-adherence to prescribed subcutaneous biologicals in rheumatoid arthritis (RA) patients in Spain. METHODS: ARCO (Study on Adherence of Rheumatoid Arthritis patients to SubCutaneous and Oral Drugs) was a multicentre, non-interventional retrospective study involving 42 rheumatology clinics from representative hospitals throughout Spain. The primary objective was to assess the percentage of patients (aged ≥18 years with an established RA diagnosis) with non-adherence to prescribed subcutaneous biologicals using clinical records and hospital pharmacy dispensing logs as the primary information sources. Adherence was assessed using the Medication Possession Ratio (MPR). Additionally, patients completed the Morisky-Green Medication Adherence Questionnaire. RESULTS: A total of 364 patients (77.5% females, mean age 54.9 years, median RA duration since diagnosis 7.8 years) were enrolled in ARCO. Non-adherence (MPR ≤80%) was reported in 52/363 evaluable patients (14.3%), and was lower in patients receiving initial monthly drug administration (6.4%) than with weekly (17.4%; p=0.034) or every two weeks (14.4%; p=0.102) administration. By multivariate analysis, non-adherence was positively associated with RA duration above the median and with using induction doses. Monthly administration, compared to weekly administration, was inversely associated with non-adherence. Age, gender, order of administration, and changes in the interval of administration, showed no association with non-adherence. Compared with the MPR, the Morisky-Green questionnaire performed poorly in detecting non-adherence. CONCLUSIONS: Non-adherence to the prescribed subcutaneous biological drug occurred in 14.3% of patients with RA. Patients using the most convenient administration period (i.e. monthly) had better adherence than those using more frequent dosing schedules.

Evaluating dose ratio of subcutaneous to intravenous immunoglobulin therapy among patients with primary immunodeficiency disease switching to 20% subcutaneous immunoglobulin therapy.

BACKGROUND: Current prescribing information recommends that physicians apply a dose ratio of 1.37:1 (1.53:1 prior to January 2015) in the United States (US) when switching patients with primary immunodeficiency disease (PI) from intravenous (IVIG) therapy to most subcutaneous therapy ([SCIG], except the 10% SCIG human hyaluronidase and immune globulin). However, a dose ratio of 1:1 was studied and approved for the European Union (EU). The dose-adjustment ratio used by prescribers in real-world US clinical practice is unknown. OBJECTIVES: To examine real-world Hizentra 20% SCIG-to-IVIG dose ratios in the US after PI patients are switched from IVIG to 20% SCIG (Hizentra). METHODS: A retrospective longitudinal study was conducted using prescription shipment data of patients with PI from specialty pharmaceutical and service providers from 2011 to 2016. Patients who had at least 1 shipment of IVIG prior to switching to 20% SCIG (Hizentra) and subsequently received at least 1 more 20% SCIG (Hizentra) shipment in the following 6 months were included. Monthly 20% SCIG (Hizentra) doses following a switch from IVIG were calculated for each 2-month interval by summing daily doses that were estimated by dividing shipped volume by days between shipments. Mean monthly IVIG dose was calculated from the total volume shipped prior to switch. Per-patient dose ratios of Hizentra 20% SCIG-to-IVIG were calculated by dividing monthly 20% SCIG (Hizentra) dose by monthly IVIG dose during each 2-month interval. To minimize the influence of outliers, median dose ratios were reported. Dose ratios at months 2 to 4, 4 to 6, and 6 to 8 were compared with the dose ratio at months 0 to 2 using the Wilcoxon signed rank test. A sensitivity analysis excluding pediatric patients was conducted to assess the impact of changes in weight. RESULTS: Data from 278 patients who met the inclusion criteria showed that median Hizentra 20% SCIG-to-IVIG dose ratios were 1.14:1 at 0 to 2 months post switch, 1.09:1 at 2 to 4 months, and stabilized at 1.05:1 at 4 to 6 and 6 to 8 months post switch. Median dose ratios at months 2 to 4, 4 to 6, and 6 to 8 were statistically significantly lower than the median dose ratio at 0 to 2 months post switch (all P < .001). Similar results were seen in the sensitivity analysis excluding pediatric patients. CONCLUSIONS: Real-world data indicate that patients were switched to 20% SCIG (Hizentra) from IVIG at dose ratios lower than recommended by US prescribing information but similar to prescribing information in the EU. The initial dose ratio of 1.14:1 at 0 to 2 months stabilized to 1.05:1 at 4 to 6 and 6 to 8 months, which was consistent with reports of dose-equivalent switching patterns used in management of PI in clinical practice in the US.

Switching Patients to Home-Based Subcutaneous Immunoglobulin: an Economic Evaluation of an Interprofessional Drug Therapy Management Program.

PURPOSE: Home-based subcutaneous immunoglobulin (SCIg) therapy is an alternative to hospital-based intravenous infusions (IVIg). However, SCIg requires patient training and long-term support to ensure proper adherence, optimal efficacy and safety. We evaluated if switching patients to home-based SCIg including an interprofessional drug therapy management program (physician, community pharmacist and nurse) would be cost-effective within the Swiss healthcare system. METHODS: A 3-year cost-minimization analysis was performed from a societal perspective comparing monthly IVIg in an outpatient clinic and home-based weekly SCIg including an interprofessional program. Healthcare costs (immunoglobulin, professional time, infusion pump and disposables) were derived from administrative data. Transportation and productivity loss were estimated by expert opinion. The results were expressed in Swiss francs (CHF) and converted to Euros and US dollars (1 CHF = 0.92€, 1 CHF = $1.02; www.xe.com , 12/14/2015). RESULTS: Under base case assumptions, SCIg was estimated to cost 35,862 CHF (33,134€; $36,595) per patient during the first year and 30,309 CHF (28,004€; $30,929) in subsequent years versus 35,370 CHF (32,679€; $36,095) per year for IVIg. The total savings from switching to SCIg with the interprofessional program were 9630 CHF (8897€; $9828) per patient over 3 years. The results were relatively sensitive to the cost per gram of IgG, the cost of equipment and the annual number of infusions. CONCLUSION: Home-based SCIg including an interprofessional therapy management program may be an efficient alternative for patients. The program provides long-term support from self-administration training to the responsible use of therapy (proper adherence, optimal efficacy and safety). Over the short term, additional costs from purchasing equipment and the drug therapy management program were offset by avoiding hospital costs.

Cost-effectiveness of continuous subcutaneous insulin infusion in people with type 2 diabetes in the Netherlands.

AIMS: Up to 30% of insulin-treated type 2 diabetes patients are unable to achieve HbA1c targets despite optimization of insulin multiple daily injections (MDI). For these patients the use of continuous subcutaneous insulin infusion (CSII) represents a useful but under-utilized alternative. The aim of the present analysis was to examine the cost-effectiveness of initiating CSII in type 2 diabetes patients failing to achieve good glycemic control on MDI in the Netherlands. METHODS: Long-term projections were made using the IMS CORE Diabetes Model. Clinical input data were sourced from the OpT2mise trial. The analysis was performed over a lifetime time horizon. The discount rates applied to future costs and clinical outcomes were 4% and 1.5% per annum, respectively. RESULTS: CSII was associated with improved quality-adjusted life expectancy compared with MDI (9.38 quality-adjusted life years [QALYs] vs 8.95 QALYs, respectively). The breakdown of costs indicated that ∼50% of costs were attributable to diabetes-related complications. Higher acquisition costs of CSII vs MDI were partially offset by the reduction in complications. The ICER was estimated at EUR 62,895 per QALY gained and EUR 60,474 per QALY gained when indirect costs were included. CONCLUSIONS: In the Netherlands, CSII represents a cost-effective option in patients with type 2 diabetes who continue to have poorly-controlled HbA1c despite optimization of MDI. Since the ICER falls below the willingness-to-pay threshold of EUR 80,000 per QALY gained, CSII is likely to represent good-value for money in the treatment of poorly-controlled T2D patients compared with MDI.