Cost effectiveness of caplacizumab in acquired thrombotic thrombocytopenic purpura.

Acquired thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease characterized by thrombotic microangiopathy leading to end-organ damage. The standard of care (SOC) treatment is therapeutic plasma exchange (TPE) alongside immunomodulation with steroids, with increasing use of rituximab ± other immunomodulatory agents. The addition of caplacizumab, a nanobody targeting von Willebrand factor, was shown to accelerate platelet count recovery and reduce TPE treatments and hospital length of stay in TTP patients treated in 2 major randomized clinical trials. The addition of caplacizumab to SOC also led to increased bleeding from transient reductions in von Willebrand factor and increased relapse rates. Using data from the 2 clinical trials of caplacizumab, we performed the first-ever cost-effectiveness analysis in TTP. Over a 5-year period, the projected incremental cost-effectiveness ratio (ICER) in our Markov model was $1 482 260, significantly above the accepted 2019 US willingness-to-pay threshold of $195 300. One-way sensitivity analyses showed the utility of the well state and the cost of caplacizumab to have the largest effects on ICER, with a reduction in caplacizumab cost demonstrating the single greatest impact on lowering the ICER. In a probabilistic sensitivity analysis, SOC was favored over caplacizumab in 100% of 10 000 iterations. Our data indicate that the addition of caplacizumab to SOC in treatment of acquired TTP is not cost effective because of the high cost of the medication and its failure to improve relapse rates. The potential impact of caplacizumab on health system cost using longer term follow-up data merits further study.

[Economic evaluation of plasma exchange combined with dual plasma adsorption therapy for early, mid and late stage liver failure].

Objective: To compare the economic characteristics of the four artificial liver models [plasma exchange, half-dose plasma exchange combined with double plasma adsorption (DPMAS), pre-equal amount of plasma exchange followed by DPMAS, and pre-DPMAS followed by equal amount of plasma exchange] in the treatment of liver failure. Methods: A decision tree model was established with the Treeage pro 2011 software. The cost-effectiveness ratio and incremental cost-effectiveness value of four different treatment modalities were calculated and compared in patients with liver failure at early, mid and late stages, respectively. The sensitivity analysis of the model was performed using data from the preliminary research results of these groups. Results: The cost-effectiveness ratio and incremental cost-effectiveness value of patients treated with artificial liver therapy with half-dose plasma exchange combined with DPAMS plan in early stage liver failure were 89 547.79 and 34 665.34, which was lower than per capita GDP, so the increased cost had cost-effective advantages. In the middle and late stage of liver failure, the cost-effectiveness ratio and incremental cost-effectiveness value of pre-DPMAS followed by equal plasma exchange plan was 122 865.5 and 284 334.97, and 70 744.55 and 75 299.48, respectively, which was less than three times of per capita GDP. The increased cost was acceptable and had economic advantages. The sensitivity analysis results showed that the basic analysis results were reliable. Conclusion: Half-dose plasma exchange combined with DPAMS plan is the most cost-effective treatment for early liver failure, while pre-DPMAS followed by equal plasma exchange plan is the most economical treatment for mid and late stage liver failure.

Economic Costs of Myasthenia Gravis: A Systematic Review.

OBJECTIVES: The objective of our study was to conduct a systematic literature review of economic costs (henceforth costs) associated with myasthenia gravis (MG). METHODS: We searched MEDLINE (through PubMed), CINAHL, Embase, PsycINFO, and Web of Science for studies reporting costs of MG published from inception up until March 18, 2020, without language restrictions. Two reviewers independently screened records for eligibility, extracted the data, and assessed included studies for risk of bias using the Newcastle-Ottawa Scale. Costs were inflated and converted to 2018 United States dollars ($). RESULTS: The search identified 16 articles for data extraction and synthesis. Estimates of costs of MG were found for samples from eight countries spanning four continents (Europe, North America, South America, and Asia). Across studies, the mean per-patient annual direct medical cost of illness was estimated at between $760 and $28,780, and cost per hospitalization between $2550 and $164,730. The indirect cost of illness was estimated at $80 and $3550. Costs varied considerably by patient characteristics, and drivers of the direct medical cost of illness included intravenous immunoglobulin and plasma exchange, myasthenic crisis, mechanical ventilatory support, and hospitalizations. CONCLUSIONS: We show that the current body of literature of costs of MG is sparse, limited to a few geographical settings and resource categories, mostly dated, and subject to non-trivial variability, both within and between countries. Our synthesis will help researchers and decision-makers identify gaps in the local health economic context of MG and inform future cost studies and economic evaluations in this patient population.

Transfusion Medicine Equations Made Internet Accessible.

Multiple mathematical equations inform the practice of transfusion medicine. These equations apply to a wide range of topics: dosage of blood products, calculation of fluid volumes, and even specific treatment decisions (e.g. corrected count increment for determination of platelet refractoriness). The calculation of these equations can be complicated, prone to error, and time-consuming. A trusted source is needed to accurately perform these calculations 24 hours a day without error and without monetary cost. We sought to build internet-enabled calculators relevant to the practice of transfusion medicine. We partnered with MDCalc, an online host of medical calculators with 1 million monthly users in 196 countries, to design and host the calculators. The calculators guide users in the application of transfusion medicine equations by providing indications for use, inputs for the equations variables, error-checking, warnings for bad inputs, and interpretive guidance of the result. The following calculators were built: blood volume, corrected count increment (CCI), plasma dosage, cryoprecipitated antihemophilic factor dosage, approximate number of units for compatibility testing, maternal-fetal hemorrhage Rh(D) immune globulin dosage, intrauterine RBC transfusion dosage, neonatal polycythemia partial exchange, theoretical removal of a substance by plasmapheresis, sickle cell RBC exchange volume, peripheral blood stem cell collection, and a calculator relevant to donor lymphocyte infusion. Clinicians can now utilize this reputable and highly visible online source to access these common transfusion medicine equations at any time with an internet-enabled device (https://www.mdcalc.com/search?filter=transfusion+medicine).

Therapeutic plasma exchange in acute liver failure.

BACKGROUND: Multi-organ dysfunction in acute liver failure (ALF) has been attributed to a systemic inflammatory response directly triggered by the injured liver. High-volume therapeutic plasma exchange (HV-TPE) has been demonstrated in a large randomized controlled trial to improve survival. Here, we investigated if a more cost-/ resource effective low-volume (LV) TPE strategy might have comparable beneficial effects. METHODS: This retrospective study evaluated the effect of LV-TPE on remote organ failure, hemodynamical and biochemical parameters as well as on survival in patients with ALF. Twenty patients treated with LV-TPE in addition to standard medical therapy (SMT) were identified and 1:1 matched to a historical ALF cohort treated with SMT only. Clinical and biochemical parameters were recorded at admission to the intensive care unit and the following 7 days after LV-TPE. RESULTS: Mean arterial pressure increased following first LV-TPE treatments (d0: 68 [61-75] mm Hg vs d7: 88 [79-98] mm Hg, P = .003) and norepinephrine dose was reduced (d0: 0.264 [0.051-0.906] µg/kg/min vs d3: 0 [0-0.024] µg/kg/min, P = .016). Multi-organ dysfunction was significantly diminished following LV-TPE (CLIF-SOFA d0: 17 [13-20] vs d7: 7 [3-11], P = .001). Thirty-day in-hospital survival was 65% in the LV-TPE cohort and 50% in the SMT cohort (Hazard-ratio for TPE: 0.637; 95% CI: 0.238-1.706, P = .369). CONCLUSIONS: Patients treated with LV-TPE showed improved surrogate parameters comparable with the effects reported with HV-TPE. These data need to be interpreted with caution due to their retrospective character. Future controlled studies are highly desirable.

The establishment of in-house neurology driven therapeutic plasma exchange infrastructure in a resource-limited public hospital in Malaysia: Adopting and integrating evidenced-based health care technology through time.

There has been an increase in the use of therapeutic plasma exchange (TPE) in immune-mediated neurological disorders in recent years. However, accessibility and availability of TPE remains low and costly, especially for a country with limited healthcare funding like Malaysia. With expanding clinical indications in neurological disorders, and increasingly expensive conventional immunomodulatory treatment such as intravenous immunoglobulin and monoclonal antibodies, TPE remains an effective part of first or second-line treatment. In this article, we detailed the historical aspects of the use of TPE in neurological disorders in Malaysia over the last four decades and discussed the challenges behind the establishment of the first in-house neurology-driven TPE service in the country. Local TPE database from a national neurology centre in Kuala Lumpur over the past 20 years was analyzed. We observed a remarkable three folds increase in the use of TPE at our center over the past 10 years (total 131 TPE treatments) compared to a decade prior, with expanding clinical indications predominantly for central nervous system demyelinating disorders. Besides using membrane filtration method, centrifugal technique was adopted, providing new opportunities for other clinical beneficiaries such as a neurologist driven "in-house TPE unit". However, there were real world challenges, especially having to provide services with limited funding, human resources, and space. In addition, much has to be done to improve accessibility, availability, and sustainability of TPE services at our center and nationwide. Nevertheless, even with limited resources and support, it is possible with concerted efforts to work within the confines of these limitations to establish a safe, successful, and sustainable TPE service.

Cost-minimization analysis in the Indian subcontinent for treating Guillain Barre Syndrome patients with therapeutic plasma exchange as compared to intravenous immunoglobulin.

BACKGROUND: Therapeutic Plasma Exchange (TPE) and Intravenous Immunoglobulin both are first-line treatments for Guillain Barre Syndrome; however, there is a significant difference in cost. We undertook this study to assess the cost minimization for treating Guillain Barre Syndrome patients. METHODS: A prospective randomized controlled trial was undertaken, in which 40 Guillain Barre Syndrome (GBS) patients with a GBS disability score of grade four and five were enrolled. A societal perspective was adopted for the analysis and assessment of both the health system cost and out-of-pocket expenditures. Cost-minimization analysis was undertaken as both the treatments were equally effective at the end of 12 weeks. RESULTS: No statistically significant differences were observed in the GBS Disability scores during overall treatment course in both treatment groups. The Out-of-pocket cost for the immunoglobulin (IVIG) group was INR 219 247 (4298 USD) and for the TPE group was INR 104 070 (2040.5 USD). Overall INR 86 685 ($1700), that is, 53% higher cost was observed in IVIG group without any concomitant health outcome benefit. CONCLUSION: In comparison with IVIG, TPE appears to be the better option for treatment of GBS in cost-constraint countries like ours to provide an economic treatment option to most average people.

Cost-minimization analysis comparing intravenous immunoglobulin with plasma exchange in the management of patients with myasthenia gravis.

INTRODUCTION: Myasthenia gravis (MG) exacerbations may be treated with intravenous immunoglobulin (IVIg) or plasma exchange (PLEX), which have equivalent effectiveness. This cost-minimization analysis compared IVIg with PLEX for treatment of patients with MG exacerbation. METHODS: We combined the Ontario-based health cost data with clinical data from a randomized clinical trial. Analyses were undertaken from the perspective of a public healthcare insurer and from the perspective of a tertiary university hospital payer. RESULTS: PLEX was less costly than IVIg among patients with a body mass index (BMI) > 15.7 kg/m(2) , from the perspective of the public healthcare insurer (P < 0.0001). However, PLEX was more costly than IVIg from the perspective of the hospital payer when the costs of blood products were excluded (P < 0.0001). CONCLUSIONS: PLEX can be considered a short-term cost-minimizing therapy when compared with IVIg for treatment of MG exacerbation among patients with BMI >15.7 kg/m(2) , from the perspective of a public healthcare insurer. Muscle Nerve 53: 872-876, 2016.

The Ethics of Paid Plasma Donation: A Plea for Patient Centeredness.

Plasma protein therapies (PPTs) are a group of essential medicines extracted from human plasma through processes of industrial scale fractionation. They are used primarily to treat a number of rare, chronic disorders ensuing from inherited or acquired deficiencies of a number of physiologically essential proteins. These disorders include hemophilia A and B, different immunodeficiencies and alpha 1-antitrypsin deficiency. In addition, acute blood loss, burns and sepsis are treated by PPTs. Hence, a population of vulnerable and very sick individuals is dependent on these products. In addition, the continued well-being of large sections of the community, including pregnant women and their children, travelers and workers exposed to infectious risk is also subject to the availability of these therapies. Their manufacture to adequate amounts requires large volumes of human plasma as the starting material of a complex purification process. Mainstream blood transfusion services run primarily by the not-for-profit sector have attempted to provide this plasma through the separation of blood donations, but have failed to provide sufficient amounts to meet the clinical demand. The collection of plasma from donors willing to commit to the process of plasmapheresis, which is not only time consuming but requires a long term, continuing commitment, generates much higher amounts of plasma and has been an activity historically separate from the blood transfusion sector and run by commercial companies. These companies now supply two-thirds of the growing global need for these therapies, while the mainstream government-run blood sector continues to supply a shrinking proportion. The private sector plasmapheresis activity which provides the bulk of treatment products has been compensating the donors in order to recognize the time and effort required. Recent activities have reignited the debate regarding the ethical and medical aspects of such compensation. In this work, we review the landscape; assess the contributions made by the compensated and non-compensated sectors and synthesize the outcomes on the relevant patient communities of perturbing the current paradigm of compensated plasma donation. We conclude that the current era of "Patient Centeredness" in health care demands the continuation and extension of paid plasma donation.

Does Remuneration for Plasma Compromise Autonomy?

In accordance with a recent statement released by the World Health Organization, the Canadian province of Ontario is moving to ban payment for plasma donation. This is partially based on contentions that remuneration for blood and blood products undermines autonomy and personal dignity. This paper is dedicated to evaluating this claim. I suggest that traditional autonomy-based arguments against commodification of human body parts and substances are less compelling in the context of plasma donation in Canada, but that there is another autonomy-based objection to paid plasma donation that has not received sufficient attention. Namely, the stigma that surrounds exchanging plasma for payment makes it difficult to make an autonomous decision to engage in this activity. I suggest that this problem can be overcome in one of two ways; by banning payment for plasma, or by reducing the stigma surrounding this practice. I provide an indication of how we might work to achieve the latter, contending that this possibility should be taken seriously, due to the difficulties in achieving a sufficient supply of plasma without remuneration.

Benefits and challenges of starting a new therapeutic apheresis service in a resource-constrained setting.

Therapeutic apheresis (TA) refers to a group of extracorporeal blood treatment modalities with clinical indications for which the clinicians' knowledge, availability and applicability vary widely worldwide. Therapeutic plasma exchange (TPE), the most common TA technique, is neither readily available nor affordable in many parts of Africa. This article focuses on the challenges of starting a TPE program in a resource-constrained economy and the result of a survey of Nigerian nephrology professionals on TPE. A critical appraisal of published manuscripts from Nigeria on TA was undertaken to assess uses, methods, and challenges encountered followed by a survey of the perceptions of Nigerian nephrology professionals on TPE. Survey results: 56.7% of respondents had very little or no knowledge of TPE; 40.5% moderate and only 2.7% admitting to having a good knowledge. Only 18.9% of respondents have ever participated or observed a TPE procedure with the remaining 81.1% not having any exposure to the procedure. A vast majority of the respondents 97.3% felt they needed better exposure and training in TPE and its applications. Among consultants, 56% had little knowledge, 88% had never participated or observed the TPE procedure, and 94% felt they needed better exposure and training. There is significant limitation in accessibility, availability, and use of TPE in Nigeria; knowledge of TPE and its applications is minimal among nephrology professionals. Efforts should be concentrated on improving the knowledge and availability of TPE in resource-constrained economy like Nigeria. Centers that would be able to manage cases requiring TA should be developed.

Effective reduction of blood product use in a community teaching hospital: when less is more.

BACKGROUND: The increased morbidity and mortality associated with liberal blood product usage have been convincingly demonstrated. The clinical problems they pose have prompted development of more restrictive evidence-based transfusion criteria. Education alone has a limited impact on the adoption of these criteria into practice. New York Methodist Hospital undertook a proactive approach to reduce unnecessary transfusions. METHOD: In November 2008, an interventional monitoring program to ensure adherence to transfusion criteria for packed red blood cells (PRBC), platelets, fresh frozen plasma (FFP), and cryoprecipitate transfusions was started. Blood bank technologists routinely monitored transfusion requests against a list of established criteria and experienced clinicians reviewed and adjudicated transfusion requests when the blood bank technologist's action was appealed. RESULTS: Transfusion usage decreased sharply in Year 1 (November 2008-October 2009) and continued to decrease in Year 2 (November 2009-October 2010). PRBC use decreased by 30.1% and 37.7%, with a 47.6% decrease in multi-unit transfusions; platelet use decreased by 24.3% and 41.2%; fresh frozen plasma use decreased by 41.8% and 31.1%; and cryoprecipitate use decreased by 38.7% and 56.1% during monitoring Years 1 and 2, respectively. Decreases occurred despite a 4.0% increase in hospital admissions during the monitoring years. The decreased blood product usage was accompanied by 28.6% reduction in complications. A 26.1% decrease in blood product requests from Year 1 to Year 2 suggested a practice change by the ordering physicians themselves. The total cost of blood products decreased by $2,235,676. CONCLUSION: We established a successful method to reduce transfusions of all blood products using strict adherence to evidence-based criteria and continuous monitoring. Our model translates into improved patient safety by decreasing the number of unnecessary transfusions. This also led to a significant reduction in hospital expenses.

Filter membrane-based automated therapeutic plasma exchange: a report of two cases from Nigeria.

These case reports demonstrated the diagnostic dilemma encountered in patients with systemic lupus erythematosus and thrombotic thrombocytopenic purpura particularly in settings with limited diagnostic facilities and laboratory support. The similarities in the diagnostic criteria for both conditions make clear distinction as well as management decisions difficult. We present the difficulties encountered with both the diagnosis and the management of these two patients that were managed in our facility.

Cost-minimization analysis of the direct costs of TPE and IVIg in the treatment of Guillain-Barré syndrome.

BACKGROUND: Controlled trials have found therapeutic plasma exchange (TPE) and intravenous immunoglobulin (IVIg) infusion therapy to be equally efficacious in treating Guillain-Barré syndrome (GBS). Due to increases in the price of IVIg compared to human serum albumin (HSA), used as a replacement fluid in TPE, we examined direct hospital-level expenditures for TPE and IVIg for meaningful cost-differences between these treatments. METHODS: Using financial data from our two institutions, hospital cost profiles for IVIg and 5% albumin were established. Reimbursement amounts were obtained from publicly available Medicare data resources to determine payment rates for TPE, non-tunneled central catheter line placement, and drug infusion therapy. A model was developed which allows hospitals to input cost and reimbursement amounts for both IVIg and TPE with HSA that results in real-time valuations of these interventions. RESULTS: The direct cost of five IVIg infusion sessions totaling 2.0 grams per kilogram (g/kg) body weight was $10,329.85 compared to a series of five TPE procedures, which had direct costs of $4,638.16. CONCLUSIONS: In GBS patients, direct costs of IVIg therapy are more than twice that of TPE. Given equivalent efficacy and similar severity and frequencies of adverse events, TPE appears to be a less expensive first-line therapy option for treatment of patients with GBS.

Plasma exchange versus intravenous immunoglobulin for myasthenia gravis crisis: an acute hospital cost comparison study.

OBJECTIVE: To compare the short-term financial costs of treating a patient in myasthenia gravis crisis with intravenous immunoglobulin (IVIG) versus plasma exchange. METHODS: An itemized comparative cost-minimization analysis of IVIG versus plasma exchange for myasthenia gravis crisis was performed. Calculations were based on each therapy's implementation cost, associated hospitalization times, and predicted cost to treat known complications. A cost superiority determination was proposed based on the total cost profile of each therapy. RESULTS: The difference in total cost favored IVIG over plasma exchange with an average savings of $22,326 per patient. Sensitivity analysis demonstrated that overall costs are highly dependent on IVIG dosing, hospital lengths of stay, and the number of plasma exchange days required. CONCLUSIONS: The use of IVIG for myasthenia gravis crisis may be a short-term cost minimizing therapy compared with plasma exchange. Additional prospective studies are required to evaluate the extended cost profile and efficacy of these therapies.

Cost-effectiveness study comparing pharmaceutically licensed plasma for transfusion (OctaplasLG®) versus fresh frozen plasma (FFP) in critically Ill patients in the UK.

This study evaluates the cost-effectiveness of OctaplasLG® (pharmaceutically licensed plasma for transfusion) versus fresh frozen plasma (FFP) in critically ill patients in the UK using a decision-analytic approach. Transfusion with OctaplasLG® resulted in 0.03 quality adjusted life years (QALYs) and 0.03 life years saved compared with FFP. The discounted cost per life year was £949 ($1504), and the discounted cost per QALY saved was £1030 ($1632) with OctaplasLG® in the UK. Based on a higher price of £70 ($111) for OctaplasLG® versus £28.42 ($45.04) for FFP, OctaplasLG® is considered to be cost-effective at a threshold of £30,000 ($47,548) per QALY.

Plasma exchange in immune-mediated neuropathies.

PURPOSE OF REVIEW: Plasma exchange is frequently used for treatment of immune-mediated neuropathies. Here, we review the current value of plasma exchange in the treatment of different forms of immune-mediated neuropathies and discuss latest developments. RECENT FINDINGS: Plasma exchange is used in various disease conditions; however, of all immune-mediated disorders of the peripheral nerve, Guillain-Barré syndrome represents the disease entity in which short and long-term efficacy, optimal frequency, side effects and cost effectiveness of plasma exchange are best documented. Although randomized trials evaluated the value of plasma exchange in chronic forms of immune-neuropathies, its long-term efficacy and its optimal frequency still remain unclear. SUMMARY: Especially in chronic forms of immune-mediated neuropathies, plasma exchange needs to be further evaluated in clinical trials to assess long-term efficacy and its potential as adjuvant treatment option.