Cost-effectiveness of eculizumab and efgartigimod for the treatment of anti-acetylcholine receptor antibody-positive generalized myasthenia gravis.

BACKGROUND: Eculizumab and efgartigimod were approved to treat anti-acetylcholine receptor antibody-positive generalized myasthenia gravis (anti-AChR Ab-positive gMG). These relatively new biological treatments provide a more rapid onset of action and improved efficacy compared with conventional immunosuppressive treatments, but at a higher cost. OBJECTIVE: To assess the cost-effectiveness of eculizumab and, separately, efgartigimod, each added to conventional therapy vs conventional therapy alone, among patients with refractory anti-AChR Ab-positive gMG and those with anti-AChR Ab-positive gMG, respectively. METHODS: A Markov model with 4 health states was developed, evaluating costs and utility with a 4-week cycle length and lifetime time horizon from a health care system perspective and a modified societal perspective including productivity losses from patients and caregiver burden. Model inputs were informed by key clinical trials and relevant publications identified from targeted literature reviews, and drug costs were identified from Micromedex Red Book. Costs and outcomes were discounted at 3% per year. Incremental cost-effectiveness ratios (ICERs; cost per quality-adjusted life-year [QALY] gained) were calculated for each comparison. RESULTS: Among the corresponding populations, lifetime costs and QALYs, respectively, for eculizumab were $5,515,000 and 11.85, and for conventional therapy, $308,000 and 10.29, resulting in an ICER of $3,338,000/QALY gained. For efgartigimod, lifetime costs and QALYs, respectively, were $6,773,000 and 13.22, and for conventional therapy, $322,000 and 9.98, yielding an ICER of $1,987,000/QALY gained. After applying indirect costs in a modified societal perspective, the ICERs were reduced to $3,310,000/QALY gained for eculizumab and $1,959,000/QALY gained for efgartigimod. CONCLUSIONS: Eculizumab and efgartigimod are rapidly acting and effective treatments for myasthenia gravis. However, at their current price, both therapies greatly exceeded common cost-effectiveness thresholds, likely limiting patient access to these therapies.

Gene therapies for sickle cell disease: Effectiveness and value.

DISCLOSURES: Drs. Nikitin, McKenna, Rind, Nhan, and Pearson report grants from Arnold Ventures, grants from Blue Cross Blue Shield of MA, grants from California Healthcare Foundation, grants from The Commonwealth Fund, grants from The Patrick and Catherine Weldon Donaghue Medical Research Foundation, during the conduct of the study; other from America's Health Insurance Plans, other from Anthem, other from AbbVie, other from Alnylam, other from AstraZeneca, other from Biogen, other from Blue Shield of CA, other from CVS, other from Editas, other from Express Scripts, other from Genentech/Roche, other from GlaxoSmithKline, other from Harvard Pilgrim, other from Health Care Service Corporation, other from Kaiser Permanente, other from LEO Pharma, other from Mallinckrodt, other from Merck, other from Novartis, other from National Pharmaceutical Council, other from Premera, other from Prime Therapeutics, other from Regeneron, other from Sanofi, other from United Healthcare, other from HealthFirst, other from Pfizer, other from Boehringer-Ingelheim, other from uniQure, other from Envolve Pharmacy Solutions, other from Humana, other from Sunlife, outside the submitted work.

Oral and monoclonal antibody treatments for relapsing forms of multiple sclerosis: Effectiveness and value.

DISCLOSURES: Ms McKenna, Dr Lin, Dr Whittington, Mr Nikitin, Ms Herron-Smith, Dr Campbell, and Dr Peterson report grants from Arnold Ventures, grants from Blue Cross Blue Shield of MA, grants from California Healthcare Foundation, grants from The Commonwealth Fund, and grants from The Peterson Center on Healthcare, during the conduct of the study; other from America's Health Insurance Plans, other from Anthem, other from AbbVie, other from Alnylam, other from AstraZeneca, other from Biogen, other from Blue Shield of CA, other from CVS, other from Editas, other from Express Scripts, other from Genentech/Roche, other from GlaxoSmithKline, other from Harvard Pilgrim, other from Health Care Service Corporation, other from Kaiser Permanente, other from LEO Pharma, other from Mallinckrodt, other from Merck, other from Novartis, other from National Pharmaceutical Council, other from Premera, other from Prime Therapeutics, other from Regeneron, other from Sanofi, other from United Healthcare, other from HealthFirst, other from Pfizer, other from Boehringer-Ingelheim, other from uniQure, other from Envolve Pharmacy Solutions, other from Humana, and other from Sun Life, outside the submitted work.

The effectiveness and value of AMX0035 and oral edaravone for amyotrophic lateral sclerosis: A summary from the Institute for Clinical and Economic Review's Midwest Comparative Effectiveness Public Advisory Council.

DISCLOSURES: Funding for this summary was contributed by Blue Cross Blue Shield of MA, California Healthcare Foundation, The Patrick and Catherine Weldon Donaghue Medical Research Foundation, Arnold Ventures, and Kaiser Foundation Health Plan Inc., to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from Aetna, America's Health Insurance Plans, AbbVie, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Boehringer Ingelheim, Cambia Health Services, CVS, Editas, Evolve Pharmacy Solutions, Express Scripts, Genentech/ Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, Health First, Health Partners, Humana, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Pfizer. Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, Sun Life Financial, uniQure, and United Healthcare. Mr Nikitin, Ms McKenna, Ms Richardson, and Drs Rind and Pearson are employed by ICER. Through their affiliated institutions, Drs Makam, Carlson, and Suh received funding from ICER for the work described in this summary.

Ash and Slag Waste Processing in Self-Shielded Atmospheric DC Arc Discharge Plasma.

In this paper, we report the experimental results obtained in slag waste processing by direct current arc discharge initiated in ambient air. The method does not employ vacuum and gas equipment, therefore increasing the energy efficiency of processing. Plasma processing of coal slag was performed at different arc exposure times: 5, 10, 15, 20, and 25 s. The obtained materials contained a significant amount of graphite, which was removed through combustion. The micropowder based on silicon carbide and aluminum nitride was obtained and then sintered by spark plasma. The bulk ceramic samples based on silicon carbide with the hardness of ~10.4 GPa were finally fabricated.

Glass waste derived silicon carbide synthesis via direct current atmospheric arc plasma.

The paper presents the results of the experimental studies addressing the production of silicon carbide from glass waste by electric arc plasma processing. A feature of the method is the possibility of its implementation without the use of vacuum equipment. It is possible due to the effect of self-shielding of the reaction volume from atmospheric oxygen. This approach significantly simplifies the design of the electric arc reactor and its performance. After plasma processing of various types of glass waste (such as bottle glass, window glass, medical glass, quartz glass, parts of worn-out scientific and industrial equipment), silicon carbide based material was produced. Silicon carbide was obtained from a mixture of various glass waste at a current 200 A, where blend was first purified from unbound carbon and then was consolidated by spark plasma sintering at 1800 °C and 60 MPa pressure for 10 min. As a result, a ceramic bulk sample was fabricated from a mixture of glass waste of various origin. Such sample was characterized with hardness of 14.8 GPa, and attained density of 92.5 %. Despite a possible increase in the density due to impurities and inhomogeneities, the hardness of the fabricated sample is comparable to that of other silicon carbide based materials, including commercial ones. Since the hardness of the produced silicon carbide based material is comparable to that of commercial materials, the use of glass waste of various origin could be feasible for synthesis of silicon carbide based powders.

The effectiveness and value of eculizumab and efgartigimod for generalized myasthenia gravis.

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, The Donaghue Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from AbbVie, America's Health Insurance Plans, Anthem, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Boehringer-Ingelheim, Cambia Health Services, CVS, Editas, Evolve Pharmacy, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, HealthFirst, Health Partners, Humana, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Pfizer, Premera, Prime Therapeutics, Regeneron, Sanofi, Sun Life Financial, uniQure, and United Healthcare. Agboola, Nikitin, and Pearson are employed by ICER. Through their affiliated institutions, Tice, Touchette, and Lien received funding from ICER for the work described in this summary.

The internet market for Kratom, an opioid alternative and variably legal recreational drug.

BACKGROUND: Amidst the opioid crisis, many people are turning to plant-based kratom for self-treatment of pain, opioid addiction, and for recreational use. Its legality is variable and its safety and medicinal effects are not agreed upon. It is broadly available from Internet Kratom Vendors (IKVs). METHODS: An examination of the online marketplace for kratom was conducted to provide context to the market amidst regulatory attempts by the Food and Drug Administration (FDA) and state legislatures. A complex search strategy identified 663 English-language IKVs selling kratom for home delivery. The 100 most popular were selected for in-depth content analysis. IKVs were visited once for content analysis data collection in December, 2017 and revisited in April 2018 to assess responses to FDA action. IKV website and social media profiles were coded for topics including location, payment and shipping options, age verification, health warnings and disclaimers, and grassroots advocacy regarding upcoming state/federal regulations. RESULTS: Forty-seven percent of IKVs claimed that kratom provides pain relief, 25% claimed it provides relief from opioid withdrawal, 81% featured a disclaimer that kratom is addictive, 54% stated that kratom is not FDA approved, and 66% featured disclaimers that it was not intended for consumption. Only 5% of vendors advertised effective age verification (such as verifying age at delivery). Compliance on the vendor's part with state and local bans varied by ban location, with only 27% prohibiting sales to Rhode Island while 65% did not ship to Indiana. CONCLUSIONS: IKVs provide easy access to a wide variety of unregulated intoxicating products with poor age verification and low adherence to US state- and local-level restrictions. There is a high prevalence of vendors featuring health claims forbidden by the Food and Drug Administration. Lessons learned from regulating the Internet cigarette sales industry could be effectively applied to IKVs with future efforts.

Arguments for amending smoke-free legislation in U.S. states to restrict use of electronic nicotine delivery systems.

The uneven diffusion of local and state laws restricting the use of electronic nicotine delivery systems (ENDS) in the United States may be a function of inconclusive scientific evidence and lack of guidance from the federal government. The objective of this study was to assess whether the rationale for amending clean indoor air acts (CIAAs) is being conflated by issues that are not directly relevant to protecting the health of ENDS non-users. Online sources were used in identifying bills (n = 25) that were presented in U.S. state legislatures from January 2009 to December 2015. The bills were categorized into one of three groups: 1) bills amending comprehensive CIAAs (n = 11), 2) bills prohibiting use of ENDS in places frequented by youth (n = 5), and 3) remaining bills that varied between the two categories (n = 9). Arguments presented in committee hearings were coded as scientific, public health, economic, enforcement, freedom, or regulatory. Arguments pertaining to amendment of clean indoor air acts spanned several categories, many of which were not directly relevant to the aims of the legislation. This finding could assist lawmakers and expert witnesses in making arguments that yield greater success in amending legislation. Alternatively, inconclusive scientific data on the hazards of ENDS aerosols might encourage lawmakers to propose legislation that prohibits ENDS use in places frequented by youths.

Linking the content to demographic reach of online advertising of electronic nicotine delivery systems.

INTRODUCTION: Recent studies have separately examined the content and demographic reach of the advertising of electronic nicotine delivery systems (ENDS). No study to our knowledge has linked the two in investigating whether racial/ethnic groups are differentially exposed to the comparative messages conveyed in online ENDS advertisements. METHODS: 932 unique ENDS advertisements (6311 total), which were posted on 3435 websites between December, 2009 and October, 2015, were categorized as either comparative or non-comparative with respect to the traditional cigarette. The race/ethnicity of website visitors was obtained from a proprietary source and used in constructing variables for racial/ethnic viewership. The variables for advertising content and website racial/ethnic viewership were then linked yielding a final sample of 551 unique ENDS advertisements (2498 total) on 1206 websites. A two-level hierarchical generalized linear model, used in estimating website racial/ethnic viewership as a predictor of comparative advertising, accounted for the nesting of advertisements (level 1) within 152 ENDS brands (level 2). RESULTS: In contrast to racial/ethnic minorities, a greater proportion of non-Hispanic whites visited websites with ENDS advertisements than the overall proportion of nonHispanic white U.S. Internet users. Yet, it was the advertisements on websites that appealed to Hispanics that had greater odds of comparing ENDS to traditional cigarettes. CONCLUSIONS: The lower exposure to ENDS advertising among racial/ethnic minorities versus non-Hispanic whites is consistent with survey data. Yet, the greater odds of comparative advertising of ENDS on websites that appeal to racial/ethnic minorities (ie, Hispanics) could impact the longterm health of minority smokers. IMPLICATIONS: This study's findings have important implications for the uptake of ENDS among minority smokers. If the comparative advertising yields greater interest and eventual use of ENDS, then minority smokers could either benefit from smoking cessation because they switch to ENDS, or adopt dual tobacco use. The fate of comparative advertising of ENDS versus the traditional cigarette will depend on the Food and Drug Administration enforcement of its deeming rules and the ensuing changes in the ENDS marketplace.

A longitudinal study of smokeless tobacco use and mortality in the United States.

Few studies in the United States have examined longitudinally the mortality risks associated with use of smokeless tobacco (SLT). The sample of our study was composed of participants from the National Longitudinal Mortality Study who completed a single Tobacco Use Supplement to the Current Population Survey between the years 1985 and 2011. Using survival methods, SLT use at the baseline survey was examined as a predictor of all-cause mortality and cause-specific mortalities in models that excluded individuals who had ever smoked cigarettes, cigars or used pipes (final n = 349,282). The participants had median and maximum follow-up times of 8.8 and 26.3 years, respectively. Regression analyses indicated that compared to the never tobacco users, the current SLT users did not have elevated mortality risks from all cancers combined, the digestive system cancers and cerebrovascular disease. However, current SLT users had a higher mortality risk for coronary heart disease (CHD) [hazard ratio (HR) (95% CI) = 1.24 (1.05, 1.46)] relative to never tobacco users. In a separate model, the elevated risk for CHD mortality corresponded to the use of moist snuff [HR (95% CI) = 1.30 (1.03, 1.63)]. The associations with CHD mortality could be attributed to long-term nicotine exposure, other SLT constituents (e.g., metals) or the confounding effects of CHD risk factors not accounted for in our study. The study's findings contribute to the ongoing dialogue on tobacco harm reduction and the US FDA's evaluation of Modified Risk Tobacco Product applications submitted by American SLT manufacturers.

The Reach and Impact of Direct Marketing via Brand Websites of Moist Snuff.

OBJECTIVE: Restricting tobacco marketing is a key element in the US Food and Drug Administration's (FDA) public health framework for regulating tobacco. Given the dearth of empirical data on direct marketing, the objective of this study was to assess the reach and impact of promotions on sales through snuff websites. METHODS: Nine brands of snuff, representing more than 90% of market share, were monitored for content of coupons, sweepstakes, contests, and other promotions on their respective websites. Monthly sales data and website traffic for the 9 brands, corresponding to the 48-month period of January 2011 through December 2014, were obtained from proprietary sources. A time-series analysis, based on the autoregressive, integrated, moving average (ARIMA) method, was employed for testing the relationships among sales, website visits, and promotions. RESULTS: Website traffic increased substantially during the promotion periods for most brands. Time-series analyses, however, revealed that promotion periods for 5 of 7 brands did not significantly correlate with monthly snuff sales. CONCLUSIONS: The success in attracting tobacco consumers to website promotions demonstrates the marketing reach of snuff manufacturers. This form of direct marketing should be monitored by the FDA given evidence of adolescents' exposure to cigarette brand websites.

Is the E-Liquid Industry Regulating Itself? A Look at E-Liquid Internet Vendors in the United States.

INTRODUCTION: The objective of this study was to assess whether the nascent, but rapidly growing e-liquid industry prohibits Internet sales to minors and employs safety measures to prevent accidental poisonings. METHODS: A stratified simple random sample (n = 120) was selected from the target population (N = 1107) of US online vendors of e-liquid in July 2015. The vendors were stratified and subsequently oversampled by trade association membership and vendor popularity. Three minors aged 16 to 17, who were supervised by adult research staff, attempted to purchase e-liquid from the 120 online vendors using debit cards issued in their names. Measures included vendors' use of age verification, warning labels on e-liquid bottles, and child-resistant packaging. RESULTS: Statistically significant differences were observed by vendor popularity, but not by membership in a trade association. The differences by vendor popularity, however, occurred for measures that were limited to an age warning and list of ingredients. The most striking finding was the scant vendors (n = 4) who successfully prevented the sale of e-liquid to the minors. In contrast, 87.5% and 53.9% of the bottles contained child-resistant packaging and a health warning label, respectively. CONCLUSIONS: Irrespective of trade association membership or vendor popularity, online vendors of e-liquids are not taking the proper precautions in preventing sales to minors. The FDA's upcoming deeming rules on e-cigarette products should include explicit requirements for offline and online e-liquid vendors, particularly the use of effective age verification, warning labels, and child-resistant packaging. IMPLICATIONS: This study demonstrates that, in the absence of any current FDA regulation of e-liquid products, self-regulation among vendors is not effective in preventing product acquisition by minors. Lax oversight of the e-liquid industry may draw consumers to bypass current tobacco control restrictions implemented in face-to-face sales settings. As a consequence, there may be an increase in online sales to minors. Further regulation of the industry may increase the already prevalent use of child-resistant packaging, leading to fewer cases of accidental nicotine poisoning.

Twenty years' follow-up of portal vein conduits in liver transplantation.

Portal vein problems remain a formidable challenge in liver transplantation. In select situations, a portal vein conduit can provide a solution. No long-term results have been reported. This study was designed to assess the impact of portal vein conduits on graft survival after liver transplantation and the safety of portal vein conduits and to establish the long-term results (up to 20 years) of portal vein conduits. Data from 2370 adult liver transplants were prospectively collected into a computerized research database and analyzed. All portal vein conduits were constructed from the donor iliac vein obtained at the liver retrieval. Portal vein conduits were required in 35 (1.5%) first transplants. The long-term (up to 20 years of follow-up) graft survival after liver transplantation using portal vein conduits was excellent and comparable to that of the control group. The graft survival was 65% with the conduit versus 66% without the conduit at 5 years of follow-up, 58% versus 51% at 10 years, and 48% versus 35% at 15 years. There was a higher rate (8.6% versus 1.4%) of portal vein thrombosis after the portal vein conduit, and the majority occurred in the first 3 months after transplantation. For the same time period, there was no statistically significant difference in graft survival or patient survival for the retransplants with and without portal vein conduits. There was no statistically significant difference in graft survival or patient survival for the transplants with portal vein conduits and with portal vein thrombendvenectomy. In conclusion, portal vein conduits can be used safely for liver transplantation with no negative impact on long-term graft survival or patient survival. Despite the higher rate of portal vein thrombosis in the immediate postoperative period, excellent long-term results can be obtained.

Twenty years of follow-up of aortohepatic conduits in liver transplantation.

Arterial problems remain a formidable challenge in liver transplantation. In many situations, an aortohepatic conduit can provide a solution. No long-term results (over 5 years) have been reported. This study was designed to assess the impact of aortohepatic conduits on graft survival after liver transplantation and the safety of aortohepatic conduits and to establish the long-term results (up to 20 years) of aortohepatic conduits. Data from 2346 adult liver transplants were prospectively collected into the computerized database and analyzed. In the majority of cases, arterial conduits were constructed from the donor iliac artery obtained at the liver retrieval. Aortohepatic conduits were required in 149 (6.4%) first transplants. The long-term graft survival after liver transplantation using aortohepatic conduits was excellent and comparable to that of the control group. The graft survival was 59% with the conduit versus 67% without the conduit at 5 years of follow-up, 50% versus 52% at 10 years, and 33% versus 35% at 15 years. With up to 20 years of follow-up, there was no statistically significant difference in graft survival, patient survival, hepatic artery complications, or biliary complications. For the same time period, there was no statistically significant difference in graft survival or patient survival for the retransplants with and without aortohepatic conduits. In conclusion, in experienced hands, aortohepatic conduits can be used safely for liver transplantation with no negative impact on long-term graft survival, patient survival, hepatic artery complications, or biliary complications. Excellent long-term results can be obtained.

Intraoperative imaging of pancreas transplant allografts using indocyanine green with laser fluorescence.

Vascular thrombosis is a cause of allograft loss after pancreas transplantation. We present the use of intraoperative fluorescence imaging with the SPY imaging device (Novadaq Technologies Inc, Toronto, Canada) in two pancreas transplants as a means to assess potency of the vascular anastomoses. Intravenous indocyanine green 2.5 mg/mL was fluoresced with the device to create the intraoperative video sequences, which were recorded. After 60-day follow-up, real-time SPY imaging on these two pancreas transplants did not demonstrate adverse effects on patients or the transplanted allografts. This method of vascular imaging could prove useful in improving short-term graft survival and possibly lowering the thrombosis rates seen with pancreas transplantation. Long-term correlation studies between intraoperative findings and graft survival must be performed to confirm the utility of this imaging method.

Use of two expanded-criteria-donor renal allografts in a single patient.

The disparity between the number of available renal donors and the number of patients on the transplant waiting list has prompted the use of expanded-criteria-donor (ECD) renal allografts to expand the donor pool. ECD allografts have shown good results in appropriately selected recipients, yet a number of renal allografts are still discarded. The use of dual renal transplantation may lower the discard rate. Additionally, the use of perfusion systems may improve acute tubular necrosis rates with these allografts. We report a successful case of a dual transplant with ECD allografts using a perfusion system. The biopsy appearance and the pump characteristics were suboptimal for these kidneys, making them unsuitable for single transplantation; however, the pair of transplanted kidneys provided increased nephron mass and functioned well. We recommend that ECD kidneys that are individually nontransplantable be evaluated for potential dual renal transplantation. Biopsy criteria and perfusion data guidelines must be developed to improve the success rates with ECD dual renal allografts. Finally, recipient selection is of utmost importance.