Optimal treatment sequence for targeted immune modulators for the treatment of moderate to severe ulcerative colitis.

BACKGROUND: Ulcerative colitis is a chronic immune-mediated inflammatory condition of the large intestine and rectum. Several targeted immune modulators (TIMs) have demonstrated effectiveness for the treatment of moderate to severe ulcerative colitis and are approved by the FDA. Patients may try multiple TIMs, and currently there are no biomarkers or prognostic factors to guide choice of treatment sequence. In 2020, the Institute for Clinical and Economic Review (ICER) conducted a review of TIMs for the treatment of ulcerative colitis as individual agents relative to conventional treatment but did not address the relative ranking of various treatment sequences to each other. OBJECTIVE: To extend the ICER framework to identify the optimal treatment sequence as informed by metrics such as maximizing incremental net health benefit (NHB), minimizing incremental total cost, or maximizing incremental quality-adjusted life-years (QALYs). METHODS: The model was developed as a Markov model with 8-week cycles over a lifetime time horizon from a US payer perspective, including only direct health care costs. Health states consisted of active moderate to severe ulcerative colitis, clinical response without achieving remission, clinical remission, and death. Efficacy of TIMs were informed by the ICER-conducted network meta-analysis. Up to 3 treatments were modeled in a sequence that consisted of 2 different TIMs followed by conventional treatment. Sequences were ranked according to each objective. NHB was calculated using a threshold of $150,000 per QALY gained. Probabilistic sensitivity analysis (PSA) was undertaken to estimate the probability of each sequence having the highest NHB rank under each objective. RESULTS: 21 possible sequences were evaluated in the base case. Two attempts at conventional treatment represented the lowest cost option and, while yielding the fewest QALYs, resulted in the highest NHB. None of the sequences had an incremental cost per QALY below $150,000 relative to 2 attempts with conventional treatment, so the resulting NHB was negative for all sequences. The sequence with the highest NHB was infliximab-dyyb followed by tofacitinib (-0.116). This regimen also had the lowest incremental costs ($37,266). For orally and subcutaneously administered TIMs, the sequence of golimumab-tofacitinib had the highest NHB (-0.344). Ustekinumab-vedolizumab was the top-ranked sequence as measured by QALY maximization (0.172 incremental QALYs) but also had the highest total incremental cost ($166,094). Results of the PSA were consistent with deterministic rankings for the top-ranking sequences but also showed that the top 2 or 3 regimens were often close together. CONCLUSIONS: Based on the results of this analysis, the optimal sequence of TIMs as measured by NHB and cost minimization was infliximab or biosimilars as first-line treatment, then moving to tofacitinib, adalimumab, or vedolizumab. Sequences that generated the most QALYs began with ustekinumab, followed by vedolizumab, tofacitinib, and adalimumab. DISCLOSURES: This study was based on an evidence synthesis and economic evaluation sponsored by the Institute for Clinical and Economic Review (ICER). Pandey and Fazioli are employees of ICER. Bloudek reports grants from ICER during the conduct of the study and personal fees from Astellas, Akcea, Dermira, GlaxoSmithKline, Sunovion, Seattle Genetics, and TerSera Therapeutics, outside the submitted work. Pandey reports grants from California Healthcare Foundation, Harvard Pilgrim Healthcare, Kaiser Foundation Health Plan Inc., and the Donoghue Foundation, during the conduct of the study, and other support from Aetna, America's Health Insurance Plans, Anthem, AbbVie, Alnylam, AstraZeneca, Biogen, Genentech/Roche, GlaxoSmithSline, Harvard Pilgrim, Health Care Service Corporation, Health Partners, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, United Healthcare, HealthFirst, Pfizer, Boehringer-Ingelheim, uniQure, Evolve Pharmacy Solutions, and Humana, outside the submitted work. Fazioli reports grants from Arnold Ventures, California Healthcare Foundation, Harvard Pilgrim Healthcare, Kaiser Foundation Health Plan Inc., and The Donaghue Foundation, during the conduct of the study, and other support from Aetna, America's Health Insurance Plans, Anthem, AbbVie, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Cambia Health Services, CVS, Editas, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, Health Partners, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, United Healthcare, HealthFirst, Pfizer, Boehringer-lngelheim, uniQure, Evolve Phamacy Solutions, and Humana, outside the submitted work. Ollendorf reports grants from ICER, during the conduct of the study, along with other support from CEA Registry sponsors and personal fees from EMD Serono, Amgen, Analysis Group, Aspen Institute/University of Southern California, GalbraithWight, Cytokinetics, Sunovion, University of Colorado, Center for Global Development, and Neurocrine, outside the submitted work. Carlson reports grants from ICER, during the conduct of the study, and personal fees from Allergan, outside the submitted work. The inputs and model framework that were leveraged for this analysis were presented as part of the ICER assessment of TIMs for the treatment of moderate to severe ulcerative colitis.

Are Drugs Priced in Accordance With Value? A Comparison of Value-Based and Net Prices Using Institute for Clinical and Economic Review Reports.

OBJECTIVES: The Institute for Clinical and Economic Review (ICER) is an independent organization that reviews drugs and devices with a focus on emerging agents. As part of their evaluation, ICER estimates value-based prices (VBP) at $50 000 to $150 000 per quality-adjusted life-year (QALY) gained thresholds. We compared actual estimated net prices to ICER-estimated VBPs. METHODS: We reviewed ICER final evidence reports from November 2007 to October 2020. List prices were combined with average discounts obtained from SSR Health to estimate net prices. If a drug had been evaluated more than once for the same indication, only the more recent VBP was included. RESULTS: A total of 34 ICER reports provided unique VBPs for 102 drugs. The net price of 81% of drugs exceeded the $100 000 per QALY VBP and 71% exceeded the $150 000 per QALY VBP. The median change in net price needed to reach the $150 000 per QALY VBP was a 36% reduction. The median decrease in net price needed was highest for drugs targeting rare inherited disorders (n = 15; 62%) and lowest for cardiometabolic disorders (n = 6; 162% price increase). The reduction in net prices needed to reach ICER-estimated VBPs was higher for drugs evaluated for the first approved indication, rare diseases, less competitive markets, and if the drug approval occurred before the ICER report became available. CONCLUSION: Net prices are often above VBPs estimated by ICER. Although gaining awareness among decision makers, the long-term impact of ICER evaluations on pricing and access to new drugs continues to evolve.

Cost-effectiveness of topical glycopyrronium tosylate for the treatment of primary axillary hyperhidrosis.

AIMS: Primary axillary hyperhidrosis (PAHH) is a condition characterized by excessive sweating that negatively impacts health-related quality of life, with significant psychological and social impacts. Glycopyrronium tosylate (GT) is a topical anticholinergic approved in the United States for treatment of PAHH in patients 9 years of age and older. Our objective was to assess the cost-effectiveness of GT as first-line topical therapy compared to topical aluminum chloride from a United States commercial perspective. MATERIALS AND METHODS: A Markov model was developed consisting of four health states based on the Hyperhidrosis Disease Severity Scale (HDSS) over a time horizon of 5 years with discount rates of 3% for both costs and outcomes. Transitions between health states were driven by HDSS response, defined as an improvement of ≥2 points. Non-responders and those who discontinue could switch to later line treatments or no treatment. Health utility scores were based on HDSS scores, supported by published literature. RESULTS: Over 5 years, GT yielded 0.12 greater QALYs and 0.93 greater LYs with response compared to treatment with prescription aluminum chloride at an incremental cost of $10,584. Relative to prescription aluminum chloride, GT resulted in an incremental cost-effectiveness ratio (ICER) of $87,238 per QALY gained, $11,349 per LY with response. The ICER fell below $100,000 for 66% of probabilistic sensitivity analysis simulations and below $150,000 for 82% of simulations. LIMITATIONS: This analysis represents a simplified scenario of a hypothetical PAHH patient. Due to sparse data, assumptions were required for treatment patterns, efficacy, and persistence. CONCLUSION: Based on the analysis of incremental cost per QALY gained, GT may be cost-effective relative to prescription aluminum chloride at commonly accepted willingness to pay thresholds.

The Effectiveness and Value of Siponimod for Secondary Progressive Multiple Sclerosis.

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, Commonwealth Fund, California Health Care Foundation, National Institute for Health Care Management (NIHCM), New England States Consortium Systems Organization, Blue Cross Blue Shield of Massachusetts, Harvard Pilgrim Health Care, Kaiser Foundation Health Plan, and Partners HealthCare 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, Anthem, Allergan, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Cambia Health Services, CVS, Editas, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, Health Partners, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, and United Healthcare. Synnott and Pearson are employed by ICER. Bloudek and Carlson report a research agreement between the University of Washington and ICER; Bloudek reports consulting fees from Allergan, Seattle Genetics, Dermira, Sunovion, TerSera Therapeutics, Cook Regentech, and Mallinckrodt Pharmaceuticals; and Carlson reports personal fees from Bayer, unrelated to this report. Sharaf reports consulting fees from ICER.

Anticipated Impact of Generic Imatinib Market Entry on the Costs of Tyrosine Kinase Inhibitors.

BACKGROUND: Imatinib was the first BCR-ABL tyrosine kinase inhibitor (TKI) approved in the United States for the treatment of patients with chronic myelogenous leukemia and is currently the most prescribed TKI. The impending loss of patent exclusivity for imatinib has the potential to reduce costs for payers. OBJECTIVE: The primary objectives of this study were to estimate the economic impact of the loss of patent exclusivity for branded imatinib and to calculate the relative impact of requiring prior authorization (PA) for the use of generic imatinib before a branded TKI. The secondary objective was to evaluate the potential relative cost impact of using a preferred branded TKI in addition to the PA requirement for generic imatinib before a branded TKI. METHODS: A Microsoft Excel-based model was developed from the perspective of a US payer (commercial and Medicare) for a 2-year period. Data on utilization, patient out-of-pocket cost, and market share were obtained from an analysis of Truven Health MarketScan claims. It was assumed that the cost of generic imatinib would be 47.8% of the price of branded imatinib. It was assumed that 70% of patients receiving branded imatinib would shift to generic imatinib in year 1, and 95% would shift in year 2 after loss of patent exclusivity. Formulary management could be applied through PA requiring the use of generic imatinib before a branded TKI for patients newly prescribed TKI therapy. It was assumed that 74% of PA requests would be approved, and that the administrative cost of each would be $20. RESULTS: In a hypothetical 1 million member commercial plan, the loss of patent exclusivity for branded imatinib produced cost-savings of $6.8 million during 2 years, or 28.8% of the total pharmacy spending on the TKI class. The savings were even greater in a 1 million member Medicare plan, at $22.9 million (28.8%). Formulary management reduced incremental TKI spending by 1.1% and 2.2% for the commercial and Medicare plans, respectively. CONCLUSIONS: In the absence of formulary management beyond generic substitution, the loss of patent exclusivity for branded imatinib is expected to reduce total pharmacy spending on TKIs by nearly 33% during 2 years. Given the small number of newly treated patients, formulary management of the TKI class through restricted access to branded imatinib, with or without a preferred branded TKI, has limited potential for incremental cost-savings.

Real-world economic impact of onabotulinumtoxinA in patients with chronic migraine.

OBJECTIVE: To determine whether the utilization of healthcare resources is reduced after chronic migraine patients are treated for 6 months with onabotulinumtoxinA. BACKGROUND: OnabotulinumtoxinA is indicated for headache prophylaxis in patients with chronic migraine, but its effect on healthcare resource use is unknown. METHODS: We analyzed data from an open-label study of 230 chronic migraine patients refractory to ≥2 oral prophylactics who presented to a headache specialty clinic and who were treated with two cycles of onabotulinumtoxinA. Frequency and cost of migraine-related healthcare resource use, including visits to emergency departments, urgent care, or hospitalization, were compared for the 6 months before and after initial treatment. Costs were based on publicly available sources. RESULTS: Compared with the 6 months predating initial treatment, patients had 55% fewer emergency department visits (174 vs 385), 59% fewer urgent care visits (61 vs 150), and 57% fewer hospitalizations (19 vs 45) during the 6-month treatment period (P < .01 for all). Analysis of treatment-related costs yielded an average reduction of $1219.33/patient, off-setting 49.7% of the total estimated cost for 6 months of treatment with onabotulinumtoxinA. CONCLUSIONS: Although we are unable to distinguish onabotulinumtoxinA's treatment effect from other potential confounding variables, our analysis showed that severely afflicted, treatment-refractory patients with chronic migraine experienced a significant cost-offset through reduced migraine-related emergency department visits, urgent care visits, and hospitalizations in the 6 months following treatment initiation of onabotulinumtoxinA. Future analyses will assess the longer-term effect of onabotulinumtoxinA treatment and the potential contribution of regression to the mean.

Headache-related health resource utilisation in chronic and episodic migraine across six countries.

OBJECTIVE: To describe headache-related health resource usage in chronic and episodic migraine across six countries. METHODS: A web-based questionnaire eliciting data on several topics, including health resource usage, was administered to panellists with migraine from the USA, Canada, UK, Germany, France and Australia. Respondents were grouped into episodic and chronic migraine, based on reported headache phenotype and headache-day frequency. ORs were calculated, comparing usage in each country to that in the US, controlling for chronic versus episodic migraine and other factors. RESULTS: Relative to the USA, the odds of visiting a provider for headache during the preceding 3 months were significantly higher in all countries, except Germany. Respondents in France were more likely to report having a provider they typically visited for headache-related care. The odds of visiting the emergency department for headache were significantly lower in France, the UK and Germany, and hospitalisation for headache was significantly more frequent in Canada and Australia. Respondents from all countries, except Canada, were more likely to report currently using a prescription-acute treatment, and those from France were more likely to report trying more than three acute treatments. Preventive treatment use did not differ significantly. CONCLUSIONS: Headache-related resource usage differed significantly between the USA and other countries. US respondents were generally less likely to report recent provider visits and use of prescription-acute treatments. They were more likely to report emergency department visits than in European countries, but less likely to report hospitalisation than in Canada and Australia.

The cost-effectiveness of onabotulinumtoxinA for the prophylaxis of headache in adults with chronic migraine in the UK.

BACKGROUND: Although chronic migraine is associated with substantial disability and costs, few treatments have been shown to be effective. OnabotulinumtoxinA (Botox, Allergan Inc., Irvine, CA) is the first treatment to be licensed in the UK for the prophylaxis of headaches in adults with chronic migraine. This study aims to evaluate the cost-effectiveness of onabotulinumtoxinA in this indication in the UK. METHODS: A state-transition (Markov) model was developed comparing onabotulinumtoxinA to placebo. Efficacy data and utility values were taken from the pooled Phase III REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical trials program (n = 1384). Estimates of resource utilisation were taken from the International Burden of Migraine Study (IBMS), and stopping rules were informed by published medical guidelines and clinical data. This study estimated 2-year discounted costs and quality-adjusted life years (QALYs) from the UK National Health Service perspective. RESULTS: At 2 years, treatment with onabotulinumtoxinA was associated with an increase in costs of £1367 and an increase in QALYs of 0.1 compared to placebo, resulting in an incremental cost-effectiveness ratio (ICER) of £15,028. Treatment with onabotulinumtoxinA reduced headache days by an estimated 38 days per year at a cost of £18 per headache day avoided. Sensitivity analysis showed that utility values had the greatest influence on model results. The ICER remained cost-effective at a willingness to pay threshold of £20,000-£30,000/QALY in the majority of scenario analyses as well as in probabilistic sensitivity analysis, where onabotulinumtoxinA was cost-effective on 96% of occasions at a threshold of £20,000/QALY and 98% of occasions at £30,000/QALY. CONCLUSION: OnabotulinumtoxinA has been shown to reduce the frequency of headaches in patients with chronic migraine and can be considered a cost-effective use of resources in the UK National Health Service. The uncertainties in the model relate to the extrapolation of clinical data beyond the 56-week trial.

Adherence with migraine prophylaxis in clinical practice.

OBJECTIVE: To characterize adherence with antidepressants, antiepileptic drugs, and beta blockers as prophylaxis against migraine in typical clinical practice. METHODS: Using a large US health insurance claims database (calendar years 2003 to 2005), we identified all patients with migraine who began prophylaxis with selected antidepressants, antiepileptic drugs, or beta blockers ("study agents"). Patients not continuously enrolled for 6 months prior to start of prophylaxis ("pretreatment") and for 6 months subsequently ("follow-up") were excluded. Treatment cohorts were constituted based on the type of prophylaxis received. Adherence with migraine prophylaxis was examined by type of agent received using medication possession ratios (MPRs), defined as total days with medication divided by total follow-up days. MPR < 0.80 was considered indicative of nonadherence. RESULTS: A total of 4,634 patients met all entry criteria and received antidepressants (n = 1,803), antiepileptics (n = 1,896), or beta blockers (n = 935) on their index date. Over the next 6 months, the mean (SD) number of prescriptions for study agents was 2.7 (1.9) for antidepressants, 2.9 (2.0) for antiepileptics, and 2.8 (2.0) for beta blockers, totaling 91.0 (71.4), 98.7 (75.6), and 96.7 (73.0) therapy-days, respectively. Mean MPR at 6 months was 0.48 for antidepressants, 0.51 for antiepileptics, and 0.51 for beta blockers. By the end of the follow-up, 73.4%, 70.2%, and 67.6% of patients who initiated migraine prophylaxis with antidepressants, antiepileptics, and beta blockers, respectively, were designated nonadherent (ie, MPR < 0.80). CONCLUSION: Our findings suggest that many patients who begin migraine prophylaxis with antidepressants, antiepileptics, or beta blockers are no longer taking these medications at 6 months.