Social Impact of Prophylactic Migraine Treatments in Germany: A State-Transition and Open Cohort Approach.

OBJECTIVES: Migraine is a highly prevalent neurological disorder. The most characteristic symptom of migraine is moderate to severe recurrent headache along with other neurological symptoms. In this study, we modeled the potential reduction in migraine days and corresponding avoided productivity losses if erenumab was prescribed to the patient population indicated for prophylactic migraine treatment (≥ 4 monthly migraine days [MMDs]) in Germany from 2020 to the end of 2027. METHODS: We simulated the incremental benefits of erenumab against the standard of care. Response rates, transition probabilities, discontinuation rates, and productivity estimates were derived from the erenumab clinical trial program. Patients had a probability of residing in 1 of 7 states, given the MMDs in addition to the probability of death. Based on accrued MMDs in every cycle, days of absenteeism and presenteeism for paid and unpaid work were derived. Paid work was monetized according to gross value added using the human capital approach, whereas unpaid work was valuated according to the proxy good method. In addition, downstream macroeconomic effects were captured using value-added multipliers. Direct medical costs were concomitantly calculated. RESULTS: Our results show that prescribing erenumab for the indicated population in Germany could lead to a reduction of 166 million migraine days annually and reduce productivity losses in the range of €27 billion. This includes €13.1 billion from direct productivity and €13.5 billion from economic value chain effects. CONCLUSIONS: This study highlights the macroeconomic effects of a systematic introduction of novel inhibitors of the calcitonin gene-related peptide pathway for migraine in Germany.

Cost-Effectiveness of Erenumab for the Preventive Treatment of Migraine in Patients with Prior Treatment Failures in Sweden.

BACKGROUND: Migraine is a common neurological disease that disproportionately affects females and has a peak incidence during productive years, resulting in significant burden. OBJECTIVE: The aim of the study was to determine the cost effectiveness of erenumab for the preventive treatment of migraine. METHODS: A hybrid decision-tree plus Markov model was developed to evaluate the cost effectiveness of erenumab as a migraine treatment compared with best supportive care only for patients experiencing at least 4 monthly migraine days for whom at least two prior preventive treatments had failed. Clinical efficacy data were based on results from four randomized controlled trials of erenumab against placebo. The primary outcomes were costs, migraine days, and quality-adjusted life-years (QALYs). An incremental cost-effectiveness ratio (ICER) was estimated as the cost per QALY gained. The cost per migraine day avoided was also estimated, as were disaggregated direct and indirect costs. The analysis was conducted from Swedish societal and healthcare system perspectives based on total migraine, chronic migraine and episodic migraine populations, using a discount rate of 3% applied to both costs and health benefits and using year 2019 values. RESULTS: In the base-case deterministic analyses, erenumab treatment resulted in ICERs of Swedish krona (SEK) 34,696 (€3310) and SEK301,565 (€28,769) per QALY gained in the total migraine and episodic migraine populations, respectively. Erenumab was dominant in the chronic migraine population. In the total migraine population, the use of erenumab resulted in a net benefit to society of SEK81,739 (€7773) per patient, assuming a willingness-to-pay threshold of SEK300,000 (€28,528) per QALY. CONCLUSIONS: Our analysis suggests that erenumab is a cost-effective treatment for migraine with a willingness-to-pay threshold of SEK300,000 per QALY.

Economic evaluations in migraine: systematic literature review and a novel approach.

Background: For novel migraine therapies, economic evaluations will be required to understand the trade-offs between additional health benefit and additional cost. The purpose of this study was to conduct a systematic literature review (SLR) to identify previous economic evaluations in migraine from the United Kingdom or Irish perspective to critically appraise these evaluations and to propose, if necessary, a novel modelling approach that can be used for future economic evaluations of migraine therapies.Methods: An SLR was conducted to identify previous economic evaluations of preventive migraine treatments. Key opinion leaders were consulted to determine the criteria for a robust migraine economic evaluation. Economic evaluations identified in the SLR were appraised against these criteria, and a novel cost-effectiveness model structure was then proposed.Results: Eight records reporting on published economic evaluations were identified and critically appraised for general quality. Expert consultation provided 6 recommendations on the ideal model structure for migraine that is both clinically and economically meaningful. A decision-tree plus Markov structure was then developed as a cost-effectiveness model for migraine therapies where each health state is associated with a patient distribution across monthly migraine day (MMD) frequencies.Conclusions: Future migraine economic evaluations should allow for assessments across the full spectrum of migraine, a response-based stopping rule, and the estimation of benefits and resource costs based on MMD frequency. The approach proposed in this paper captures all of the desired elements for an economic evaluation of migraine therapy and is suitable to assess new migraine therapies.

Potential impact of vaccination against Neisseria meningitidis on Neisseria gonorrhoeae in the United States: results from a decision-analysis model.

Components in 4CMenB vaccine against Neisseria meningitidis serogroup B have shown to potentially cross-react with Neisseria gonorrhoeae. We modeled the theoretical impact of a US 4CMenB vaccination program on gonorrhea outcomes. A decision-analysis model was populated using published healthcare utilization and cost data. A two-dose adolescent vaccination campaign was assumed, with protective immunity starting at age 15 years and a base-case efficacy against gonorrhea of 20%. The 20%-efficacy level is an assumption since no clinical data have yet quantified the efficacy of 4CMenB against Neisseria gonorrhoea. Key outcome measures were reductions in gonorrhea and HIV infections, reduction in quality-adjusted life-years (QALYs) lost, and the economically justifiable price assuming a willingness-to-pay threshold of $75,000 per QALY gained. Adolescent vaccination with 4CMenB would prevent 83,167 (95% credible interval [CrI], 44,600-134,600) gonorrhea infections and decrease the number of HIV infections by 55 (95% CrI, 2-129) per vaccinated birth cohort in the USA. Excluding vaccination costs, direct medical costs for gonorrhea would reduce by $28.7 million (95% CrI, $6.8-$70.0 million), and income and productivity losses would reduce by $40.0 million (95% CrI, $8.2-$91.7 million). Approximately 83% of the reduction in lost productivity is generated by avoiding HIV infections. At a cost of $75,000 per QALY gained, and incremental to the vaccine's effect on meningococcal disease, a price of $26.10 (95% CrI, $9.10-$57.20) per dose, incremental to the price of the meningococcal vaccine, would be justified from the societal perspective. At this price, the net cost per infection averted would be $1,677 (95% CrI, $404-$2,564). Even if the cross-immunity of 4CMenB vaccine and gonorrhea is only 20%, the reduction in gonorrhea infections and associated costs would be substantial.

Drug versus vaccine investment: a modelled comparison of economic incentives.

BACKGROUND: Investment by manufacturers in research and development of vaccines is relatively low compared with that of pharmaceuticals. If current evaluation technologies favour drugs over vaccines, then the vaccines market becomes relatively less attractive to manufacturers. METHODS: We developed a mathematical model simulating the decision-making process of regulators and payers, in order to understand manufacturers' economic incentives to invest in vaccines rather than curative treatments. We analysed the objectives and strategies of manufacturers and payers when considering investment in technologies to combat a disease that affects children, and the interactions between them. RESULTS: The model confirmed that, for rare diseases, the economically justifiable prices of vaccines could be substantially lower than drug prices, and that, for diseases spread across multiple cohorts, the revenues derived from vaccinating one cohort per year (routine vaccination) could be substantially lower than those generated by treating sick individuals. CONCLUSIONS: Manufacturers may see higher incentives to invest in curative treatments rather than in routine vaccines. To encourage investment in vaccines, health authorities could potentially revise their incentive schemes by: (1) committing to vaccinate all susceptible cohorts in the first year (catch-up campaign); (2) choosing a long-term horizon for health technology evaluation; (3) committing higher budgets for vaccines than for treatments; and (4) taking into account all intangible values derived from vaccines.

Association between respiratory syncytial virus hospitalizations in infants and respiratory sequelae: systematic review and meta-analysis.

BACKGROUND: The association between hospitalization for respiratory syncytial virus (RSV) infection in infancy and asthma/wheezing in later life has long been studied. However, no published studies have combined systematic review and meta-analysis of existing evidence. PURPOSE: To quantify the link between RSV hospitalization in early life and subsequent diagnosis of asthma. METHOD: A systematic search was conducted using MEDLINE and EMBASE databases. Studies were selected for meta-analysis if they assessed the association between RSV-confirmed hospitalization for up to 3 years of age and asthma/wheezing later in life. Potential sources of heterogeneity were identified by stratified analysis. RESULTS: Twenty articles representing 15 unique studies of 82,008 unique individuals (including 1533 with RSV-confirmed hospitalization) were selected for meta-analysis. Children who had RSV disease in early life had a higher incidence of asthma/wheezing in later life (odds ratio: 3.84; 95% confidence interval: 3.23-4.58). There was moderate heterogeneity between studies (I² = 45%). The association was found to decrease with age at follow-up, consistent with the findings of longitudinal studies. When age at follow-up was considered, heterogeneity was low (residual I² = 17%). LIMITATIONS: Study quality was generally poor because randomization to hospitalization for RSV infection was not possible, appropriate blinding was rare and adjustment for confounding variables was not always appropriate. CONCLUSIONS: The meta-analysis suggests an association between infant RSV hospitalization and respiratory morbidity that decreases with age. If the association is causal, the development of an effective vaccine against RSV could decrease the burden of asthma.

The efficacy of bisphosphonates in the prevention of vertebral, hip, and nonvertebral-nonhip fractures in osteoporosis: a network meta-analysis.

OBJECTIVE: To evaluate the efficacy of available bisphosphonate therapies regarding the prevention of vertebral, hip, and nonvertebral-nonhip fractures in postmenopausal women with osteoporosis. METHODS: Eight randomized placebo controlled trials investigating the effects of zoledronic acid (1 study), alendronate (3), ibandronate (1), risedronate (2), and etidronate (1) in terms of fractures with a follow-up of 3 years (or 2 years if used for registration purposes) were identified with a systematic literature search. The endpoints of interest were morphometric vertebral fractures, hip fractures, and nonvertebral-nonhip fractures. Results of all trials were analyzed simultaneously with a Bayesian network meta-analysis by which the relative treatment effect of 1 intervention to another can be obtained in the absence of head-to-head evidence. Given the estimated treatment effects and their uncertainty, the Bayesian approach allowed for calculations of the probability of which bisphosphonate is best in terms of overall fracture reductions by weighting the impact of each by type of fracture on costs, quality of life, and incidence. RESULTS: There is a 79% probability that zoledronic acid shows the greatest reduction in vertebral fractures of all bisphophonates compared. Zoledronic acid showed a relative risk (RR) of 0.30 (95% Credible Interval 0.23-0.37) relative to placebo, an RR of 0.55 (0.41-0.76) relative to alendronate, an RR of 0.50 (0.36-0.70) relative to risedronate, and an RR of 0.58 (0.37-0.92) relative to ibandronate. Regarding hip fractures, there is a 47% probability that zoledronic acid shows the greatest risk reduction, followed by alendronate (36%) and risedronate (11%). RRs of zoledronic acid relative to placebo, alendronate, and risedronate were 0.58 (0.41-0.82), 0.95 (0.54-1.68), and 0.73 (0.37-1.44), respectively. Risedronate showed the greatest reduction in nonvertebral-nonhip fractures, followed by zoledronic acid. The RR of zoledronic acid relative to risedronate was 1.28 (0.87-1.90). Overall, there was a 94% probability that zoledronic acid showed the greatest reduction in any fracture. Weighting the impact of the different type of fractures by incidence, cost, or quality of life showed similar results. CONCLUSION: Of the available bisphosphonates for osteoporosis, zoledronic acid has the highest probability of offering the best overall fracture protection.

Prevention of vertebral fractures in osteoporosis: mixed treatment comparison of bisphosphonate therapies.

OBJECTIVE: The objective was to compare the efficacy of bisphosphonates regarding the prevention of vertebral fractures in postmenopausal women with osteoporosis. METHODS: Seven randomized placebo controlled trials investigating the effects of zoledronic acid (one study), alendronate (three studies), ibandronate (one study), and risedronate (two studies) in terms of fractures with a follow-up of 3 years were identified with a systematic literature search. The endpoint of interest was vertebral fractures. Results of all trials were analyzed simultaneously with a Bayesian mixed treatment comparison (MTC). With MTC the relative treatment effect of one intervention to another can be obtained in the absence of head-to-head evidence. MTC can be considered a valid method when included studies are comparable regarding effect modifying baseline patient and study characteristics. RESULTS: There is a 98% probability that zoledronic acid shows the greatest reduction in vertebral fractures of all four bisphophonates compared. Zoledronic acid showed an OR of 0.28 (95% Credible Interval 0.22; 0.35) relative to placebo, an OR of 0.57 (0.36; 0.92) relative to ibandronate, an OR of 0.54 (0.39; 0.75) relative to alendronate, and an OR of 0.49 (0.34; 0.69) relative to risedronate. Alendronate, ibandronate, and risedronate showed comparable vertebral fracture reductions. Indirect comparisons using a conservative random effects model supported these findings. CONCLUSION: An indirect comparison of findings from placebo controlled randomized studies indicates that zoledronic acid provides a greater vertebral fracture risk reduction in postmenopausal women with osteoporosis than ibandronate, alendronate, or risedronate.

Clinical relevance of health-related quality of life outcomes with darifenacin.

OBJECTIVE: To determine the clinical relevance of changes in health-related quality of life (HRQoL) in patients with overactive bladder (OAB) treated with darifenacin. PATIENTS AND METHODS: Data were pooled from three randomized, placebo-controlled, parallel-group, fixed-dose, 12-week studies. After 2-week washout, treatment-free or placebo run-in periods, patients with OAB (n = 1059; 85% women; age 19-88 years) were randomized to 12 weeks' treatment with darifenacin controlled-release 7.5 mg (n = 337) or 15 mg once daily (n = 334) or placebo (n = 388). The King's Health Questionnaire (KHQ) was used to assess HRQoL at baseline and Week 12. The clinical significance of changes in KHQ domain scores was assessed using the concept of minimum important difference (MID), using two different methods. RESULTS: Darifenacin treatment was associated with significantly greater improvements than placebo in six primary KHQ domain scores known to be of importance to patients with OAB. In addition, a significantly greater proportion of darifenacin-treated patients met or exceeded reference MID vs placebo in these domains (Incontinence Impact, Severity Measures, Role Limitations, Social Limitations, Emotions and Physical Limitations; P = 0.01). In darifenacin-treated patients, there were significant correlations between the reductions in incontinence episodes per week and improvements in KHQ scores (P < 0.001). The strongest correlations were in the Incontinence Impact, Social Limitations, Role Limitations, Severity Measures and Emotions domains. CONCLUSIONS: Darifenacin treatment was associated with significant, clinically relevant improvements in HRQoL in patients with OAB, shown using the concept of MID to interpret change in KHQ scores.

The benefit of pimecrolimus (Elidel, SDZ ASM 981) on parents' quality of life in the treatment of pediatric atopic dermatitis.

OBJECTIVE: Two 26-week US clinical trials of identical design were conducted to evaluate the efficacy and safety of pimecrolimus (Elidel, SDZ ASM 981) cream 1% in pediatric atopic dermatitis (AD). A secondary aim of both trials, and the focus of this article, was to evaluate the quality-of-life (QoL) impact of pimecrolimus compared with its vehicle. METHODS: A 6-week randomized, double-blind treatment phase was followed by a 20-week open-label phase during which all patients received pimecrolimus (403 patients 2 to 17 years old with mild to moderate AD; 267 randomized to pimecrolimus and 136 to vehicle). QoL analyses were conducted on the intention-to-treat data and included patients 8 years old or younger. QoL was evaluated with the Parent's Index of Quality of Life in Atopic Dermatitis (PIQoL-AD) at baseline, 6 weeks, and 6 months. The PIQoL-AD is a 28-item measure completed by the parents of children with AD (0 to 8 years old). RESULTS: PIQoL-AD scores were available for 241 cases at baseline (158 pimecrolimus, 83 vehicle), 193 at 6 weeks (132 pimecrolimus, 61 vehicle), and 161 at 6 months (113 pimecrolimus, 48 vehicle). Improvement in parents' QoL was seen for both groups between baseline and 6 weeks and 6 months. Analysis of covariance on PIQoL-AD scores at 6 weeks showed statistically significant superiority of pimecrolimus compared with vehicle. After all patients were switched to receive pimecrolimus at week 6, mean PIQoL-AD scores were the same across both groups at 6 months. Positive but low levels of association were observed between changes in PIQoL-AD scores and changes in severity of AD (Investigator's Global Assessment and parent-perceived severity of pruritus). CONCLUSION: The results showed that pimecrolimus had a beneficial effect on parents' QoL in pediatric AD.