Axicabtagene ciloleucel compared to standard of care in Swedish patients with large B-cell lymphoma: a cost-effectiveness analysis of the ZUMA-7 trial.

AIM: Our study aimed to evaluate the cost-effectiveness of the chimeric antigen receptor (CAR) T-cell therapy, axicabtagene ciloleucel (axi-cel), compared to standard of care (SOC) in Sweden for second-line (2L) treatment of adult transplant-intended diffuse large B-cell lymphoma (DLBCL) patients who relapse within 12 months from completion of, or are refractory to (early r/r), first-line (1L) chemoimmunotherapy. METHODS: Cost-effectiveness was assessed using a three-state partitioned survival model. Mixture cure models were used to extrapolate time-to-event data from the ZUMA-7 trial (NCT03391466) beyond the observational period. Sensitivity and scenario analyses were performed to test the robustness of the base case results, including an analysis that assumed no switching to off-protocol CAR T-cell therapy in subsequent lines in the SOC arm. RESULTS: The model estimated an incremental cost-effectiveness ratio (ICER) of SEK 534,704 (EUR 50,303) per quality-adjusted life year (QALY) gained over a lifetime horizon of 50 years, with an incremental cost of SEK 812,944 (EUR 76,479) and incremental QALY of 1.52 for axi-cel compared with SOC. The probabilistic sensitivity analysis showed that axi-cel was cost-effective in 73% of the simulations when assuming a willingness-to-pay threshold of SEK 1,000,000 (EUR 94,077) per QALY. The ICER was SEK 694,351 (EUR 65,313) in the scenario analysis where the costs and effects of treatment switching were not included. CONCLUSION: 2L treatment with axi-cel in transplant-intended DLBCL patients with early r/r after completing 1L chemoimmunotherapy was cost-effective compared to SOC in a Swedish setting. Administering axi-cel in 2L is cost-effective as it enhances the possibility of curing more patients, resulting in not just a survival advantage, but also a reduction in the burden on quality of life and cost of subsequent therapy. This will be advantageous to both patients and society.

The Cost-Effectiveness of Anti-IL17 Biologic Therapies for Moderate-to-Severe Plaque Psoriasis Treatment in Italy and Germany: A Sequential Treatment Analysis.

Objective: The objective of this study was to optimise the cost-effectiveness of different anti-IL17 treatment sequences used in the treatment of moderate-to-severe plaque psoriasis in Italy and Germany over a five-year time horizon. Methods: We adjusted a previously published treatment sequence model for biologic drugs used in psoriasis treatment to an Italian and German setting, respectively. The model included all anti-IL17 biologics currently available in the treatment of moderate-to-severe plaque psoriasis in the markets of scope (secukinumab, ixekizumab, brodalumab and bimekizumab). Real-world discontinuation rates were used to model switches between the four anti-IL17 biologics included in the study. The treatment costs were based on label dosing recommendations for each drug, including induction and maintenance therapy, and the manufacturer prices of each drug in Italy and Germany, respectively. We used long-term Psoriasis Area and Severity Index 100 (PASI100) measures to inform the model on the efficacy for each treatment. The cost-effectiveness in the analysis was evaluated based on the cost per PASI100-responder. Results: We found that the most cost-effective treatment sequence was achieved by using brodalumab as first-line treatment, bimekizumab as second-line treatment, ixekizumab as third-line treatment and secukinumab as fourth-line treatment in both Italy and Germany, which resulted in a total cost per responder of €128,200 and €138,212, respectively, over a five-year period. Several scenario analyses were also conducted and ensured that the results were robust to changes in key input parameters. Conclusion: Our study showed that using brodalumab as a first-line therapy to treat moderate-to-severe psoriasis in both Italy and Germany leads to the most cost-effective treatment sequence, when compared to all possible combinations of anti-IL17s over a five-year time horizon. In addition, we found that treatment discontinuation and switching are important factors when assessing the cost-effectiveness of biologic therapies.

Real-world evidence on efmoroctocog alfa in patients with haemophilia A: A systematic literature review of treatment experience in Europe.

INTRODUCTION: The real-world effectiveness of the efmoroctocog alfa (recombinant FVIII Fc fusion protein, a rFVIIIFc) has been investigated in numerous studies, however, currently, there exists no comprehensive collection of the existing real-world evidence (RWE) on the performance of prophylactic use of rFVIIIFc. AIM: The aims of this systematic literature study were to identify, review, evaluate and collate the RWE of prophylactic rFVIIIFc for patients with haemophilia A reported in Europe. METHODS: We searched Medline and Embase from 2014 to February 2022 to identify publications reporting the effectiveness of rFVIIIFc in patients with haemophilia A. The outcomes of interest were annualised bleeding rates (ABR, AjBR, AsBR), injection frequency, factor consumption, adherence, development of inhibitors and quality-of-life measures. RESULTS: 46 eligible publications (eight full-text articles) were included. rFVIIIFc showed a low ABR in patients with haemophilia A. Studies assessing treatment switching from a standard half-life (SHL) treatment to rFVIIIFc found that the ABR and consumption were reduced in most patients. Studies assessing rFVIIIFc effectiveness reported a median ABR between 0.0 and 2.0 with median injections per week ranging between 1.8 and 2.4 and median doses between 60 and 105 IU/kg/week. Of the studies assessing inhibitor development, only one study reported an incidence of a low titre inhibitor, and no patients developed clinically significant inhibitors. CONCLUSION: rFVIIIFc prophylaxis treatment results in a low ABR across studies in patients with haemophilia A in a European real-world setting, which correlates with findings from clinical trials assessing the efficacy of rFVIIIFc in patients with haemophilia A.

Cost per responder of biologic drugs used in the treatment of moderate-to-severe plaque psoriasis in France and Germany.

OBJECTIVE: The treatment of moderate-to-severe plaque psoriasis has seen significant improvements in recent years with the advent of biologic drugs. The aim of this study was to assess the cost-effectiveness of anti-IL17 drugs and other biologic therapies used to treat moderate-to-severe plaque psoriasis in France and Germany over a one-year time horizon. METHODS: We developed a cost per responder model for biologic drugs used in psoriasis treatment. The model included anti-IL17s (brodalumab, secukinumab, ixekizumab and bimekizumab), anti-TNFs (adalimumab, etanercept, certolizumab and infliximab), an anti-IL12/23 (ustekinumab), and anti-IL23s (risankizumab, guselkumab and tildrakizumab). Efficacy estimates were collected through a systematic literature review of network meta-analyses on long-term Psoriasis Area and Severity Index (PASI) measures. Dose recommendations and country-specific prices were used to calculate drug costs. Biosimilar drug prices were used when available as a substitute for the originator drugs. RESULTS: After one year, brodalumab had the lowest cost per PASI100-responder in both France (€20,220) and Germany (€26,807) across all available biologic treatments. Among the anti-IL17s, brodalumab had a 23% lower cost per PASI100-responder vs. the nearest comparator in France (bimekizumab, €26,369), and 30% lower vs. nearest comparator in Germany (ixekizumab, €38,027). Brodalumab also had the lowest cost per PASI75- and PASI90-responder among the anti-IL17s in both France and Germany after one year. Adalimumab had the lowest cost per PASI100-responder among the anti-TNFs in both France (€23,418) and Germany (€38,264). Among the anti-IL-23s, risankizumab had the lowest cost per PASI100-responder in both France (€20,969) and Germany (€26,994). CONCLUSION: Driven by its lower costs and high response rates, brodalumab was the most cost-effective treatment option for moderate-to-severe plaque psoriasis over a one-year time-horizon within the anti-IL17 class and when compared to all other biologics in France and Germany.

Economic benefits of remimazolam compared to midazolam and propofol for procedural sedation in colonoscopies and bronchoscopies.

BACKGROUND: Sedation is common practice in endoscopic procedures to suppress a patient's level of consciousness while maintaining the cardio-respiratory function. Midazolam and propofol are the sedatives most frequently used for procedural sedation at hospitals in Scandinavia. Remimazolam is a new ultra-short-acting benzodiazepine sedative and the present analysis aimed at estimating the economic benefits of introducing remimazolam for procedural sedation in colonoscopies and bronchoscopies in hospitals in Scandinavia. METHOD: We developed a cost model applying a micro-costing approach that comprised the cost components that are affected by differences in the efficacy of remimazolam, midazolam, and propofol, and the model estimated the cost per successful colonoscopy and bronchoscopy when using remimazolam, midazolam or propofol as sedation. A micro-costing approach was applied, and the model consisted of six stages representing the journey for patients undergoing endoscopies and was informed primarily by data from clinical studies on remimazolam. RESULTS: We found a total cost of DKK 1200 per successful colonoscopy procedure when using remimazolam, a total cost of DKK 1320 when using midazolam, and a total cost of DKK 1255 when using propofol. Hence, the incremental saving per successful colonoscopy procedure of using remimazolam was estimated to be DKK 120 compared to midazolam and DKK 55 compared to propofol. The total cost per successful bronchoscopy procedure when using remimazolam was DKK 1353 and DKK 1724 for midazolam, resulting in an incremental saving per bronchoscopy of DKK 372 when using remimazolam. Performed sensitivity analyses identified the time in recovery as the largest contributor to uncertainty in the analyses of remimazolam compared to midazolam in colonoscopies and bronchoscopies. In the comparison of remimazolam and propofol in colonoscopies, procedure time was the largest contributor to uncertainty. CONCLUSION: We found that procedural sedation with remimazolam was associated with economically meaningful savings compared to procedural sedation with midazolam and propofol in colonoscopies and to midazolam in bronchoscopies.

A novel, fixed-dose calcipotriol and betamethasone dipropionate cream for the topical treatment of plaque psoriasis: Direct and indirect evidence from phase 3 trials discussed at the 30th EADV Congress 2021.

Four posters about the novel, fixed-dose calcipotriol and betamethasone dipropionate cream (CAL/BDP cream) based on Poly-Aphron Dispersion (PAD) Technology were presented at the 30th European Academy of Dermatology and Venereology (EADV) Congress 2021 and are summarized here. CAL/BDP cream was compared in two randomized, phase 3 trials to vehicle and active comparator (CAL/BDP gel/topical suspension [TS]) in adults with plaque psoriasis (NCT03802344 and NCT03308799). Pooled data from both trials demonstrated significant greater efficacy in favour of CAL/BDP cream for all efficacy endpoints, including PGA treatment success, mPASI, and mPASI75 compared to CAL/BDP gel/TS. CAL/BDP cream was well tolerated and comparable to CAL/BDP gel/TS with no adverse drug reactions with a frequency >1%. In the NCT03308799 study, CAL/BDP cream demonstrated a substantial improvement in the proportion of participants achieving a minimum 4-point improvement on the peak pruritus numeric rating scale (NRS) score compared with vehicle at Weeks 1, 4 and 8. CAL/BDP cream also improved quality of life (QoL), as assessed through the Dermatology Life Quality Index (DLQI), and the EQ-VAS at Week 8 compared with active comparator. Treatment convenience of CAL/BDP cream, as measured by the Psoriasis Treatment Convenience Scale, was superior to CAL/BDP gel/TS at all studied timepoints, including questions addressing formulation's greasiness and overall treatment satisfaction. Finally, an indirect comparison following the Bucher's method of adjusted indirect comparison and the difference-in-differences method was conducted to compare CAL/BDP cream and CAL/BDP foam, as both therapies have been compared to CAL/BDP gel/TS. Indirect evidence showed that treatment with CAL/BDP cream was associated with a trend for greater QoL improvement than CAL/BDP foam when DLQI improvement was assessed at the recommended treatment duration of 8 weeks for CAL/BDP cream and 4 weeks for CAL/BDP foam. CAL/BDP cream was statistically superior versus CAL/BDP foam in four out of five treatment satisfaction domains.

Administration and patient-incurred costs associated with opioid agonist treatment in Norway.

OBJECTIVES: Opioid use disorder is associated with high rates of mortality and has become an escalating global health issue. Opioid agonist treatment (OAT) with oral methadone or daily sublingual buprenorphine hydrochloride, either administered separately or in combination with naloxone hydrochloride (SL-BPN, SL-BPN/NX), is supervised by a healthcare professional experienced in treating opioid use disorder to ensure proper dosing and prevent misuse. For that reason, there may be substantial direct and indirect costs associated with OAT. Recently, weekly and monthly subcutaneous depot formulations of buprenorphine (SC-BPN) have been approved. This study aimed to estimate management and patient-incurred costs associated with the most commonly used OATs compared to the cost of weekly and monthly SC-BPN. METHODS: We conducted a cost-minimisation analysis comparing the monthly costs of OAT treatment with oral formulations, i.e. oral methadone, SL-BPN, SL-BPN/NX and SC-BPN. The analysis assessed treatment acquisition costs and costs associated with management, supervision and administration of therapy, patients' transportation costs and the indirect costs associated with patients' time-use. The model was set up to reflect the Norwegian medically assisted rehabilitation system and considered the costs of a stable maintenance OAT regimen given continuously to patients already initiated and titrated on the therapy. RESULTS: OAT management with monthly formulation of SC-BPN was associated with a reduction in monthly costs of €605, €586, and €411 per month compared to SL-BPN, SL-BPN/NX and oral methadone, respectively. Similar results were estimated when comparing to the weekly formulation of SC-BPN. CONCLUSION: The analysis showed that the monthly formulation of SC-BPN was the cost-minimising alternative, followed by the weekly formulation, when considering all cost components.

Efficacy, quality of life, and treatment satisfaction: an indirect comparison of calcipotriol/betamethasone dipropionate cream versus foam for treatment of psoriasis.

OBJECTIVE: To assess how the use of calcipotriol and betamethasone dipropionate (Cal/BDP) cream impacted efficacy, patients' quality of life (QoL), and treatment satisfaction versus Cal/BDP foam. METHODS: Data from clinical trials of Cal/BDP cream and foam were analyzed, by applying the common anchor Cal/BDP gel. Efficacy was assessed by Physician Global Assessment (PGA) treatment success and ≥75% reduction in Psoriasis Area and Severity Index (PASI75 response); QoL by Dermatology Life Quality Index (DLQI); treatment satisfaction by Psoriasis Treatment Convenience Scale (PTCS) and Topical Product Usability Questionnaire (TPUQ). RESULTS: Treatment with Cal/BDP cream was on par with foam on PGA treatment success (risk ratio (RR) for Cal/BDP cream versus foam: 0.80; 95%CI: 0.56, 1.14; p = .21) and PASI75 response (RR for Cal/BDP cream vs. foam: 0.85; 95%CI: 0.64, 1.13; p = .27) when assessed at the treatment duration of 8 weeks for Cal/BDP cream and 4 weeks for Cal/BDP foam. Treatment with Cal/BDP cream was associated with significantly greater treatment satisfaction versus foam on the domains: overall treatment satisfaction (p = .01), "ease of application" (p < .001), "lack of greasiness" (p < .001), "moisturizing effect" (p = .01), and almost significantly greater improvement on the domain "easily incorporated into daily routine" (p = .07). Furthermore, there was a trend for greater DLQI improvement with cream versus foam when assessed at recommended treatment duration [mean difference (MD) for Cal/BDP cream vs. foam: -1.00; 95%CI: -2.20, 0.20; p = .10]. CONCLUSIONS: Indirect comparison analyses showed that Cal/BDP cream significantly improves treatment satisfaction and tends to improve QoL versus foam. Cal/BDP cream is on par with foam on efficacy.

Modeling the optimal sequence of biologic therapies in plaque psoriasis in Spain.

AIM: The purpose of this manuscript was to illustrate the impact of the place in the treatment sequence on the cost and cost-effectiveness of different biologics for patients with moderate-to-severe plaque psoriasis. MATERIALS AND METHODS: We developed a treatment sequence model and focused on seven different biological treatment options and 840 combinations of treatment sequences. The model converted cost of treatment to a cost per responder by dividing treatment cost by expected number of patients achieving PASI100 after 52 weeks of treatment. We used Spanish ex-factory price levels, dosing recommendations and real-world data on drug survival to calculate the treatment costs. RESULTS: The most cost-effective treatment sequence was brodalumab-risankizumab-guselkumab-ixekizumab, with a cost per responder of €139,281 during the first five years of treatment. In comparison, if brodalumab was not recommended as first-line therapy, total costs would increase by 7.4% to €149,616. If brodalumab was not recommended as any of the first four lines of treatment, total costs would increase by 13.1% to €157,527 relative to the most cost-effective treatment sequence. CONCLUSIONS: A sequential therapy model may improve efficiency in the treatment of psoriasis. According to our results, brodalumab as the first-line therapy in Spain leads to the most cost-effective treatment sequence.

Optimising immune tolerance induction strategies in the management of haemophilia patients with inhibitors: a cost-minimisation analysis.

BACKGROUND: The objective of this study was to model the economic impact of optimal dosing of immune tolerance induction (ITI) in haemophilia patients with inhibitors. Evidence based research suggests that, in the right patient population characterised by ITI risk status, the use of high-dose ITI regimen in 'poor risk' patients, and the low-dose regimen in 'good risk' patients, would be the cost effective strategy. The model also explored the impact of anamnestic response (AR), a phenomenon which worsens patients' ITI risks. METHOD: A cost-minimisation technique was used to compare the cost of managing inhibitor patients whose bleeds were managed pre-ITI with an immunogenic bypassing agent, activated prothrombin complex concentrate (APCC), with patients previously on a non-immunogenic product, recombinant activated factor VII (rFVIIa). Patients were subsequently offered a low-dose or high-dose ITI regime depending on their ITI risk status. The study perspective was that of the United Kingdom NHS, hence, all resources used were based on UK costs. RESULTS: The model estimated the mean cost of managing inhibitor patients from detection of titres through ITI to be 959,250.39 pound sterling and 770,834.17 pound sterling in the APCC and rFVIIa treatment options, respectively. Meanwhile, the costs per effectively tolerised patients were 1,505,279 pound sterling and 1,196,706 pound sterling for APCC and rFVIIa treated patients, respectively. Of the incremental cost in the APCC-treated patients in the model, 129,367 pound sterling (68%) represents additional ITI cost attributable to anamnestic response to earlier treatment with an immunogenic bypassing agent (APCC). CONCLUSION: The study concludes that decreasing factor VIII usage during ITI, through the identification and management of 'good risk' ITI patients with low-dose protocol, while managing 'poor risk' patients with high-dose regimen, will significantly lower the cost of ITI. Furthermore, avoiding AR prior to ITI by using non-immunogenic bypassing agents to manage spontaneous bleeds also has the potential for significant cost savings.

Systematic review of efficacy of rFVIIa and aPCC treatment for hemophilia patients with inhibitors.

INTRODUCTION: The primary treatment for mild-to-moderate bleeding disorders in hemophilia is either recombinant activated factor VII (rFVIIa) or activated prothrombin complex concentrate (aPCC). The efficacy of both products has been evaluated in individual studies; however, there has not been an overall review to compare the efficacy from these individual studies of rFVIIa and aPCC. Our aim is to establish robust estimates of the efficacy, speed of bleed resolution, and adverse event profile of both rFVIIa and aPCC. METHODS: A systematic review was conducted of the relevant literature. RESULTS: We identified 11 open-label cohort studies, six randomized clinical trials, including two head-to-head clinical trials, and a meta-analysis. The definition of efficacy varies between these studies, but is usually a composite measure of definite pain relief, reduction in the size of the hemorrhage, and cessation of bleeding. The individual making the interpretation of efficacy and the time from treatment initiation to recording the efficacy endpoint also varies across the studies. Overall, estimates of efficacy from randomized clinical trials using dosing regimens in line with the guidelines are higher for rFVIIa (81%-91%) than for aPCC (64%-80%). Conclusions from a meta-analysis suggest that treatment with rFVIIa may be associated with a faster time to joint bleed resolution than aPCC due to higher efficacy levels at different time points. The results from a comparative trial support the improved efficacy rates associated with rFVIIa compared with aPCC. CONCLUSION: The wide variations in definitions of efficacy and study methods make comparison of results across studies difficult. Further head-to-head trials should incorporate a standardized measurement for defining efficacy.

Job displacement and stress-related health outcomes.

We investigate whether job loss as the result of displacement causes hospitalization for stress-related diseases which are widely thought to be associated with unemployment. In doing this, we use much better data than any previous investigators. Our data are a random 10% sample of the male population of Denmark for the years 1981-1999 with full records on demographics, health and work status for each person, and with a link from every working person to a plant. We use the method of 'matching on observables' to estimate the counter-factual of what would have happened to the health of a particular group of displaced workers if they had not in fact been displaced. Our results indicate unequivocally that being displaced in Denmark does not cause hospitalization for stress-related disease. An analysis of the power of our test suggests that even though we are looking for a relatively rare outcome, our data set is large enough to show even quite small an effect if there were any. Supplementary analyses do not show any causal link from displacement or unemployment to our health outcomes for particular groups that might be thought to be more susceptible.

Road injuries and long-run effects on income and employment.

This paper investigates whether unexpected shocks in terms of road injuries 'cause' a permanent change in disposable income, earnings, employment, and public transfer income. We use 'propensity score matching' and apply a difference-in-difference matching method to estimate the counterfactual of what the disposable income, earnings, employment, and the amount of public transfer income would have been of a particular group of persons injured by road accidents if they had not in fact been injured. We find that road injuries have important consequences. Older injured persons and injured persons in the lower part of the income distribution have significantly lower disposable incomes than older and low-income non-injured persons. In both the short and the long run the employment rates for the injured men are significantly lower than for non-injured persons. No effects on the employment rate are found for women. Besides, earnings are reduced in the long run for men where significant effects are only found for older women. The analysis shows that both injured men and women are compensated in terms of a significant increase in public transfer incomes in both the short and the long run.