Real-world clinical outcomes and healthcare costs in patients with Crohn's disease treated with vedolizumab versus ustekinumab in the United States.

OBJECTIVE: To compare real-world treatment persistence, dose escalation, rates of opportunistic or serious infections, and healthcare costs in patients with Crohn's disease (CD) receiving vedolizumab (VDZ) vs ustekinumab (UST) in the United States. METHODS: A retrospective observational study in adults with CD initiated on VDZ or UST on/after 26 September 2016, was performed using the IBM Truven Health MarketScan databases (1 January 2009-30 September 2018). Rates of treatment persistence, dose escalation, opportunistic or serious infection-related encounters, and healthcare costs per patient per month (PPPM) were evaluated. Entropy balancing was used to balance patient characteristics between cohorts. Event rates were assessed using weighted Kaplan-Meier analyses and compared between cohorts using log-rank tests. Healthcare costs were compared between cohorts using weighted 2-part models. RESULTS: 589 VDZ and 599 UST patients were included (172 [29.2%] and 117 [19.5%] were bio-naïve, respectively). After weighting, baseline characteristics were comparable between cohorts. No significant difference in rates of treatment persistence (12-month: VDZ, 76.5%; UST, 82.1%; p = .17), dose escalation (12-month: VDZ, 29.3%; UST, 32.7%; p = .97), or opportunistic or serious infection-related encounters were observed between VDZ and UST. Total mean healthcare costs were significantly lower for patients treated with VDZ vs UST (mean cost difference = -$5051 PPPM; p < .01). Findings were consistent in bio-naïve patients. CONCLUSIONS: In this real-world study, similar treatment persistence, dose escalation, and rates of opportunistic or serious infections were observed with VDZ- and UST-treated patients with CD. However, VDZ was associated with a significantly lower cost outlay for healthcare systems.

Crohn's disease (CD) causes inflammation in the digestive system. Vedolizumab (VDZ) and ustekinumab (UST) are therapies for patients with CD. Little is known about the clinical outcomes and healthcare costs of VDZ versus UST in the real world in the United States. We used health claims data and found that VDZ and UST had comparable real-world clinical outcomes. After 12 months of treatment, the proportions of patients with CD who stayed on treatment and those who needed to increase therapy dose were similar with VDZ and UST. The rate of infection was also similar between the two groups of patients. However, the monthly healthcare costs were $5051 less for patients treated with VDZ than with UST. This was mainly due to the lower cost of VDZ, which was almost half of that of UST. The lower treatment costs with VDZ may provide substantial savings for the healthcare system and patients specifically. Future cost-effectiveness studies on VDZ and UST are needed to aid treatment selection for patients with CD.

Real-world treatment patterns and healthcare costs of biologics and apremilast among patients with moderate-to-severe plaque psoriasis by metabolic condition status.

OBJECTIVES: To compare treatment patterns and costs among psoriasis patients with and without metabolic conditions newly initiating a biologic or apremilast. METHODS: Adult patients included had ≥1 prescription for secukinumab, adalimumab, ustekinumab, etanercept, or apremilast between 01/01/2015 and 08/31/2018 (date of first prescription was index date) and no index drug use in the 12-months pre-index, and continuous enrollment in the 12-month pre-index and 24-month post-index periods. Patients were divided into mutually exclusive treatment cohorts and stratified by their pre-index metabolic condition status. Treatment patterns (adherence, non-persistence, switching, discontinuation, use of combination therapy, and re-initiation) and healthcare costs were compared. RESULTS: Overall, 7773 patients were included; 47.5-56.7% had a metabolic condition. Except for the apremilast group, patients with metabolic conditions had higher discontinuation (secukinumab: 50.6% vs. 43.7%; adalimumab*: 53.9% vs. 48.7%; ustekinumab*: 41.9% vs. 35.1%; etanercept: 42.8% vs. 41.2%; apremilast: 43.1% vs. 46.1%) and switching (secukinumab: 48.1% vs. 41.2%; adalimumab*: 47.8% vs. 41.9%; ustekinumab*: 34.5% vs. 25.3%; etanercept*: 53.6% vs. 51.5%; apremilast: 45.8% vs. 44.6%) than patients without (*p < .05). Patients with metabolic conditions incurred significantly higher costs. CONCLUSION: Many psoriasis patients initiating biologics or apremilast had metabolic conditions. These patients had higher discontinuation and switching, and significantly higher healthcare costs.

Continuation of Anti-TNF in Patients With Ulcerative Colitis in Remission Is Not Cost-effective Compared With Treatment Withdrawal: A Markov Model.

BACKGROUND AND AIMS: Anti-tumour necrosis factor alpha [anti-TNF] treatment accounts for 31% of health care expenditures associated with ulcerative colitis [UC]. Withdrawal of anti-TNF in patients with UC in remission may decrease side effects and infections, while promoting cost containment. Approximately 36% of patients relapse within 12-24 months of anti-TNF withdrawal, but reintroduction of treatment is successful in 80% of patients. We aimed to evaluate the cost-effectiveness of continuation versus withdrawal of anti-TNF in patients with UC in remission. METHODS: We developed a Markov model comparing cost-effectiveness of anti-TNF continuation versus withdrawal, from a health care provider perspective. Transition probabilities were calculated from literature, or estimated by an expert panel of 11 gastroenterologists. Deterministic and probabilistic sensitivity analyses were performed to account for assumptions and uncertainty. The cost-effectiveness threshold was set at an incremental cost-effectiveness ratio of €80,000 per quality-adjusted life-year [QALY]. RESULTS: At 5 years, anti-TNF withdrawal was less costly [-€10,781 per patient], but also slightly less effective [-0.04 QALY per patient] than continued treatment. Continuation of anti-TNF compared with withdrawal costs €300,390/QALY, exceeding the cost-effectiveness threshold. Continued therapy would become cost-effective if the relapse rate following anti-TNF withdrawal was ≥43% higher, or if adalimumab or infliximab [biosimilar] prices fell below €87/40 mg and €66/100 mg, respectively. CONCLUSIONS: Continuation of anti-TNF in UC patients in remission is not cost-effective compared with withdrawal. A stop-and-reintroduction strategy is cost-saving but is slightly less effective than continued therapy. This strategy could be improved by identifying patients at increased risk of relapse.

Biological Retention Rates, the Reasons of Switching, and Prognostic Factors in Patients with Psoriasis Treated Biologics.

OBJECTIVE: To review patients who were treated at Tokai University Hospital with biologic agents for psoriasis vulgaris and psoriatic arthritis and analyze the biological retention rate, reasons for switching biologics, and investigate possible clinical prognostic factor which may affect whether a patient preferred one biologic to another. METHODS: Clinical courses of 63 patients who received biologic agents between Sep of 2010 to June of 2019 were investigated. Biological retention rate of each biologic agents, reasons of switching to another biologic agent, and prognostic factors, if any, between switched and non-switched patients were examined. RESULTS: The biological retention rate of ustekinumab (UST) was significantly longer than that of infliximab (IFX) or adalimumab (ADA). The major reason of switching was due to secondary loss of efficacy. Patients being treated with UST were more likely to switch to another biologic when they exhibited nail lesions. CONCLUSION: These results suggested that biological retention rate of UST was superior than that of IFX or ADA. Furthermore, with patients administered UST, nail symptom suggested possible clinical prognostic factor for switching to other biologic agents.

Biologic Therapy for Ulcerative Colitis.

Five biologics are approved for the treatment of ulcerative colitis (UC): infliximab, adalimumab, golimumab, vedolizumab, and ustekinumab. These drugs have varying levels of efficacy and are recommended as first-line treatment of moderate to severe UC. There has been only 1 head-to-head trial comparing the efficacy of the biologics, adalimumab and vedolizumab, which has important implications for management. Therapeutic drug monitoring of biologics, especially anti-TNF alpha agents, may improve the long-term efficacy of these agents. The future of treatment may include personalization of medications, based on patient-specific and disease-specific characteristics as well as biomarkers, along with appropriate therapeutic drug monitoring.

Persistence, Dose Titration, and Health Care Resource Utilization Among Crohn's Disease Patients Treated With Ustekinumab: A Real-World Analysis in the United States.

INTRODUCTION: Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. This real-world study evaluated persistence, dose titration, health care resource utilization (HCRU) and associated costs, and medication use among CD patients treated with ustekinumab (UST) in several pooled US commercial database populations. METHODS: CD patients aged ≥ 18 years with medical or pharmacy claims for UST were selected from pooled data from 3 large, national commercial databases. The first observed medical or pharmacy claim for UST was the index date. Patients were required to have had ≥ 1 medical claim with a CD diagnosis during the 12 months prior to the index date and continuous health plan enrollment for a minimum of 12 months prior to and 12 months after the index date. Comparisons of outcomes during the baseline and follow-up periods were conducted using inferential statistical tests. RESULTS: A total of 214 eligible UST patients were selected. The majority (74.8%) were biologic experienced (mean age: 41 years), and 83.6% remained treatment persistent during the 12-month post-index period. Among discontinuers, 25.7% restarted UST, and 8.6% switched from UST in the 12-month observation period. The mean treatment duration was 329 days. Most patients (77%) used the recommended UST dose, as defined as being within a 20% dose variation from label (90 mg/8 weeks ± 20%), 17.9% experienced dose escalation, and 5.1% experienced dose reduction. Post-index immunomodulator and corticosteroid use reduced by 20% and 28%, respectively, as compared with pre-index use among CD patients using UST. Annual all-cause ER visits and inpatient stays decreased by 20.5% and 30.3%, respectively, with similar downward trends for annual CD-related HCRU. CONCLUSIONS: The majority of CD patients prescribed UST were biologic experienced, and persistence was high over the 1-year follow-up. UST treatment initiation was associated with reductions in ER visits, inpatient stays, and steroid and other medication use.

Number needed to treat and cost per remitter for biologic treatments of Crohn's disease in Japan.

Aims: Adalimumab, infliximab, and ustekinumab have been approved for patients with moderate-to-severe Crohn's disease in Japan. This study compared the relative efficacy and cost-effectiveness of adalimumab, infliximab, and ustekinumab in patients with Crohn's disease based on data from randomized controlled trials.Methods: Data were extracted from four phase 3 clinical trials: CHARM, NCT00445432, ACCENT I, and IM-UNITI. A network meta-analysis (NMA) compared 1-year clinical remission rates in patients who responded to treatment during an induction phase. Remission was defined as a Crohn's Disease Activity Index score <150. The number needed to treat (NNT) was defined as the inverse of the risk reduction (compared with placebo) estimated from the NMA among initial responders. Cost per incremental remitter was calculated based on the projected per patient drug cost (2018 Japanese Yen [¥]) and the NNT.Results: Among initial responders, the remission rates were 45.2%, 31.9%, 27.4%, 24.1%, and 15.6% for adalimumab 40 mg every other week (EOW), infliximab 5 mg/kg every 8 weeks, ustekinumab 90 mg every 8 weeks, ustekinumab 90 mg every 12 weeks, and placebo, respectively. The NNT was the lowest for adalimumab 40 mg EOW. Compared with adalimumab, the incremental cost per remitter was numerically higher for infliximab (¥5,375,470) and statistically higher for ustekinumab 90 mg every 8 weeks and ustekinumab 90 mg every 12 weeks (¥42,788,597 and ¥41,495,543, respectively).Limitations: Indirect comparisons are limited by the availability of suitable clinical evidence and there may be residual heterogeneity that could not be adjusted for.Conclusion: Adalimumab was associated with a numerically lower cost per remitter compared with infliximab and a statistically lower cost per remitter compared with ustekinumab in patients with moderate-to-severe Crohn's disease in Japan.

Drug Survival of Biological Therapies for Psoriasis Treatment in Germany and Associated Costs: A Retrospective Claims Database Analysis.

INTRODUCTION: Our aim was to study drug survival and associated costs of biologic treatment in a German real-world cohort of biologic-naïve psoriasis patients. METHODS: We utilized a German claims database base with 3,682,561 enrolled patients between 2001 and 2015. Kaplan-Meier curves were plotted to show the persistence of different biologics. To determine factors that influence persistence, a Cox regression analysis was performed. In addition, associated costs were calculated 12 months before and after treatment start with biologics. RESULTS: Among 75,561 patients with a diagnosis of psoriasis, we identified 347 patients who received a biologic; 176 of them were biologic-naïve prior to initiating therapy. Overall, the 1-year persistence rate was 56%. The highest persistence rate was observed for ustekinumab (80%). Younger patients, and those with a high comorbidity index, had a numerically increased risk of treatment discontinuation. However, parameter values were not statistically significant. While the overall costs after treatment start increased due to the acquisition costs of biologics, we found a strong decrease (- 41%) in sick leave after treatment with biologics had been initiated. CONCLUSION: Observed drug survival rates in this real-world setting were relatively low. In line with previous studies, ustekinumab had a higher persistence rate than other biologics. FUNDING: Janssen-Cilag.

A Cost-per-Number Needed to Treat Analysis Assessing the Efficiency of Biologic Drugs in Moderate to Severe Plaque Psoriasis. / Evaluación de la eficiencia de los tratamientos biológicos en la psoriasis moderada a grave en España: análisis de coste por número necesario a tratar (NNT).

BACKGROUND AND OBJECTIVES: Psoriasis is a chronic inflammatory skin disease with an estimated prevalence in Spain of 2.3% of the population. Approximately 30% of patients have moderate-to-severe forms. Treatment with biologic agents is proving to be a step forward in the management of the disease, although these treatments are very expensive. The objective of this study was to determine the efficiency, in terms of cost per number needed to treat (NNT), of the biologic drugs available in Spain for the treatment of moderate to severe plaque psoriasis. METHODS: NNT data were obtained from a network meta-analysis that included all randomized clinical trials of biologic drugs sold in Spain. The cost of each treatment was calculated based on the approved dosage for the first year of treatment, as indicated in the Summary of Product Characteristics. These data were used to calculate the cost per NNT of the drugs for various PASI scores (75, 90, and 100). A sensitivity analysis was performed taking into consideration only the PASI-response measurement time (after 10, 12, or 16 weeks, depending on the drug). RESULTS: The order of efficiency, from most to least efficient, in the case of a PASI 75 response was ixekizumab > ustekinumab 45mg > ustekinumab 90mg > secukinumab > infliximab > etanercept > adalimumab. The order for PASI 90 was ixekizumab >secukinumab >ustekinumab 45mg > ustekinumab 90mg > infliximab > adalimumab > etanercept. The order for PASI 100 was ixekizumab > secukinumab > infliximab > ustekinumab 90mg > ustekinumab 45mg > adalimumab > etanercept. The sensitivity analysis showed some changes in the order, depending on the response-assessment period. CONCLUSIONS: The findings show a link between the efficacy of the biologic therapies available in Spain for the treatment of moderate-to-severe plaque psoriasis and their efficiency. Ixekizumab had the lowest cost per NNT for all PASI-response scores (75, 90, and 100) during the first year of treatment.

Dose increase beyond labelled dose of biologics is associated with incremental pharmacy costs: results from a real-world study in the UK.

Background: There is limited evidence regarding biologics dosing patterns and its costs among psoriasis patients in the United Kingdom (UK). Objective: This retrospective study assessed biologics dose increase beyond labelled dose and associated UK pharmacy costs in moderate to severe psoriasis patients. Methods: Adult psoriasis patients on biologic prescription for ≥12 continuous months between January 2010 and March 2015 with their diagnosis recorded in the UK Hospital Treatment Insights Database within one month of such prescription were included. The proportion of patients receiving ≥30% higher the average daily maintenance dose as per the UK product label, and associated 12-month costs were reported. Results: The study included 362 patients, receiving adalimumab (48%), etanercept (17%), ustekinumab (12%), and infliximab (23%). Beyond labelled dose increase was noted in 14% adalimumab, 20% etanercept, 18% ustekinumab and 28% infliximab patients with an associated mean annual extra cost per patient of £7936, £5912, £2422 and £2275, respectively. Conclusion: Dose increase beyond labelled dose of biologics was commonly observed in moderate to severe psoriasis in the UK and resulted in substantial annual incremental pharmacy costs.

Cost-Effectiveness Comparison of Ustekinumab, Infliximab, or Adalimumab for the Treatment of Moderate-Severe Crohn's Disease in Biologic-Naïve Patients.

STUDY OBJECTIVE: Ustekinumab was recently approved by the United States U.S. Food and Drug Administration for the treatment of Crohn's disease. In this analysis, we aimed to compare the cost-effectiveness of ustekinumab, infliximab, or adalimumab for the treatment of moderate-severe Crohn's disease in patients who failed conventional therapy (i.e., corticosteroids and immunomodulators) but were naïve to tumor necrosis factor antagonists (i.e., biologic drugs). DESIGN: Cost-effectiveness analysis using a hybrid model structure (decision tree and Markov model). MEASUREMENTS AND MAIN RESULTS: A decision tree simulated biologic induction, and a Markov model simulated biologic and conventional therapy maintenance. Cycle length was 2 weeks with a discounted 5-year time horizon and a limited U.S. societal perspective in the base case; results from a payer perspective are also reported. Transition probabilities, direct costs, indirect costs, and utilities were obtained from the literature. To measure relative treatment value (i.e., order of treatment cost-effectiveness), net monetary benefits were reported for a $150,000 willingness-to-pay threshold per quality-adjusted life-year in the base case. Infliximab dominated both adalimumab and ustekinumab, with a net monetary benefit (NMB) of $9943 and $29,798, respectively, in the base case. Adalimumab dominated ustekinumab, with an NMB of $19,855. All biologics yielded similar quality-adjusted life-years (~3.5), whereas costs varied substantially ($50,510, $54,985, and $72,921 for infliximab, adalimumab, and ustekinumab, respectively). The payer perspective, alternate time horizons, and scenario analyses consistently showed infliximab dominance. One-way, threshold, and probabilistic sensitivity analyses confirmed the robustness of these results with respect to all parameters. Although biosimilars were not explicitly modeled as comparators, one-way sensitivity analysis showed that drug acquisition costs could alter relative treatment value but would have to be varied by at least 50%. CONCLUSION: For moderate-severe Crohn's disease, infliximab yields significantly more NMBs compared with both adalimumab and ustekinumab. Additional clinical (e.g., empiric dosing, biologic cycling) and quality-of-life (e.g., lost productivity, disutility of home injections) research is needed to allow for model frameworks and parameters that more accurately reflect the nuances of Crohn's disease treatment.

Prescribing trends for biologic drugs among Ohio dermatologists.

The role of biologic therapies in the field of dermatology continues to evolve as newer drugs and biosimilars are introduced to the U.S. market. Prescribing patterns and expenditures regarding biologic drugs are not well described. To address this knowledge gap, a retrospective review was conducted using the Medicare Provider Utilization and Payment Data: Part D Prescriber dataset between January 1st, 2013 and December 31st, 2015. The primary outcome was claims per provider per calendar year. Secondary outcomes included drug cost, shared cost per dermatologist, and practice location. Median claims per provider remained stable between 2013 and 2014 (24 versus 23, respectively; P=0.64). The majority of 2015 claims were for adalimumab (50.1%) and etanercept (41.4%). Total spending from Medicare payment data for biologic drugs prescribed by Ohio dermatologists increased by $3 million during the study period. The Gini coefficient for provider contributions to overall costs was 0.47, indicating moderate inequality among Ohio dermatologists. Spending associated with biologic drugs used for dermatologic indications is increasing in Ohio. As the market changes, providers should be aware of these patterns to better care for patients in need of biologic therapies.

Persistence rates and medical costs of biological therapies for psoriasis treatment in Japan: a real-world data study using a claims database.

BACKGROUND: Biological therapies (BTs) including infliximab (IFX), adalimumab (ADL), secukinumab (SCK) and ustekinumab (UST) are approved in Japan for the treatment of psoriasis. Although the persistence rates and medical costs of BTs treatment have been investigated in multiple foreign studies in recent years, few such studies have been conducted in Japan and the differences between patients who adhered to treatment and those who did not have not been reported. This study is aimed at investigating the persistence rates and medical costs of BTs in the treatment of psoriasis in Japan, using the real-world data from a large-scale claims database. METHODS: Claims data from the JMDC database (August 2009 to December 2016) were used for this analysis. Patient data were extracted using the ICD10 code for psoriasis and claims records of BT injections. Twelve-month and 24-month persistence rates of BTs were estimated by Kaplan-Meier methodology, and 12-month-medical costs before and after BT initiation were compared between persistent and non-persistent patient groups at 12 months. RESULTS: A total of 205 psoriasis patients treated with BTs (BT-naïve patients: 177) were identified. The 12-month/24-month persistence rates for ADL, IFX, SCK, and UST in BT-naïve patients were 46.8% ± 16.6%/46.8 ± 16.6%, 53.0% ± 14.9%/41.0% ± 15.5%, 55.4%/55.4% (95% CI not available) and 79.4% ± 9.9%/71.9% ± 12.2%, respectively. Statistically significant differences in persistence were found among different BT treatments, and UST was found to have the highest persistence rate. The total medical costs during the 12 months after BT initiation in BT-naïve patients were (in 1000 Japanese Yen): 2218 for ADL, 3409 for IFX, 465 for SCK, 2824 for UST (average: 2828). Compared with the 12-month persistent patient group, the total medical costs in the persistent group was higher (Δ:+ 118), but for some medications such as IFX or UST cost increases were lower for persistent patients. CONCLUSIONS: UST was found to have the highest persistence rate among all BTs for psoriasis treatment in Japan. The 12-month medical costs after BT initiation in the persistent patient group may not have increased as much as in the non-persistent patient group for some medications.

Cost-effectiveness analysis of sequential biologic therapy with ixekizumab versus secukinumab as first-line treatment of moderate-to-severe psoriasis in the UK.

AIMS: Patients with psoriasis often undergo treatment with a sequence of biologic agents because of poor/loss of response to initial therapy. With the availability of newer agents like ixekizumab and secukinumab, there is a need for cost-effectiveness analyses to better reflect current clinical practice. This study aimed to assess the cost-effectiveness of a sequence of biologic therapies containing first-line ixekizumab vs first-line secukinumab in patients with moderate-to-severe plaque psoriasis in the UK. MATERIALS AND METHODS: A Markov model with a lifetime horizon was developed to compare the cost-effectiveness of ixekizumab and secukinumab treatment sequences: ixekizumab → ustekinumab → infliximab → best supportive care (BSC) vs secukinumab → ustekinumab → infliximab → BSC. The model used monthly cycles, and included four health states: trial period, treatment maintenance, BSC, and death. At the end of the trial period, responders transitioned to maintenance therapy; non-responders transitioned to the next biologic in the sequence. An annual discontinuation rate of 20% was assumed for maintenance therapy. RESULTS: The ixekizumab sequence provided cost savings of £898 (£176,203 vs 177,101) [year 2015 values] and gained 0.03 more quality-adjusted life-years (QALYs: 1.45 vs 1.42) vs the secukinumab sequence over the lifetime horizon. Probabilistic sensitivity analysis showed an 89.8% likelihood that the ixekizumab sequence would be cost-effective at a threshold of £20,000 per QALY gained. LIMITATIONS: The analysis used list prices for drugs rather than confidential, preferentially priced Patient Access Scheme costs. In addition, efficacy input data were based on a network meta-analysis, as there were no head-to-head trials comparing ixekizumab and secukinumab. CONCLUSION: First-line treatment with ixekizumab as part of a specific sequential biologic therapy for moderate-to-severe plaque psoriasis in the UK provided slight advantages in cost savings and QALYs gained over a similar treatment sequence initiated with secukinumab. In view of the small magnitude of these differences, factors such as patient preferences (e.g. for number of injections) and long-term safety (e.g. related to time on the market) may also be important for clinical decision-making.

Cost-effectiveness of secukinumab as first biologic treatment, compared with other biologics, for moderate to severe psoriasis in Germany.

BACKGROUND: Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin 17A, has demonstrated strong and sustained efficacy in adults with moderate to severe psoriasis in clinical trials. OBJECTIVE: This analysis compared the cost per responder of secukinumab as first biologic treatment of moderate to severe psoriasis, with adalimumab, infliximab, etanercept and ustekinumab in Germany. METHODS: A 52-week decision-tree model was developed. Response to treatment was assessed based on the likelihood of achieving a predefined Psoriasis Area and Severity Index (PASI) response to separate the cohort into responders (PASI ≥75), partial responders (PASI 50 to 74) and non-responders (PASI <50). Responders at week 16 continued initial treatment, whereas partial responders and non-responders were switched to standard of care, which included methotrexate, cyclosporine, phototherapy and topical corticosteroids. Sustained response was defined as 16-week response maintained at week 52. A German healthcare system perspective was adopted. Clinical efficacy data were obtained from a mixed-treatment comparison; 2016 resource unit costs from national sources; and adverse events and discontinuation rates from the literature. We calculated cost per PASI 90 responder over week 16 and week 52, as well as cost per sustained responder between weeks 16 and 52. RESULTS: Secukinumab had the lowest cost per PASI 90 responder over 16 weeks (€18 026) compared with ustekinumab (€18 080), adalimumab (€23 499), infliximab (€29 599) and etanercept (€34 037). Over 52 weeks, costs per PASI 90 responder ranged from €42 409 (secukinumab) to €70 363 (etanercept). Likewise, secukinumab had the lowest cost per sustained 52-week PASI 90 responder (€22 690) compared with other biologic treatments. Sensitivity analyses, excluding patient copayments, showed similar results. CONCLUSIONS: First biologic treatment with secukinumab for moderate to severe psoriasis is cost-effective, with lowest cost per responder compared with other biologic treatments in Germany.

Cost-Effectiveness Analysis of Crohn's Disease Treatment with Vedolizumab and Ustekinumab After Failure of Tumor Necrosis Factor-α Antagonist.

OBJECTIVE: The aim was to evaluate the cost-effectiveness of Crohn's disease (CD) treatment with vedolizumab and ustekinumab after failure of therapy with tumor necrosis factor-α antagonists (anti-TNFs). METHODS: The Markov model incorporated the lifetime horizon, synthesis-based estimates of biologics' efficacy in relation to anti-TNF exposure, and administration of biologics reflecting clinical practice (e.g., sequence of biologics, retreatment, 12-month treatment). The utilities, non-medical costs and indirect costs were derived from a study of 200 adult patients with CD, while the healthcare costs were from a study of 1393 adults with CD who used biologics in Poland. The quality-adjusted life years (QALYs) and costs (the societal perspective) were discounted with the annual rates of 3.5 and 5%, respectively. RESULTS: The addition of vedolizumab (ustekinumab) to the sequence of available anti-TNFs (after first-line infliximab or after second-line adalimumab) led to a gain of 0.364 (0.349) QALYs at an additional cost of €5600.24 (€6593.82). The incremental cost-effectiveness ratios (ICERs) were €15,369 [95% confidence interval (CI) 7496-61,354] and €18,878 (95% CI 9213-85,045) per QALY gained with vedolizumab and ustekinumab, respectively. Sensitivity analyses revealed a high impact on the ICERs of the relapse rate after discontinuation of biologic treatment. The highest value of vedolizumab/ustekinumab was estimated after the failure of therapies with both anti-TNFs. CONCLUSIONS: CD treatment with ustekinumab or vedolizumab after failure of anti-TNF therapy appears to be cost-effective at a threshold of €31,500. The replacement of the second-line anti-TNF with ustekinumab/vedolizumab and the course of the disease after discontinuation of biologics are influential drivers of the cost-effectiveness.

Comparison of the cost-effectiveness of biologic drugs used for moderate-to-severe psoriasis treatment in the United States.

PURPOSE: To compare the cost-effectiveness of the newly approved biologic drug, brodalumab, with other commonly used biologics for the treatment of moderate-to-severe psoriasis in the United States. METHODS: An economic model was constructed in Excel to compare average costs to achieve Psoriasis Area and Severity Index (PASI) 75, 90 and 100 among moderate-to-severe psoriasis patients treated with biologics. Total annual costs to health plans associated with treatment with five different biologics were estimated and cost-effectiveness compared using the estimated average cost per PASI 75, PASI 90 and PASI 100. RESULTS: Total annual costs to a health plan per patient with adalimumab, brodalumab, ixekizumab, secukinumab and ustekinumab were estimated at $51,246, $38,538, $65,484, $57,510 and $57,013. Mean annual treatment costs per PASI 75, 90 and 100 were the lowest for brodalumab, with the annual cost per PASI 75 for brodalumab, adalimumab, ixekizumab, secukinumab and ustekinumab estimated at $48,782, $82,655, $77,957, $75,671 and $87,243, per PASI 90 at $51,383, $119,178, $94,904, $108,509 and $130,615, and per PASI 100 at $87,585, $284,702, $176,983, $205,393, and $366,645. CONCLUSIONS: Brodalumab, which had the lowest drug cost and high drug efficacy, was associated with the lowest cost per PASI 75, 90 and 100 among the biologics evaluated.

Ixekizumab for Treating Moderate-to-Severe Plaque Psoriasis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

The National Institute for Health and Care Excellence invited Eli Lilly and Company Ltd, the company manufacturing ixekizumab (tradename Taltz®), to submit evidence for the clinical and cost effectiveness of ixekizumab. Ixekizumab was compared with tumour necrosis factor-α inhibitors (etanercept, infliximab, adalimumab), ustekinumab, secukinumab, best supportive care and, if non-biological treatment or phototherapy is suitable, also compared with systemic non-biological therapies and phototherapy with ultraviolet B radiation for adults with moderate-to-severe plaque psoriasis. Kleijnen Systematic Reviews Ltd, in collaboration with Maastricht University Medical Center, was commissioned as the independent Evidence Review Group. This article presents a summary of the company submission, the Evidence Review Group report and the development of the National Institute for Health and Care Excellence guidance for the use of this drug in England and Wales by the Appraisal Committee. The Evidence Review Group produced a critical review of the clinical and cost effectiveness of ixekizumab based on the company submission. The company submission presented three randomised controlled trials identified in a systematic review. All randomised controlled trials were phase III, multicentre placebo-controlled trials including 3866 participants with moderate-to-severe psoriasis. Two trials also included an active comparator (etanercept). All randomised controlled trials showed statistically significant increases in two primary outcomes, static Physician Global Assessment (0,1) and improvement of 75% from baseline in the Psoriasis Area and Severity Index. Ixekizumab was generally well tolerated in the randomised controlled trials, with similar discontinuation rates because of adverse events as placebo or etanercept. The most frequent adverse events of special interest were infections and injection-site reactions. The company submission also included a network meta-analysis of relevant comparators. The Evidence Review Group highlighted some issues regarding the systematic review process and an issue with the generalisability of the findings in that the trials failed to include patients with moderate psoriasis according to a widely used definition. This issue was considered by the Appraisal Committee and the population was deemed generalisable to patients in England and Wales. Based on the network meta-analysis, the Appraisal Committee concluded that ixekizumab was more clinically effective than adalimumab and ustekinumab, and agreed it was likely that ixekizumab was similarly effective compared with secukinumab and infliximab while tolerability was similar to other biological treatments approved for treating psoriasis. The Evidence Review Group's critical assessment of the company's economic evaluation highlighted a number of concerns, including (1) the use of relative outcomes such as Psoriasis Area and Severity Index response to model the cost effectiveness; (2) the exclusion of the consequences of adverse events; (3) the assumption of no utility gain in the induction phase; (4) equal annual discontinuation rates for all treatments; (5) the selection of treatment sequences for consideration in the analyses and; (6) the transparency of the Visual Basic for Applications code used to develop the model. Although some of these issues were adjusted in the Evidence Review Group base case, the Evidence Review Group could not estimate the impact of all of these issues, and thus acknowledges that there are still uncertainties concerning the cost-effectiveness evidence. In the Evidence Review Group base-case incremental analysis, the treatment sequence incorporating ixekizumab in the second line has an incremental cost-effectiveness ratio of £25,532 per quality-adjusted life-year gained vs. the etanercept sequence. Ixekizumab in the first-line sequence has an incremental cost-effectiveness ratio of £39,129 per quality-adjusted life-year gained compared with the treatment sequence incorporating ixekizumab in the second line. Consistent with its conclusion regarding clinical effectiveness, the Appraisal Committee concluded that the cost effectiveness of ixekizumab for treating moderate-to-severe plaque psoriasis was similar to that of other biological treatments, already recommended in previous National Institute for Health and Care Excellence guidance. The committee concluded that the incremental cost-effectiveness ratio was within the range that could be considered a cost-effective use of National Health Service resources.