Ulipristal acetate compared to levonorgestrel emergency contraception among current oral contraceptive users: a cost-effectiveness analysis.

OBJECTIVE: To estimate the cost-effectiveness of ulipristal acetate (UPA) and levonorgestrel (LNG) emergency contraception (EC) on pregnancy prevention among combined oral contraceptive (COC) pill users with an extended pill-free interval. We accounted for the potential interaction of COCs and obesity on EC efficacy. METHODS: We built a decision-analytic model using TreeAge software to evaluate the optimal oral EC strategy in a hypothetical cohort of 100,000 twenty-five-year-old women midcycle with a prolonged "missed" pill episode (8-14 days). We used a 5-year time horizon and 3% discount rate. From a healthcare perspective, we obtained probabilities, utilities and costs inflated to 2018 dollars from the literature. We set the threshold for cost-effectiveness at a standard $100,000 per quality-adjusted life-year. We included the following clinical outcomes: number of protected cycles, unintended pregnancies, abortions, deliveries and costs. RESULTS: We found that UPA was the optimal method of oral EC, as it resulted in 720 fewer unintended pregnancies, 736 fewer abortions and 80 fewer deliveries at a total cost savings of $50,323 and 79 additional adjusted life-years. UPA continued to be the optimal strategy even in the case of obesity or COCs impacting UPA efficacy, in which a COC interaction would have to change efficacy of UPA by 160% before LNG was the dominant strategy. CONCLUSION: Our models found that UPA was the dominant choice of oral EC among COC users with a prolonged "missed" pill episode, regardless of body mass index or an adverse interaction of COCs on UPA. IMPLICATIONS: Ulipristal acetate is the dominant choice of oral emergency contraception among combined oral contraceptive users.

Ulipristal acetate for pre-operative management of uterine fibroids: Modeling outcomes and costs.

OBJECTIVES: The aim of this study was to evaluate the pharmacoeconomic profile in Italy of preoperative treatment with ulipristal acetate at the dose of 5 mg/day for 13 weeks in comparison with placebo prior to surgical management of symptomatic uterine fibroids. STUDY DESIGN: The pharmacoeconomic analysis was based on the calculation of incremental cost-effectiveness ratio (ICER). Effectiveness data were derived from the randomized-controlled trial PEARL-1, whilst costs data were retrieved from the published literature. A Markov model was employed to simulate the pattern of costs and two univariate sensitivity analyses tested the robustness of the results. RESULTS: In comparison with placebo, ulipristal acetate 5 mg for presurgical therapy was estimated to be associated with an incremental cost of €351 per patient. Costs per patient were €3836 for ulipristal acetate vs €3485 for placebo. The incremental effectiveness was 0.01931 QALYs per patient (around 7 quality-adjusted days per patient). Hence, the cost effectiveness ratio was calculated to be €18,177 per QALY gained. CONCLUSIONS: Preoperative use of ulipristal acetate 5 mg in patients with uterine fibroids has a favourable pharmacoeconomic profile.

Cost-effectiveness of emergency contraception options over 1 year.

BACKGROUND: The copper intrauterine device is the most effective form of emergency contraception and can also provide long-term contraception. The levonorgestrel intrauterine device has also been studied in combination with oral levonorgestrel for women seeking emergency contraception. However, intrauterine devices have higher up-front costs than oral methods, such as ulipristal acetate and levonorgestrel. Health care payers and decision makers (eg, health care insurers, government programs) with financial constraints must determine if the increased effectiveness of intrauterine device emergency contraception methods are worth the additional costs. OBJECTIVE: We sought to compare the cost-effectiveness of 4 emergency contraception strategies-ulipristal acetate, oral levonorgestrel, copper intrauterine device, and oral levonorgestrel plus same-day levonorgestrel intrauterine device-over 1 year from a US payer perspective. STUDY DESIGN: Costs (2017 US dollars) and pregnancies were estimated over 1 year using a Markov model of 1000 women seeking emergency contraception. Every 28-day cycle, the model estimated the predicted number of pregnancy outcomes (ie, live birth, ectopic pregnancy, spontaneous abortion, or induced abortion) resulting from emergency contraception failure and subsequent contraception use. Model inputs were derived from published literature and national sources. An emergency contraception strategy was considered cost-effective if the incremental cost-effectiveness ratio (ie, the cost to prevent 1 additional pregnancy) was less than the weighted average cost of pregnancy outcomes in the United States ($5167). The incremental cost-effectiveness ratios and probability of being the most cost-effective emergency contraception strategy were calculated from 1000 probabilistic model iterations. One-way sensitivity analyses were used to examine uncertainty in the cost of emergency contraception, subsequent contraception, and pregnancy outcomes as well as the model probabilities. RESULTS: In 1000 women seeking emergency contraception, the model estimated direct medical costs of $1,228,000 and 137 unintended pregnancies with ulipristal acetate, compared to $1,279,000 and 150 unintended pregnancies with oral levonorgestrel, $1,376,000 and 61 unintended pregnancies with copper intrauterine devices, and $1,558,000 and 63 unintended pregnancies with oral levonorgestrel plus same-day levonorgestrel intrauterine device. The copper intrauterine device was the most cost-effective emergency contraception strategy in the majority (63.9%) of model iterations and, compared to ulipristal acetate, cost $1957 per additional pregnancy prevented. Model estimates were most sensitive to changes in the cost of the copper intrauterine device (with higher copper intrauterine device costs, oral levonorgestrel plus same-day levonorgestrel intrauterine device became the most cost-effective option) and the cost of a live birth (with lower-cost births, ulipristal acetate became the most cost-effective option). When the proportion of obese women in the population increased, the copper intrauterine device became even more most cost-effective. CONCLUSION: Over 1 year, the copper intrauterine device is currently the most cost-effective emergency contraception option. Policy makers and health care insurance companies should consider the potential for long-term savings when women seeking emergency contraception can promptly obtain whatever contraceptive best meets their personal preferences and needs; this will require removing barriers and promoting access to intrauterine devices at emergency contraception visits.

Economic impact of ulipristal acetate on surgical procedures for uterine fibroids in France.

OBJECTIVE: To assess the budget impact of using ulipristal acetate (UPA) 5 mg to treat women with uterine fibroids (UF) causing moderate to severe symptoms. DESIGN: We modelled trends in the number of surgical procedures for symptomatic UF, with and without the use of UPA for preoperative or intermittent treatment and assessed the budget impact of UPA use from the French national healthcare insurance system perspective. SETTING: A French national hospital database (PMSI) that records admissions and relative procedures to public and private hospitals. PARTICIPANTS: Women eligible for surgical procedures for uterine fibroids. MAIN OUTCOME MEASURES: Economic impact of UPA treatment. RESULTS: This study based on observational retrospective data shows that the current use of UPA in its preoperative indication was associated with 5645 fewer surgeries from 2013 to 2015. Extrapolation suggests 17 885 fewer surgeries from 2016 to 2019. Overall, preoperative use of UPA results in substantial cost savings for the French national healthcare insurance system, with a cumulated budget impact estimated at €-5 million from 2013 to 2015 and €-13.5 million from 2016 to 2019. In addition, treating women nearing the menopause (≥48 years old) with intermittent treatment from 2017 to 2019 could produce an incremental cost saving of €19 million. CONCLUSIONS: This study shows that the use of UPA in women eligible for surgical procedures for UF is associated with considerable savings for the French national healthcare insurance system in both preoperative and intermittent indications by decreasing the need to perform surgeries.

Ulipristal acetate for pre-operative treatment of moderate-to-severe uterine fibroids in women of reproductive age in The Netherlands: cost minimization analysis and budget impact analysis.

OBJECTIVE: Ulipristal acetate has been found to be non-inferior to other pre-operative treatments of uterine fibroids, particularly leuprolide. The objective of this study was to assess the pharmacoeconomic profile of ulipristal acetate compared to leuprolide for the pre-operative treatment of moderate-to-severe uterine fibroids in women of reproductive age in The Netherlands. The analysis was performed and applied within the framework of the ulipristal acetate submission for reimbursement in 2012. METHODS: A decision model was developed to compare the total costs of ulipristal acetate compared to leuprolide, the standard care in The Netherlands. The target population of this study corresponded to the type of patients included in the PEARL II clinical trial; i.e. women of reproductive age requiring pre-operative treatment for uterine fibroids. Sensitivity analysis was implemented to assess uncertainties. Data regarding costs, effects, and other input parameters were obtained from relevant published literatures, the Dutch Healthcare Insurance Board, and expert opinion obtained by means of a panel of experts from several medical centers in The Netherlands. RESULTS: In The Netherlands, the total costs of ulipristal acetate and leuprolide were estimated at €4,216,027 and €4,218,095, respectively. The annual savings of ulipristal acetate were, therefore, estimated at €2,068. The major driver of this cost difference was the cost of administration for leuprolide. Sensitivity analyses showed that ulipristal acetate mostly remained cost-saving over a range of assumptions. The budget impact analysis indicated that the introduction of ulipristal acetate was estimated to result in cost savings in the first 3 years following the introduction. The results of this study were used in the decision on reimbursement of ulipristal acetate according to the Dutch Reference Pricing system in 2012. CONCLUSION: Ulipristal acetate was cost saving compared to leuprolide and has the potential to provide substantial savings on the healthcare budget in The Netherlands.

Emergency Contraception.

Emergency contraception (EC) may help prevent pregnancy in various circumstances, such as contraceptive method failure, unprotected sexual intercourse, or sexual assault, yet it remains underused. There are 4 approved EC options in the United States. Although ulipristal acetate requires a provider's prescription, oral levonorgestrel (LNG) is available over the counter for women of all ages. The most effective method of EC is the copper intrauterine device, which can be left in place for up to 10 years for efficacious, cost-effective, hormone-free, and convenient long-term primary contraception. Ulipristal acetate tends to be more efficacious in pregnancy prevention than is LNG, especially when taken later than 72 hours postcoitus. The mechanism of action of oral EC is delay of ovulation, and current evidence reveals that it is ineffective postovulation. Women who weigh more than 75 kg or have a body mass index greater than 25 kg/m(2) may have a higher risk of unintended pregnancy when using oral LNG EC; therefore, ulipristal acetate or copper intrauterine devices are preferable in this setting. Providers are often unaware of the range of EC options or are unsure of how to counsel patients regarding the access and use of EC. This article critically reviews current EC literature, summarizes recommendations, and provides guidance for counseling women about EC. Useful tips for health care providers are provided, with a focus on special populations, including breast-feeding women and those transitioning to long-term contraception after EC use. When treating women of reproductive age, clinicians should be prepared to counsel them about EC options, provide EC appropriately, and, if needed, refer for EC in a timely manner.

Repeated-intermittent use of ulipristal acetate for the management of uterine fibroids: an Italian pharmacoeconomic evaluation.

BACKGROUND: The aim of this paper was to evaluate an Italian pharmacoeconomic profile of repeated-intermittent (from 4 to 10 cycles) use of ulipristal acetate 5 mg (UPA 5 mg) in comparison with the use of UPA 5 mg before surgery (2 cycles) for the management of symptomatic uterine fibroids. METHODS: The pharmacoeconomic analysis was performed in two steps: 1) estimating an incremental cost-effectiveness ratio (ICER); 2) assuming a nationwide prediction of future expenditure in the Italian scenario. Effectiveness data were derived from the randomized-controlled trial, whilst quality of life and costs data were retrieved from the published literature. RESULTS: In comparison with the use of UPA 5 mg before surgery, the values of ICER per patient were the following: 1) €20,600 euros (UPA 5 mg 4 cycles); 2) €26,884 (UPA 5mg 6 cycles); 3) €30,244 (UPA 5 mg 8 cycles); 4) €31,906 (UPA 5 mg 10 cycles). In comparison with the use of UPA 5 mg before surgery plus subsequent surgery, the saving per patient for the National Healthcare System (NHS) by adding repeated-intermittent use of UPA 5 mg were the following: 1) €26 million (UPA 5 mg 4 cycles); 2) €17.6 million (UPA 5mg 6 cycles); 3) €8.9 million (UPA 5 mg 8 cycles); 4) €0.2 million (UPA 5 mg 10 cycles). CONCLUSIONS: The results showed that repeated-intermittent use of UPA 5 mg for the long-term treatment of uterine fibroids has a favourable pharmacoeconomic profile up to 10 repeated cycles and may be a cost-saving treatment option for the NHS. Although the data are encouraging, more data are needed regarding the benefits and risks of long-term treatment with UPA.

The Cost-Effectiveness of Emergency Hormonal Contraception with Ulipristal Acetate versus Levonorgestrel for Minors in France.

OBJECTIVE: To evaluate the cost-effectiveness of ulipristal acetate and levonorgestrel in minors in France, and analyze whether it is worthwhile to provide ulipristal acetate to minors free of charge. METHODS: The cost-effectiveness of two emergency contraceptive methods was compared based on a decision-analytical model. Pregnancy rates, outcomes of unintended pregnancies, and resource utilization were derived from the literature. Resources and their costs were considered until termination or a few days after delivery. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: The cost of an unintended pregnancy in a French minor is estimated to be 1,630 € (range 1,330 € - 1,803 €). Almost 4 million € (3.1 € - 13.7 € million) in unintended pregnancy spending in 2010 could have been saved by the use of ulipristal acetate instead of levonorgestrel. The incremental cost of ulipristal acetate compared to levonorgestrel is 3.30 € per intake, or 418 € per pregnancy avoided (intake within 72 hours). In the intake within 24 hours subgroup, ulipristal acetate was found to be more efficacious at a lower cost compared to levonorgestrel. CONCLUSIONS: Ulipristal acetate dominates levonorgestrel when taken within 24 hours after unprotected intercourse, i.e., it is more effective at a lower cost. When taken within 72 hours, ulipristal acetate is a cost- effective alternative to levonorgestrel, given that the cost of avoiding an additional pregnancy with ulipristal acetate is less than the average cost of these pregnancies. In the light of these findings, it is worthwhile to provide free access to minors.

The cost-effectiveness of ulipristal acetate tablets in treating patients with moderate to severe symptoms of uterine fibroids.

OBJECTIVES: Ulipristal acetate is a selective progesterone receptor modulator that has been demonstrated to be an effective 3-month pre-operative treatment for moderate to severe symptoms of uterine fibroids in adult women of reproductive age. The aim of this analysis was to assess the cost-effectiveness of 5mg ulipristal as an add-on therapy to standard pre-surgical observation and treatment in Hungary. STUDY DESIGN: A Markov model was developed using a 10-year time horizon. Ulipristal was compared with pre-surgical observation and immediate hysterectomy. The model comprised the following mutually exclusive health states: mild, moderate, severe, or persistent severe excessive bleeding disorder; myomectomy; post-myomectomy with mildly to moderately excessive bleeding disorder; post-myomectomy with severely excessive bleeding disorder; hysterectomy; post-hysterectomy; post-menopause; and death. Transition probabilities and utility values were obtained from clinical trials and the scientific literature. Resource utilisation and unit costs were derived from a consensus panel of clinical experts, National Health Insurance Fund tariffs, and publications. RESULTS: Adding a 3-month course of ulipristal to pre-operative observation was predicted to achieve an additional 0.021 quality-adjusted life years (QALYs) at an estimated incremental cost of €397, which would result in an incremental cost of €19,200/QALY. When 3 months of ulipristal therapy was compared with immediate hysterectomy, the incremental cost-effectiveness ratio was reduced to €3575/QALY. The results were most sensitive to the utility value of the post-hysterectomy health state but responsive to changes in other model parameters. CONCLUSIONS: The results of this analysis suggest that adding ulipristal treatment to standard pre-surgical therapy represents a good value for money in Hungary. The inclusion of societal benefits may considerably reduce the cost-effectiveness ratio.

The price of emergency contraception in the United States: what is the cost-effectiveness of ulipristal acetate versus single-dose levonorgestrel?

BACKGROUND: Ulipristal acetate (UPA) is a novel form of emergency contraception (EC) that appears to be more effective than the prevailing method, single-dose levonorgestrel (LNG). This study examines the cost-efficacy of UPA compared with LNG. STUDY DESIGN: A decision-analytic model was developed to compare the cost-effectiveness of UPA versus LNG in preventing unintended pregnancy when taken within 120 h of unprotected intercourse. Univariate and bivariate sensitivity analyses, as well as Monte Carlo simulation and threshold analyses, were performed. RESULTS: Utilizing UPA instead of LNG would result in 37,589 fewer unintended pregnancies per 4,176,572 estimated US annual EC uses (UPA 54,295 pregnancies; LNG 91,884 pregnancies) and a societal savings of $116.3 million annually. Cost-effectiveness acceptability curve analyses suggest a 96% probability that UPA is more cost-effective at a willingness to pay $100,000 per quality-adjusted life year. CONCLUSIONS: UPA is cost-effective in preventing unintended pregnancy after unprotected intercourse. Efforts should be promoted to increase access to UPA.

Emergency contraception: an underutilized resource.

This emergency contraception update and telephone triage guide can help ensure that your patients get the help they need, when they need it.

Ulipristal acetate: review of the efficacy and safety of a newly approved agent for emergency contraception.

BACKGROUND: Emergency contraception (EC) is used to prevent unintended pregnancies. The current gold standard for oral EC is levonorgestrel (LNG) administered as a single 1.5-mg dose or in 2 doses of 0.75 mg separated by 12 hours. LNG has shown to be effective up to 72 hours after coitus. Ulipristal acetate (UPA) is a selective progesterone receptor modulator approved for EC use in the United States in August 2010. UPA is administered as a one-time, 30-mg dose within 120 hours of intercourse. OBJECTIVE: The goal of this review was to provide a summary of the available literature on the use of UPA for EC. METHODS: PubMed, Cochrane Library, ClinicalTrials.gov, International Pharmaceutical Abstracts, EBSCO, and Iowa Drug Information Service were searched from February 2011 through September 2011 to identify relevant articles. Search terms included ulipristal acetate, CDB-2914, VA 2914, and emergency contraception. RESULTS: In an open-label study, UPA was effective in preventing pregnancy in 1241 women who presented for EC up to 120 hours (5 days) after unprotected intercourse, with an observed pregnancy rate of 2.1% (95% CI, 1.4%-3.1%) versus 5.5% (ie, the expected pregnancy rate without EC). The efficacy of UPA did not decrease significantly (P = 0.44) over time, with pregnancy rates at intervals between >48 and 72 hours at 2.3% (95% CI, 1.4%-3.8%), >72 and 96 hours at 2.1% (95% CI, 1.0%-4.1%), and >96 and 120 hours at 1.3% (95% CI, 0.1%-4.8%). In a single-blind, comparative noninferiority study of 1696 women, UPA was at least as effective as LNG when used within 72 hours for EC, with 15 pregnancies in the UPA group and 22 pregnancies in the LNG group (odds ratio = 0.68 [95% CI, 0.35-1.31]). In addition, UPA prevented significantly (P = 0.037) more pregnancies than LNG when used between 72 and 120 hours after unprotected intercourse, with 0 pregnancies in the UPA group and 3 pregnancies in the LNG group. In a meta-analysis, UPA prevented a greater percentage of pregnancies than LNG at intervals up to 24 hours (0.9% UPA vs 2.5% LNG; P = 0.035), up to 72 hours (1.4% UPA vs 2.2% LNG; P = 0.046), and up to 120 hours (1.3% UPA vs 2.2% LNG; P = 0.025). The most commonly (>10%) reported adverse events included headache, nausea, and abdominal pain. In addition, UPA delayed onset of menstruation by a mean of 2.1 to 2.8 days. CONCLUSIONS: Based on clinical trials, UPA seems to be a reasonably tolerable and effective method of EC when used within 120 hours of intercourse. UPA is at least as effective as LNG when used within the first 72 hours after unprotected intercourse. However, UPA may be more effective than LNG when used between 72 to 120 hours after unprotected intercourse, extending the window of opportunity for EC. UPA may provide a new option for women who require EC up to 5 days after unprotected intercourse.

Adolescents and emergency contraception: update 2011.

PURPOSE OF REVIEW: This review presents the most up-to-date information regarding available methods, safety, efficacy, and availability of emergency contraception for adolescents. RECENT FINDINGS: Recent reanalysis suggests that previously reported efficacy rates for the levonorgestrel-only method emergency contraception were probably overestimated. A newer and more efficacious method of emergency contraception, ulipristal acetate, was FDA approved in August 2010. SUMMARY: Emergency contraception provides young women with an opportunity to prevent pregnancy in the event of unprotected sexual intercourse. Several dedicated products are available commercially in the USA with varying efficacy rates. Barriers, including cost and accessing emergency contraception within the designated time frame, often prevent use among young women.

Ulipristal acetate: a review of its use in emergency contraception.

Ulipristal acetate (ellaOne®; ella®) is the first of a new class of selective progesterone receptor modulators, and is indicated for emergency contraception within 120 hours after unprotected sexual intercourse or contraceptive failure. The principal effect of ulipristal acetate is to inhibit or delay ovulation. This effect may result from the drug's ability to delay the onset of luteinizing hormone (LH) surge or postpone LH peak if LH surge has started, or possibly by a direct inhibitory effect on follicular rupture, when administered in the follicular phase (including just before ovulation). In clinical trials, a single oral dose of ulipristal acetate 30 mg was effective in preventing pregnancies in women requesting emergency contraception after unprotected sexual intercourse and provided sustained efficacy throughout the 120-hour postcoital period in which it is indicated. When compared with levonorgestrel in well designed noninferiority trials, it was no less effective in preventing pregnancies when administered within 72 hours of unprotected intercourse, but was more effective when administered later (within 72-120 hours). Results of a meta-analysis suggest that ulipristal acetate may be more effective than levonorgestrel from day 1 and throughout the entire 5-day period following unprotected sexual intercourse. Ulipristal acetate is generally well tolerated, with a similar tolerability profile to that of levonorgestrel. In general, the onset of menses is delayed by 2-3 days following treatment. Although, ulipristal acetate is more expensive than levonorgestrel, it may represent a cost-effective alternative to levonorgestrel for women requesting emergency contraception within 120 hours of unprotected intercourse. Thus, ulipristal acetate provides effective, sustained and well tolerated emergency contraception when taken within 120 hours of unprotected sexual intercourse, thereby offering an extended treatment window compared with levonorgestrel, which should be administered within 72 hours.

Is it worth paying more for emergency hormonal contraception? The cost-effectiveness of ulipristal acetate versus levonorgestrel 1.5 mg.

BACKGROUND AND METHODOLOGY: Emergency hormonal contraception (EHC) can reduce unintended pregnancy and the associated costs and consequences for the individual and National Health Service (NHS). Levonorgestrel (LNG 1.5 mg) is currently the standard of care in the UK; however, it is not licensed for use >72 hours after unprotected sexual intercourse (UPSI). This cost-effectiveness analysis compares LNG 1.5 mg with ulipristal acetate (UPA) (ellaOne(®)), a new emergency hormonal contraceptive that is licensed for use up to 120 hours post-UPSI. The costs of both drugs and the costs of the consequences of unintended pregnancy - namely miscarriage, induced abortion and birth - are compared in a decision model from the perspective of the UK NHS. RESULTS: The incremental cost-effectiveness ratio (ICER) is the cost of preventing one additional unintended pregnancy with UPA and is calculated to be £311 compared to LNG 1.5 mg when taken up to 120 hours post-UPSI. In sensitivity analysis, looking at different time frames and costs, the ICER ranges from £183 to £500. All these costs are less than the estimated cost of an unintended pregnancy (£948) regardless of the outcome or the cost of an induced abortion (£672). DISCUSSION AND CONCLUSIONS: Even when considering only the direct costs of an unintended pregnancy, UPA represents value for money as a method of EHC when taken up to 120 hours post-UPSI. UPA is a cost-effective alternative to LNG 1.5 mg for all women presenting for EHC.

Ulipristal - a new emergency contraceptive pill.

Until recently, women in the UK who wanted emergency contraception had two options: an oral hormonal method (levonorgestrel), which is licensed for use up to 3 days after unprotected sexual intercourse; or a copper-bearing intrauterine device (IUD), which can be inserted up to 5 days after unprotected intercourse or up to 5 days after the earliest likely calculated ovulation. Now ulipristal acetate (ellaOne - HRA Pharma), a new oral hormonal emergency contraceptive, has been licensed in the European Union for use within 120 hours (5 days) of unprotected intercourse. Here we assess whether it is an advance for emergency contraception.