OPT-In; Optimized Patient Treatment Outcomes in Plaque Psoriasis: A 3-Year State-Transition Treatment-Sequencing Model in the Italian Setting.

INTRODUCTION: There are several treatment options for plaque psoriasis (PsO), but uncertainty remains around the optimal sequencing of treatments. The aims of this study were to investigate how adopting a best-treatment-first treatment sequence impacts patient outcomes and healthcare systems and to quantify the cost of treatment failure to the healthcare system. METHODS: A 3-year state-transition treatment-sequencing model which identifies all possible treatment sequences in PsO was adapted to the Italian healthcare setting. Treatments considered in the model are those with European Medicines Agency marketing authorization and reimbursement in Italy as of December 2022. Italian market share data (2019-2021) and list prices (2022) informed the current prescribed sequences; these sequences were compared against all possible sequences to determine opportunities for improvement. Both the national perspective in Italy as well as the local perspective from seven regions were considered. The cost of treatment failure was informed through a questionnaire circulated to Italian dermatologists. RESULTS: Overall, 1284 possible treatment sequences are possible when four lines of treatment are considered for patients with moderate-to-severe PsO in Italy. Within the estimated range of treatment failures across those sequences (0.97-2.56 per patient over 3 years), current prescribing behavior from the national perspective suggests patients will face 1.44 failures on average; this highlights the potential for improvement. For every treatment failure, the cost borne by the Italian National Healthcare Service (NHS) is €676.80. Overall, prescribing more optimized treatment sequences results in a 22.95% reduction in failures with a 2.27% increase in costs. The regional analyses found similar trends. CONCLUSIONS: Results suggest that selecting the most effective treatment sequences for incident patients provides the greatest opportunity to reduce treatment failures and maximize patient outcomes with a modest impact on costs. While regional variations exist, there is room for improvement across the board, which could translate to more efficient local healthcare systems.

Modelling Treatment Sequences in Immunology: Optimizing Patient Outcomes.

INTRODUCTION: For some immune-mediated disorders, despite the range of therapies available there is limited evidence on which treatment sequences are best for patients and healthcare systems. We investigated how their selection can impact outcomes in an Italian setting. METHODS: A 3-year state-transition treatment-sequencing model calculated potential effectiveness improvements and budget reallocation considerations associated with implementing optimal sequences in ankylosing spondylitis (AS), Crohn's disease (CD), non-radiographic axial spondyloarthritis (NR-AxSpA), plaque psoriasis (PsO), psoriatic arthritis (PsA), rheumatoid arthritis (RA), and ulcerative colitis (UC). Sequences included three biological or disease-modifying treatments, followed by best supportive care. Disease-specific response measures were selected on the basis of clinical relevance, data availability, and data quality. Efficacy was differentiated between biologic-naïve and experienced populations, where possible, using published network meta-analyses and real-world data. All possible treatment sequences, based on reimbursement as of December 2022 in Italy (analyses' base country), were simulated. RESULTS: Sequences with the best outcomes consistently employed the most efficacious therapies earlier in the treatment pathway. Improvements to prescribing practice are possible in all diseases; however, most notable was UC, where the per-patient 3-year average treatment failure was 37.3% higher than optimal. The results focused on the three most crowded and prevalent immunological sub-condition diseases in dermatology, rheumatology, and gastroenterology: PsO, RA, and UC, respectively. By prescribing from within the top 20% of the most efficacious sequences, the model found a 15.1% reduction in treatment failures, with a 1.59% increase in drug costs. CONCLUSIONS: Prescribing more efficacious treatments earlier provides a greater opportunity to improve patient outcomes and minimizes treatment failures.

Comparing Efficacy of Guselkumab versus Ustekinumab in Patients with Psoriatic Arthritis: An Adjusted Comparison Using Individual Patient Data from the DISCOVER and PSUMMIT Trials.

INTRODUCTION: Two biologic therapies for psoriatic arthritis (PsA), guselkumab and ustekinumab, have demonstrated superior efficacy versus placebo in clinical trials. However, no head-to-head studies have been conducted comparing these two treatments for PsA. The objective was to indirectly compare guselkumab and ustekinumab on joint and skin efficacy up to week 52, using pooled individual patient-level data (IPD) from PsA trials. METHODS: IPD, including baseline characteristics, American College of Rheumatology (ACR) scores and Psoriasis Area Severity Index (PASI) response from guselkumab (DISCOVER-1 and -2) and ustekinumab (PSUMMIT 1 and 2) trials were pooled. Differences in patient characteristics across trials were adjusted using multivariate logistic regression. Odds ratios (OR) were used to derive absolute response probabilities in the guselkumab trial population and were presented with 95% confidence intervals. RESULTS: Most baseline characteristics for guselkumab-treated patients (100 mg every 8 weeks [Q8W]; 100 mg every 4 weeks [Q4W]) were comparable to ustekinumab-treated patients (45/90 mg). In biologic-naïve patients, both guselkumab doses showed significantly higher ACR 20 (Q8W: 1.97; 1.37, 2.84; Q4W: 2.04; 1.40, 2.96) and PASI 90 (Q8W: 2.33; 1.52, 3.56; Q4W: 2.57; 1.67, 3.97) versus ustekinumab from week 16 onwards. In biologic-experienced patients, both guselkumab doses showed significantly higher ACR 20 (Q8W: 2.57; 1.11, 5.93; Q4W: 2.63; 1.12, 6.17) versus ustekinumab from week 24 onwards; for PASI 90, both guselkumab doses were superior to ustekinumab at week 16 and 52 (Q8W: 3.96; 1.39, 11.27; Q4W: 13.10; 4.18, 41.04). Guselkumab efficacy was similar and robust across primary, scenario, and sensitivity analyses. CONCLUSIONS: IPD analysis demonstrated that both guselkumab doses were superior to ustekinumab for ACR 20 from weeks 16 (biologic-naïve) and 24 (biologic-experienced) onwards, and for PASI 90 at weeks 16 and 52 for both subgroups.

Matching-adjusted indirect comparison (MAIC) results confirmed by head-to-head trials: a case study in psoriasis.

BACKGROUND: Head-to-head comparisons through randomized controlled trials (RCTs) provide high-quality evidence to inform healthcare decisions. In their absence, indirect comparisons are often performed; however, evidence is limited on how valid matching-adjusted indirect comparison (MAIC)-based comparative efficacy estimates are vs. RCT-based estimates. OBJECTIVES: Compare MAIC and RCT results of guselkumab vs. secukinumab and ixekizumab to provide insight into the validity of results generated using MAIC methods. METHODS: Previously reported results from MAICs of guselkumab vs. secukinumab and ixekizumab were compared with results from ECLIPSE and IXORA-R RCTs based on risk differences between Psoriasis Area and Severity Index (PASI) 90 response rates. RESULTS: Risk difference (95% confidence interval) in PASI 90 response rates at week 48 for guselkumab vs. secukinumab was 14.4% (9.4%; 19.4%) in ECLIPSE and 9.4% (4.7%; 14.0%) in the MAIC. The risk difference at week 24 for guselkumab vs. ixekizumab was 0.0% (-5.4%; 5.4%) in IXORA-R and 0.7% (-5.1%; 6.4%) in the MAIC. CONCLUSIONS: Comparative efficacy results were consistent between MAICs and RCTs of guselkumab vs. secukinumab and ixekizumab. This analysis demonstrates that MAIC methods can provide valid relative treatment effect estimates when direct comparisons are lacking, particularly when trials with similar designs and patient populations inform the analysis.

Comparative effectiveness of guselkumab in psoriatic arthritis: updates to a systematic literature review and network meta-analysis.

OBJECTIVE: The IL-23 p19-subunit inhibitor guselkumab has been previously compared with other targeted therapies for PsA through network meta-analysis (NMA). The objective of this NMA update was to include new guselkumab COSMOS trial data, and two key comparators: the IL-23 inhibitor risankizumab and the Janus kinase (JAK) inhibitor upadacitinib. MATERIAL AND METHODS: A systematic literature review was conducted to identify randomized controlled trials up to February 2021. A hand-search identified newer agents up to July 2021. Bayesian NMAs were performed to compare treatments on ACR response, Psoriasis Area and Severity Index (PASI) response, modified van der Heijde-Sharp (vdH-S) score, and serious adverse events (SAEs). RESULTS: For ACR 20, guselkumab 100 mg every 8 weeks (Q8W) and every 4 weeks (Q4W) were comparable (i.e. overlap in credible intervals) to most other agents, including risankizumab, upadacitinib, subcutaneous TNF inhibitors and most IL-17A inhibitors. For PASI 90, guselkumab Q8W and Q4W were better than multiple agents, including subcutaneous TNF and JAK inhibitors. For vdH-S, guselkumab Q8W was similar to risankizumab, while guselkumab Q4W was better; both doses were comparable to most other agents. Most agents had comparable SAEs. CONCLUSIONS: Guselkumab demonstrates better skin efficacy than most other targeted PsA therapies, including upadacitinib. For vdH-S, both guselkumab doses are comparable to most treatments, with both doses ranking higher than most, including upadacitinib and risankizumab. Both guselkumab doses demonstrate comparable ACR responses to most other agents, including upadacitinib and risankizumab, and rank favourably in the network for SAEs.

The Cost of Unintended Pregnancies in Canada: Estimating Direct Cost, Role of Imperfect Adherence, and the Potential Impact of Increased Use of Long-Acting Reversible Contraceptives.

OBJECTIVE: Unintended pregnancies (UPs) are associated with a significant cost burden, but the full cost burden in Canada is not known. The objectives of this study were to quantify the direct cost of UPs in Canada, the proportion of cost attributable to UPs and imperfect contraceptive adherence and the potential cost savings with increased uptake of long-acting reversible contraceptives (LARCs). METHODS: A cost model was constructed to estimate the annual number and direct costs of UP in women aged 18 to 44 years. Adherence-associated UP rates were estimated using perfect- and typical-use contraceptive failure rates. Change in annual number of UPs and impact on cost burden were projected in three scenarios of increased LARC usage. One-way sensitivity analyses were conducted to assess the impact of key variables on scenarios of increased LARC use. RESULTS: There are more than 180 700 UPs annually in Canada. The associated direct cost was over $320 million. Fifty-eight percent (58%) of UPs occurred in women aged 20 to 29 years at an annual cost of $175 million; 82% of this cost ($143 million) was attributable to contraceptive non-adherence. Increased LARC uptake produced cost savings of over $34 million in all three switching scenarios; the largest savings ($35 million) occurred when 10% of oral contraceptive users switched to LARCs. The minimum duration of LARC usage required before cost savings was realized was 12 months. CONCLUSION: The cost of UPs in Canada is significant and much of it can be attributed to imperfect contraceptive adherence. Increased LARC uptake may reduce contraceptive non-adherence, thereby reducing rates of UP and generating significant cost savings, particularly in women aged 20 to 29.

Objectif : Les grossesses non planifiées (GNP) sont associées à un fardeau financier considérable; au Canada, l'ampleur de ce fardeau demeure inconnue. Cette étude avait pour objectif de quantifier les coûts directs des GNP au Canada, la proportion des coûts liés aux GNP attribuables à une observance imparfaite du schéma posologique contraceptif et les économies potentielles associées à un accroissement de l'utilisation de modes de contraception réversible à action prolongée (CRAP). Méthodes : Un modèle de coût a été conçu pour estimer le nombre annuel de GNP et leurs coûts directs chez les femmes âgées de 18 à 44 ans. Les taux de GNP associés à l'observance ont été estimés au moyen des taux d'échec de la contraception en utilisation parfaite et en utilisation typique. Les modifications du nombre annuel de GNP et les effets sur le fardeau financier ont été projetés dans le cadre de trois scénarios prévoyant un accroissement du recours aux modes de CRAP. Des analyses simples de la variance en matière de sensibilité ont été menées pour évaluer les effets de variables clés sur les scénarios prévoyant un accroissement du recours aux modes de CRAP. Résultats : On compte plus de 180 700 GNP chaque année au Canada. Les coûts directs qui leur sont associés sont de plus de 320 millions de dollars. Cinquante-huit pour cent (58 %) des GNP se sont manifestées chez des femmes de 20 à 29 ans, ce qui représente un coût annuel de 175 millions de dollars; 82 % de ce coût (143 millions de dollars) étaient attribuables à la non-observance du schéma posologique contraceptif. L'accroissement du recours aux modes de CRAP a généré des économies de plus de 34 millions de dollars dans le cadre des trois scénarios de transition envisagés; les économies les plus importantes (35 millions de dollars) ont été constatées dans le cadre du scénario prévoyant que 10 % des utilisatrices de contraceptifs oraux adopteraient un mode de CRAP. La durée minimale d'utilisation d'un mode de CRAP nécessaire pour l'obtention d'économies était de 12 mois. Conclusion : Au Canada, le coût des GNP est considérable; de plus, une bonne partie de ce coût est attribuable à une observance imparfaite du schéma posologique contraceptif. L'accroissement du recours aux modes de CRAP pourrait mener à une baisse du taux de non-observance du schéma posologique contraceptif, ce qui entraînerait une baisse des taux de GNP et générerait des économies considérables, particulièrement chez les femmes de 20 à 29 ans.

Direct costs of unintended pregnancy in Spain.

OBJECTIVE: The aim of the study was to estimate the burden and direct medical costs of unintended pregnancy to the public payer in Spain. METHODS: An economic model evaluating the costs and outcomes of contraceptive use over a 1-year period was constructed for women in Spain aged 15 to 44 years at risk of pregnancy. Model inputs were derived from published literature and national survey data. Outcomes evaluated included: (i) the annual number of unintended pregnancy events and their cost; (ii) the proportion of unintended pregnancy events and their cost due to non-adherence; and (iii) the use and cost of contraceptive methods in Spain. RESULTS: Of the total number of pregnancies, 35% are estimated to be unintended and are associated with a direct cost burden of €292.8 million per year. Most unintended pregnancies (26%) occur in women aged 30 to 34 years, whilst 69% of the total cost burden is estimated to be attributable to poor adherence to contraceptive methods. CONCLUSIONS: The cost associated with unintended pregnancy is high. The major proportion of the burden is estimated to be attributable to imperfect adherence and is likely avoidable. Shifts in patterns of contraceptive use, combined with measures to improve adherence, could have a substantial and positive impact on this burden.

Achieving cost-neutrality with long-acting reversible contraceptive methods.

OBJECTIVES: This analysis aimed to estimate the average annual cost of available reversible contraceptive methods in the United States. In line with literature suggesting long-acting reversible contraceptive (LARC) methods become increasingly cost-saving with extended duration of use, it aimed to also quantify minimum duration of use required for LARC methods to achieve cost-neutrality relative to other reversible contraceptive methods while taking into consideration discontinuation. STUDY DESIGN: A three-state economic model was developed to estimate relative costs of no method (chance), four short-acting reversible (SARC) methods (oral contraceptive, ring, patch and injection) and three LARC methods [implant, copper intrauterine device (IUD) and levonorgestrel intrauterine system (LNG-IUS) 20 mcg/24 h (total content 52 mg)]. The analysis was conducted over a 5-year time horizon in 1000 women aged 20-29 years. Method-specific failure and discontinuation rates were based on published literature. Costs associated with drug acquisition, administration and failure (defined as an unintended pregnancy) were considered. Key model outputs were annual average cost per method and minimum duration of LARC method usage to achieve cost-savings compared to SARC methods. RESULTS: The two least expensive methods were copper IUD ($304 per women, per year) and LNG-IUS 20 mcg/24 h ($308). Cost of SARC methods ranged between $432 (injection) and $730 (patch), per women, per year. A minimum of 2.1 years of LARC usage would result in cost-savings compared to SARC usage. CONCLUSIONS: This analysis finds that even if LARC methods are not used for their full durations of efficacy, they become cost-saving relative to SARC methods within 3 years of use. IMPLICATIONS: Previous economic arguments in support of using LARC methods have been criticized for not considering that LARC methods are not always used for their full duration of efficacy. This study calculated that cost-savings from LARC methods relative to SARC methods, with discontinuation rates considered, can be realized within 3 years.

Cost-effectiveness analysis of levonorgestrel-releasing intrauterine system (LNG-IUS) 13.5 mg in contraception.

BACKGROUND: Levonorgestrel-releasing intrauterine system (LNG-IUS) 13.5 mg (total content) is a low-dose levonorgestrel intrauterine system for up to 3 years of use. This analysis evaluated the cost-effectiveness of LNG-IUS 13.5 mg in comparison with short-acting reversible contraceptive (SARC) methods in a cohort of young women in the United States from a third-party payer's perspective. STUDY DESIGN: A state transition model consisting of three mutually exclusive health states -- initial method, unintended pregnancy (UP) and subsequent method -- was developed. Cost-effectiveness of LNG-IUS 13.5 mg was assessed vs. SARC methods in a cohort of 1000 women aged 20-29 years. SARC methods comprise oral contraceptives (OC), ring, patch and injections, which are the methods commonly used by this cohort. Failure and discontinuation probabilities were based on published literature, contraceptive uptake was determined by the most recent data from the National Survey of Family Growth, and costs were taken from standard US databases. One-way sensitivity analysis was conducted around key inputs, while scenario analysis assessed a comparison between LNG-IUS 13.5 mg and the existing IUS, LNG-IUS 20 mcg/24 h. The key model output was cost per UP avoided. RESULTS: Compared to SARC methods, initiating contraception with LNG-IUS 13.5 mg resulted in fewer UP (64 UP vs. 276 UP) and lower total costs ($1,283,479 USD vs. $1,862,633 USD, a 31% saving) over the 3-year time horizon. Results were most sensitive to the probability of failure on OC, the probability of LNG-IUS 13.5 mg discontinuation and the cost of live births. Scenario analysis suggests that further cost savings may be generated with the initiation of LNG-IUS 20 mcg/24 h in place of SARC methods. CONCLUSIONS: From a third-party payer perspective, LNG-IUS 13.5 mg is a more cost-effective contraceptive option than SARC. Therefore, women switching from current SARC use to LNG-IUS 13.5 mg are likely to generate cost savings to third-party health care payers, driven principally by decreased UP-related expenditures and long-term savings in contraceptive costs.

Burden of unintended pregnancy in the United States: potential savings with increased use of long-acting reversible contraception.

BACKGROUND: This study evaluated the total costs of unintended pregnancy (UP) in the United States (US) from a third-party health care payer perspective and explored the potential role for long-acting reversible contraception (LARC) in reducing UP and resulting health care expenditure. STUDY DESIGN: An economic model was constructed to estimate direct costs of UP as well as the proportion of UP costs that could be attributed to imperfect contraceptive adherence. The model considered all women requiring reversible contraception in the US: the pattern of contraceptive use and the rates of UP were derived from published sources. The costs of UP in the United States and the proportion of total cost that might be avoided by improved adherence through increased use of LARC were estimated. RESULTS: Annual medical costs of UP in the United States were estimated to be $4.6 billion, and 53% of these were attributed to imperfect contraceptive adherence. If 10% of women aged 20-29 years switched from oral contraception to LARC, total costs would be reduced by $288 million per year. CONCLUSIONS: Imperfect contraceptive adherence leads to substantial UP and high, avoidable costs. Improved uptake of LARC may generate health care cost savings by reducing contraceptive non-adherence.