The landscape of biosimilars in Saudi Arabia: preparing for the next decade.

INTRODUCTION: The government of the Kingdom of Saudi Arabia (KSA) has developed a well-defined strategy to restructure the health sector and operate on value-based principles. Biosimilars are a viable option for increasing accessibility while lowering health-care costs. AREAS COVERED: We describe the current and future biosimilar landscape in KSA. We discuss the growth of the biosimilar market, the regulatory approval process, biosimilar adoption, and the potential impact on health-care systems and patient outcomes. EXPERT OPINION: The biosimilar market in KSA is expanding and expected to continue this trajectory in the coming decade. The growth of the market is influenced by the KSA health transformation initiative, the well-defined regulatory framework for biosimilars set by the Saudi Food and Drug Authority (SFDA), and the adoption of biosimilars by health-care providers. Overall, the biosimilar regulation is evolving and the future of biosimilars looks promising in KSA. Biosimilars offer a more cost-effective alternative, which can help to expand access to more treatment options for patients and contribute to cost saving for the health-care system.

Cost-efficiency analysis and expanded treatment access modeling of conversion to rituximab biosimilars from reference rituximab in Jordan.

AIM: To assess the cost-efficiency and expanded access of three rituximab biosimilars versus the reference rituximab from the perspective of the Jordanian national health payer. METHODS: A 1-year cost-efficiency and expanded access model of conversion from reference rituximab (Mabthera) to the approved biosimilars (Truxima, Rixathon, and Tromax) to assess five metrics: total annual cost to treat a hypothetical patient; head-to-head cost comparison; changes in patients' access to rituximab; number-needed-to-convert (NNC) to provide an additional 10 patients access to a rituximab treatment; and relative amount of Jordanian Dinar (JOD) spent on rituximab options. The model included rituximab doses at 100 mg/10 ml and 500 mg/50 ml and considered both cost-saving and cost-wastage scenarios. Costs of treatments were based on the fiscal year 2022 tender prices received by the Joint Procurement Department (JPD). RESULTS: Rixathon was associated with the lowest average annual cost per patient (JOD2,860) across all six indications among all rituximab comparators, followed by Truxima (JOD4,240), Tromax (JOD4,365) and reference Mabthera (JOD11,431). The highest percentage of patient access to rituximab treatment (321%) was achieved when switching patients from Mabthera to Rixathon in the RA and PV indications. At four patients, Rixathon was associated with the lowest NNC to provide an additional 10 patients access to rituximab treatment. For each JOD1 spent on Rixathon, an additional JOD3.21 must be spent on Mabthera, an additional JOD0.55 on Tromax, and an additional JOD0.53 on Truxima. CONCLUSION: Rituximab biosimilars were associated with cost savings in all approved indications in Jordan compared to reference rituximab. Rixathon was associated with the lowest annual cost, the highest percentage of expanded patient access for all six indications, and the lowest NNC providing 10 additional patients with access.

Cost-effectiveness of Favipiravir in moderately to severely ill COVID-19 patients in the real-world setting of Saudi arabian pandemic referral hospitals.

Purpose: We aimed to evaluate the cost effectiveness of Favipiravir treatment versus standard of care (SC) in moderately to severely ill COVID-19 patients from the Saudi healthcare payer perspective. Methods: We used the patient-level simulation method to simulate a cohort of 415 patients with moderate to severe COVID-19 disease who were admitted to two Saudi COVID-19 referral hospitals: 220 patients on Favipiravir and 195 patients on SC. We estimated the incremental cost-effectiveness ratio (ICER) of Favipiravir versus SC in terms of the probability to be discharged alive from hospital and the mean time in days to discharge one patient alive. The model was performed twice: first, using unweighted, and second, using weighted clinical and economic data. Weighting using the inverse weight probability method was performed to achieve balance in baseline characteristics. Results: In the unweighted model, base case (probabilistic) ICER estimates favored Favipiravir at savings of Saudi Riyal (SAR)1,611,511 (SAR1,998,948) per 1% increase in the probability of being discharged alive. As to mean time to discharging one patient alive, ICERs favored Favipiravir at savings of SAR11,498 (SAR11,125). Similar results were observed in the weighted model with savings using Favipiravir of SAR1,514,893 (SAR2,453,551) per 1% increase in the probability of being discharged alive, and savings of SAR11,989 (SAR11,277) for each day a patient is discharged alive. Conclusion: From the payer perspective, the addition of Favipiravir in moderately to severely ill COVID-19 patients was cost-savings over SC. Favipiravir was associated with a higher probability of discharging patients alive and lower daily spending on hospitalization than SC.

Economic Evaluation of Three BRAF + MEK Inhibitors for the Treatment of Advanced Unresectable Melanoma With BRAF Mutation From a US Payer Perspective.

BACKGROUND: The combinations of BRAF + MEK inhibitors-encorafenib (ENC) + binimetinib (BIN), cobimetinib (COB) + vemurafenib (VEM), and dabrafenib (DAB) + trametinib (TRA)-are recommended for the treatment of BRAF-mutated advanced melanoma. OBJECTIVE: To assess the cost-effectiveness and cost-utility of ENC + BIN versus COB + VEM versus DAB + TRA from a US payer perspective. METHODS: A Markov model was constructed to simulate a hypothetical cohort over a time horizon of 10 years. The overall survival (OS) and progression-free survival (PFS) curves were independently digitized from a randomized controlled trial for ENC + BIN and fitted using R software. Published and indirectly estimated hazard ratios were used to fit OS and PFS curves for COB + VEM and DAB + TRA. Costs, life-year gains, and quality-adjusted life years (QALYs) associated with the 3 treatment combinations were estimated. A base case analysis and probabilistic sensitivity analysis (PSA) were conducted to estimate the incremental cost-utility ratio (ICUR). A discount rate of 3.5% was applied on cost and outcomes. RESULTS: The ENC + BIN versus COB + VEM comparison was associated with an ICUR of $656 233 per QALY gained. The ENC + BIN versus DAB + TRA comparison was associated with an ICUR of $3 135 269 per QALY gained. The DAB + TRA combination dominated COB + VEM. The base case analysis estimates were confirmed by the PSA estimates. ENC + BIN was the most cost-effective combination at a high willingness-to-pay (WTP) threshold of $573 000 per QALY and $1.5 million/QALY when compared to COB + VEM and DAB + TRA, respectively. CONCLUSION AND RELEVANCE: Given current prices and acceptable WTP thresholds, our study suggests that DAB + TRA is the optimum treatment. In this study, ENC + BIN was cost-effective only at a very high WTP per QALY threshold.

Economic analysis of glucagon like peptide-1 receptor agonists from the Saudi Arabia payer perspective.

Objectives: To perform a cost of control analysis of glucagon like peptide-1 receptor agonists (GLP1RA) in Saudi Arabia (SA) and determine the economic impact of adopting GLP1RAs. Methods: A budget impact model that captures the cost of control model was constructed to simulate hypothetical patient on six treatment options: a current mix of 60% liraglutide and 40% dulaglutide, semaglutide, liraglutide, dulaglutide, exenatide, and lixisenatide. We estimated the relative amounts of SAR spend to achieve HbA1c targets (≤6.5% or < 7.0%). For each treatment option, annual treatment cost, proportion of patients achieving HbA1c targets, and cost to treat major adverse cardiovascular events (MACE) were aggregated to estimate the cost of control per patient per year (CCPPPY) over 5-year horizon (2021-2025). Probabilistic sensitivity analysis (PSA) was performed as a confirmatory analysis. Results: The CCPPPY to achieve HbA1c ≤ 6.5%/<7.0% using current mix, semaglutide, liraglutide, dulaglutide, exenatide, and lixisenatide were SAR 17,097/SAR 14,113, SAR 12,889/SAR 11,123, SAR 15,594/SAR 12,892, SAR 19,184/SAR 15,940, SAR 580,211/SAR 380,936, and SAR 246,570/SAR 143,759, respectively. The relative amounts of SAR spend to achieve HbA1c ≤ 6.5%/<7.0% relative to 1 SAR on semaglutide in case of adopting current mix, liraglutide, dulaglutide, exenatide, and lixisenatide were SAR 1.42/SAR 1.18, SAR 1.30/SAR 1.07, SAR 1.60/SAR 1.33, SAR 48.33/SAR 31.73, and SAR 20.54/SAR 11.97, respectively. These results were confirmed in the PSA. Conclusions: Semaglutide 1 mg once weekly was the most economically favorable GLP1RA; associated with the least CCPPPY, and amount of SAR spent to achieve HbA1c of ≤6.50%/<7.00% versus all other GLP1RAs.

Immune checkpoint inhibitors-associated risk of immune-related hypothyroidism in older patients with advanced melanoma: a real-world analysis of US SEER-Medicare data.

Background: The risk of immune-related(ir)-hypothyroidism in older patients with advanced melanoma treated with anti-CTLA4 or anti-PD1 therapies is poorly understood, especially in the real-world setting.Research design and methods: We identified older patients (≥65 years) diagnosed with advanced melanoma between 2011-2015 and treated with anti-CTLA4 or anti-PD1 agents in the SEER-Medicare database. Applying probability-of-treatment-weighting for confounder adjustment and proportional hazards models, we estimated the risk of ir-hypothyroidism between treatment initiation and up to 90 days from last dose between anti-PD1 and anti-CTLA4 users.Results: Of 210 older patients with advanced melanoma identified, 164 received anti-CTLA4 (ipilimumab) and 46 anti-PD1 agents (11 nivolumab, 35 pembrolizumab). There was no statistically significant difference in ir-hypothyroidism risk between anti-PD1 and anti-CTLA4 users (HR=2.15, 95%CI=0.83-5.53). Pairwise medication comparisons showed a lower risk among ipilimumab versus nivolumab (HR=0.15, 95%CI=0.06-0.40) and pembrolizumab versus nivolumab users (HR=0.13, 95%CI=0.03-0.55). Sensitivity analyses using an all-stages melanoma cohort did not show a difference in ir-hypothyroidism risk between medication classes and individual medications.Conclusions:This retrospective claims data analysis revealed no statistically significant difference in ir-hypothyroidism risk between anti-CTLA4 or anti-PD1 users. However, patients with advanced melanoma treated with ipilimumab or pembrolizumab may have a lower ir-hypothyroidism risk compared to nivolumab users.

A comparison of the pharmacologic and nonpharmacologic strategies used to manage chronic pain: Opioid users versus nonusers.

BACKGROUND: Multimodal and multidomain strategies are currently recommended for the management of chronic pain. However, there is little information available on how individuals (opioid users versus nonusers) with chronic pain use multimodal strategies in pain management. METHODS: This cross-sectional study used questionnaire data from a sample of pharmacists with chronic pain. The questionnaire collected data on demographics, pain characteristics, pain management strategies, and pain management outcomes. The association between the number of strategies used and opioid use were evaluated by linear regression. Differences between the groups in nonsteroidal anti-inflammatory drugs (NSAIDs) use and types of strategies used in managing the pain were analyzed using logistic regressions. A hierarchical logistic regression was performed to identify potential predictors differentiating opioid users from nonusers. RESULTS: Fifty-seven opioid users and 100 nonusers with chronic pain completed the questionnaire. Opioid users reported higher levels of pain at baseline (7.6 ± 1.7 vs. 6.7 ± 2.2; P = 0.011); however, pain levels after treatment were comparable (2.9 ± 1.9 vs. 3.2 ± 2.4; P = 0.33). Although there was no significant difference in the total number of strategies, the number of pharmacologic strategies was significantly higher in opioid users (P = 0.007). The type of pain management strategies and the use of NSAIDs were similar in both groups after adjusting for potential confounders. The significant predictors of opioid use from hierarchical logistic regression analysis were: lower use of over-the-counter NSAIDs (odds ratio [OR] 0.4; 95% CI 0.2-0.9), using more interventions (OR 1.2; 95% CI 1.1-1.3), reliance on pharmacologic strategies (OR 10.8; 95% CI 2.1-55.7), using combination of pharmacologic and nonpharmacologic strategies (OR 3.7; 95% CI 0.9-15.8), and less interference with daily activities after treatment (OR 0.2; 95% CI 0.1-0.9). CONCLUSION: Opioid use was primarily related to the use of prescription pharmacologic strategies, but not to age or gender. Posttreatment pain levels were similar between opioid users and nonusers; however, opioid users used more nonopioid medications than nonusers did.

Economic Evaluation of Talimogene Laherparepvec Plus Ipilimumab Combination Therapy vs Ipilimumab Monotherapy in Patients With Advanced Unresectable Melanoma.

Importance: A phase 2 trial comparing talimogene laherparepvec plus ipilimumab vs ipilimumab monotherapy in patients with advanced unresectable melanoma found no differential benefit in progression-free survival (PFS) but noted objective response rates (ORRs) of 38.8% (38 of 98 patients) vs 18.0% (18 of 100 patients), respectively. Objective: To perform an economic evaluation of talimogene laherparepvec plus ipilimumab combination therapy vs ipilimumab monotherapy. Design, Setting, and Participants: For PFS, cost-effectiveness and cost-utility analyses using a 2-state Markov model (PFS vs progression or death) was performed. For ORRs, cost-effectiveness analysis of the incremental cost of 1 additional patient achieving objective response was performed. In this setting based on a US payer perspective (2017 US dollars), participants were patients with advanced unresectable melanoma. Main Outcomes and Measures: The PFS life-years and PFS quality-adjusted life-years were determined, and the associated incremental cost-effectiveness ratios (ICERs) and incremental cost-utility ratios (ICURs) were estimated. Also estimated was the ICER per 1 additional patient (out of 100 treated patients) achieving objective response. Base-case analyses were validated by sensitivity analyses. Results: In PFS analyses, the cost of talimogene laherparepvec plus ipilimumab ($494 983) exceeded the cost of ipilimumab monotherapy ($132 950) by $362 033. The ICER was $2 129 606 per PFS life-years, and the ICUR was $2 262 706 per PFS quality-adjusted life-year gained. Probabilistic sensitivity analyses yielded an ICER of $1 481 208 per PFS life-year gained and an ICUR of $1 683 191 per PFS quality-adjusted life-year gained. In 1-way sensitivity analyses, the PFS hazard ratio and the utility of response were the most influential parameters. Talimogene laherparepvec plus ipilimumab has a 50% likelihood of being cost-effective at a willingness-to-pay threshold of $1 683 191 per PFS quality-adjusted life-year gained. In ORR analyses, talimogene laherparepvec plus ipilimumab ($474 904) vs ipilimumab alone ($132 810), a $342 094 difference, yielded an ICER of $1 629 019 per additional patient achieving objective response. In subgroup analyses by disease stage and BRAFV600E mutation status, ICERs ranged from $1 069 044 to $17 104 700 per 1 additional patient achieving objective response. Conclusions and Relevance: The cost to gain 1 additional progression-free quality-adjusted life-year, 1 additional progression-free life-year, or to have 1 additional patient attain objective response is about $1.6 million. This amount may be beyond what payers typically are willing to pay. Combination therapy of talimogene laherparepvec plus ipilimumab does not offer an economically beneficial treatment option relative to ipilimumab monotherapy at the population level. This should not preclude treatment for individual patients for whom this regimen may be indicated.

Establishing the Validity and Reliability Evidence of Preceptor Assessment of Student Tool.

Objective. To evaluate the validity and reliability evidence of the preceptor assessment of student tool (PAST) which was designed to assess doctor of pharmacy (PharmD) student rotation performance. Methods. Evaluation data were loaded into WINSTEPS software to conduct a Rasch rating scale analysis. Validity evidence was examined from construct and content validity perspectives, and reliability was assessed via student and item separation index and reliability coefficient. Data from 435 observations were included in the analysis. Results. All 19 items measured the same construct of interest and the five-point rating scale functioned appropriately and differentiated students' ability. However, the item/person map indicated an absence of items at the end of the measurement continuum. Conclusion. Although adding items at the end of the measurement continuum may be beneficial, PAST showed good validity and reliability evidence when used to evaluate PharmD student rotations and is suitable to assess mastery learning.