Cost-Effectiveness Analysis of L-Asparaginase versus PEG-Asparaginase in the Treatment Regimen of Acute Lymphoblastic Leukemia

Abstract

Background: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, with asparaginase-based regimens forming the backbone of therapy. While both PEG-asparaginase and L-asparaginase are commonly employed, they differ significantly in pricing, drug metabolism, and dosing frequency. This study evaluates the economic efficiency of PEG-asparaginase relative to L-asparaginase for pediatric ALL treatment. Method: This pharmacoeconomic evaluation included 55 pediatric ALL patients, with treatment distribution as follows: 50 received PEG-asparaginase, 9 received L-asparaginase, and 4 patients were treated with both agents. Therapeutic efficacy was assessed using an established clinical outcome metric, while direct medical expenditures were systematically documented. The economic evaluation incorporated calculation of the incremental cost-effectiveness ratio (ICER). Statistical comparisons of cost and effectiveness measures were performed using independent sample t-tests, and variable relationships were examined through Pearson correlation analysis. Result: The average cost per patient for PEG-asparaginase was INR. 27,960.00, compared to INR. 2,244.40 for L-asparaginase. Mean effectiveness scores were 0.97 and 0.68, respectively. The ICER for PEG-asparaginase versus L-asparaginase was calculated at INR. 88,674.48 per unit of effectiveness gained. The difference in cost between the two treatments was statistically significant (p = 0.008), while the difference in effectiveness was not (p = 0.436). Pearson correlation analysis indicated a significant positive correlation between drug type and cost (r = 0.525, p < 0.001), but not between cost andeffectiveness (r = 0.084, p = 0.529). Conclusion: While PEG-asparaginase demonstrated slightly higher clinical effectiveness, its significantly higher cost did not yield a statistically significant improvement in outcomes over L-asparaginase. These findings suggest that L-asparaginase may offer a more cost-effective option for pediatric ALL treatment, particularly in resource-limited settings. Further research with larger sample sizes is recommended to validate these results.

Keywords

Introduction

Figure 1. Research Process flowchart

Study Methodology Flow Chart

 

To evaluate the relationships between treatment cost, effectiveness, and the type of asparaginase used, a Pearson correlation analysis was conducted.

A moderate to strong positive correlation was identified between the drug type and cost (r = 0.525), which was found to be statistically significant (p < 0.001). This indicates that the cost of treatment varied significantly depending on whether PEG-asparaginase or L-asparaginase was used, with PEG-asparaginase being associated with higher treatment expenses.

There was also a positive correlation between drug type and treatment effectiveness (r = 0.640); however, this association was not statistically significant (p = 0.629), suggesting no conclusive evidence that drug type directly influenced treatment outcomes in this cohort.

Additionally, the correlation between cost and effectiveness was weak (r = 0.084) and not statistically significant (p = 0.529), indicating that increased spending did not necessarily correspond with improved clinical outcomes.

DISCUSSION

This pharmacoeconomic analysis evaluated the cost-effectiveness of PEG-asparaginase compared to native L-asparaginase for treating pediatric acute lymphoblastic leukemia (ALL). Although PEG-asparaginase demonstrated a marginally higher mean effectiveness (0.97 vs. 0.68), the difference was not statistically significant (p = 0.436). In contrast, the cost disparity was considerable and statistically significant (p = 0.008), with PEG-asparaginase costing INR 27,960.00 per patient on average, while L-asparaginase was significantly cheaper at INR 2,244.40. The incremental cost-effectiveness ratio (ICER) of INR 88,674.48 per effectiveness unit highlights the substantial additional expense of PEG-asparaginase without a commensurate clinical benefit. These findings align with previous study, who found that while PEG-asparaginase was associated with improved pharmacokinetics and longer asparagine depletion, this did not always translate into significantly better clinical outcomes, especially in standard-risk patients. ^[9]

This study ICER results aligns with a previous study conducted by Kumar et al. who reported an ICER of INR 81,000 for PEG-asparaginase versus L-asparaginase in a pediatric ALL patients and concluded that native L-asparaginase was more cost-effective for low-risk groups. ^[10] Additionally, Neumann et al. highlighted that therapies with minor effectiveness often lead to disproportionately high ICERs, making them economically viable only when accompanied by meaningful survival of QOL benefits. ^[5] This current study finding add to the existing evidence that PEG-asparaginase may be best reserved for specific cases particularly high-risk or relapsed patients, as well as those with hypersensitivity to the native form. While 87.27% of patients in our study developed toxicities (without differentiation between formulations), future studies should investigate whether PEG-asparaginase lowers adverse event rates, which could otherwise lead to increased treatment expenses.

PEG-asparaginase, a pegylated version of the enzyme, was developed to minimize immunogenic reactions and prolong its half-life, enabling less frequent administration and better treatment compliance. Previous study by Panosyan et al. (2004) and Avramis et al. (2005) demonstrated that this modified formulation sustains effective asparagine depletion for extended periods, which may enhance therapeutic outcomes while lowering hypersensitivity risks. ^[11,3] Nevertheless, real-world clinical benefits in terms of long-term survival do not always show significant advantages over conventional L-asparaginase, especially in low-risk or standard-risk pediatric ALL cases.

Toxicity represents a critical consideration in asparaginase-based treatment regimens. While our investigation observed substantial treatment-related adverse events (87.27% overall incidence), we did not differentiate these occurrences between the two formulations. Earlier research by Tong et al. (2013) suggested that PEG-asparaginase may offer advantages in terms of reduced allergic reactions and possibly fewer hypersensitivity-related hospitalizations, potentially yielding economic benefits through decreased supportive care requirements. However, our current study did not specifically evaluate these potential cost-saving aspects. ^[12]

CONCLUSION

This pharmacoeconomic analysis compared PEG-asparaginase and L-asparaginase for pediatric ALL treatment. The results showed marginally better clinical outcomes with PEG-asparaginase, though this advantage lacked statistical significance. More strikingly, PEG-asparaginase's treatment costs exceeded those of L-asparaginase by a factor of ten, a difference that was statistically robust. The calculated ICER of INR 88,674.48 per effectiveness unit gain underscores the significant financial implications of choosing the pegylated formulation. The evidence indicates L-asparaginase presents a more economically viable choice, particularly valuable in resource-constrained healthcare systems where cost considerations critically influence treatment availability and patient compliance. While PEG-asparaginase maintains clinical relevance for specific cases such as patients needing reduced dosing frequency or those with native formulation intolerance its widespread adoption appears economically unsustainable in low- and middle-income country settings without substantial clinical justification. The findings advocate for judicious, patient-specific utilization of the more expensive formulation rather than routine application.

Conflict of Interest

The author (s) declare that they have no potential conflict of interest

Funding

No funding’s were received for this study. The research was conducted independently without financial support from any funding agency, commercial entity or non-profit organization.

Acknowledgments

We sincerely thank to Pediatric Hemato-oncology Department for their invaluable support and guidance throughout this study also thankful to all the study participants for their voluntarily participation in this study. We extend our gratitude to KLES College of Pharmacy, Belagavi, KAHER-Belagavi and KLE’s Dr. Prabhakar kore Hospital and MRC, Belagavi for providing the necessary facilities and resources to conduct this research. Their contributions and encouragement have been instrumental in this successful completion of this work.

Ethical clearance

The study was approved by Institutional Ethics committee of KLE college of pharmacy, Belagavi (Ref no. KLECOPBGMEC/D015-2024). The patient’s identities were kept confidential and rewards were not provided to the participant.

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