Evaluating the cost-effectiveness of voclosporin for the treatment of lupus nephritis in the United States

Abstract

BACKGROUND:

Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus; up to 30% of patients with LN will develop end-stage kidney disease (ESKD). One of the main treatment goals for LN is preservation of kidney function, with early decreases in proteinuria associated with improved long-term outcomes. Voclosporin, a second-generation calcineurin inhibitor, was approved in the United States in 2021 for the treatment of active LN combined with background immunosuppression. The AURORA 1 study found that the use of voclosporin with low doses of mycophenolate mofetil and glucocorticoids yielded significant reductions in proteinuria. The AURORA 2 study showed long-term efficacy and safety of voclosporin over a 3-year period with kidney function preservation. The Institute for Clinical and Economic Review (ICER) is a nonprofit organization that evaluates medical evidence to help improve patient outcomes and control costs. In 2021, ICER published an economic model to estimate the impact and cost-effectiveness of LN therapies. From a US health care perspective, voclosporin was cost-effective at $149,260 per quality-adjusted life-year (QALY) and $131,528 per equal value of life-years gained (evLYG). At the time of the LN cost-effectiveness model (CEM) development, voclosporin was not yet approved in the United States and the cost of treating patients with LN with ESKD was not captured in the literature.

OBJECTIVE:

To evaluate the cost-effectiveness of voclosporin given the emergence of new data.

METHODS:

The LN CEM uses a short-term trial-based Markov model and long-term extrapolation using partitioned survival modeling data assuming adults with LN start with active disease, transitioning to complete or partial renal response, kidney failure, or death. In the current analysis, clinical data for voclosporin, duration of voclosporin treatment for nonresponders, and drug costs reflecting the 2023 price of voclosporin were updated. Additionally, health care payer costs of disease management were incorporated based on real-world claims data on the costs of treating patients with LN.

RESULTS:

Using the LN CEM with inputs reflecting the latest and most relevant evidence, the incremental cost of voclosporin per QALY was $88,076 and per evLYG was $77,643. For a subpopulation of Black, Hispanic, and Latino patients, the incremental cost of voclosporin per QALY was $77,435 and per evLYG was $67,828.

CONCLUSIONS:

Following the inclusion of updated data in the cost-effectiveness analysis, voclosporin remains a cost-effective therapy for the treatment of active LN including in a Black, Hispanic, and Latino subpopulation, substantially below the ICER willingness-to-pay threshold of $150,000/QALY.

Plain language summary

Voclosporin is the first US Food and Drug Administration–approved oral treatment for lupus nephritis (LN) in adults. This study evaluated health care plan provider costs including the use of voclosporin for managing LN in the United States. Results based on the latest evidence demonstrated that voclosporin is a cost-effective treatment.

Implications for managed care pharmacy

This study provides insights for managed care organizations about cost implications when treating and managing patients with LN. Voclosporin has been shown to be effective and safe in adult patients with active LN treated for 3 years in clinical trials. The original and updated cost-effectiveness analyses support voclosporin as a cost-effective therapy.

A severe complication of systemic lupus erythematosus (SLE), lupus nephritis (LN) is an autoimmune disease with a prevalence in the United States of approximately 200,000 to 300,000 patients.¹ In adults with SLE, between 40% and 70% will develop LN.^2-4 This proportion is higher in non-White populations; Black and Hispanic patients develop LN earlier and have poorer outcomes and a faster progression to renal failure and death.^5,6 In the overall LN population, diagnosis often occurs at a young age (between 20 and 40 years), with women affected more than men.⁷ Compared with the general population, mortality is increased 14-fold and life expectancy shortened by up to 24 years in patients with SLE and renal damage.⁸

LN is typically characterized by kidney inflammation, proteinuria, and kidney failure, with early reductions in urinary protein in response to treatment shown to be predictive of improved long-term renal outcomes.^2,9-13 Thus, current treatment recommendations are focused on lowering proteinuria and stabilizing renal function within the first few months of treatment.^14-16 Unfortunately, up to 60% of patients remain unable to achieve treatment targets for proteinuria, and within 15 years of an LN diagnosis, 10%-30% of patients progress to end-stage kidney disease (ESKD) requiring kidney dialysis or transplantation.⁴

Guidelines recommend the use of glucocorticoids (GCs) with immunosuppressants such as mycophenolate mofetil (MMF) for the management of LN.^14-16 Of note, recent updates to recommendations published by the European Alliance of Associations for Rheumatology (EULAR) in 2023 specify initial and subsequent therapy for LN with an immunosuppressive regimen that includes voclosporin, a novel second-generation calcineurin inhibitor (CNI).¹⁴ Indeed, the use of voclosporin as a first-line treatment for both initial and subsequent care of LN, over a period of 3 years, was a grade A recommendation. Moreover, voclosporin studies were the only CNI studies with this level of quality of evidence.¹⁴

Voclosporin is the first and only US Food and Drug Administration (FDA)– and European Medicines Agency–approved oral treatment for adults with active LN, in combination with immunosuppressive therapy. Approval of voclosporin was based on results from the pivotal phase 2 AURA-LV and phase 3 AURORA 1 clinical trials. These trials were global, double-blind, randomized controlled studies that evaluated the efficacy and safety of voclosporin compared with placebo, in combination with low-dose MMF and low-dose GCs, in adults with active LN.^17,18

An integrated analysis of pooled data from these pivotal studies revealed a favorable safety profile alongside increased rates of complete renal response (CRR), the definition of which included reductions in proteinuria, at 6 months and 1 year with the addition of voclosporin, compared with MMF and GCs alone.¹⁹

The AURORA 2 continuation study evaluated voclosporin in combination with MMF and GCs for an additional 2 years after AURORA 1 and demonstrated continued efficacy, with no increase in safety signals across a total of 3 years of treatment.²⁰ Similar to the overall LN population, a subgroup of Black, Hispanic, and Latino patients treated with voclosporin achieved meaningful and sustained reductions in proteinuria over 3 years of treatment and achieved those reductions significantly faster than placebo-treated patients (4.6 months vs 18.0 months for Hispanic or Latino patients [n = 72]; 5.6 months vs 18.0 months for Black patients [n = 45]).^21,22

The Institute for Clinical and Economic Review (ICER) is a nonprofit research organization that provides evaluations of medical evidence, while convening public deliberative bodies, to help stakeholders determine the value of medical interventions from a US health care perspective. In 2019, ICER developed an economic model (the LN cost-effectiveness model [CEM]) to assess the cost-effectiveness of LN therapies. The model, which is available on the ICER Analytics platform, allows users to conduct cost-effectiveness analyses as new data become available.²³

In 2021, inputting medical evidence from clinical trials and published literature, ICER reported on a cost-effectiveness analysis (CEA) of voclosporin for the treatment of adult patients with LN. Reporting on health utility metrics including the quality-adjusted life-year (QALY; a measure of the value of health outcomes) and the complementary equal value of life-years gained (evLYG; uniform appraisal of life extension benefits irrespective of quality-of-life [QoL] enhancements), the ICER CEA found voclosporin to be a cost-effective therapy at $149,260 per QALY and $131,528 per evLYG.^24-27

Newly available medical evidence, relevant to the management of LN and use of voclosporin, mandates an updated CEA of voclosporin for the treatment of LN. We examined voclosporin for the treatment of adult patients with LN from a US health care sector perspective.

Methods

This current study uses the ICER LN CEM, which allows stakeholders to amend clinical and cost inputs for an updated CEA of voclosporin for the treatment of LN from the US health care sector perspective. Details of the model have been published previously.^26,27 Briefly, key model inputs consist of clinical data including complete and partial renal response (PRR) rates, health care costs (costs of drug and costs attributable to each LN health state), and utility values for each health state. Primary patient data were not collected or evaluated in this study; thus, institutional review board approval and informed consent were not required.

THE LUPUS NEPHRITIS COST-EFFECTIVENESS MODEL

The LN CEM was accessed by subscription on the ICER Analytics platform (https://analytics.icer.org). The LN CEM simulates treatment of LN with voclosporin in the United States with a short-term (3-year) trial-based Markov model and long-term (lifetime) extrapolation using partitioned survival modeling data, where patients start in an active disease (AD) state, with the possibility to transition to CRR, PRR, kidney failure, or death (Supplementary Figure 1 ^{(394.3KB, pdf)} , available in online article). Health state definitions were defined by ICER (Supplementary Table 1 ^{(394.3KB, pdf)} ), with each health state having an associated cost (Table 1). Each cycle length is 1 month, and during each cycle, a patient is assigned a health state and accrues the cost associated with that state. Consistent with the original CEA, a discount rate of 3% per year was applied to both health costs and outcomes.^26,27 This discount represents an individual and societal preference to take benefits now and defer costs to as far in the future as possible.²⁸

TABLE 1.

Summary of Inputs for the Cost-Effectiveness Analysis of Voclosporin

Model inputs		Source
Complete renal response rate at 1 yeara	Voclosporin arm, 43.7%; Control arm, 23.3%	Arriens et al19
Partial renal response rate at 1 yeara	Voclosporin arm, 69.4%; Control arm, 50.6%	Arriens et al19
Treatment duration for responders	3 years	Mandrik et al; Fanouriakis et al14,26
Treatment duration for nonresponders	0.5 years	LUPKYNIS package insert31
Voclosporin unit costb	$7.46/mg	Aurinia Pharmaceuticals Inc. Data on file. 2023
Annual health care payer costs for complete renal responsec	$19,660	Barber et al; Dall’Era et al; Mandrik et al26,29,30
Annual health care payer costs for partial renal responsec	$20,446	Barber et al; Dall’Era et al; Mandrik et al26,29,30
Annual health care payer costs for active diseased	$79,344	Dall’Era et al29
Annual health care payer costs for ESKDd	$262,128	Dall’Era et al29

^a Both the voclosporin and controls arms in the clinical trials received an immunosuppression regimen of low-dose mycophenolate mofetil and tapered low-dose glucocorticoids. Clinical trials included 268 patients in the voclosporin arm and 266 patients in the control arm.

^b Derived from a base cost of $6.46/mg reported in Mandrik et al and adjusting to its 2023 price.²⁶

^c Cost calculations consistent with the approach by Mandrik et al. Calculations applied the multipliers per Barber et al (0.075 for complete renal response and 0.078 for partial renal response) to the cost of ESKD reported by Dall’Era et al.^26,30

^d Includes payer costs for medical and pharmacy health care.

ESKD = end-stage kidney disease.

A one-way sensitivity analysis was conducted to evaluate changes in cost per additional QALY by varying input parameters including cost and pricing variables (±20%) and altering the nonresponder time on therapy in 3-month increments (eg, 3 months, 6 months, and 9 months on therapy).

CLINICAL INPUTS

Proportions of patients with CRR and PRR were derived from a pooled analysis of the phase 2 AURA-LV and phase 3 AURORA 1 LN clinical trials.¹⁹ Both studies enrolled patients with biopsy-proven active LN (class III, IV, or V ± III/IV), estimated glomerular filtration rate (eGFR) greater than 45 mL/minute/1.73 m2, and proteinuria greater than or equal to 1.5 g/g (≥2 g/g for pure class V). AURA-LV and AURORA 1 were global, double-blind, randomized controlled clinical trials, with similar designs and endpoints that evaluated the efficacy and safety of voclosporin compared with placebo, with all patients receiving low-dose MMF (target dose 2 g/day) and low-dose GCs (administered on a protocol-defined rapid taper from a starting intravenous dose on days 1 and 2, followed by oral doses of 20-25 mg/day tapered to a target dose of ≤2.5 mg/day by week 16 and thereafter).^17,18 Data from the 23.7-mg twice-daily dosing arms of voclosporin (n = 268) and control arms (n = 266) of both studies were included in the CEA.

The efficacy outcome of the studies of CRR at approximately 1 year (week 48 data from AURA-LV and week 52 from AURORA 1) was defined as urine protein creatinine ratio less than or equal to 0.5 g/g, stable eGFR greater than 60 mL/minute/1.73 m2 or no confirmed decrease from baseline in eGFR of greater than 20%, and no more than 10 mg/day prednisone equivalent for at least 3 consecutive days or for at least 7 days during the 8 weeks prior to efficacy assessment, and no rescue medication; PRR was defined as greater than or equal to 50% reduction from baseline urine protein creatinine ratio.^17,18

Patients in the clinical trials demonstrated a CRR of 43.7% in the voclosporin arm (n = 117/268) and 23.3% in the control arm (n = 62/266) and a PRR of 69.4% in the voclosporin arm (n = 186/268) and 50.6% in the control arm (n = 134/266) at 1 year of treatment. For a subpopulation CEA, patients who self-identified as Black, Hispanic, and/or Latino (hereinafter referred to as Black, Hispanic, and Latino) in the AURA-LV and AURORA 1 studies were evaluated based on clinical outcomes; CRR at 1 year was 37.6% in the voclosporin arm (n = 32/85) and 18.0% in the control arm (n = 16/89); PRR was 67.1% in the voclosporin arm (n = 57/85) and 47.7% in the control arm (n = 42/89) (see Supplementary Table 2 ^{(394.3KB, pdf)} for details of all LN CEM inputs).¹⁹

HEALTH STATE COST INPUTS

A summary of health state costs can be found in Table 1. At the time of the original CEA, there were no data specific for the health care payer costs of patients with both LN and ESKD. Since then, real-world evidence using the Optum claims database was published by Dall’Era et al, which provides a cost for AD and ESKD in patients with LN.²⁹ Criteria to identify patients with LN can be found in Supplementary Table 3 ^{(394.3KB, pdf)} . AD was classed as time without evidence of low disease activity (defined based on LN medication use) or ESKD (defined based on codes for ESKD, dialysis, or treatment with phosphate binders or kidney transplant). There was evidence of AD in 67.3% of patients and ESKD in 10.5% of patients. The study provides all-cause pharmacy and medical cost data for treating patients with LN including costs related to LN and conditions other than LN. These data represented costs covered by a commercial payer for the period between January 1, 2007, and December 31, 2019, and were based on a total of 21,251 patients with LN.²⁹ As the estimated cost of dialysis provided by the US Renal Data System did not provide data specifically on the cost of dialysis in patients with LN or address overall health care costs, it was not incorporated into the current CEA.

For CRR and PRR, the approach for the cost calculation of each health state taken into account by ICER in the original CEA was used. The costs of CRR and PRR were calculated by applying a multiplier determined by Barber et al for each response (0.075 for CRR and 0.078 for PRR) to the cost of ESKD (Table 1; Supplementary Table 2 ^{(394.3KB, pdf)} ).^26,29,30

COST OF DRUG INPUTS

The cost of voclosporin was derived from a base cost of $6.46/mg used in the original CEA and adjusting to its 2023 price.²⁶ By implementing a percentage increase to adjust the price based on the base cost, the pricing assumptions and rebates applied in the original CEA were maintained.

DURATION OF TREAMENT INPUTS

The model allowed for modifying the duration of voclosporin treatment based on achieving renal response (ie, responder or nonresponder). Treatment duration for patients achieving a renal response remained 3 years, consistent with the original CEA and recently published LN treatment recommendations.^14,26 Treatment duration for nonresponders (ie, patients remaining in an AD state) was updated to 6 months, informed by the FDA-approved labeling for voclosporin that was not yet available at the time of the original CEA.³¹

QUALITY-OF-LIFE INPUTS

The utility values used for health states CRR, PRR, AD, and ESKD were 0.8, 0.71, 0.624, and 0.549, respectively, matching the utility values in the original CEA.²⁶ All utilities were capped to ensure they did not exceed the utilities of the general population.

OUTCOMES

The primary outcomes of this CEA are the cost per QALY and cost per evLYG.

Results

Using the LN CEM with inputs reflecting the latest evidence, the cost of voclosporin per QALY was $88,076 and per evLYG was $77,643 for all patients with LN, from a health care sector perspective (Figure 1).

FIGURE 1.

Incremental Cost-Effectiveness Ratios for Patients With Active Lupus Nephritis

For the subpopulation of Black, Hispanic, and Latino patients, the cost of voclosporin per QALY was $77,435 and per evLYG was $67,828 (Figure 2).

FIGURE 2.

Incremental Cost-Effectiveness Ratios for Patients With Active Lupus Nephritis Self-Identifying as Black, Hispanic, and Latino

Key drivers of uncertainty included the cost of voclosporin and the annual cost of AD, with the annual cost of ESKD having a lower impact on the cost per additional QALY (Supplementary Figure 2 ^{(394.3KB, pdf)} ; Supplementary Table 4 ^{(394.3KB, pdf)} ).

Discussion

This study assessed the cost-effectiveness of voclosporin, evaluating the health utility gains and costs attributable to the treatment of active LN. Economic modeling of LN applied clinical and cost inputs reflecting the most up-to-date and relevant evidence and found the incremental cost of voclosporin for patients with active LN per QALY to be $88,076 and the cost per evLYG to be $77,643.

Commonly set cost-effectiveness thresholds range from $50,000 to $200,000, with drugs found to produce cost per QALY or cost per evLYG beneath these thresholds often deemed cost-effective, although there is no strong consensus on the most appropriate health utility metric. In 2021, ICER used a range up to $150,000 per QALY and per evLYG as benchmarks for their original CEA of LN treatments.²⁷ It is important to highlight that relatively few new medications, of any class, sit below this threshold.³² At the time of the ICER evidence report, the incremental ratio for voclosporin, compared with standard of care, was reported to be below the willingness-to-pay threshold, at $149,260 per QALY. The authors concluded that the resulting improved clinical outcomes support voclosporin as a cost-effective initial therapy for LN.²⁶ Here, following updates to clinical and cost inputs, we find that voclosporin is substantially more cost-effective at $88,076 per QALY for the general population of patients with LN. Moreover, cost-effectiveness outcomes were replicated in subpopulations historically considered to be more difficult to treat, with the incremental cost of voclosporin for Black, Hispanic, and Latino patients also found to be well below this threshold, underpinning the ongoing cost-effectiveness of voclosporin for the treatment of LN. A one-way sensitivity analysis demonstrated that drug cost is a key driver in the cost-effectiveness of voclosporin, yet even with a 20% increase, the cost-effectiveness remained under the willingness-to-pay threshold. Other analyzed variables had smaller impacts on the incremental cost per QALY. These findings support the robustness of the LN CEM.

LN can have a significant impact on a patient’s quality and quantity of life, with patients typically experiencing health complications including frequent hospital admissions.^2,33,34 The significant health risks attributable to LN are, inevitably, associated with higher health care costs compared with the treatment of nonrenal SLE. As such, there is a substantial long-term socioeconomic impact on the US population, recognizing the relatively young age at diagnosis. Effective and safe disease management is required to minimize this burden.^35,36

Voclosporin is a potential disease-modifying agent in LN; in addition to its immunosuppressive properties, a result of decreased T-cell activation, it has a protective effect on podocytes with the potential to reduce levels of proteinuria and the subsequent prevention of disease progression.³⁷ As a second-generation CNI, voclosporin use in LN is associated with a distinct pharmacological and clinical profile without the need for the therapeutic drug level monitoring or increased safety concerns attributed to first-generation CNIs, such as hyperlipidemia and diabetes mellitus.

Voclosporin was evaluated in AURORA 1 and its 2-year continuation study, AURORA 2, which, collectively, represent the longest placebo-controlled clinical program in LN evaluating a CNI-based treatment regimen and the only prospective, recent study to include 3 years of continuous LN treatment and follow-up. During 3 years of voclosporin treatment, mean corrected eGFR remained stable and within normal range. Further, rapid and early reductions in proteinuria were observed during AURORA 1 and were maintained throughout AURORA 2, demonstrating a benefit of long-term preservation of kidney function and an anticipated reduction in the incidence of ESKD and its associated morbidity and mortality in patients with LN. Indeed, failure to obtain an early CRR in patients with LN is known to increase the risk of renal loss.^9,38,39 The beneficial effects of voclosporin have been observed over a 3-year period across races and ethnicities, both factors that have been shown to affect treatment response in LN.^18,19,21,22 Black patients with active LN have a lower reported 5-year renal survival rate compared with White patients, with a higher incidence of ESKD.⁴⁰ Moreover, the LN age-standardized mortality rate is significantly higher among racial and ethnic groups, including Black, Hispanic, and Latino patients, when compared with White patients with LN.⁴¹ As such, there is recognition of an urgent need for an earlier and more effective screening and intervention in this patient population. Hence, it is of interest that the current updated CEA presented here demonstrates a more favorable estimated cost-effectiveness of voclosporin in Black, Hispanic, and Latino patients, compared with the general LN population.

Notably, the superior outcomes observed in the voclosporin clinical trials were achieved with administration of MMF and GCs at doses lower than those used in other recent LN trials, particularly with regard to the rapidly tapered GCs; these findings support the use of lower doses of these medications in the treatment of LN.^42,43 The low-dose GC regimen used in voclosporin trials may limit the toxic effects seen with prolonged GC use, given that chronic exposure to GCs increases the risk of infections and metabolic and psychiatric complications, which has both clinical and cost implications to patients and the health care system.⁴⁴ Moreover, the 2023 update of the EULAR treatment guidelines for LN recommends tapering GCs to a maintenance dose of less than or equal to 5 mg/day, informed partly by the steroid-sparing voclosporin regimen used in clinical trials.¹⁴ Indeed, of the patients in the voclosporin clinical trials, more than 80% were receiving a prednisone dose of less than or equal to 2.5 mg/day by week 16, with approximately 75% on less than or equal to 2.5 mg/day at 1 year.¹⁹ Notably, a study assessing clinical and economic outcomes associated with oral GC use in US patients with SLE found that within the first year of initiating oral GC treatment, patients experienced a substantial clinical and economic burden with significantly higher all-cause health care resource utilization, health care costs, and risk of adverse events. Therefore, using a treatment regimen that includes a rapid steroid taper may circumvent many of the safety concerns and health care costs associated with chronic GC use.

Treatment goals for LN emphasize early intervention with effective and safe treatments to control disease activity, in turn reducing the incidence of ESKD and mortality associated with LN. Overall disease management costs will be reduced with the improved short- and long-term safety and efficacy outcomes associated with the use of a voclosporin-based regimen in combination with low doses of MMF and GCs for LN. Additionally, every effort should be made to address prompt disease management and control in all adult patients with active LN, including those patients in LN care deserts, by improving health care resources and cost-effective treatment options such as voclosporin.

LIMITATIONS

Inputs into the current updated CEA, including health care payer costs of AD and ESKD, were acquired from a claims study published in 2023.²⁹ The authors acknowledge the cost of dialysis for commercial insurers is substantially more than for Medicare, and that data in the claims study were solely from a US commercial perspective; therefore, a proportion of Centers for Medicare & Medicaid Services–covered patients are not captured, and data may not be attributable to the overall LN population.^29,45 The patients included in the claims study may also be considered a limitation, with the underrepresentation of Black and Hispanic patients and potential for an older age group to be sicker and more costly. However, patients had a mean comorbidity index similar to or lower than that of patients of lower average age in other LN and SLE studies.²⁹

The LN CEM used in this current updated CEA has inherent limitations. Without the availability of long-term prognostic data since the approval of voclosporin, the analysis assumes different health states persist until death, or ESKD, based on previous studies. Indeed, early economic modeling of newly approved therapies will be dependent on the data available at the time of initial approval, with a dearth of long-term outcomes and a notable lack of real-world data informing the economic model. It is worth highlighting the Enlight-LN registry, an actively enrolling, prospective, observational registry designed to characterize the real-world effectiveness and use patterns of voclosporin in the United States. It is hoped that the real-world data obtained from this study will inform future CEA of voclosporin.⁴⁶

Although the model considers the clinical benefits associated specifically with LN, it does not consider related benefits, such as those concerning the management of SLE, or the overall benefit to the patients and health care system with the use of lower doses of GCs in the voclosporin regimen for LN. We acknowledge that such benefits would be difficult to quantify, meaning current cost benefits may be underestimated in this CEA. However, it may be reasonable to surmise that long-term health benefits, extending beyond the primary endpoint of a clinical study, may lead to further improved cost-effectiveness ratios. This is of particular relevance to voclosporin, demonstrating early and sustained reductions in urinary protein, a widely accepted indicator of improved long-term patient outcomes.

Finally, the original CEA included a voclosporin cost rebate of 22.5%. Although it was not clear how this was determined, we retained the same discount in the updated CEA for completeness.

A current gap in the literature is QALY and evLYG utility values by ethnicity and race. By using an average value for all ethnicities and races, the health gain of a specific population may not have been fully captured. The practice of using QALYs and evLYG to assess health utility has limitations, and in the future, there could be established metrics that take into account the composite improvements in clinical outcomes and QoL addressing health gains and disparities in specific populations.^47,48 Future CEAs can address the advent of relevant data on the management of LN and the use of voclosporin. Importantly, these CEAs will look to address gaps in ethnicity and race across all measures.

Conclusions

Economic modeling of LN evaluated the cost-effectiveness of voclosporin. Following the inclusion of updated data in an LN CEM, voclosporin was found to be cost-effective and substantially below the willingness-to-pay threshold of $150,000 per QALY. These results are consistent with the original ICER CEA, highlighting that voclosporin continues to be a cost-effective treatment for adult patients with active LN.