Healthcare costs prevent or delay up to 26% of US adults from seeking medical treatment.1 Botulinum neurotoxin type A (BoNT-A) is a frequently used and effective treatment for many chronic neurologic conditions, but the economic implications of repeated treatments can be worrisome to patients. BoNT-A inhibits the release of acetylcholine into neuromuscular junctions, and can provide relief lasting 8 to 12 weeks after each injection, regardless of the indication.2,3 Among the 3 commercial preparations of BoNT-A available today, the costs of injection for patients can vary widely, depending on the dose, the brand of BoNT-A administered, and the patient insurance coverage.
The 3 commercially prepared types of BoNT-A available on the market today are onabotulinumtoxinA (Botox), abobotulinumtoxinA (Dysport), and incobotulinumtoxinA (Xeomin). No clear differences have been found in clinical efficacy between these 3 available type A toxins in blinded comparative studies to date.4-6
Although the dosage potency conversion ratio between onabotulinumtoxinA and incobotulinumtoxinA is an equivalent 1:1 ratio,5,7,8 abobotulinumtoxinA’s 3:1 conversion ratio to onabotulinumtoxinA has been extensively debated in scientific literature, which has historically detracted our practice from using the drug on a larger scale.4
At least 2 studies have reported that incobotulinumtoxinA is more cost-effective than onabotulinumtoxinA,9,10 given a lower per-unit cost in addition to the availability of smaller 50-unit vials, which allows for reduced wastage.
The aim of the present analysis was to quantify the cost-savings in a real-world setting of switching patients from treatment with incobotulinumtoxinA to treatment with onabotulinumtoxinA.
This study was a single-center, retrospective review of a large, private practice in Spokane, WA, serving a catchment area of approximately 2.2 million people throughout the Inland Northwest. Our clinic provides BoNT-A treatment to patients with neurologic conditions, including chronic migraine, cervical dystonia, spasmodic dysphonia, blepharospasm, hemifacial spasm, hyperhidrosis, sialorrhea, spasticity, and organic writer’s cramp.
The source data were retrieved by retrospectively reviewing individual medical and financial records from patients within our practice who switched from treatment with onabotulinumtoxinA to treatment with incobotulinumtoxinA between 2012 and 2019. Each patient was evaluated for the 1 year before the change in BoNT-A therapy and for 1 year after the change. Patients without 1 year of data before or 1 year after the switch were excluded from the study, to prevent missing data points of cost and time intervals.
The patients’ charts were evaluated to assess the potential differences in dose requirements, treatment intervals, treatment costs, the number of unavoidable wastage units paid to the clinic, and patient eligibility for out-of-pocket cost reimbursement through patient savings programs.
The numbers of annual injections and injection intervals were based on the actual number of injections and the duration of intervals between injections throughout the respective year that the patients received treatment with each toxin. Data were also collected for patients who switched back from incobotulinumtoxinA to onabotulinumtoxinA. Subjective data were collected to determine the patient-reported rationale for all the switchbacks to onabotulinumtoxinA using a chart review.
Patients were considered for study inclusion if they met the study criteria that included receipt of an unchanging dose of noncosmetic onabotulinumtoxinA therapy for 1 year before the switch and receipt of a stable dose of noncosmetic incobotulinumtoxinA therapy for 1 year after the switch. The exception to these criteria was that we continued to follow all patients who elected to switch back to onabotulinumtoxinA before the end of the review period (they were included to elicit switchback data).
For this review, cost was defined strictly as the cost of BoNT-A incurred by payers and patients that was paid to the clinic for providing and administering the treatment. To extract these cost data, the patients’ individual medical billing records were used corresponding to each toxin’s J code (J0585 for 1 unit of onabotulinumtoxinA and J0588 for 1 unit of incobotulinumtoxinA).
Because the procedural cost of an injection is not dependent on the specific BoNT-A used and is not the costliest aspect of the treatment, we elected to focus strictly on the cost of the BoNT-A that was used at the time of administration, and we excluded procedural costs from our analysis.
The clinical practice involved in this study used a buy-and-bill purchasing and reimbursement scheme. The practice purchased all BoNT-A agents directly from the manufacturer and was not eligible for any rebates or discounts tied to volume-based purchasing. BoNT-A is supplied in single-use vials; therefore, unavoidable waste may occur depending on the dosage given to the patient.
We calculated unavoidable waste as unit averages across the treated conditions. Assumptions were made within the patient savings programs. Reimbursement associated with patient assistance programs was not readily retrievable in the medical record system; therefore, the values were reported based on estimated allowances according to the patient’s insurance plan and the respective eligibility rules of the copay programs at the time of treatment.
Commercial insurance is a requirement for patient savings program eligibility.11,12 Thus, any patient with a federal- or state-funded insurance health plan was excluded from the patient program savings analysis. Patient saving programs have changed over time. For data we collected before 2013, we considered the program used at the time of treatment. For data collected after 2013, we used the 2019 patient saving program stipulations; patient saving programs offered by each manufacturer have their own qualifying criteria and may not be offered continuously throughout the patient treatment cycle by each drug manufacturer.11,12
No adjustments for inflation were made. The dose of BoNT-A that was administered did not change in conjunction with the type of BoNT-A administered, except in the case of chronic migraine, in which the dose was decreased from 155 units of onabotulinumtoxinA to 150 units of incobotulinumtoxinA. The reason for this change in dose was that incobotulinumtoxinA is offered in 100-unit and 50-unit vials, whereas onabotulinumtoxinA is only offered in 100-unit and 200-unit vials.
A total of 127 patients were identified who converted from onabotulinumtoxinA to incobotulinumtoxinA therapy. Of these patients, 15 were excluded because they did not have at least 1 year of receiving onabotulinumtoxinA therapy before switching to incobotulinumtoxinA. The 112 remaining patients who were eligible for this analysis had a total of 486 injections recorded of onabotulinumtoxinA and a total of 519 injections of incobotulinumtoxinA.
Of the 112 patients, cervical dystonia and chronic migraine were the 2 most frequently treated conditions, the patients’ mean age was 57.9 years (standard deviation, ± 14.3 years), and 86% of the patients were female (Figure and Table 1). Of the 112 total patients, 111 were Caucasian and 1 was African American. A majority (63%) of the cohort had commercial health insurance, and the remaining 37% of patients were insured through Medicare coverage. A majority (86%) of the Medicare-insured patients received treatment for US Food and Drug Administration (FDA)-approved indications of incobotulinumtoxinA (ie, cervical dystonia or blepharospasm).
The injection frequency and intervals between injection cycles were calculated for each patient. When evaluating the entire patient cohort and each clinical condition separately, no significant differences were found for BoNT-A with regard to injection frequency or the intervals between the injections (Table 2).
Because BoNT-A is supplied as single-use vials, the amount of BoNT-A in the vial often exceeds the specified treatment amount, which results in unavoidable wastage; this wastage is billed to the payer and to the patient. After switching to incobotulinumtoxinA, an average of 131.8 units of wastage per patient were saved annually. Although onabotulinumtoxinA is only available in vials of 100-unit and 200-unit vials designated for therapeutic use, the availability of a 50-unit vial of incobotulinumtoxinA (in addition to 100- and 200-unit vials) explains the vast majority of these wastage reductions (Table 3).
As a result of switching these 112 patients to incobotulinumtoxinA, a total of 14,635 units of the drug (equivalent to approximately 146 wasted 100-unit vials) were saved in the year after the treatment was switched.
As of 2019, a unit of onabotulinumtoxinA costs our clinic approximately $6.01, whereas a unit of incobotulinumtoxinA costs approximately $4.82. The combination of a lower per-unit cost of incobotulinumtoxinA and a decrease in wastage through the availability of 50-unit vials with the switch in treatment results in a significant decrease of the per-patient annual cost by an average of $1647, or 32.2% (Table 4).
Some conditions that required smaller per-treatment doses (eg, blepharospasm and hemifacial spasm) saved more than 40% in cost, because the availability of 50-unit vials allowed for a higher wastage reduction.
In all, a total of $182,792 in charges for BoNT-A were saved in 1 year as a result of switching 112 patients to incobotulinumtoxinA therapy. The cost-savings from having a lower drug acquisition cost ($94,982) accounted for 52% of the total cost-savings; however, the savings were nearly doubled from a reduction of drug wastage ($87,810, representing 48% of the total cost-savings).
Of our original 112 patients, 70 patients were eligible for each specific agent’s patient savings program. Overall, the patients were reimbursed an average of $2076 per patient more annually, or 241.5% more, in out-of-pocket costs as a result of switching from onabotulinumtoxinA to incobotulinumtoxinA (Table 5).
Of the 112 patients who switched to incobotulinumtoxinA, 8 (7.1%) patients subsequently switched back to onabotulinumtoxinA within the next year. Of these 8 patients who switched back, 5 patients were receiving BoNT-A therapy for cervical dystonia, and 3 patients were receiving it for chronic migraine. Of note, 3 (2.7%) of the 8 patients returned to onabotulinumtoxinA therapy because their insurance plans were switched to plans that did not cover treatment with incobotulinumtoxinA (1 patient with cervical dystonia and 2 patients with chronic migraine).
The other 5 (4.5%) patients returned to treatment with onabotulinumtoxinA because they felt that it was more effective. Of these 5 patients who switched back because of efficacy concerns, 2 patients did not feel improvement subsequent to returning to treatment with onabotulinumtoxinA. Of these 2 patients, 1 patient had analgesic rebound headache, which was exacerbating that patient’s symptoms, and the second patient subsequently needed a much higher dose of BoNT-A to address that patient’s dystonia adequately. Therefore, it was most likely not the BoNT-A type that led to nonresponse to treatment.
Consequently, in all, 3 of the 8 patients had switched back to onabotulinumtoxinA and still felt that it addressed their symptoms to a higher degree than incobotulinumtoxinA (1 patient with cervical dystonia and 2 patients with chronic migraine).
Our analysis showed that transitioning patients to incobotulinumtoxinA from onabotulinumtoxinA resulted in substantial cost-savings and reduced wastage, with a low rate of switchbacks. To our knowledge, this is one of the first publications documenting this particular treatment switch in a large private practice in the United States, although similar retrospective switch studies that documented other combinations of botulinum toxins have been conducted throughout the world.6,13 In addition, the change in BoNT-A type throughout the study did not elicit significant changes in dosage, injection frequency, or injection intervals.
Our outcomes are supported by a recent real-world data analysis that was conducted on a cohort of 15 million commercially insured individuals in the United States with cervical dystonia, limb spasticity, or blepharospasm that showed similar injection frequency and dosing for incobotulinumtoxinA versus onabotulinumtoxinA, while significantly reducing costs.14
The ability to deliver smaller increments of BoNT-A via 50-unit vials dramatically reduced unavoidable wastage and further contributed to the overall cost-savings. Similarly, incobotulinumtoxinA can be kept in ambient storage conditions, which reduces the costs and space restrictions associated with ongoing refrigeration.
There is a vast difference in eligibility criteria among patient savings programs, which largely contributed to our interest in pursuing this review. At the time of our study, patients covered by federal- or state-funded insurance were not eligible for the patient assistance program for either drug.11,12
Furthermore, at the time of this review, onabotulinumtoxinA’s patient savings funding was diagnosis-dependent and limited the maximum annual amount and number of treatments for which patients could receive funding.12 However, incobotulinumtoxinA’s patient savings program provided an annual non–diagnosis-dependent $5000 maximum for eligible patients.11 Thus, patients enrolled in incobotulinumtoxinA’s patient savings program could often receive more financial assistance for these recurring and costly treatments, especially if the number of treatments exceeded onabotulinumtoxinA’s stipulations.
Our practice’s ineligibility to receive volume-based buying discounts could have affected the cost data. The results might have underestimated the potential savings if other group purchasing organization–linked practices were to implement the same switch. Raw data from patient charts were used rather than wholesale acquisition cost data, because we believed that doing so would be more reflective of a real-world clinical practice. Future studies could explore wholesale acquisition costs in relation to toxin purchasing on a broader scale to confirm our results.
Considering this analysis on a larger scale in the context of future US healthcare models, one recurring notion is that federal insurance could pay clinics a fixed rate for injectable drugs to encourage the use of inexpensive but equally effective treatments.15 Another proposal to decreasing costs would be to allow Medicare to negotiate drug pricing directly with drug manufacturers and to threaten limiting coverage altogether if drug prices were deemed unreasonable.16 As US healthcare costs continue to rise,17 we believe that it is ethically and economically beneficial to find medications that are comparable in price and unequivocally efficacious to more costly medications.
This analysis has several limitations. As a retrospective analysis from a single, private, and largely Caucasian practice in the Inland Northwest, we cannot guarantee the external validity of these results to other practice settings where insurance and payer distributions may differ. The lack of diversity in this review is congruent with the lack of diversity represented in Spokane County and its surrounding counties. At the time of this analysis, the US Census Bureau reported that 89.1% of people identify as Caucasian in Spokane County.18 Consequently, our results could vary in other parts of the world in relation to variations in demographics, insurance coverage, and other factors.
Furthermore, our sample of 112 patients was relatively small, especially for certain clinical conditions represented (blepharospasm, N = 4; hemifacial spasm, N = 3; and organic writer’s cramp, N = 2); therefore, replicating this study in a larger population and geographic spread would be beneficial to explore the variances related to the treated condition and the demographic information. However, to our knowledge, this is the largest analysis of real-world data regarding onabotulinumtoxinA versus incobotulinumtoxinA in the literature to date.
An additional limitation is that incobotulinumtoxinA is not FDA-approved for the treatment of chronic migraine or hemifacial spasm. Although Medicare may reimburse the off-label use of BoNT-A if there is documentation stating why the off-label or unapproved form is used, it should not be assumed that this is the case with all commercial payers.19 However, the most common indication in this analysis was an approved indication of incobotulinumtoxinA for cervical dystonia (N = 61).
Finally, in this analysis we were not able to capture the actual out-of-pocket charges for patients to understand patient burden fully nor did we address reimbursement issues. Analyzing the different reimbursement schemes among the various commercial payers was outside the scope of this analysis.
Our findings show that switching from onabotulinumtoxinA to incobotulinumtoxinA at similar intervals and dosages achieves considerable cost-savings, with a low incidence of switching back. Overall, the switch in treatment to incobotulinumtoxinA in this study resulted in wastage reduction to zero, and the cost of treatment was also reduced for patients and for payers. Future larger studies should be conducted to confirm the results found in this analysis.
This study was funded by Merz North America via an unrestricted investigator-initiated trial grant. The study was conducted without the participation of Merz.
Author Disclosure Statement
Dr Greeley has served as a consultant, but not at the time of this study, for Merz North America and for Allergan North America. Ms Karschney has no conflicts of interest to report.
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- Benecke R, Jost WH, Kanovsky P, et al. A new botulinum toxin type A free of complexing proteins for treatment of cervical dystonia. Neurology. 2005;64:1949-1951.
- Tilden D, Guarnieri C, Jackson D. Cost-effectiveness of incobotulinumtoxin-A with flexible treatment intervals compared to onabotulinumtoxin-A in the management of blepharospasm and cervical dystonia. Value Health. 2015;18:A759.
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- Tedroff K, Befrits G, Tedroff CJ, Gantelius S. To switch from Botox to Dysport in children with CP, a real world, dose conversion, cost-effectiveness study. Eur J Paediatr Neurol. 2018;22:412-418.
- Eckwright DJ, Burke JP, Gleason PP. Real-world botulinum toxin utilization and treatment cost for cervical dystonia and limb spasticity among 15 million commercially insured members. Poster presented at the Academy of Managed Care Pharmacy Nexus; October 29-November 1, 2019; National Harbor, MD.
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- United States Census Bureau. Spokane County, Washington; Washington. QuickFacts. www.census.gov/quickfacts/fact/table/spokanecountywashington,WA/PST045218. Accessed November 19, 2019.
- Noridian Healthcare Solutions: Medicare. Local coverage determination (LCD): botulinum toxin types A and B policy (L35170). September 26, 2019. https://med.noridianmedicare.com/documents/10546/6990981/Botulinum+Toxin+Types+A+and+B+Policy+LCD. Accessed June 16, 2020.