Health economic outcomes of switching to alemtuzumab from other disease-modifying therapies in people with multiple sclerosis in the USA

Using data from commercially insured population from the USA, we found that MS-specific HCRU for outpatient and inpatient services were significantly reduced for the 2-year period after pwMS initiated alemtuzumab treatment. A reduction in healthcare costs was also seen, for both all-cause and MS-specific services (particularly MRI and laboratory services), although costs associated with all-cause inpatient visits/services increased. The increase in costs associated with inpatient visits/services could potentially include the infusion costs of alemtuzumab itself considering that the infusion must be performed in a hospital or infusion center setting. Short-term (1-year) reductions in average PPPY costs, including out-of-pocket costs and hospital charges, were also seen, including reduced PPPY total costs over the longer (2-year) term. Collectively, our observations demonstrate that switching to alemtuzumab therapy was generally associated with favorable economic reductions in both MS-related and overall HCRU and in total and PPPY costs for these pwMS.

As MS is a life-long disease, it is associated with a considerable economic burden and additional HCRU and costs are incurred every time a patient switches from one DMT to another [26,27]. Therefore, ensuring that pwMS find a well-tolerated and cost-effective DMT early in their treatment trajectory is a priority, not only for the individual but also for the healthcare providers and the healthcare system as a whole. In this real-world analysis, HCRU and other costs were reduced over the 2-year period after the pwMS initiated alemtuzumab. These reductions in cost were likely due to the infrequent dosing regimen of alemtuzumab and the reduction in relapses leading to reduced need for acute visits. Of note, natalizumab was the most commonly used DMT prior to switching (41% were prescribed natalizumab during the 1-year pre-index period) and the treatment regimen for natalizumab involves a monthly, not yearly, infusion, as is the case for alemtuzumab. Although we did not specifically compare drug versus drug, this change in treatment regimen may have been a key driver behind the reduction in HCRU and laboratory visits (and associated costs) seen post-switching, due to the change in frequency of infusion visits and associated tests. However, other key factors were also driving costs; for example, costs associated with MRI visits reduced by $750 PPPY within 1-year of switching to alemtuzumab. Most of the study population (70%) remained on alemtuzumab throughout the 2-year follow-up period, and received the standard, pre-defined two courses [19], with 27% receiving one course and the remainder (4%) receiving a third dose during the 2-year post-index period. This suggests that the efficacy of alemtuzumab was maintained over the 2-year post-index period as those pwMS not achieving a sufficient response to treatment would be expected to discontinue from treatment or request a further course of treatment. These findings add to those of a previous 8-year post-hoc analysis of the randomized phase III CARE-MS studies showing that 48–53% of pwMS across age cohorts (ranging from 18 to 55 years) received no additional alemtuzumab or DMT beyond the 2-year core study period, and approximately 70% of pwMS remained in the study and received alemtuzumab throughout 8-years of follow-up [28].

In the present study, most pwMS (89.2%) had used only one other DMT prior to initiating alemtuzumab and the DMT used most frequently was natalizumab, as noted above. The importance of the number of DMTs used prior to switching to alemtuzumab (and in which sequence) has been highlighted in previous literature [29], because the therapeutic response and susceptibility for developing secondary autoimmunity in pwMS initiating alemtuzumab is associated with the number and sequence of previous DMTs. Moreover, there is a risk for outcomes potentially being greater with increasing numbers of previous DMTs, such as with previous use of fingolimod [29]. Findings from the current study indicate that healthcare professionals were following contemporary practice guidelines in the USA and prescribing alemtuzumab after only one previous DMT [20]. Furthermore, the observation that pwMS were switching from 1 high efficacy DMT to another high efficacy DMT suggests that the switch was most likely due to efficacy or safety reasons. Overall, initiating treatment with a high efficacy DMT, such as alemtuzumab, early in the disease trajectory may prevent the need to switch DMT so frequently, thereby reducing overall HCRU and healthcare costs, as indicated by the economic observations in the current study.

People with MS have a broad range of disease presentations and traditional assessment of efficacy in clinical trials is through monitoring of relapses (ARR) and/or changes in the Expanded Disability Status Scale (EDSS) [30]. Unfortunately, no EDSS data were available in the current dataset to indicate disease activity. Clinical outcomes are not reported in claims data and therefore proxy assessments, as the ones used in the current study, are often used to evaluate relapses rather than assessments commonly used in clinical trials. By assessing relapses we demonstrated that switching to alemtuzumab was associated with a significant reduction in ARR and this provided a comparative assessment in the real world with efficacy trials of alemtuzumab versus other DMTs for the treatment of MS [17,18,31,32]. The importance of reducing relapse rates in MS has been highlighted previously [22,33,34]. High relapse rates are associated with higher HCRU and are predictive of treatment-experienced pwMS switching DMT [22,35]. The reduction in ARR following initiation with alemtuzumab may explain the reduction in HCRU observed during the 2-year post-index period in this study. Indeed, with fewer relapses, pwMS receiving alemtuzumab may be more likely to remain compliant with their treatment and less likely to switch to other DMTs, thereby reducing future costs and allowing them to remain on stable therapy.

Some additional considerations should be highlighted when interpreting our study. First, as with all claims-data studies, individuals may have been misclassified due to misdiagnosis or miscoding; therefore, it is possible that not all pwMS switching to alemtuzumab were captured in our dataset. Not all disease entities and variables have their own billing codes; therefore, information on points of interest can be limited when conducting claims-data research. For example, information on MS phenotype and race or ethnicity were not available in the database and therefore not included in this analysis. Some pwMS were lost to follow-up due to noncontinuous enrollment between 1 year pre- and 1-year post-index. Unlike other biologics with different treatment schedules, alemtuzumab has a 2-year administration period. The first course of study drug is administered over five consecutive days, followed by no treatment for 12 months and then a three-day course of drug. This study was designed to include a 2-year post-index period, given the dosing schedule of alemtuzumab as outlined above [19]. Of further note, since pwMS were included up to December 2019 only, the study was not impacted by the COVID-19 pandemic. This is particularly relevant for pwMS receiving alemtuzumab, as they are required to visit an infusion center or hospital for treatment administration, and this may have been disrupted during the COVID-19 pandemic period from March 2020 onward. Finally, as hospitalization and corticosteroid use were used as proxies to determine number of relapses and calculate ARR, only moderate-to-severe relapses (and not mild) were included in the calculation of ARR. Despite the lack of data on mild relapses, our study did demonstrate that alemtuzumab reduced moderate-to-severe MS relapses and these are obviously of greater burden to pwMS, healthcare providers and the healthcare system. Due to the nature of data collection in this study, EDSS scores were not available to assess disability progression as a measure of MS disease status. Despite these limitations, our study demonstrates that significant reductions in HCRU and some costs are associated with switching to alemtuzumab therapy, particularly from other high-efficacy DMTs (e.g., fingolimod, ocrelizumab and natalizumab) for individuals with RMS.

This retrospective analysis of claims data from the USA demonstrate the economic benefits of switching to alemtuzumab from other DMTs in the treatment of RMS. Moreover, the efficacy of alemtuzumab demonstrated in clinical trials has been translated into real-world effectiveness, with corresponding reductions in MS-related HCRU and cost savings associated with MS relapses when people with MS switch to an alemtuzumab treatment regimen.

All authors were involved in the design and conduct of the study, and in interpreting the data. All authors were involved in drafting the manuscript and revising it critically for intellectual content. All authors had access to the study data.

The authors are grateful to N Roesch (Medical Director Neurology of Sanofi) for her contributions to aspects of the study design and feedback on measure of relapses.

This study was funded by Sanofi. L Araujo, K Higuchi and N Greene are employees of Sanofi and may hold stock or stock options. KG Bzdek was an employee of Sanofi at the time of the study. S Kyatham was an employee of Axtria at the time of the study. Axtria were paid consultants to Sanofi in relation to this project. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Medical writing support was provided by K Burrows of CURO (part of Envision Pharma Group) and was funded by Sanofi.

This work is licensed under the Attribution-NonCommercial-NoDerivatives 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/