Background Multiple sclerosis (MS) is a chronic, demyelinating disease of the central nervous system that results in progressive and irreversible disability. Fatigue is one of the most common MS-related symptoms and is characterized by a persistent lack of energy that impairs daily functioning. The burden of MS-related fatigue is complex and multidimensional, and to our knowledge, no systematic literature review has been conducted on this subject. The purpose of this study was to conduct a systematic literature review on the epidemiology and burden of fatigue in people with multiple sclerosis (pwMS). Methods Systematic searches were conducted in MEDLINE, Embase, and Evidence-Based Medicine Reviews to identify relevant studies of fatigue in pwMS. English-language records published from 2010 to January 2020 that met predefined eligibility criteria were included. We initially selected studies that reported quality of life (QoL) and economic outcomes according to categories of fatigue (e.g., fatigued vs non-fatigued). Studies assessing associations between economic outcomes and fatigue as a continuous measure were later included to supplement the available data. Results The search identified 8147 unique records, 54 of which met the inclusion criteria. Of these, 39 reported epidemiological outcomes, 11 reported QoL, and 9 reported economic outcomes. The supplementary screen for economic studies with fatigue as a continuous measure included an additional 20 records. Fatigue prevalence in pwMS ranged from 36.5 to 78.0%. MS-related fatigue was consistently associated with significantly lower QoL. Results on the economic impact of fatigue were heterogeneous, but most studies reported a significant association between presence or severity of fatigue and employment status, capacity to work, and sick leave. There was a gap in evidence regarding the direct costs of MS-related fatigue and the burden experienced by caregivers of pwMS. Conclusion Fatigue is a prevalent symptom in pwMS and is associated with considerable QoL and economic burden. There are gaps in the evidence related to the direct costs of MS-related fatigue and the burden of fatigue on caregivers. Addressing fatigue over the clinical course of the disease may improve health and economic outcomes for patients with MS.

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New classes of therapies have emerged for treating Relapsed or Refractory Multiple Myeloma (RRMM) patients, including chimeric antigen receptor T-cell (CAR-T) therapies targeting the B-cell maturation antigen. While CAR-T therapies are expected to be a more expensive class of treatment compared to chemotherapy, 1 they have been shown to have a high overall response rate (ORR) and progression-free survival (PFS). 2,3 As newer, more innovative RRMM therapies are developed and brought to market, payers will need to balance their higher efficacy and total treatment costs when assessing potential value. To assess the value of RRMM CAR-T therapies (ciltacabtagene autoleucel [cilta-cel] and idecabtagene vicleucel [ide-cel]), we developed a cost per responder (CPR) model that incorporates efficacy and total cost of treatment. In the absence of head-to-head trial data for CAR-T therapies, indirect treatment comparisons (ITCs) can be used to evaluate comparative efficacy, and the results can be used to inform a CPR model. Matching-adjusted indirect comparisons (MAIC) is a form of ITC that involves matching and adjusting a treatment group from a clinical study with individual patient-level data (IPD) available to a comparator for which only summary-level data are available. This method mitigates potential bias arising from differences in patient characteristics between trials and is widely used and accepted in comparative effectiveness research. Unanchored matching adjusted indirect comparison (MAIC) analyses were used to inform the comparative efficacy of cilta-cel versus ide-cel in our CPR model. MAIC results indicated that cilta-cel was associated with statistically significantly improved ORR (odds ratio [OR]: 87.99 [95% confidence interval [CI]: 20.32, 381.01; p < .0001]), complete response or better (≥CR) rate (OR: 5.96 [95% CI: 2.76, 12.88; p < .0001]) and PFS (hazard ratio [HR]: 0.36 [95% CI: 0.22, 0.59; p < .0001]) when compared with ide-cel. 4 To adequately capture total treatment costs for each treatment of interest, CPR models should include all costs related to acquisition and delivery of treatment. Relevant costs of CAR-T therapy for RRMM include the cost of apheresis, bridging therapy, costs of CAR-T acquisition and administration, supportive care and monitoring costs, adverse event management costs, and any costs associated with delivery of inpatient or outpatient clinical services. Preliminary results of the CPR analysis indicate that ide-cel is associated with a cost per ORR of approximately $743,000, a cost per CR or better of $1.66 million and a cost per month in PFS of approximately $55,000. Corresponding results for cilta-cel will be generated after the PDUFA date (November 29, 2021), and presented at ASH 2021. In conclusion, CPR models have significant potential to assist payers in evaluating the value of newer, more innovative RRMM therapies by integrating information on both total costs and efficacy. References 1 Pagliarulo N. FDA approves first CAR-T cell therapy for multiple myeloma. https://www.biopharmadive.com/news/fda-car-t-multiple-myeloma-approval-bristol-myersbluebird/597438/#:~:text=The%20pharma%2C%20which%20licensed%20the,other%20approve d%20CAR%2DT%20therapies. Published 27 March 2021. Accessed 22 June 2021. 2 Munshi NC, Anderson Jr LD, Shah N, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med. 2021;384(8):705-16. 3 Madduri D, Berdeja JG, Usmani SZ, et al. CARTITUDE-1: phase 1b/2 study of ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy, in relapsed/refractory multiple myeloma [abstract]. Blood. 2020;136(1 supplement). Abstract 177. 4 Martin T, Usmani SZ, Schecter JM, Vogel M, Jackson CC et al. (2021) Matching-adjusted indirect comparison of efficacy outcomes for ciltacabtagene autoleucel in CARTITUDE-1 versus idecabtagene vicleucel in KarMMa for the treatment of patients with relapsed or refractory multiple myeloma. Curr Med Res Opin 1-10. Disclosures Martin: Sanofi: Research Funding; Oncopeptides: Consultancy; Janssen: Research Funding; Amgen: Research Funding; GlaxoSmithKline: Consultancy. Usmani: Pharmacyclics: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Merck: Consultancy, Research Funding; SkylineDX: Consultancy, Research Funding; Bristol-Myers Squibb: Research Funding; Takeda: Consultancy, Research Funding, Speakers Bureau; Janssen Oncology: Consultancy, Research Funding; Abbvie: Consultancy; Array BioPharma: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding, Speakers Bureau; Celgene/BMS: Consultancy, Research Funding, Speakers Bureau; GSK: Consultancy, Research Funding; EdoPharma: Consultancy; Janssen: Consultancy, Research Funding, Speakers Bureau; Amgen: Consultancy, Research Funding, Speakers Bureau. Joseph: Johnson and Johnson: Current Employment, Current equity holder in publicly-traded company. Crivera: Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Valluri: Janssen: Current Employment, Current equity holder in publicly-traded company. Jackson: Memorial Sloan Kettering Cancer Center: Consultancy; Janssen: Current Employment. Cohen: Eversana Life Science Services: Current Employment, Other: Eversana Life Science Services was contracted by Janssen to work on this project.. Singh: Eversana Life Science Services: Current Employment, Other: Eversana Life Science Services was contracted by Janssen to work on this project..