Cladribine Effects on Patient-reported Outcomes and Their Clinical and Biometric Correlates in Highly Active Relapsing Multiple Sclerosis at First Switch: the Observational, Multicenter, Prospective, Phase IV CLADFIT-MS Study

Overview

Journal Front Neurol

Specialty Neurology

Date 2024 Aug 8

PMID 39114529

Authors

Giovanna Borriello

Clara Grazia Chisari

Davide Maimone

Massimiliano Mirabella

Damiano Paolicelli

Francesco Assogna

Sandro Caradonna

Francesco Patti

Affiliations

Soon will be listed here.

Abstract

Patient-reported outcomes (PROs) are essential for understanding the effects of MS and its treatments on patients' lives; they play an important role in multiple sclerosis (MS) research and practice. We present the protocol for an observational study to prospectively assess the effect of cladribine tablets on PROs and their correlation to disability and physical activity in adults with highly active relapsing MS switching from a first disease modifying drug (DMD) to cladribine tablets in routine clinical practice at study sites in Italy. The primary objective will be to evaluate changes from baseline in the impact of highly active MS on self-assessed physical functioning 52 weeks after the switch to cladribine tablets using the Multiple Sclerosis Impact Scale-29 (MSIS-29). Secondary objectives will include self-assessed psychological impact of highly active MS in daily life and general health after the switch to cladribine tablets as well as changes in cognitive function, anxiety, and depression symptoms. Additional PRO measures will include the Hospital Anxiety and Depression Scale (HADS), the EuroQoL 5-Dimension 5-Level (EQ-5D-5L), the Work Productivity and Activity Impairment Questionnaire: Multiple Sclerosis (WPAI:MS), and the Patient-Reported Outcomes Measurement Information System (PROMIS). Wearable devices will acquire activity data (step counts, walking speed, time asleep, and energy expenditure). Additional clinical, radiological, and laboratory data will be collected when available during routine management. The findings will complement data from controlled trials by providing insight from daily clinical practice into the effect of cladribine tablets on the patient's experience and self-assessed impact of treatment on daily life.

References

Yang J, Rempe T, Whitmire N, Dunn-Pirio A, Graves J . Therapeutic Advances in Multiple Sclerosis. Front Neurol. 2022; 13:824926. PMC: 9205455. DOI: 10.3389/fneur.2022.824926. View

Belbasis L, Bellou V, Evangelou E, Ioannidis J, Tzoulaki I . Environmental risk factors and multiple sclerosis: an umbrella review of systematic reviews and meta-analyses. Lancet Neurol. 2015; 14(3):263-73. DOI: 10.1016/S1474-4422(14)70267-4. View

Feehan L, Geldman J, Sayre E, Park C, Ezzat A, Yoo J . Accuracy of Fitbit Devices: Systematic Review and Narrative Syntheses of Quantitative Data. JMIR Mhealth Uhealth. 2018; 6(8):e10527. PMC: 6107736. DOI: 10.2196/10527. View

Kern K, Sarcona J, Montag M, Giesser B, Sicotte N . Corpus callosal diffusivity predicts motor impairment in relapsing-remitting multiple sclerosis: a TBSS and tractography study. Neuroimage. 2010; 55(3):1169-77. DOI: 10.1016/j.neuroimage.2010.10.077. View

Cella D, Riley W, Stone A, Rothrock N, Reeve B, Yount S . The Patient-Reported Outcomes Measurement Information System (PROMIS) developed and tested its first wave of adult self-reported health outcome item banks: 2005-2008. J Clin Epidemiol. 2010; 63(11):1179-94. PMC: 2965562. DOI: 10.1016/j.jclinepi.2010.04.011. View

Jeng B, DuBose N, Martin T, Silic P, Flores V, Zheng P . Updated Systematic Review and Quantitative Synthesis of Physical Activity Levels in Multiple Sclerosis. Am J Phys Med Rehabil. 2023; 103(4):284-292. DOI: 10.1097/PHM.0000000000002312. View

Weinshenker B . Epidemiology of multiple sclerosis. Neurol Clin. 1996; 14(2):291-308. DOI: 10.1016/s0733-8619(05)70257-7. View

Block V, Bove R, Nourbakhsh B . The Role of Remote Monitoring in Evaluating Fatigue in Multiple Sclerosis: A Review. Front Neurol. 2022; 13:878313. PMC: 9272225. DOI: 10.3389/fneur.2022.878313. View

Bierhansl L, Hartung H, Aktas O, Ruck T, Roden M, Meuth S . Thinking outside the box: non-canonical targets in multiple sclerosis. Nat Rev Drug Discov. 2022; 21(8):578-600. PMC: 9169033. DOI: 10.1038/s41573-022-00477-5. View

10.

Polhemus A, Sieber C, Haag C, Sylvester R, Kool J, Gonzenbach R . Non-equivalent, but still valid: Establishing the construct validity of a consumer fitness tracker in persons with multiple sclerosis. PLOS Digit Health. 2023; 2(1):e0000171. PMC: 9931345. DOI: 10.1371/journal.pdig.0000171. View

11.

Zwibel H, Smrtka J . Improving quality of life in multiple sclerosis: an unmet need. Am J Manag Care. 2011; 17 Suppl 5 Improving:S139-45. View

12.

Leist T, Weissert R . Cladribine: mode of action and implications for treatment of multiple sclerosis. Clin Neuropharmacol. 2011; 34(1):28-35. DOI: 10.1097/WNF.0b013e318204cd90. View

13.

Giovannoni G, Lang S, Wolff R, Duffy S, Hyde R, Kinter E . A Systematic Review and Mixed Treatment Comparison of Pharmaceutical Interventions for Multiple Sclerosis. Neurol Ther. 2020; 9(2):359-374. PMC: 7606402. DOI: 10.1007/s40120-020-00212-5. View

14.

Wattjes M, Rovira A, Miller D, Yousry T, Sormani M, de Stefano M . Evidence-based guidelines: MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis--establishing disease prognosis and monitoring patients. Nat Rev Neurol. 2015; 11(10):597-606. DOI: 10.1038/nrneurol.2015.157. View

15.

Nocentini U, Giordano A, Di Vincenzo S, Panella M, Pasqualetti P . The Symbol Digit Modalities Test - Oral version: Italian normative data. Funct Neurol. 2006; 21(2):93-6. View

16.

Ellenberger D, Parciak T, Brola W, Hillert J, Middleton R, Stahmann A . Comparison of employment among people with Multiple Sclerosis across Europe. Mult Scler J Exp Transl Clin. 2022; 8(2):20552173221090653. PMC: 9052831. DOI: 10.1177/20552173221090653. View

17.

Hirst C, Pace A, Pickersgill T, Jones R, McLean B, Zajicek J . Campath 1-H treatment in patients with aggressive relapsing remitting multiple sclerosis. J Neurol. 2008; 255(2):231-8. DOI: 10.1007/s00415-008-0696-y. View

18.

Jones E, Pike J, Marshall T, Ye X . Quantifying the relationship between increased disability and health care resource utilization, quality of life, work productivity, health care costs in patients with multiple sclerosis in the US. BMC Health Serv Res. 2016; 16:294. PMC: 4957342. DOI: 10.1186/s12913-016-1532-1. View

19.

Hedstrom A . Risk factors for multiple sclerosis in the context of Epstein-Barr virus infection. Front Immunol. 2023; 14:1212676. PMC: 10406387. DOI: 10.3389/fimmu.2023.1212676. View

20.

Leist T, Comi G, Cree B, Coyle P, Freedman M, Hartung H . Effect of oral cladribine on time to conversion to clinically definite multiple sclerosis in patients with a first demyelinating event (ORACLE MS): a phase 3 randomised trial. Lancet Neurol. 2014; 13(3):257-67. DOI: 10.1016/S1474-4422(14)70005-5. View