Oral Cladribine in Patients who Change From First-Line Disease Modifying Treatments for Multiple Sclerosis: Protocol of a Prospective Effectiveness and Safety Study (CLAD CROSS)

Georgios Tsivgoulis; Spyros Deftereos; Claudio Gobbi; Elisabeth Gulowsen Celius; Alina Kulakowska; Giorgia Maniscalco; Irene Mendes; Nicolaos Grigoriadis

doi:10.1177/11795735211069441

Oral Cladribine in Patients who Change From First-Line Disease Modifying Treatments for Multiple Sclerosis: Protocol of a Prospective Effectiveness and Safety Study (CLAD CROSS)

J Cent Nerv Syst Dis. 2022 Apr 1:14:11795735211069441. doi: 10.1177/11795735211069441. eCollection 2022.

Authors

Georgios Tsivgoulis^{1

2}, Spyros Deftereos³, Claudio Gobbi^{4

5}, Elisabeth Gulowsen Celius⁶, Alina Kulakowska⁷, Giorgia Maniscalco⁸, Irene Mendes⁹, Nicolaos Grigoriadis¹⁰

Affiliations

¹ Second Department of Neurology, National and Kapodistrian University of Athens, School of Medicine, "Attikon" University Hospital, Athens, Greece.
² Department of Neurology, The University of Tennessee Health Science Center, Memphis, TN, USA.
³ An Affiliate of Merck KGaA, Merck A.E., Marousi, Greece.
⁴ Multiple Sclerosis Center (MSC), Department of Neurology, Neurocenter of Southern Switzerland, Lugano, Switzerland.
⁵ Faculty of Biomedical Sciences, Università Della Svizzera Italiana (USI), Lugano, Switzerland.
⁶ Department of Neurology, Oslo University Hospital and Faculty of Medicine, University of Oslo, Oslo, Norway.
⁷ Department of Neurology, Medical University of Bialystok, Bialystok, Poland.
⁸ Dipartimento di Neurologia, Centro Regionale Sclerosi Multipla, Napoli, Italy.
⁹ Hospital Dia Neurologia, Hospital Garcia de Orta, Pragal, Portugal.
¹⁰ Second Department of Neurology, Special Unit for Biomedical Research and Education (S.U.B.R.E.), School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Abstract

Background: Recently, the number of available disease modifying therapies for multiple sclerosis (MS) has increased. However, a proportion of patients treated with these agents continue to experience relapses and disease progression. Cladribine tablets, approved in 2017 for highly active relapsing MS, comprise a sparsely administered oral treatment which exerts its therapeutic effect through a reduction and subsequent repletion of the lymphocyte population.

Purpose/study sample: Here we describe the design of CLAD CROSS, a prospective, non-interventional, multicenter, Phase IV study in patients with a confirmed diagnosis of RRMS who switch from first-line disease modifying drugs (DMDs) to treatment with cladribine tablets in routine clinical practice. 242 adult patients will be recruited in 61 sites (6 countries) over 30 months and will be followed up for 2 years following prescription of cladribine tablets per the decision of the treating physicians.

Research design: The primary endpoint is the change in annualized relapse rate (ARR) between the 12-month pre-baseline period and over the 12-month period before end of study. Secondary endpoints are the percentage of patients with 6-month disability progression or improvement at the end of the study, measured by the Expanded Disability Status Scale, Timed 25 Foot Walk and 9-Hole Peg Test scales and quality of life, treatment satisfaction, and healthcare resource utilization, measured through the MSIS-29, TSQM 1.4, and EQ-5D-3L scales, respectively. MRI lesions will be compared in the exploratory setting between the 12-month pre-baseline period, baseline, and at years 1 and 2. Adverse events will be monitored throughout the study. Interim analyses are pre-planned when 30% and 60% of patients will complete the 12-month follow-up visit.

Conclusions: CLAD CROSS will provide efficacy data on cladribine tablets, used as a follow-up treatment to first-line DMDs in the real-world setting, will further establish its safety profile and will collect information to support pharmacoeconomic studies.

Keywords: CLAD CROSS study; cladribine tablets; multiple sclerosis.