Long-term management of multiple sclerosis patients treated with cladribine tablets: an expert opinion

ABSTRACT

Introduction

Oral cladribine is a highly effective pulsed selective immune reconstitution therapy licensed for relapsing multiple sclerosis. A full treatment course comprises two treatment cycles given with 1 year of intermission. Further dosing is not routinely recommended in years 3 and 4.

Areas covered

The long-term management of patients treated with oral cladribine has not been fully defined on the basis of clinical studies as of yet. The authors provide their expert opinion on this.

Expert opinion

Based on available evidence and experience from routine clinical use, the authors suggest a structured approach to the long-term management of patients treated with cladribine tablets according to their responder type, i. e. the degree and timing of disease activity, if any, after treatment initiation. Informed treatment decisions require structured patient monitoring by established clinical and imaging parameters. In patients with relevant disease activity in year 3 or 4 and beyond, the use of additional cycle(s) of oral cladribine might become an option. For patients requiring a treatment switch, the choice of therapies primarily includes moderately to highly effective MS drugs.

KEYWORDS:

• Multiple sclerosis
• cladribine tablets
• long-term management
• pulsed selective immune reconstitution therapy
• responder

Article highlights

• Oral cladribine (Mavenclad®) is a highly effective pulsed selective immune reconstitution therapy (PSIRT) for MS.

• Efficacy, safety, and tolerability of cladribine tablets have been confirmed in a clinical study program with follow-up durations of up to 14 years. After completing two cycles (in years 1 and 2), further treatment with oral cladribine is not regularly scheduled.

• We suggest a long-term management approach guided by responder type – defined by disease activity and/or disease progression (see text for definitions) – which is based on consistent and regular monitoring of disease evolution and should be interpreted in the light of the previous disease course of the individual patient.

• Optimal responders and delayed responders having received the licensed treatment courses in years 1 and 2 are not expected to need any additional MS therapy within the 4 years after treatment initiation, while retreatment may be considered in year 5 as needed or as a default to prevent the reappearance of disease activity.

• Non-responders and midterm-responders will need additional treatment cycle(s) or a switch to a different disease-modifying drug within the second to the fourth year.

• Expansion of the clinical evidence supporting this tentative approach is expected from ongoing prospective clinical trials, long-term registries, and observational data from routine clinical use.

Authors contributions

All authors developed and consented the content of the manuscript. S. Meuth and M. Mäurer drafted the manuscript. All authors read, commented and approved the final manuscript.

Acknowledgments

Medical writing services were provided by Markus Fischer, PhD (Fischer BioMedical Wissenschaftskommunikation, Germany).

Declaration of interest

A Bayas has received personal fees from Merck Serono, Biogen Idec, Novartis, Teva, Roche, Celgene, and Sanofi/Genzyme and grants for congress trips and participation from Biogen, Teva, Novartis, Sanofi/Genzyme, Celgene, and Merck Serono. B Kallmann has received financial compensation for activities with Bayer, Biogen Idec, Biologix, Celgene, Merck Serono, Novartis, Roche, Sanofi and Teva. C Kleinschnitz has received speaker’s fees, honoraria for attending advisory boards, and financial support for conducting research projects from Merck Serono GmbH, Germany and Merck KGaA, Germany. R Linker received compensation for activities with Bayer, Biogen, Celgene, Genzyme, Merck Serono, Novartis, Roche, and TEVA as well as research support from Biogen, Merck Serono and Novartis. S Meuth received honoraria for lecturing, and travel expenses for attending meetings from Almirall, Amicus Therapeutics Germany, Bayer Healthcare, Biogen, Celgene, Diamed, Genzyme, MedDay Pharmaceuticals, Merck Serono, Novartis, Novo Nordisk, ONO Pharma, Roche, Sanofi, Chugai Pharma, Quintiles IMS and Teva. His research is funded by the German Ministry for Education and Research (BMBF), the Bundesinstitut für Risikobewertung (BfR), the Deutsche Forschungsgemeinschaft (DFG), the Else Kröner Fresenius Foundation, the Gemeinsamer Bundesausschuss (G-BA), the German Academic Exchange Service, the Hertie Foundation, the Interdisciplinary Center for Clinical Studies (IZKF) Muenster, the German Foundation Neurology and Alexion, Almirall, Amicus Therapeutics Germany, Biogen Idec, Diamed, Fresenius Medical Care, Genzyme, HERZ Burgdorf, Merck Serono, Novartis, ONO Pharma, Roche, and Teva. M Mäurer received honoraria for lecturing, travel expenses for attending meetings, and financial support for research from Almirall, Bayer Healthcare, Boehringer Ingelheim, Biogen Idec, Genzyme/Sanofi, Merck Serono, Novartis, Roche, Talecris and Teva. He serves on a steering committee for Biogen and Novartis and as a consultant for Biogen, Genzyme and Roche. Finally, P Rieckmann received honoraria for lectures from Almiral, Apple Healthcare, Baxter, Bayer, Biogen Idec, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Genpharm, Genzyme, Medtronic, Merck Serono, Novartis, Pfizer, Roche, Sanofi, Siemens AG, and Teva. He received research grants from Brainlight, German Neurology Foundation, h/p/Cosmos, Max Aicher Foundation, Oberfranken-Stiftung, Red Bull, and Teva. He served on advisory boards or steering committees for Aycan, Bayer, Biogen Idec, Canada Drug Review, the German Multiple Sclerosis Society, Novartis, Merck Serono, and Teva. 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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This research was financially supported by Merck Serono, an affiliate of Merck KGaA, Darmstadt, Germany. Writing support was utilized in this manuscript and funded by Merck Serono.