Subcutaneous cladribine to treat multiple sclerosis: experience in 208 patients

Author:

Allen-Philbey Kimberley12ORCID,De Trane Stefania2,Mao Zhifeng34,Álvarez-González Cesar56,Mathews Joela7,MacDougall Amy8,Stennett Andrea19,Zhou Xia1,Yildiz Ozlem12,Adams Ashok10,Bianchi Lucia2,Blain Camilla11,Chapman Christine2,Chung Karen12,Constantinescu Cris S1314,Dalton Catherine11,Farrell Rachel A1215,Fisniku Leonora16,Ford Helen17,Gran Bruno1314,Hobart Jeremy18,Khaleeli Zhaleh15,Mattoscio Miriam19,Pavitt Sue20,Pearson Owen21,Peruzzotti-Jametti Luca22,Scalfari Antonio23,Sharrack Basil2425,Silber Eli26,Tallantyre Emma C2728,Webb Stewart29,Turner Benjamin P12,Marta Monica12,Gnanapavan Sharmilee12,Juliusson Gunnar3031,Giovannoni Gavin12ORCID,Baker David2,Schmierer Klaus32ORCID

Affiliation:

1. Neuroscience, Clinical Board Medicine, The Royal London Hospital, Barts Health NHS Trust, London, UK

2. Neuroscience, Surgery and Trauma, The Blizard Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, London, UK

3. Kingmed College of Laboratory Medicine, Guangzhou Medical University, Guangzhou, China

4. Department of Clinical Medicine, Medical School, Xiangnan University, Chenzhou, China

5. Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, Basel, Switzerland

6. Research Center for Clinical Neuroimmunology and Neuroscience, University of Basel, Basel, Switzerland

7. Pharmacy Department, The Royal London Hospital, Barts Health NHS Trust, London, UK

8. Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK

9. Preventive Neurology Unit, Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, London, UK

10. Neuroradiology Department, The Royal London Hospital, Barts Health NHS Trust, London, UK

11. St George’s University Hospitals NHS Foundation Trust, London, UK

12. The National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, UK

13. Department of Neurology, Nottingham University Hospitals NHS Trust, Nottingham, UK

14. Mental Health and Clinical Neuroscience Academic Unit, School of Medicine, University of Nottingham, Nottingham, UK

15. Department of Neuroinflammation, National Hospital for Neurology and Neurosurgery, London, UK

16. Brighton and Sussex University Hospitals NHS Trust, Brighton, UK; Brighton and Sussex Medical School, Brighton, UK

17. Leeds Teaching Hospitals NHS Trust, Leeds, UK

18. Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, UK

19. Queen’s Hospital, Barking Havering and Redbridge Hospital NHS Trust, Romford, UK; Department of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK

20. Dental Translational and Clinical Research Unit, School of Dentistry, University of Leeds, Leeds, UK

21. Department of Neurology, Swansea Bay University Health Board, Port Talbot, UK

22. Department of Clinical Neurosciences and National Institute for Health Research (NIHR) Biomedical Research Centre, University of Cambridge, Cambridge, UK

23. Centre of Neuroscience, Department of Medicine Charing Cross Hospital, Imperial College London, London, UK

24. Department of Neurology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK

25. Department of Neuroscience and NIHR Neurosciences Biomedical Research Centre, University of Sheffield, Sheffield, UK

26. Department of Neurology, King’s College Hospital, London, UK

27. Department of Neurology, University Hospital of Wales, Cardiff, UK

28. Division of Psychological Medicine and Clinical Neuroscience, School of Medicine, Cardiff University, Cardiff, UK

29. Institute of Neuroscience, Department of Neurology, Queen Elizabeth University Hospital, Glasgow, UK

30. Department of Hematology, Skåne University Hospital, Lund, Sweden

31. Stem Cell Centre, Department of Laboratory Medicine, Lund University, Lund, Sweden

32. Neuroscience, Clinical Board Medicine, The Royal London Hospital, Barts Health NHS Trust, London, UK Neuroscience, Surgery and Trauma, The Blizard Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, 4 Newark Street, London E1 2AT, UK

Abstract

Objective: To report on safety and effectiveness of subcutaneous cladribine (Litak®) in multiple sclerosis (MS) patients. Methods: Litak® was offered to MS-patients irrespective of disease course. Litak® 10 mg was administered for 3–4 days during week 1. Based on lymphocyte count at week 4, patients received another 0–3 doses at week 5. A second course was administered 11 months later. Follow-up included adverse events, relapses, expanded disability status scale (EDSS), 9-hole-peg and Timed-25-foot-walking tests, no-evidence-of-disease-activity (NEDA), no-evidence-of-progression-or-active-disease (NEPAD), MRI, cerebrospinal fluid (CSF) neurofilament light chain (NfL), and lymphocyte counts. Results: In all, 208 patients received at least one course of treatment. Age at baseline was 44 (17–72) years and EDSS 0–8.5. Cladribine was generally well tolerated. One myocardial infarction, one breast cancer, and three severe skin reactions occurred without long-term sequelae. Two patients died (one pneumonia, one encephalitis). Lymphopenia grade 3 occurred in 5% and grade 4 in 0.5%. In 94 out of 116 pwMS with baseline and follow-up (BaFU) data after two treatment courses, EDSS remained stable or improved. At 18 months, 64% of patients with relapsing MS and BaFU data ( n = 39) had NEDA. At 19 months, 62% of patients with progressive MS and BaFU data ( n = 13) had NEPAD. Of n = 13 patients whose CSF-NfL at baseline was elevated, 77% were normalised within 12 months. Conclusions: Litak® was well tolerated. Effectiveness in relapsing MS appeared similar to cladribine tablets and was encouraging in progressive MS. Our data suggest cladribine may be safe and effective in MS-patients irrespective of their disease stage.

Publisher

SAGE Publications

Subject

Neurology (clinical),Neurology,Pharmacology

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