To compare the cancer risk of cladribine and other disease-modifying drugs (DMDs) in trials of people with relapsing multiple sclerosis (pwRMS).
Meta-analysis of phase III trials of licensed DMDs for pwRMS and a phase III trial of cladribine (CLARITY). Cancer rates were compared using Fisher exact test.
Eleven trials were included. Investigated treatments included cladribine, dimethyl fumarate, fingolimod, teriflunomide, natalizumab, alemtuzumab, and glatiramer acetate. The cancer rate in the CLARITY treatment group (0.34%) was not increased compared to all other treatment groups, whether including placebo-controlled trials only (0.6%, p = 0.4631) or all trials, i.e., including those with an active comparator arm (0.67%, p = 0.3669). No cancer was reported in the CLARITY placebo group, whereas the combined cancer rate of all other placebo groups was 1.19% ( p = 0.0159). The cancer rate of zero in the CLARITY placebo group was also lower than that in the phase III trial of cladribine in people with clinically isolated syndrome (ORACLE MS, 2.91%, p = 0.0012). In fact, no difference was detected between cancer rates in the treatment groups of CLARITY (0.34%) and ORACLE MS (0.49%) ( p = 0.6546).
Our study does not support an increased cancer risk from cladribine in the doses used in CLARITY and ORACLE MS, which previously contributed to refusal of market authorization of cladribine in Europe. Longer-term follow-up is required to assess the safety profile of cladribine, as well as currently licensed DMDs, to definitively assess cancer risk.
M. Marta has received travel funding from Biogen-Idec and Abbott Laboratories and has received research support from Merck-Serono.
Merck-Serono UK paid my salary through unrestricted funding for an Investigator-Led Study sponsored by the University.
Patent filed via the university concerning the treatment of multiple sclerosis with cladribine and other compounds
Consultant for a Commercial entity (Canbex Therapeutics) that is unrelated to the subject of the manuscript
My laboratory received funds for research from a commercial entity (Genzyme Sanofi), unrelated to the subject of the manuscript in the past two years
The laboratory received funds for research from a academic entities unrelated to the subject of the manuscript
The laboratory received funds for research from Charities (Multiple sclerosis Society, Innovative UK/Technology Strategy Board, Diabetes UK, National Multiple Sclerosis Society) for studies unrelated to the subject of the manuscript
I have recieved stock options from a commercial entity (Canbex Therapeutics) in the past to years or studies unrelated to the subject of the manuscript.
UK MRC/Efficacy and Mechanism Evaluation Programme MS-SMART Trial; Grant number 11/30/11; Chief Investigator; 2013-2017
UK National Institute of Health Research (NIHR) University College London Hospitals/UCL Biomedical Research Centres funding scheme.
Funding information and disclosures are provided at the end of the article. Go to Neurology.org/nn for full disclosure forms. The Article Processing Charge was paid by Barts Charity, London, UK.
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