title: No evidence for higher risk of cancer in patients with multiple sclerosis taking cladribine.
abstract: OBJECTIVE
  To compare the cancer risk of cladribine and other disease-modifying drugs (DMDs) in trials of people with relapsing multiple sclerosis (pwRMS).
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Blizard Institute (Neuroscience) (J.P., G.D., M.M., D.B., K.S.), Queen Mary University of London, Barts and The London School of Medicine and Dentistry, London, UK; Oxford University Medical School (J.P.), John Radcliffe Hospital, Oxford, UK; London School of Hygiene and Tropical Medicine (D.R.A.), London, UK; Centre for Health Services Research (S.P.), Leeds Institute of Health Sciences, University of Leeds, Leeds, UK; Barts Health NHS Trust (B.P.T., M.M., K.S.), The Royal London Hospital, London, UK; Stem Cell Centre (G.J.), Lund University, Lund, Sweden; and Queen Square Multiple Sclerosis Centre (J.C.), Department of Neuroinflammation, UCL Institute of Neurology, University College London and National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London UK.
authors.forename: Julia
authors.initials: J
authors.lastname: Pakpoor
authors.affiliation: Blizard Institute (Neuroscience) (J.P., G.D., M.M., D.B., K.S.), Queen Mary University of London, Barts and The London School of Medicine and Dentistry, London, UK; Oxford University Medical School (J.P.), John Radcliffe Hospital, Oxford, UK; London School of Hygiene and Tropical Medicine (D.R.A.), London, UK; Centre for Health Services Research (S.P.), Leeds Institute of Health Sciences, University of Leeds, Leeds, UK; Barts Health NHS Trust (B.P.T., M.M., K.S.), The Royal London Hospital, London, UK; Stem Cell Centre (G.J.), Lund University, Lund, Sweden; and Queen Square Multiple Sclerosis Centre (J.C.), Department of Neuroinflammation, UCL Institute of Neurology, University College London and National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London UK.
authors.forename: Giulio
authors.initials: G
authors.lastname: Disanto
authors.affiliation: Blizard Institute (Neuroscience) (J.P., G.D., M.M., D.B., K.S.), Queen Mary University of London, Barts and The London School of Medicine and Dentistry, London, UK; Oxford University Medical School (J.P.), John Radcliffe Hospital, Oxford, UK; London School of Hygiene and Tropical Medicine (D.R.A.), London, UK; Centre for Health Services Research (S.P.), Leeds Institute of Health Sciences, University of Leeds, Leeds, UK; Barts Health NHS Trust (B.P.T., M.M., K.S.), The Royal London Hospital, London, UK; Stem Cell Centre (G.J.), Lund University, Lund, Sweden; and Queen Square Multiple Sclerosis Centre (J.C.), Department of Neuroinflammation, UCL Institute of Neurology, University College London and National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London UK.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Altmann
authors.affiliation: Blizard Institute (Neuroscience) (J.P., G.D., M.M., D.B., K.S.), Queen Mary University of London, Barts and The London School of Medicine and Dentistry, London, UK; Oxford University Medical School (J.P.), John Radcliffe Hospital, Oxford, UK; London School of Hygiene and Tropical Medicine (D.R.A.), London, UK; Centre for Health Services Research (S.P.), Leeds Institute of Health Sciences, University of Leeds, Leeds, UK; Barts Health NHS Trust (B.P.T., M.M., K.S.), The Royal London Hospital, London, UK; Stem Cell Centre (G.J.), Lund University, Lund, Sweden; and Queen Square Multiple Sclerosis Centre (J.C.), Department of Neuroinflammation, UCL Institute of Neurology, University College London and National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London UK.
authors.forename: Sue
authors.initials: S
authors.lastname: Pavitt
authors.affiliation: Blizard Institute (Neuroscience) (J.P., G.D., M.M., D.B., K.S.), Queen Mary University of London, Barts and The London School of Medicine and Dentistry, London, UK; Oxford University Medical School (J.P.), John Radcliffe Hospital, Oxford, UK; London School of Hygiene and Tropical Medicine (D.R.A.), London, UK; Centre for Health Services Research (S.P.), Leeds Institute of Health Sciences, University of Leeds, Leeds, UK; Barts Health NHS Trust (B.P.T., M.M., K.S.), The Royal London Hospital, London, UK; Stem Cell Centre (G.J.), Lund University, Lund, Sweden; and Queen Square Multiple Sclerosis Centre (J.C.), Department of Neuroinflammation, UCL Institute of Neurology, University College London and National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London UK.
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Turner
authors.affiliation: Blizard Institute (Neuroscience) (J.P., G.D., M.M., D.B., K.S.), Queen Mary University of London, Barts and The London School of Medicine and Dentistry, London, UK; Oxford University Medical School (J.P.), John Radcliffe Hospital, Oxford, UK; London School of Hygiene and Tropical Medicine (D.R.A.), London, UK; Centre for Health Services Research (S.P.), Leeds Institute of Health Sciences, University of Leeds, Leeds, UK; Barts Health NHS Trust (B.P.T., M.M., K.S.), The Royal London Hospital, London, UK; Stem Cell Centre (G.J.), Lund University, Lund, Sweden; and Queen Square Multiple Sclerosis Centre (J.C.), Department of Neuroinflammation, UCL Institute of Neurology, University College London and National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London UK.
authors.forename: Monica
authors.initials: M
authors.lastname: Marta
authors.affiliation: Blizard Institute (Neuroscience) (J.P., G.D., M.M., D.B., K.S.), Queen Mary University of London, Barts and The London School of Medicine and Dentistry, London, UK; Oxford University Medical School (J.P.), John Radcliffe Hospital, Oxford, UK; London School of Hygiene and Tropical Medicine (D.R.A.), London, UK; Centre for Health Services Research (S.P.), Leeds Institute of Health Sciences, University of Leeds, Leeds, UK; Barts Health NHS Trust (B.P.T., M.M., K.S.), The Royal London Hospital, London, UK; Stem Cell Centre (G.J.), Lund University, Lund, Sweden; and Queen Square Multiple Sclerosis Centre (J.C.), Department of Neuroinflammation, UCL Institute of Neurology, University College London and National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London UK.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Juliusson
authors.affiliation: Blizard Institute (Neuroscience) (J.P., G.D., M.M., D.B., K.S.), Queen Mary University of London, Barts and The London School of Medicine and Dentistry, London, UK; Oxford University Medical School (J.P.), John Radcliffe Hospital, Oxford, UK; London School of Hygiene and Tropical Medicine (D.R.A.), London, UK; Centre for Health Services Research (S.P.), Leeds Institute of Health Sciences, University of Leeds, Leeds, UK; Barts Health NHS Trust (B.P.T., M.M., K.S.), The Royal London Hospital, London, UK; Stem Cell Centre (G.J.), Lund University, Lund, Sweden; and Queen Square Multiple Sclerosis Centre (J.C.), Department of Neuroinflammation, UCL Institute of Neurology, University College London and National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London UK.
authors.forename: David
authors.initials: D
authors.lastname: Baker
authors.affiliation: Blizard Institute (Neuroscience) (J.P., G.D., M.M., D.B., K.S.), Queen Mary University of London, Barts and The London School of Medicine and Dentistry, London, UK; Oxford University Medical School (J.P.), John Radcliffe Hospital, Oxford, UK; London School of Hygiene and Tropical Medicine (D.R.A.), London, UK; Centre for Health Services Research (S.P.), Leeds Institute of Health Sciences, University of Leeds, Leeds, UK; Barts Health NHS Trust (B.P.T., M.M., K.S.), The Royal London Hospital, London, UK; Stem Cell Centre (G.J.), Lund University, Lund, Sweden; and Queen Square Multiple Sclerosis Centre (J.C.), Department of Neuroinflammation, UCL Institute of Neurology, University College London and National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London UK.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Chataway
authors.affiliation: Blizard Institute (Neuroscience) (J.P., G.D., M.M., D.B., K.S.), Queen Mary University of London, Barts and The London School of Medicine and Dentistry, London, UK; Oxford University Medical School (J.P.), John Radcliffe Hospital, Oxford, UK; London School of Hygiene and Tropical Medicine (D.R.A.), London, UK; Centre for Health Services Research (S.P.), Leeds Institute of Health Sciences, University of Leeds, Leeds, UK; Barts Health NHS Trust (B.P.T., M.M., K.S.), The Royal London Hospital, London, UK; Stem Cell Centre (G.J.), Lund University, Lund, Sweden; and Queen Square Multiple Sclerosis Centre (J.C.), Department of Neuroinflammation, UCL Institute of Neurology, University College London and National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London UK.
authors.forename: Klaus
authors.initials: K
authors.lastname: Schmierer