Analysis of clinical outcomes according to original treatment groups 16 years after the pivotal IFNB-1b trial
- G C Ebers1,
- A Traboulsee2,
- D Li2,
- D Langdon3,
- A T Reder4,
- D S Goodin5,
- T Bogumil6,
- K Beckmann7,
- C Wolf7,
- A Konieczny7,
- for the Investigators of the 16-year Long-Term Follow-Up Study
- 1University Department of Clinical Neurology, John Radcliffe Hospital, Oxford, UK
- 2University of British Columbia, Vancouver, British Columbia, Canada
- 3Department of Psychology, Royal Holloway, University of London, London, UK
- 4Department of Neurology, University of Chicago, Chicago, Illinois, USA
- 5Department of Neurology, University of California, San Francisco, California, USA
- 6Bayer Healthcare Pharmaceuticals, Montville, New Jersey, USA
- 7Bayer Schering Pharma AG, Berlin, Germany
- Correspondence to Professor George Ebers, University Department of Clinical Neurology, 3rd Floor, West Wing, John Radcliffe Hospital, Oxford OX3 9DU, UK;
- Received 24 December 2009
- Accepted 25 February 2010
- Published Online First 19 June 2010
Background Evidence for efficacy of disease-modifying drugs in multiple sclerosis (MS) comes from trials of short duration. We report results from a 16 y, retrospective follow-up of the pivotal interferon β-1b (IFNB-1b) study.
Methods The 372 trial patients were randomly assigned to placebo (n=123), IFNB-1b 50 μg (n=125) or IFNB-1b 250 μg (n=124) subcutaneously every other day for at least 2 y. Some remained randomised for up to 5 y but, subsequently, patients received treatment according to physicians' discretion. Patients were re-contacted and asked to participate. Efficacy related measures included MRI parameters, relapse rate, the Expanded Disability Status Scale, the Multiple Sclerosis Functional Composite Measure and conversion to secondary progressive MS.
Results Of the 88.2% (328/372) of patients who were identified, 69.9% (260/372) had available case report forms. No differences in outcome between original randomisation groups could be discerned using standard disability and MRI measures. However, mortality rates among patients originally treated with IFNB-1b were lower than in the original placebo group (18.3% (20/109) for placebo versus 8.3% (9/108) for IFNB-1b 50 μg and 5.4% (6/111) for IFNB-1b 250 μg).
Conclusions The original treatment assignment could not be shown to influence standard assessments of long-term efficacy. On-study behaviour of patients was influenced by factors that could not be controlled with the sacrifice of randomisation and blinding. Mortality was higher in patients originally assigned to placebo than those who had received IFNB-1b 50 μg or 250 μg. The dataset provides important resources to explore early predictors of long-term outcome.
Linked articles 208017.
16 y long-term follow-up study investigators: University of Chicago, Illinois, USA: B Arnason (Principal Investigator (PI)), A Reder, A Javed, A Noronha (Investigators (I]), B Harding-Clay, M Valentine, K Ivy (Study co-ordinators (SC)), J Fink, T Nader, M Lacy (Neuropsychological testers (NT)); University of California, San Francisco, USA: DS Goodin (PI), E Kornyeyeva (SC), D Cox (NT); Greenstein Associates & MS Institute, Philadelphia, USA: J Greenstein (PI), I Gold (SC); University of Maryland, Baltimore, USA: K Johnson (PI), C Bever, H Rus, R Shin (I), E Katz, V Wells, K Naunton (SC), M Rogerson (NT); Jefferson University Hospital, Philadelphia, USA: T Leist (PI), S Gallardo, J Davis (SC), A Okai (NT); University of Arizona, Tucson, USA: WA Sibley (PI), J Wendt, DA Weidman, RD Wachter (I), J Laguna, B Peterson (SC), D Brown (NT); University of Alabama at Birmingham, USA: K Bashir (PI), B Layton (SC), J Castillo, S Krzywanski (NT); Hôpital de Notre-Dame, Montréal: P Duquette (PI), R Dubois (SC), J Poirier (NT); Institut et Hôpital Neurologiques de Montréal, Canada: Y Lapierre (PI), S Hum (SC and NT); University of British Columbia, Vancouver, Canada: J Oger (PI), V Devonshire, J Hooge, A Traboulsee, P Smyth, S Hashimoto, L Kastrukoff (I), W Morrison, F Lum (SC), B Kosaka (NT); London Health Sciences Centre, Ontario, Canada: GPA Rice (PI), M Kremenchutzky, R Deshpande (I), J Lesaux (SC), H Armstrong (NT), J Moussa, T Bentall (Research assistants); University of Oxford, Oxford, UK: GC Ebers (Signatory Investigator), A Scalfari (I); University of London, London, UK: D Langdon (Neuropsychology Coordinator); Radcliffe Infirmary, Oxford, UK: J Gurd (Neuropsychology Coordinator); MRI Center, Vancouver, British Columbia, Canada: D Li, A Traboulsee (PI), R Tam (Research assistant), M Medina, A Riddlebough (SC).
Competing interests This study was sponsored by Bayer HealthCare Pharmaceuticals. At the time of the study, TB, CW, KB and AK were salaried employees of Bayer Schering Pharma AG, Berlin, Germany. GE has received research support from Bayer Schering Pharma AG/Bayer HealthCare Pharmaceuticals. AT has received honoraria from Bayer Schering Pharma AG/Bayer HealthCare Pharmaceuticals, Biogen, Serono and Teva. DL is Director of the UBC MS/MRI Research Group, which has been contracted to perform central analysis of MRI scans for therapeutic trials with Angiotech, Bayer HealthCare, Berlex-Schering, Bio-MS, Centocor, Daiichi Sankyo, Hoffmann-LaRoche, Merck-Serono, Schering-Plough, Teva Neurosciences, Sanofi-Aventis and Transition Therapeutics. DL has received research support from Bayer Schering Pharma AG/Bayer HealthCare Pharmaceuticals and honoraria from Bayer Schering Pharma AG/Bayer HealthCare Pharmaceuticals, Serono Symposia, Merck Serono, Biogen and Hoffman La Roche. DG has received research support and honoraria from Bayer Schering Pharma AG/Bayer HealthCare Pharmaceuticals. AR has received research support from the Berlex, Bayer, Biogen, Teva, Serono, National Institutes of Health, the National MS Society, the Brain Research Foundation, the American Academy of Allergy & Immunology, Howard Hughes Foundation, North American Symptomatic Carotid Endarterectomy Trial, Egypt Arab Republic Peace Fellowship, Turkish Ministry of Defense Fellowship Award and the State of Illinois, USA.
Ethics approval Obtained from the institutional review boards (IRBs) or independent ethics committees of the participating centres before LTF planning, which began in 2004.
Provenance and peer review Not commissioned; externally peer reviewed.