5th Joint triennial congress of the European and Americas Committees
for Treatment and Research in Multiple Sclerosis
Amsterdam, The Netherlands

19.10.2011 - 22.10.2011
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Home - 20.10.2011 - Immunomodulation 1


Immunomodulation 1

Thursday, October 20, 2011, 15:30 - 17:00

Extension of a phase III trial (TEMSO) of oral teriflunomide in multiple sclerosis with relapses: safety outcomes with up to 4 years of follow-up

G. Comi, P. O'Connor, J. Wolinsky, C. Confavreux, L. Kappos, T. Olsson, H. Benzerdjeb, M. Benamor, P. Truffinet, D. Wang, A. Miller, M. Freedman on behalf of the Teriflunomide Multiple Sclerosis Trial Group

Background: Teriflunomide is a novel oral disease modifier in development for the treatment of relapsing forms of multiple sclerosis (RMS). Teriflunomide significantly reduced clinical and MRI disease activity and was well tolerated in the 2-year Phase III TEMSO study.
Objective: To report safety and tolerability of teriflunomide from the ongoing long-term extension of TEMSO (data cut-off: 23 February 2011).
Methods: Initially, 1088 RMS patients (18–55 years; Expanded Disability Status Scale scores <=5.5; >=1 relapse in the previous year or >=2 in the previous 2 years) were randomised (1:1:1) to placebo or teriflunomide, 7 mg or 14 mg/day for 108 weeks. 742 patients entered the long-term double-blind extension from 16 October 2006 to 29 April 2010; actively treated patients continued on their original dose, while those originally randomised to placebo were re-allocated to teriflunomide, 7 mg or 14 mg/day.
Results: Median duration of treatment in the extension was 2 years for both groups (min/max [days]: 5/1592 and 39/1527, for 7 mg and 14 mg, respectively). The incidence of treatment-emergent adverse events (TEAEs) reported in the extension was similar in both groups (7 mg: 83.6%; 14 mg: 84.6%). Most commonly reported TEAEs (MedDRA preferred term; 7 mg and 14 mg, respectively) were: nasopharyngitis (21.4% and 23.5%); headache (11.0% and 12.3%); ALT increase (12.0% and 11.8%); pain in extremity (7.6% and 10.6%); back pain (7.6% and 10.4%); diarrhoea (6.3% and 10.4%); urinary tract infection (7.3% and 9.5%); influenza (9.7% and 9.2%); paresthesia (6.3% and 8.4%); fatigue (11.2% and 7.8%). Serious TEAEs (7 mg: 15.4%; 14 mg: 11.5%) and TEAEs leading to permanent treatment discontinuation (7 mg: 9.1%; 14 mg: 6.2%) were higher in the 7 mg group. Two deaths (1 in each group) were reported in the extension. Medically confirmed malignancies as solid tumors only were reported with a low frequency: 2 cases in the 7 mg group (1 basal cell carcinoma, 1 colon cancer) and 2 cases in the 14 mg group (1 breast neoplasm, 1 small renal cell cancer). A low and similar incidence of serious infections and hepatic disorders was reported in both groups. Asymptomatic liver enzyme elevations, mostly ALT increases <3xULN, were the most commonly reported hepatic disorders.
Conclusion: Both doses of teriflunomide were well tolerated with up to 4 years of follow-up in the extension period with a favourable safety profile. Results were consistent with the core 2-year TEMSO study.

Study supported by sanofi-aventis NCT00803049 PO’C: Consulting fees and/or research support for MS trials (Actelion, Bayer, Biogen Idec, BioMS, Cognosci, Daiichi Sankyo, EMD Serono, Genentech, Genmab, Novartis, Roche, sanofi-aventis, Teva, and Warburg Pincus) JSW: Consulting agreements or speaker (Acorda Therapeutics, Bayer HealthCare, Consortium of MS Clinics, Eli Lilly, EMD Serono, Facet Biotech, Johns Hopkins University, Medscape CME, Novartis, Peptimmune, sanofi-aventis, Serono Symposia International Foundation, Teva and Teva Neurosciences, the National MS Society, Northwestern University, the University of Buffalo, the University of South Florida Professionals Conferencing, and UCB), royalties (Millipore [Chemicon International] Corporation), and research or contractual support (Clayton Foundation for Research, NIH, and sanofi-aventis) CC: Consulting fees (Biogen Idec, Genzyme Corporation, Novartis, Merck Serono, sanofi-aventis, Teva Pharma, and UCB Pharma), lecture fees (Bayer Schering, Biogen Idec, LFB, Merck Serono, sanofi-aventis, and Teva Pharma), and research support (Bayer Schering, Biogen Idec, Merck Serono, Novartis, sanofi-aventis, and Teva Pharma) GC: Personal compensation (Bayer Schering, Serono Symposia International Foundation, Merck Serono International, sanofi-aventis, Biogen Dompè, and Teva Pharmaceutical Ind. Ltd), and speaking fees (Novartis, Bayer Schering, Serono Symposia Int. Foundation, Merck Serono International, sanofi-aventis, Biogen Dompè, and Teva Pharmaceutical Ind. Ltd) LK: Research support (Actelion, Advancell, Allozyne, BaroFold, Bayer HealthCare Pharmaceuticals, Bayer Schering Pharma, Bayhill, Biogen Idec, BioMarin, CSL Behring, Elan, Genmab, Genmark, GeNeuro SA, GlaxoSmithKline, Lilly, Merck Serono, MediciNova, Novartis, Novo Nordisk, Peptimmune, sanofi-aventis, Santhera, Roche, Teva, UCB, and Wyeth, and from the Swiss MS Society, the Swiss National Research Foundation, the European Union, and the Gianni Rubatto, Novartis and Roche Research Foundations) TPO: Consulting fees and/or research support for MS trials (Biogen Idec, Merck Serono, Pfizer, and sanofi-aventis), scientific advisory boards and/or speaking activities (Merck Serono, Biogen Idec, and sanofi-aventis) HB, PT, LW: Employees of sanofi-aventis AM: Research support (Acorda Therapeutics, Biogen Idec, Genentech, Genzyme, sanofi-aventis, and Teva Neuroscience), consulting fees (Acorda Therapeutics, Biogen Idec, BioMarin, Daiichi-Sankyo, EMD Serono, GlaxoSmithKline, Merck Serono, Novartis, ONO, and Teva Neuroscience), and speakers bureaus (Acorda Therapeutics, Biogen Idec, EMD Serono, Pfizer, and Teva Neuroscience) MSF: Grant support (Genzyme), advisor/consultant/steering committee member or speaker (Bayer, Biogen Idec, Teva, Merck Serono, Novartis, and sanofi-aventis)