Teriflunomide added to interferon-β in relapsing multiple sclerosis
2012; Lippincott Williams & Wilkins; Volume: 78; Issue: 23 Linguagem: Inglês
10.1212/wnl.0b013e318258f7d4
ISSN1526-632X
AutoresM. S. Freedman, Jerry S. Wolinsky, Barbara D. Wamil, Christian Confavreux, Cristoforo Comi, Ludwig Kappos, Tomas Olsson, Aaron Miller, Hadj Benzerdjeb, H. Li, Catherine Simonson, Paul O’Connor, Suzanne Gazda, Cynthia Huffman, Daniel Kantor, Michael Stein, Barry Hendin, François Grand’Maison, M. Kremenchutzky, Ruth Ann Marrie, François Jacques, Mathias Mäurer, Karl Otta Sigel, Wolfgang-Gerhard Elias, Tjalf Ziemssen, Klaus Tiel‐Wilck, Eckart Lensch, Ruggero Capra, Carlo Pozzilli, Albert Saiz, Txomin Arbizu, Xavier Montalbán, Alfredo Rodríguez Antigüedad, Óscar Fernández, Antonio Garcia Merino, Rafael Arroyo, Javier Olascoaga, J. Meca, Ponnada A. Narayana, Flavia Nelson, Irina Vainrub, Sushmita Datta, Renjie He, Brandi Gates, K. Ton,
Tópico(s)Systemic Lupus Erythematosus Research
ResumoObjective: To evaluate teriflunomide as add-on therapy to ongoing stable-dosed interferon-β (IFNβ) in patients with relapsing forms of multiple sclerosis (RMS). Methods: A total of 118 patients with RMS were randomly assigned 1:1:1 to receive oral placebo or teriflunomide, 7 or 14 mg, once daily for 24 weeks; 86 patients entered the 24-week extension. The primary objective was to evaluate safety; secondary objectives were to evaluate the effects of treatment on disease activity assessed by MRI and relapse rate. Results: Teriflunomide was well tolerated with a low and similar incidence of treatment-emergent adverse events (TEAEs) across the 3 groups; TEAEs led to treatment discontinuation of 4.9%, 8.1%, and 7.9% of patients in the placebo, 7-mg, and 14-mg groups, respectively. The number of gadolinium-enhancing T1 (T1-Gd) lesions was reduced in both teriflunomide groups, with relative risk reductions (RRRs) of 84.6% ( p = 0.0005) and 82.8% ( p < 0.0001) for 7 and 14 mg, respectively, compared with IFNβ alone at 48 weeks. T1-Gd lesion volume was also reduced in the 7-mg group (RRR 72.1%, p = 0.1104) and 14-mg group (RRR 70.6%, p = 0.0154). A trend toward dose-dependent reduction in annualized relapse rate was also noted (RRRs 32.6% [ p = 0.4355] and 57.9% [ p = 0.1005] for 7 and 14 mg, respectively). Conclusion: Teriflunomide as add-on therapy to IFNβ had acceptable safety and tolerability and reduced MRI disease activity compared with IFNβ alone. Classification of evidence: This study provides Class II evidence that teriflunomide, 7 and 14 mg, added to IFNβ, is safe. The T1-Gd lesion burden was significantly reduced with both teriflunomide doses. AE= : adverse event; ALT= : alanine aminotransferase; ARR= : annualized relapse rate; DMT= : disease-modifying therapy; EDSS= : Expanded Disability Status Scale; IFNβ= : interferon-β; MS= : multiple sclerosis; NAb= : neutralizing antibody; PML= : progressive multifocal leukoencephalopathy; RMS= : relapsing multiple sclerosis; RRR= : relative risk reduction; TEAE= : treatment-emergent adverse event; TEMSO= : Teriflunomide Multiple Sclerosis Oral; T1-Gd= : gadolinium-enhancing T1; ULN= : upper limit of normal
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