Long-term follow-up of a phase 2 study of oral teriflunomide in relapsing multiple sclerosis: safety and efficacy results up to 8.5 years.

BACKGROUND: Teriflunomide, an oral disease-modifying therapy in development for patients with relapsing forms of multiple sclerosis (RMS), was well tolerated and effective in reducing magnetic resonance imaging (MRI) lesions in 179 RMS patients in a phase 2 36-week, placebo-controlled study. METHODS: A total of 147 patients who completed the core study entered an open-label extension. Teriflunomide patients continued their assigned dose, and placebo patients were re-allocated to teriflunomide, 7 mg/day or 14 mg/day. An interim analysis was performed at a cut-off on January 8 2010. RESULTS: The mean and median duration of study treatment, including both the core and extension phase, from baseline to the interim cut-off, was 5.6 years (standard deviation: 2.7 years) and 7.1 years (range: 0.05-8.5 years), respectively. Of 147 patients, 62 (42.2%) discontinued (19% due to treatment-emergent adverse events (TEAEs)). The most common TEAEs were mild infections, fatigue, sensory disturbances and diarrhoea. No serious opportunistic infections occurred, with no discontinuations due to infection. Asymptomatic alanine aminotransferase increases (≤3× upper limit of normal (ULN)) were common (7 mg, 64.2%; 14 mg, 62.1%); increases >3×ULN were similar across groups (7 mg, 12.3%; 14 mg, 12.1%). Mild decreases in neutrophil counts occurred; none led to discontinuation. The incidence of malignancies was comparable to that of the general population, and cases were not reminiscent of those observed in immunocompromised patients. Annualised relapse rates remained low, minimal disability progression was observed, with a dose-dependent benefit with teriflunomide 14 mg for several MRI parameters. CONCLUSION: Teriflunomide had a favourable safety profile for up to 8.5 years.

Bacteriophage-based rapid and sensitive detection of Escherichia coli O157:H7 isolates from ground beef.

We investigated the efficacy of bacteriophage-based detection technology to detect Escherichia coli O157:H7 from ground beef. The assay involved a short enrichment period of 8 h followed by capture of the pathogen on O157-specific immunomagnetic beads. The captured cells were treated with O157-specific lytic bacteriophage, CSLO157. Upon phage-induced lysis, the enzyme adenylate kinase, which was released from the lysed cells, was measured in terms of relative light units using luciferin-luciferase assay. The plaque forming efficiency (e.g., phage susceptibility) and ability to capture cells with immunomagnetic beads were examined using an array of 74 E. coli O157:H7 isolates obtained from various clinical and foodborne samples. Immunmagnetic beads successfully captured all 74 isolates; however, only 53 isolates showed susceptibility toward the bacteriophage. Susceptible isolates were further classified into two broad groups, moderately sensitive isolates, which generated phage titer ∼ 10(7)pfu/mL (group I, n=15), and highly susceptible isolates, which generated high phage titer ∼ 10(9)pfu/mL (group II, n=38). We selected 15 isolates (9 from group I and 6 from group II) and individually spiked beef samples (ca. 3-8 cells/25 g beef) to evaluate the bacteriophage-based detection system. Eight out of nine isolates from group I and all six isolates from group II were successfully detected. Pathogenic E. coli strains belonging to other serogroups (12 serogroups, 67 isolates) as well as nontarget microorganisms (n=18) were not lysed by the bacteriophage and hence were not detected. The method is high-throughput compatible, is rapid, and can provide live culture the following day by streaking an aliquot before phage lysis on conventional selective agar media.