| 1. |
|
|
| 2. |
- Vermersch, P, et al.
(author)
-
Teriflunomide versus subcutaneous interferon beta-1a in patients with relapsing multiple sclerosis: a randomised, controlled phase 3 trial
- 2014
-
In: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 20:6, s. 705-716
-
Journal article (peer-reviewed)abstract
- In previous studies, teriflunomide significantly reduced the annualised relapse rate (ARR) and disability progression. Objective: This phase 3, rater-blinded study (NCT00883337) compared teriflunomide with interferon-beta-1a (IFNβ-1a). Methods: Patients with relapsing multiple sclerosis were randomised (1:1:1) to oral teriflunomide 7-or 14mg, or subcutaneous IFNβ-1a 44µg. The primary composite endpoint was time to failure, defined as first occurrence of confirmed relapse or permanent treatment discontinuation for any cause. Secondary endpoints included ARR, Fatigue Impact Scale (FIS) and Treatment Satisfaction Questionnaire for Medication (TSQM). The study was completed 48 weeks after the last patient was randomised. Results: Some 324 patients were randomised (IFNβ-1a: 104; teriflunomide 7 mg: 109; teriflunomide 14 mg: 111). No difference in time to failure was observed. There was no difference in ARR between teriflunomide 14 mg and IFNβ-1a, but ARR was significantly higher with teriflunomide 7 mg. FIS scores indicated more frequent fatigue with IFNβ-1a, though differences were only significant with teriflunomide 7 mg. TSQM scores were significantly higher with teriflunomide. There were no unexpected safety findings. Conclusion: Effects on time to failure were comparable between teriflunomide and IFNβ-1a. There was no difference between teriflunomide 14 mg and IFNβ-1a on ARR, though ARR was higher with teriflunomide 7 mg. The teriflunomide safety profile was consistent with previous studies.
|
|
| 3. |
- Barnes, D, et al.
(author)
-
SAFETY AND TOLERABILITY OF TERIFLUNOMIDE IN CLINICAL STUDIES
- 2015
-
In: JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY. - : BMJ. - 0022-3050 .- 1468-330X. ; 86:11
-
Conference paper (other academic/artistic)abstract
- Teriflunomide, approved for the treatment of relapsing-remitting multiple sclerosis, has a well-characterized safety profile based on individual clinical studies. We report pooled safety and tolerability data from four, double-blind, placebo-controlled trials of teriflunomide. Post-approval updates on hair thinning and pregnancy outcomes, sometimes concerns for patients initiating teriflunomide, are reported.MethodsData were pooled from phase 2 (NCT01487096) and phase 3 TEMSO (NCT00134563), TOWER (NCT00751881), and TOPIC (NCT00622700) studies. Patients were randomized to receive teriflunomide 14 mg, 7 mg, or placebo. Safety analyses were performed for all patients exposed to teriflunomide.ResultsThe pooled dataset included 3044 patients. Commonly reported adverse events (AEs) were in accordance with individual clinical studies, most being transient and mild-to-moderate in intensity. Incidence of hepatic AEs was higher in teriflunomide groups; however, serious hepatic AEs were similar across groups (∼2–3%). Hair thinning was higher in teriflunomide than placebo groups, but typically resolved on treatment without intervention and led to discontinuation in <2% of patients. No structural or functional abnormalities were reported in 42 newborns from teriflunomide-exposed parents.ConclusionsThese data from >6800 patient-years of teriflunomide exposure were consistent with individual studies and no new, unexpected safety signals were observed. (Study supported by Genzyme, a Sanofi company).
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Miller, AE, et al.
(author)
-
Pre-specified subgroup analyses of a placebo-controlled phase III trial (TEMSO) of oral teriflunomide in relapsing multiple sclerosis
- 2012
-
In: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 18:11, s. 1625-1632
-
Journal article (peer-reviewed)abstract
- The Teriflunomide Multiple Sclerosis Oral (TEMSO) trial, a randomized, double-blind, placebo-controlled phase III study, demonstrated that teriflunomide significantly reduced annualized relapse rate (ARR), disease progression and magnetic resonance imaging (MRI) activity, with a favorable safety profile in relapsing multiple sclerosis (RMS) patients. Objective: The purpose of this study was to report the effects of teriflunomide on ARR and disability progression in pre-specified subgroups. Methods: RMS patients ( n=1088) were randomized to placebo or teriflunomide, 7 mg or 14 mg, once daily, for 108 weeks. Subgroup analyses were performed for ARR and disability progression by baseline demographics (gender, race, age), disease characteristics (Expanded Disability Status Scale (EDSS) strata, relapse history, multiple sclerosis (MS) subtype), MRI parameters (gadolinium-enhancing lesions, total lesion volume) and prior use of MS drugs. A generalized estimating equation method and Cox regression model were used to assess consistency of the treatment effect across subgroups, utilizing a treatment-by-subgroup interaction test for each factor separately. Results: Reductions in ARR and disability progression were consistent across subgroups in favor of teriflunomide, with no treatment-by-subgroup interaction test reaching statistical significance. Conclusion: The positive effects of teriflunomide were demonstrated consistently across subgroups in TEMSO.
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
- Weller, B, et al.
(author)
-
EFFECT OF TERIFLUNOMIDE ON LYMPHOCYTE AND NEUTROPHIL COUNTS
- 2015
-
In: JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY. - : BMJ. - 0022-3050 .- 1468-330X. ; 86:11
-
Conference paper (other academic/artistic)abstract
- Teriflunomide is an immunomodulator known to decrease the proliferation of stimulated lymphocytes via inhibition of dihydro-orotate dehydrogenase. Lymphocyte/neutrophil counts were assessed in pooled data from one phase 2 and three phase 3 (TEMSO, TOWER, and TOPIC) placebo-controlled studies.MethodsPatients were randomized to receive once-daily teriflunomide 14mg (n=1002), 7mg (n=1045), or placebo (n=997). Blood samples were collected throughout the studies.ResultsMean baseline lymphocyte and neutrophil counts were similar across groups. Small decreases in mean lymphocyte and neutrophil counts occurred within the first 12 weeks (lymphocytes) or 6 weeks (neutrophils) of treatment, and stabilized within the normal range for most patients thereafter. Patients with neutrophil counts <1×10^9^/L were to discontinue treatment; 11 (1.1%; 14 mg), 8 (0.8%; 7 mg), and 1 (0.1%; placebo) patients discontinued due to neutropenia or neutrophil count decrease as per protocol requirements. Neutropenia was reported as a serious adverse event (SAE) in 7 (0.7%; 14 mg), 2 (0.2%; 7 mg), and 3 (0.3%; placebo) patients; there were no lymphopenia SAEs. No link between neutrophil or lymphocyte count decreases and infection was observed.ConclusionsThese data demonstrate that teriflunomide has small, reversible effects on lymphocyte/neutrophil counts, with no increase in infection risk observed. (Study supported by Genzyme, a Sanofi company).
|
|
| 20. |
- Wolinsky, JS, et al.
(author)
-
Magnetic resonance imaging outcomes from a phase III trial of teriflunomide
- 2013
-
In: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 19:10, s. 1310-1319
-
Journal article (peer-reviewed)abstract
- The purpose of this study was to determine the effects of oral teriflunomide on multiple sclerosis (MS) pathology inferred by magnetic resonance imaging (MRI). Methods: Patients ( n=1088) with relapsing MS were randomized to once-daily teriflunomide 7 mg or 14 mg, or placebo, for 108 weeks. MRI was recorded at baseline, 24, 48, 72 and 108 weeks. Annualized relapse rate and confirmed progression of disability (sustained ≥12 weeks) were the primary and key secondary outcomes. The principal MRI outcome was change in total lesion volume. Results: After 108 weeks, increase in total lesion volume was 67.4% ( p=0.0003) and 39.4% ( p=0.0317) lower in the 14 and 7 mg dose groups versus placebo. Other measures favoring teriflunomide were accumulated enhanced lesions, combined unique activity, T2-hyperintense and T1-hypointense component lesion volumes, white matter volume, and a composite MRI score; all were significant for teriflunomide 14 mg and most significant for 7 mg versus placebo. Conclusions: Teriflunomide provided benefits on brain MRI activity across multiple measures, with a dose effect evident on several markers. These effects were also consistent across selected subgroups of the study population. These findings complement clinical data showing significant teriflunomide-related reductions in relapse rate and disease progression, and demonstrate containment of MRI-defined disease progression.
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
- Freedman, MS, et al.
(author)
-
A randomized trial of teriflunomide added to glatiramer acetate in relapsing multiple sclerosis
- 2015
-
In: Multiple sclerosis journal - experimental, translational and clinical. - : SAGE Publications. - 2055-2173. ; 1, s. 2055217315618687-
-
Journal article (peer-reviewed)abstract
- Teriflunomide is a once-daily oral immunomodulator for the treatment of relapsing−remitting MS. Objective To evaluate the safety and tolerability of teriflunomide as add-on therapy to a stable dose of glatiramer acetate (GA) in patients with relapsing forms of MS (RMS). Methods Phase II, randomized, double-blind, add-on, placebo-controlled study. The primary objective was to assess safety and tolerability; secondary objectives were to evaluate effects of treatment on disease activity assessed by MRI and relapse. Results Patients with RMS on GA ( N = 123) were randomized 1:1:1 to receive teriflunomide 14 mg ( n = 40), 7 mg ( n = 42), or placebo ( n = 41) for 24 weeks; 96 patients entered the 24-week extension, remaining on original treatment allocation. Teriflunomide was well tolerated over 48 weeks. The frequency of adverse events (AEs) was low across all groups; 5 (12.2%), 3 (7.1%), and 2 (5.0%) patients in the 14 mg, 7 mg, and placebo groups, respectively, discontinued treatment due to AEs. Teriflunomide reduced the number of T1-Gd lesions vs placebo (14 mg: 46.6% relative reduction, p = 0.1931; 7 mg: 64.0%: relative reduction, p = 0.0306). Conclusions Teriflunomide added to stable-dose GA had acceptable safety and tolerability, and reduced some MRI markers of disease activity compared with GA alone. NCT00475865 (core study); NCT00811395 (extension).
|
|
| 24. |
- Freedman, MS, et al.
(author)
-
The efficacy of teriflunomide in patients who received prior disease-modifying treatments: Subgroup analyses of the teriflunomide phase 3 TEMSO and TOWER studies
- 2018
-
In: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 24:4, s. 535-539
-
Journal article (peer-reviewed)abstract
- Teriflunomide is a once-daily oral immunomodulator approved for relapsing-remitting multiple sclerosis (MS). The objective of this post hoc analysis of the phase 3, pooled TEMSO (NCT00134563) and TOWER (NCT00751881) dataset is to evaluate the effect of teriflunomide treatment on annualised relapse rate and disability worsening across patient subgroups defined according to prior disease-modifying therapy exposure. This analysis provides further supportive evidence for a consistent effect of teriflunomide across a broad range of patients with relapsing MS, including patients who have used and discontinued other disease-modifying therapies.
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
|
|
