The efficacy of teriflunomide in patients who received prior disease-modifying treatments: Subgroup analyses of the teriflunomide phase 3 TEMSO and TOWER studies

Freedman, Mark S.; Wolinsky, Jerry S.; Comi, Giancarlo; Kappos, Ludwig; Olsson, Tomas; Miller, Aaron; Thangavelu, Karthinathan; Bénamor, Myriam; Truffinet, Philippe; O’Connor, Paul; Groups, Tower Study

doi:10.1177/1352458517695468

Cited by 16 publications

(7 citation statements)

References 7 publications

(19 reference statements)

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“…A study comparing relapse activity between patients who remained on injectable DMTs and patients who switched due to tolerability issues to teriflunomide or DMF, found that switchers had a lower risk of relapse (HR 0.43, p=0.048) or any disease activity (HR 0.55, p=0.035) compared with patients who remained on injectable therapy (Saraceno et al, 2019). In a post-hoc analysis of the pooled phase 3 TEMSO and TOWER studies, teriflunomide 14 mg was associated with reductions in ARR and risk of disability worsening across all subgroups defined by prior DMT exposure in the previous 2 years (≥2 prior DMTs, 1 prior DMT, or no prior DMT) compared with placebo (Freedman et al, 2018b). In the real-world Teri-PRO study, patients who switched to teriflunomide from an injectable DMT had statistically significant increases in treatment satisfaction across all four TSQM domains (effectiveness, side effects, convenience, and global satisfaction) after 48 weeks (Coyle et al, 2018).…”

Section: Efficacy and Treatment Satisfaction In Patients Switching Fr...mentioning

confidence: 99%

Teriflunomide vs injectable disease modifying therapies for relapsing forms of MS

Vermersch

Cascione

et al. 2020

Multiple Sclerosis and Related Disorders

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Section: Efficacy and Treatment Satisfaction In Patients Switching Fr...mentioning

confidence: 99%

Teriflunomide vs injectable disease modifying therapies for relapsing forms of MS

Vermersch

Cascione

et al. 2020

Multiple Sclerosis and Related Disorders

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“…And also, in the here presented in vivo paradigm long-term (constant) teri unomide application did not negatively affect remyelination indicating that prolonged application as occurring in the context of the RMS therapy will not interfere with neuroregeneration. It is therefore tempting to speculate that the here described restoration of myelinated axons could in fact also contribute to the reduced disability progression in treated patients (TEMSO, ClinicalTrials.gov number NCT00134563; TOWER, ClinicalTrials.gov number NCT00751881) (43).…”

Section: Discussionmentioning

confidence: 98%

Teriflunomide as a Therapeutic Means for Myelin Repair

Göttle

Groh

Reiche

et al. 2022

Preprint

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Background: Promotion of myelin repair in the context of demyelinating diseases such as multiple sclerosis (MS) still represents a clinical unmet need, given that this disease is not only characterized by autoimmune activities but also by impaired regeneration processes. Hence, this relates to replacement of lost oligodendrocytes and myelin sheaths - the primary targets of autoimmune attacks. Endogenous remyelination is mainly mediated via activation and differentiation of resident oligodendroglial precursor cells (OPCs) whereas its efficiency remains limited and declines with disease progression and aging. Teriflunomide has been approved as a first-line treatment for relapsing remitting MS. Beyond its role in acting via inhibition of de novo pyrimidine synthesis leading to a cytostatic effect on proliferating lymphocyte subsets, this study aims to uncover its potential to foster myelin repair. Methods: Within the cuprizone mediated de-/remyelination model teriflunomide dependent effects on oligodendroglial homeostasis and maturation, related to cellular processes important for myelin repair were analyzed in vivo. Teriflunomide administration was performed either as pulse or continuously and markers specific for oligodendroglial maturation and mitochondrial integrity were examined by means of gene expression and immunohistochemical analyses. In addition, axon myelination was determined using electron microscopy. Results: Both pulse and constant teriflunomide treatment efficiently boosted myelin repair activities in this model, leading to accelerated generation of oligodendrocytes and restoration of myelin sheaths. Moreover, teriflunomide restored mitochondrial integrity within oligodendroglial cells. Conclusion: The link between de novo pyrimidine synthesis inhibition, oligodendroglial rescue, and maintenance of mitochondrial homeostasis appears as a key for successful myelin repair and hence for protection of axons from degeneration.

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“…Different from previous real-world studies, all the patients included in this study were not on any DMT at least for 1 year prior to teriflunomide initiation. Since the efficacy of teriflunomide was reported in subgroup analyses of pivotal studies to be different between patients with and without prior DMT [ 22 ], the data of our study might better represent the effectiveness and safety data of teriflunomide in treatment-naïve patients.…”

Section: Discussionmentioning

confidence: 99%

Real-world outcomes of teriflunomide in relapsing–remitting multiple sclerosis: a prospective cohort study

et al. 2022

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Objectives To explore efficacy, risk factors, safety, and persistence of teriflunomide in relapsing–remitting multiple sclerosis (RRMS) cohort. Methods This prospective, observational cohort study included 217 consecutive teriflunomide treated RRMS patients, 192 of which with at least 3-month persistence on teriflunomide were included in effectiveness and risk factor analyses. Multivariate Cox proportional regression analysis was performed to identify factors associated with failure of no evidence of disease activity (NEDA) 3. Results At baseline 82% patients were treatment naïve while 18.0% interferon-β1b treated patients had stopped treatments for more than 1 year. After treatment, 79.0% patients achieved NEDA 3 at 12-month, mean annualized relapse rate (ARR) reduced significantly (0.79 ± 0.80 vs 0.16 ± 0.70; P < 0.001), and mean expanded disability status score (EDSS) remained stable (1.40 ± 1.67 vs 1.56 ± 1.88; P > 0.05). Male sex (hazard ratio [HR] 1.856; 95% confidence interval [CI] 1.118–3.082, P < 0.05), baseline EDSS score ≥ 4 (HR 2.682; 95% CI 1.375–5.231, P < 0.01), and frequent relapses before treatment (HR 3.056; 95% CI 1.737–5.377, P < 0.01) were independent factors significantly associated with failure of NEDA 3. The most frequent adverse events (AEs) were hair thinning, alanine aminotransferase (ALT) elevation, and leukopenia, the latter two most commonly lead to teriflunomide discontinuation during the first 3 months. Persistence rates at 6, 12, and 24 months after teriflunomide initiation were 86.9%, 72.4%, and 52.8%, respectively. Conclusions Our results support efficacy and tolerability of teriflunomide for treatment-naïve RRMS patients in real-world practice. Female patients, patients with less relapses and less disability before treatment are most likely to benefit from teriflunomide treatment.

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The efficacy of teriflunomide in patients who received prior disease-modifying treatments: Subgroup analyses of the teriflunomide phase 3 TEMSO and TOWER studies

Cited by 16 publications

References 7 publications

Teriflunomide vs injectable disease modifying therapies for relapsing forms of MS

Teriflunomide vs injectable disease modifying therapies for relapsing forms of MS

Teriflunomide as a Therapeutic Means for Myelin Repair

Real-world outcomes of teriflunomide in relapsing–remitting multiple sclerosis: a prospective cohort study

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