A Phase II study of the safety and efficacy of teriflunomide in multiple sclerosis with relapses

O’Connor, Paul; Li, D; Freedman, M. S.; Bar‐Or, Amit; Rice, George P.; Confavreux, Christian; Paty, Donald W.; Stewart, Jeffrey A.; Scheyer, Richard D.

doi:10.1212/01.wnl.0000203121.04509.31

Cited by 333 publications

(230 citation statements)

References 12 publications

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“…[2][3][4] The trials demonstrated a consistent safety and tolerability profile for teriflunomide used for 2 years. [2][3][4] A randomized trial comparing subcutaneous interferon (IFN)-b-1a with teriflunomide in relapsing MS demonstrated that efficacies of teriflunomide 14 mg and IFN-b1a were in the same range, and treatment satisfaction was greater with teriflunomide. 5 To collect long-term safety data and monitor disease activity with continued teriflunomide treatment, extension studies were established.…”

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confidence: 83%

Long-term safety and efficacy of teriflunomide: Nine-year follow-up of the randomized TEMSO study

2016

Neurology

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Objective: To report safety and efficacy outcomes from up to 9 years of treatment with teriflunomide in an extension (NCT00803049) of the pivotal phase 3 Teriflunomide Multiple Sclerosis Oral (TEMSO) trial (NCT00134563).Methods: A total of 742 patients entered the extension. Teriflunomide-treated patients continued the original dose; those previously receiving placebo were randomized 1:1 to teriflunomide 14 mg or 7 mg.Results: By June 2013, median (maximum) teriflunomide exposure exceeded 190 (325) weeks per patient; 468 patients (63%) remained on treatment. Teriflunomide was well-tolerated with continued exposure. The most common adverse events (AEs) matched those in the core study. In extension year 1, first AEs of transient liver enzyme increases or reversible hair thinning were generally attributable to patients switching from placebo to teriflunomide. Approximately 11% of patients discontinued treatment owing to AEs. Twenty percent of patients experienced serious AEs. There were 3 deaths unrelated to teriflunomide. Soon after the extension started, annualized relapse rates and gadolinium-enhancing T1 lesion counts fell in patients switching from placebo to teriflunomide, remaining low thereafter. Disability remained stable in all treatment groups (median Expanded Disability Status Scale score #2.5; probability of 12-week disability progression #0.48). Conclusions:In the TEMSO extension, safety observations were consistent with the core trial, with no new or unexpected AEs in patients receiving teriflunomide for up to 9 years. Disease activity decreased in patients switching from placebo and remained low in patients continuing on teriflunomide. Classification of evidence:This study provides Class III evidence that long-term treatment with teriflunomide is well-tolerated and efficacy of teriflunomide is maintained long-term. Neurology ® 2016;86:920-930 GLOSSARY AE 5 adverse event; ALT 5 alanine aminotransferase; ARR 5 annualized relapse rate; EDSS 5 Expanded Disability Status Scale; Gd 5 gadolinium; IFN 5 interferon; MS 5 multiple sclerosis; OI 5 opportunistic infection; RMS 5 relapsing multiple sclerosis; RRMS 5 relapsing-remitting multiple sclerosis; TEMSO 5 Teriflunomide Multiple Sclerosis Oral; ULN 5 upper limit of normal.Teriflunomide (Aubagio; Genzyme, Cambridge, MA) is a once-daily oral immunomodulator approved for relapsing-remitting multiple sclerosis (RRMS). Teriflunomide selectively and reversibly inhibits dihydro-orotate dehydrogenase, a key mitochondrial enzyme in de novo pyrimidine synthesis. This exerts a cytostatic effect on proliferation of activated T and B lymphocytes, potentially limiting their contribution to multiple sclerosis (MS) pathogenesis.

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confidence: 83%

Long-term safety and efficacy of teriflunomide: Nine-year follow-up of the randomized TEMSO study

2016

Neurology

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“…Были проведены сравнения терифлу-номида с плацебо и высокодозным бета-интерфероном-1а (βИФН-1а) [5][6][7][8][9]. В ходе нескольких многоцентровых плацебо-контролируемых международных исследова-ний II фазы была выявлена эффективность и безопас-ность препарата терифлуномид, что стало поводом для проведения дальнейших исследований.…”

Section: результаты клинических исследованийunclassified

Teriflunomide - A New Tableted Drug for Therapy of Remitting Disseminated Sclerosis (Review)

Попова¹,

Бойко²,

Давыдовская³

et al. 2016

Med. sov.

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В данном обзоре представлены результаты экспериментальных и клинических исследований нового перорального пре-парата терифлуномид для патогенетического лечения рассеянного склероза (РС). Приведены механизм действия, данные клинических исследований II и III фаз по клинической эффективности, переносимости и безопасности. Обсуждается место терифлуномида в патогенетическом лечении РС.Ключевые слова: рассеянный склероз, терифлуномид.

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“…76 In a 36-week study of 179 patients with RRMS or secondary progressive MS (SPMS), subjects received oral teriflunomide at either of 2 doses (7 mg or 14 mg per day) or placebo. 77 For the primary efficacy endpoint of the number of combined active unique lesions per MRI scan, significantly reduced mean numbers of lesions compared with placebo were seen in both the 7 mg (1.04 vs. 2.68, P < 0.030) and 14 mg teriflunomide groups (1.06 vs. 2.68, P < 0.010). Teriflunomide-treated patients also had significantly fewer T1-enhancing lesions per MRI scan (0.87 [7 mg ing T2-hyperintense lesions, new T1-hypointense lesions, and relapse rates.…”

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confidence: 91%

Current and Future Directions in MS Management: Key Considerations for Managed Care Pharmacists

Lipsy

Schapiro²,

Prostko³

2009

JMCP

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This educational activity discusses several medications that are in phase III clinical trials and have not been approved by the FDA for treatment or management of multiple sclerosis at the time of publication. This list of medications includes cladribine, dimethyl fumarate, fingolimod, laquinimod, teriflunomide, fampridine, alemtuzumab, daclizumab, and rituximab. AcknowledgementsThe authors wish to thank Frank L. Urbano, MD, FACP, of PRIME ® for his assistance with the development of this publication. Alexandria, VA 22314; 703.683.8416; 703.683.8417 (fax F a c u l t y Supplement Policy Statement Standards for Supplements to the Journal of Managed Care PharmacySupplements to the Journal of Managed Care Pharmacy are intended to support medical education and research in areas of clinical practice, health care quality improvement, or efficient administration and delivery of health benefits. The following standards are applied to all JMCP supplements to ensure quality and assist readers in evaluating potential bias and determining alternate explanations for findings and results. 1. Disclose the principal sources of funding in a manner that permits easy recognition by the reader. 2. Disclose the existence of all potential conflicts of interest among supplement contributors, including financial or personal bias. 3. Describe all drugs by generic name unless the use of the brand name is necessary to reduce the opportunity for confusion among readers. 4. Identify any off-label (unapproved) use by drug name and specific off-label indication. 5. Strive to report subjects of current interest to managed care pharmacists and other managed care professionals. 6. Seek and publish content that does not duplicate content in the Journal of Managed Care Pharmacy. 7. Subject all supplements to expert peer review. S1 Introduction S3 Results of Educational Needs Assessment S3 Immunopathology of MS S4 Diagnosis of MS S4 Clinically Isolated Syndrome S5 Is the Current Definition of CIS Adequate? S6 Imaging Modalities in MS S7 Treatment of Patients with CIS: Overview of Clinical Trials S8 Key Implications of Clinical Trials for Managed Care Pharmacists S9 Emerging Therapies for MS S9 Oral Agents S12 Monoclonal Antibodies S12 Key Implications of Emerging Therapies for Managed Care Pharmacists S13 Summary S16 Continuing Education: CE/CME Submission Instructions and Posttest QuestionsTarget Audience This activity is intended for managed care pharmacists and managed care physicians. This is an application-based learning activity. Learning ObjectivesUpon completion of this program, participants will be able to:1. Evaluate data submitted by managed care pharmacists pertaining to current pharmacy practice trends in multiple sclerosis (MS) management.2. Assess newest evidence in MS diagnosis and treatment impacting pharmacy practice.3. Identify paradigm shifts in MS treatment and management and the rapidly evolving role of the managed care pharmacist. Funding and Original Presentation of This Learning ActivityThis supplement was sponsored by P...

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A Phase II study of the safety and efficacy of teriflunomide in multiple sclerosis with relapses

Abstract: Oral teriflunomide was effective in reducing MRI lesions and was well tolerated in patients with relapsing multiple sclerosis.

Cited by 333 publications

References 12 publications

Long-term safety and efficacy of teriflunomide: Nine-year follow-up of the randomized TEMSO study

Long-term safety and efficacy of teriflunomide: Nine-year follow-up of the randomized TEMSO study

Teriflunomide - A New Tableted Drug for Therapy of Remitting Disseminated Sclerosis (Review)

Current and Future Directions in MS Management: Key Considerations for Managed Care Pharmacists

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