| 1. |
- Barnes, D, et al.
(författare)
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SAFETY AND TOLERABILITY OF TERIFLUNOMIDE IN CLINICAL STUDIES
- 2015
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Ingår i: JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY. - : BMJ. - 0022-3050 .- 1468-330X. ; 86:11
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)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).
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| 2. |
- Weller, B, et al.
(författare)
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EFFECT OF TERIFLUNOMIDE ON LYMPHOCYTE AND NEUTROPHIL COUNTS
- 2015
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Ingår i: JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY. - : BMJ. - 0022-3050 .- 1468-330X. ; 86:11
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)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).
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