Abstract: P742
Type: Poster
Abstract Category: Therapy - disease modifying - 28 Long-term treatment monitoring
Background: In TEMSO (NCT00134563) and TOWER (NCT00751881) core studies, teriflunomide was associated with reduced lymphocyte counts early in treatment, although mean counts remained within the normal range. Lower grade lymphopenia was reported infrequently during the long-term extension studies and was not associated with increased risk of infection.
Objective(s): To describe the effect of long-term teriflunomide treatment on lymphocyte counts and infection rates in the pooled TEMSO and TOWER core and extension studies.
Methods: Data from the pooled core studies are reported for patients treated with placebo or teriflunomide 14 mg. Placebo-treated patients were re-randomized to active treatment in the extensions; results from the pooled core and extension studies are reported for the teriflunomide 14-mg group. Lymphocyte counts were obtained every 6 weeks until Week 24, and every 24 weeks thereafter. Lymphopenia was identified from 2 consecutive assessments of lymphocyte counts that remained below the lower limit of normal and was graded by the Common Terminology Criteria for Adverse Events.
Results: The cumulative duration of exposure to teriflunomide 14 mg in the pooled core and extension studies was 4449 patient-years. In the core studies, placebo- (n=745) and teriflunomide-treated patients (n=729) experienced Grade 1 (0.7%; 2.1%) and 2 (0.5%; 1.4%) lymphopenias infrequently. Infections occurred in placebo/teriflunomide-treated patients with Grade 1 (0.3%/1.5%) and 2 (0.4%/0.3%) lymphopenia. No patients with Grade 1 lymphopenia and only 1 (0.1%) placebo-treated patient with Grade 2 lymphopenia experienced serious infection. Teriflunomide-treated patients in the combined core and extension studies (n=1354) experienced few Grade 1 (3.0%) or 2 (2.5%) lymphopenias; infections were reported in 1.8% and 1.4% of these patients, respectively, vs 53.0% of patients without lymphopenia. Serious infections occurred in patients without lymphopenia (3.5%) and in those with Grade 1 (0.1%) or Grade 2 (0.2%) lymphopenia. No Grade 3 or 4 lymphopenia was reported.
Conclusions: In this analysis of TEMSO/TOWER, low-grade lymphopenia was infrequent in the long-term extension studies, with no reports of high-grade lymphopenia. Infection rates were similar in patients with or without lymphopenia. These data are consistent with a limited impact of teriflunomide on protective immunity and further support the evidence of an immunomodulatory mechanism of action of teriflunomide.
Disclosure: Study supported by Sanofi Genzyme.
GC: Compensation in past year for consulting services and/or speaking activities (Almirall, Biogen, Celgene, Excemed, Forward Pharma, Genzyme, Merck, Novartis, Receptos, Roche, Sanofi, Teva).
AEM: Consulting fees (Accordant Health Services, Acorda Therapeutics, Alkermes, Biogen Idec, EMD Serono, Genentech/Roche, Genzyme, GSK, Mallinckrodt Pharmaceuticals [Questcor], Novartis, Roche, Teva); contracted research (Biogen Idec, Genentech, Novartis, Questcor, Roche, Sanofi).
MB, KT, MM: Employees of Sanofi Genzyme.
PT: Employee of Sanofi Genzyme, with ownership interest.
MSF: Research/educational grant support (Bayer HealthCare, Genzyme); honoraria/consulting fees (Bayer HealthCare, Biogen Idec, EMD Canada, Novartis, Sanofi, Teva Canada Innovation); member of company advisory boards/board of directors/other similar group (Bayer HealthCare, Biogen Idec, Chugai, Merck Serono, Novartis, Opexa Therapeutics, Sanofi, Teva Canada Innovation).
Abstract: P742
Type: Poster
Abstract Category: Therapy - disease modifying - 28 Long-term treatment monitoring
Background: In TEMSO (NCT00134563) and TOWER (NCT00751881) core studies, teriflunomide was associated with reduced lymphocyte counts early in treatment, although mean counts remained within the normal range. Lower grade lymphopenia was reported infrequently during the long-term extension studies and was not associated with increased risk of infection.
Objective(s): To describe the effect of long-term teriflunomide treatment on lymphocyte counts and infection rates in the pooled TEMSO and TOWER core and extension studies.
Methods: Data from the pooled core studies are reported for patients treated with placebo or teriflunomide 14 mg. Placebo-treated patients were re-randomized to active treatment in the extensions; results from the pooled core and extension studies are reported for the teriflunomide 14-mg group. Lymphocyte counts were obtained every 6 weeks until Week 24, and every 24 weeks thereafter. Lymphopenia was identified from 2 consecutive assessments of lymphocyte counts that remained below the lower limit of normal and was graded by the Common Terminology Criteria for Adverse Events.
Results: The cumulative duration of exposure to teriflunomide 14 mg in the pooled core and extension studies was 4449 patient-years. In the core studies, placebo- (n=745) and teriflunomide-treated patients (n=729) experienced Grade 1 (0.7%; 2.1%) and 2 (0.5%; 1.4%) lymphopenias infrequently. Infections occurred in placebo/teriflunomide-treated patients with Grade 1 (0.3%/1.5%) and 2 (0.4%/0.3%) lymphopenia. No patients with Grade 1 lymphopenia and only 1 (0.1%) placebo-treated patient with Grade 2 lymphopenia experienced serious infection. Teriflunomide-treated patients in the combined core and extension studies (n=1354) experienced few Grade 1 (3.0%) or 2 (2.5%) lymphopenias; infections were reported in 1.8% and 1.4% of these patients, respectively, vs 53.0% of patients without lymphopenia. Serious infections occurred in patients without lymphopenia (3.5%) and in those with Grade 1 (0.1%) or Grade 2 (0.2%) lymphopenia. No Grade 3 or 4 lymphopenia was reported.
Conclusions: In this analysis of TEMSO/TOWER, low-grade lymphopenia was infrequent in the long-term extension studies, with no reports of high-grade lymphopenia. Infection rates were similar in patients with or without lymphopenia. These data are consistent with a limited impact of teriflunomide on protective immunity and further support the evidence of an immunomodulatory mechanism of action of teriflunomide.
Disclosure: Study supported by Sanofi Genzyme.
GC: Compensation in past year for consulting services and/or speaking activities (Almirall, Biogen, Celgene, Excemed, Forward Pharma, Genzyme, Merck, Novartis, Receptos, Roche, Sanofi, Teva).
AEM: Consulting fees (Accordant Health Services, Acorda Therapeutics, Alkermes, Biogen Idec, EMD Serono, Genentech/Roche, Genzyme, GSK, Mallinckrodt Pharmaceuticals [Questcor], Novartis, Roche, Teva); contracted research (Biogen Idec, Genentech, Novartis, Questcor, Roche, Sanofi).
MB, KT, MM: Employees of Sanofi Genzyme.
PT: Employee of Sanofi Genzyme, with ownership interest.
MSF: Research/educational grant support (Bayer HealthCare, Genzyme); honoraria/consulting fees (Bayer HealthCare, Biogen Idec, EMD Canada, Novartis, Sanofi, Teva Canada Innovation); member of company advisory boards/board of directors/other similar group (Bayer HealthCare, Biogen Idec, Chugai, Merck Serono, Novartis, Opexa Therapeutics, Sanofi, Teva Canada Innovation).