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Long-term clinical and magnetic resonance imaging outcomes from patients treated with teriflunomide: Results from a phase 2 extension study
Sleep quality among patients with multiple sclerosis in West Azerbaijan http://dx.doi.org/10.1016/j.msard.2014.09.190
P042
Effect of natalizumab on clinical/radiological disease activity and EDSS of relapsing remitting multiple sclerosis patients
M. Agiela Libya Introduction: Natalizumab is a humanized monoclonal antibody that blocks T-cell transmigration through the blood–brain barrier into CNS. Objective: AFFIRM showed monotherapy with Natalizumab for 2 year reduced the annualized relapse rate ARR by 68% and the disability progression rate by 42%. This is our first experince in use of Natalizumab in Benghazi-Libya. So we want to evalute its efficacy. Methods: Four patients of relapsing remitting multiple scerosis on Natalizumab (JC virus negative and MRI prior to use drug done) followed in our clinical practice regarding frequency of relapse, EDSS and new T2-hyperintense lesion on MRI for 24 months for 3 patients and 1 ptient for 12 months. Results: All the patients have no relapse (frequency of relapse zero) during 24 months in 3 patients and 12 months in 1 patient, no new T2 hyperintense MRI lesion in 3 patients. there are decrease in EDSS in 3 patients. Table and graphs will show more details later on. Conclusion: The efficency of Natalizumab on disease activity i.e. relapse free is higher in my study which 100% in comparsion with AFFIRM which was 68% (our study is small size) so our recommondation to have bigger size for right comparsion and more evalution of efficacy. No reaction to the drug (side effect) recorded during this follow up. http://dx.doi.org/10.1016/j.msard.2014.09.191
755
program. Animal data suggest that teriflunomide may be associated with a risk of teratogenicity. Teriflunomide plasma concentrations o0.02 mg/L in the mother confer minimal risk of teratogenicity, and can be achieved with an accelerated elimination procedure in humans. Design and methods: Despite the requirement for reliable contraception, pregnancies were reported across the teriflunomide clinical trial program. Upon discovery of pregnancy, patients were instructed to discontinue treatment and undergo an accelerated elimination procedure. Pregnancy outcomes were collected across phase 2 and 3 clinical studies in the teriflunomide clinical development program and available data through October 2013 are reported. Results: Eighty-three pregnancies were reported in female patients and 22 in partners of male patients; 26 live births occurred in female patients and 16 in partners of male patients receiving teriflunomide. Twenty-nine pregnancies in female patients and two in partners of male patients were terminated electively. Newborns whose parents were exposed to teriflunomide were healthy and had no structural defects or functional deficits at birth. Spontaneous abortion rate (18.6%) was within the range for general population. Median birth weight for 18 newborns was 3.3 kg, and mean gestational age at birth among 23 cases was 39 weeks, all within typical ranges for general population. Conclusions: Data from the clinical program have shown no teratogenic signals for teriflunomide in humans, consistent with findings of the Organization of Teratology Information Specialists registry and over 2.5 million patient-years of postmarketing data for leflunomide. Further prospective data in the postmarketing setting are being collected in global teriflunomide pregnancy registries. http://dx.doi.org/10.1016/j.msard.2014.09.192
P044
Long-term clinical and magnetic resonance imaging outcomes from patients treated with teriflunomide: Results from a phase 2 extension study
M.A. Jumah, D.B. Li, B. Yamout, Philippe Truffinet, D. Dukovic, P.W. O’Connor P043
Pregnancy outcomes in female patients and partners of male patients in the teriflunomide clinical development program
R. Alroughani, B. Kieseier, R. Gouider, M. Benamor, P. Truffinet, L. Henson Kuwait Background/objectives: Teriflunomide is a once-daily oral immunomodulator approved for relapsing-remitting multiple sclerosis. Consistent efficacy and safety of teriflunomide were demonstrated in a large clinical trial
Saudi Arabia Background/objectives: Teriflunomide is a once-daily oral immunomodulator for the treatment of relapsingremitting multiple sclerosis. The clinical development program for teriflunomide demonstrated consistent efficacy and a well-characterized, manageable safety and tolerability profile. Here we report efficacy outcomes from patients treated long-term with teriflunomide in a phase 2 study (nct01487096) and its extension (nct00228163). Design and methods: Patients with relapsing multiple sclerosis were randomized 1:1:1 to teriflunomide 14 mg or 7 mg, or placebo. Of 160 patients completing the 36-week core study, 147 entered the long-term extension.
756
S. Taghavifar et al.
Teriflunomide-treated patients continued on their original dose; placebo-treated patients were rerandomized 1:1 to teriflunomide, 14 mg or 7 mg. Expanded disability status scale score was assessed every 24 weeks, magnetic resonance imaging was performed every 48 weeks until week 480, and clinical relapses were reported throughout the study. Results: At june 28, 2013, cumulative duration of teriflunomide exposure, including both dose groups, was 4990 patient-years: 63 patients remained on study. Increases in mean expanded disability status scale score following up to 528 weeks of treatment were minimal. Annualized relapse rates were low: 0.190 (14-mg group) and 0.254 (7-mg group). In both dose groups, mean numbers of gadoliniumenhancing t1 lesions and newly active t2 lesions were lower at week 480 vs. core study end. Compared with the 7-mg group, the teriflunomide 14-mg group had less of an increase from baseline in t2 lesion volume and less decline from baseline in cerebral volume at week 432. There were no new or unexpected safety signals with continued teriflunomide exposure. Conclusions: Clinical and radiological signs of disease remained low in patients receiving teriflunomide for up to 12 years in a phase 2 study and its extension. These data are consistent with sustained efficacy of long-term teriflunomide treatment in patients with multiple sclerosis.
treatment (12 mg/day intravenously on 3 consecutive days) ?1 year apart or other disease-modifying therapy. Crossover patients received 2 alemtuzumab courses (5 days then 3 days) 12 months apart. Results: The extension enrolled 393 (93%) eligible patients from the core study alemtuzumab arm. Through 4 years, 68% received the first 2, but no additional courses; 24% and 7% received 1 or 2 additional courses, respectively; 5% received another disease-modifying therapy during the extension. Twenty-five patients (6%) discontinued study, none from adverse events. Among former interferon beta1a patients, 146 (83%) entered the extension; 131 (90%) received 2 alemtuzumab courses. Seven extension withdrawals (5%) occurred in crossover patients, 1 from an adverse event. Efficacy and safety data will be reported. Conclusions: Most patients receiving alemtuzumab in the core study required no re-treatment during the first 2 extension years; few received alternative therapies or withdrew from study. Among crossover patients, most received both treatment courses and remained in the study.
http://dx.doi.org/10.1016/j.msard.2014.09.193
Cumulative review of thrombotic microangiopathy, thrombotic thrombocytopenic purpura and hemolytic uremic syndrome reports with SC interferon beta-1a
P045
A.F. Amor, A. Trochanov, J. Johnson
Efficacy and safety of alemtuzumab in patients with relapsing-remitting multiple sclerosis who relapsed on prior therapy: Four-year follow-up of the Care-MS II study
B.C. Kieseier, M.A. Sahraian, A.J. Coles, H.P. Hartung, E. Havrdova, K.W. Selmaj, D.H. Margolin, J. Palmer, P. Oyuela USA Background/objectives: Alemtuzumab is approved in over 30 countries for relapsing-remitting multiple sclerosis. In the 2-year, phase 3 CARE-MS II study (NCT00548405), alemtuzumab had superior efficacy over subcutaneous interferon beta-1a and manageable safety over 2 years; follow-up at Year 3 showed durable efficacy of alemtuzumab. Here we report results for years 3 and 4 after alemtuzumab initiation, and for years 1 and 2 after alemtuzumab initiation in patients initially treated with subcutaneous interferon beta-1a (crossover cohort). Design and methods: In CARE-MS II, patients with active relapsing-remitting multiple sclerosis who relapsed on prior therapy received 2 courses of alemtuzumab (12 mg/day intravenously on 5 consecutive days and on 3 consecutive days 12 months later) or subcutaneous interferon beta-1a (44 ?g 3 times/week). In the extension study (NCT00930553), alemtuzumab-treated patients could receive as-needed re-
http://dx.doi.org/10.1016/j.msard.2014.09.194
P046
Switzerland, USA Background/objectives: Rare cases of thrombotic microangiopathy, manifested as thrombotic thrombocytopenic purpura or hemolytic uremic syndrome have been reported with interferon beta products. This was a cumulative review of thrombotic microangiopathy cases recorded in a Global Safety Database for subcutaneous interferon beta-1a. Methods: Search criteria were all reported cases, serious and non-serious, from all sources (including nonhealthcare professionals and clinical trial reports), regardless of event ranking and causality assessment by reporter or Company; data lock was 03 May 2014. Results: Ninety one cases with 105 events were retrieved; 76.9% (70/91) patients were female, consistent with the underlying disease of multiple sclerosis. Time-toonset varied from 2 months to 14 years; 31.9% events occurred within 2-years of treatment initiation. 7 patients had a fatal outcome (5 were secondary to other causes; 2 had insufficient information). 44 patients recovered, 32 had not recovered at the time of the report and in 8 cases the outcome was not reported/unknown. Treatment was discontinued in 84.6% (77/91). In 67.0% (61/91), a causal association between treatment and the occurrence of thrombotic microangiopathy, thrombotic thrombocytopenic purpura-hemolytic uremic syndrome was suspected. Risk factors and/or confounding factors were present in 41/91 cases (45.1%). Early prodromal syndrome or specific
P042
Effect of natalizumab on clinical/radiological disease activity and EDSS of relapsing remitting multiple sclerosis patients
M. Agiela Libya Introduction: Natalizumab is a humanized monoclonal antibody that blocks T-cell transmigration through the blood–brain barrier into CNS. Objective: AFFIRM showed monotherapy with Natalizumab for 2 year reduced the annualized relapse rate ARR by 68% and the disability progression rate by 42%. This is our first experince in use of Natalizumab in Benghazi-Libya. So we want to evalute its efficacy. Methods: Four patients of relapsing remitting multiple scerosis on Natalizumab (JC virus negative and MRI prior to use drug done) followed in our clinical practice regarding frequency of relapse, EDSS and new T2-hyperintense lesion on MRI for 24 months for 3 patients and 1 ptient for 12 months. Results: All the patients have no relapse (frequency of relapse zero) during 24 months in 3 patients and 12 months in 1 patient, no new T2 hyperintense MRI lesion in 3 patients. there are decrease in EDSS in 3 patients. Table and graphs will show more details later on. Conclusion: The efficency of Natalizumab on disease activity i.e. relapse free is higher in my study which 100% in comparsion with AFFIRM which was 68% (our study is small size) so our recommondation to have bigger size for right comparsion and more evalution of efficacy. No reaction to the drug (side effect) recorded during this follow up. http://dx.doi.org/10.1016/j.msard.2014.09.191
755
program. Animal data suggest that teriflunomide may be associated with a risk of teratogenicity. Teriflunomide plasma concentrations o0.02 mg/L in the mother confer minimal risk of teratogenicity, and can be achieved with an accelerated elimination procedure in humans. Design and methods: Despite the requirement for reliable contraception, pregnancies were reported across the teriflunomide clinical trial program. Upon discovery of pregnancy, patients were instructed to discontinue treatment and undergo an accelerated elimination procedure. Pregnancy outcomes were collected across phase 2 and 3 clinical studies in the teriflunomide clinical development program and available data through October 2013 are reported. Results: Eighty-three pregnancies were reported in female patients and 22 in partners of male patients; 26 live births occurred in female patients and 16 in partners of male patients receiving teriflunomide. Twenty-nine pregnancies in female patients and two in partners of male patients were terminated electively. Newborns whose parents were exposed to teriflunomide were healthy and had no structural defects or functional deficits at birth. Spontaneous abortion rate (18.6%) was within the range for general population. Median birth weight for 18 newborns was 3.3 kg, and mean gestational age at birth among 23 cases was 39 weeks, all within typical ranges for general population. Conclusions: Data from the clinical program have shown no teratogenic signals for teriflunomide in humans, consistent with findings of the Organization of Teratology Information Specialists registry and over 2.5 million patient-years of postmarketing data for leflunomide. Further prospective data in the postmarketing setting are being collected in global teriflunomide pregnancy registries. http://dx.doi.org/10.1016/j.msard.2014.09.192
P044
Long-term clinical and magnetic resonance imaging outcomes from patients treated with teriflunomide: Results from a phase 2 extension study
M.A. Jumah, D.B. Li, B. Yamout, Philippe Truffinet, D. Dukovic, P.W. O’Connor P043
Pregnancy outcomes in female patients and partners of male patients in the teriflunomide clinical development program
R. Alroughani, B. Kieseier, R. Gouider, M. Benamor, P. Truffinet, L. Henson Kuwait Background/objectives: Teriflunomide is a once-daily oral immunomodulator approved for relapsing-remitting multiple sclerosis. Consistent efficacy and safety of teriflunomide were demonstrated in a large clinical trial
Saudi Arabia Background/objectives: Teriflunomide is a once-daily oral immunomodulator for the treatment of relapsingremitting multiple sclerosis. The clinical development program for teriflunomide demonstrated consistent efficacy and a well-characterized, manageable safety and tolerability profile. Here we report efficacy outcomes from patients treated long-term with teriflunomide in a phase 2 study (nct01487096) and its extension (nct00228163). Design and methods: Patients with relapsing multiple sclerosis were randomized 1:1:1 to teriflunomide 14 mg or 7 mg, or placebo. Of 160 patients completing the 36-week core study, 147 entered the long-term extension.
756
S. Taghavifar et al.
Teriflunomide-treated patients continued on their original dose; placebo-treated patients were rerandomized 1:1 to teriflunomide, 14 mg or 7 mg. Expanded disability status scale score was assessed every 24 weeks, magnetic resonance imaging was performed every 48 weeks until week 480, and clinical relapses were reported throughout the study. Results: At june 28, 2013, cumulative duration of teriflunomide exposure, including both dose groups, was 4990 patient-years: 63 patients remained on study. Increases in mean expanded disability status scale score following up to 528 weeks of treatment were minimal. Annualized relapse rates were low: 0.190 (14-mg group) and 0.254 (7-mg group). In both dose groups, mean numbers of gadoliniumenhancing t1 lesions and newly active t2 lesions were lower at week 480 vs. core study end. Compared with the 7-mg group, the teriflunomide 14-mg group had less of an increase from baseline in t2 lesion volume and less decline from baseline in cerebral volume at week 432. There were no new or unexpected safety signals with continued teriflunomide exposure. Conclusions: Clinical and radiological signs of disease remained low in patients receiving teriflunomide for up to 12 years in a phase 2 study and its extension. These data are consistent with sustained efficacy of long-term teriflunomide treatment in patients with multiple sclerosis.
treatment (12 mg/day intravenously on 3 consecutive days) ?1 year apart or other disease-modifying therapy. Crossover patients received 2 alemtuzumab courses (5 days then 3 days) 12 months apart. Results: The extension enrolled 393 (93%) eligible patients from the core study alemtuzumab arm. Through 4 years, 68% received the first 2, but no additional courses; 24% and 7% received 1 or 2 additional courses, respectively; 5% received another disease-modifying therapy during the extension. Twenty-five patients (6%) discontinued study, none from adverse events. Among former interferon beta1a patients, 146 (83%) entered the extension; 131 (90%) received 2 alemtuzumab courses. Seven extension withdrawals (5%) occurred in crossover patients, 1 from an adverse event. Efficacy and safety data will be reported. Conclusions: Most patients receiving alemtuzumab in the core study required no re-treatment during the first 2 extension years; few received alternative therapies or withdrew from study. Among crossover patients, most received both treatment courses and remained in the study.
http://dx.doi.org/10.1016/j.msard.2014.09.193
Cumulative review of thrombotic microangiopathy, thrombotic thrombocytopenic purpura and hemolytic uremic syndrome reports with SC interferon beta-1a
P045
A.F. Amor, A. Trochanov, J. Johnson
Efficacy and safety of alemtuzumab in patients with relapsing-remitting multiple sclerosis who relapsed on prior therapy: Four-year follow-up of the Care-MS II study
B.C. Kieseier, M.A. Sahraian, A.J. Coles, H.P. Hartung, E. Havrdova, K.W. Selmaj, D.H. Margolin, J. Palmer, P. Oyuela USA Background/objectives: Alemtuzumab is approved in over 30 countries for relapsing-remitting multiple sclerosis. In the 2-year, phase 3 CARE-MS II study (NCT00548405), alemtuzumab had superior efficacy over subcutaneous interferon beta-1a and manageable safety over 2 years; follow-up at Year 3 showed durable efficacy of alemtuzumab. Here we report results for years 3 and 4 after alemtuzumab initiation, and for years 1 and 2 after alemtuzumab initiation in patients initially treated with subcutaneous interferon beta-1a (crossover cohort). Design and methods: In CARE-MS II, patients with active relapsing-remitting multiple sclerosis who relapsed on prior therapy received 2 courses of alemtuzumab (12 mg/day intravenously on 5 consecutive days and on 3 consecutive days 12 months later) or subcutaneous interferon beta-1a (44 ?g 3 times/week). In the extension study (NCT00930553), alemtuzumab-treated patients could receive as-needed re-
http://dx.doi.org/10.1016/j.msard.2014.09.194
P046
Switzerland, USA Background/objectives: Rare cases of thrombotic microangiopathy, manifested as thrombotic thrombocytopenic purpura or hemolytic uremic syndrome have been reported with interferon beta products. This was a cumulative review of thrombotic microangiopathy cases recorded in a Global Safety Database for subcutaneous interferon beta-1a. Methods: Search criteria were all reported cases, serious and non-serious, from all sources (including nonhealthcare professionals and clinical trial reports), regardless of event ranking and causality assessment by reporter or Company; data lock was 03 May 2014. Results: Ninety one cases with 105 events were retrieved; 76.9% (70/91) patients were female, consistent with the underlying disease of multiple sclerosis. Time-toonset varied from 2 months to 14 years; 31.9% events occurred within 2-years of treatment initiation. 7 patients had a fatal outcome (5 were secondary to other causes; 2 had insufficient information). 44 patients recovered, 32 had not recovered at the time of the report and in 8 cases the outcome was not reported/unknown. Treatment was discontinued in 84.6% (77/91). In 67.0% (61/91), a causal association between treatment and the occurrence of thrombotic microangiopathy, thrombotic thrombocytopenic purpura-hemolytic uremic syndrome was suspected. Risk factors and/or confounding factors were present in 41/91 cases (45.1%). Early prodromal syndrome or specific