Contributions
Abstract: EP1613
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: Interferon beta-1a (IFN-β1a) medicines are widely used as the first-line therapy in relapsing-remitting multiple sclerosis (RRMS). PEGylated interferon-beta-1a (PEG-IFN-β1a) is expected to have better efficacy, decreased frequency of administrations and increased patient compliance.
Airms: То evaluate pharmacokinetics (PK) and pharmacodynamics (PD) of the original PEG-IFN-β1a medicine after intramuscular administrations in patients with RRMS in the double-blind placebo-controlled study.
Methods: During the first year, all patients (n=399) will be randomized (2:2:2:1) and administered with either PEG-IFN-β1a 180 µg or PEG-IFN-β1a 240 µg or Avonex® 30 µg or placebo. The PK/PD analysis was performed using blood samples obtained during the first 12 weeks of treatment of 70 patients.
Results: Intramuscular administration of PEG-IFN-β1a in a single dose of 180 µg or 240 µg provides approximately 30 and 40 times higher exposure (AUC0-168 and AUC0-336) and approximately 25-40 times higher Cmax values compared to Avonex® 30 µg. The peak serum concentrations were reached after 48 hours in PEG-IFN-β1a groups and after 12 hours (p˂0.05, test Mann-Whithney) in Avonex® 30 µg group. We observed a monophasic decline and a median half-life of 70, 82 and 53 hours in PEG-IFN-β1a 180 µg, PEG-IFN-β1a 240 µg and Avonex® 30 µg, respectively. No accumulation was observed. Elevated neopterin levels were sustained for 7-14 days in PEG-IFN-β1a arms, with the statistically significant increase in AUC0-168 and AUC0-336 in PEG-IFN-β1a groups over Avonex® (p˂0.05, test Mann-Whithney).
Conclusion: These data confirm the statistically significant difference in PK and PD parameters of PEGylated and non-PEGylated interferon beta-1a in patients with RRMS. As expected, PEGylation of IFN-β1a can improve the dosing regimen reducing the frequency of administration compared to Avonex®. Morever the higher amplitude of neopterin elevation in PEG-IFN-β1a groups supports higher PD effects and, potentially, better efficacy of the pegylated product.
Disclosure: This study was sponsored by JSC BIOCAD.
A. Zinkina-Orikhan and Y. Linkova are employees for BIOCAD Company.
Abstract: EP1613
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: Interferon beta-1a (IFN-β1a) medicines are widely used as the first-line therapy in relapsing-remitting multiple sclerosis (RRMS). PEGylated interferon-beta-1a (PEG-IFN-β1a) is expected to have better efficacy, decreased frequency of administrations and increased patient compliance.
Airms: То evaluate pharmacokinetics (PK) and pharmacodynamics (PD) of the original PEG-IFN-β1a medicine after intramuscular administrations in patients with RRMS in the double-blind placebo-controlled study.
Methods: During the first year, all patients (n=399) will be randomized (2:2:2:1) and administered with either PEG-IFN-β1a 180 µg or PEG-IFN-β1a 240 µg or Avonex® 30 µg or placebo. The PK/PD analysis was performed using blood samples obtained during the first 12 weeks of treatment of 70 patients.
Results: Intramuscular administration of PEG-IFN-β1a in a single dose of 180 µg or 240 µg provides approximately 30 and 40 times higher exposure (AUC0-168 and AUC0-336) and approximately 25-40 times higher Cmax values compared to Avonex® 30 µg. The peak serum concentrations were reached after 48 hours in PEG-IFN-β1a groups and after 12 hours (p˂0.05, test Mann-Whithney) in Avonex® 30 µg group. We observed a monophasic decline and a median half-life of 70, 82 and 53 hours in PEG-IFN-β1a 180 µg, PEG-IFN-β1a 240 µg and Avonex® 30 µg, respectively. No accumulation was observed. Elevated neopterin levels were sustained for 7-14 days in PEG-IFN-β1a arms, with the statistically significant increase in AUC0-168 and AUC0-336 in PEG-IFN-β1a groups over Avonex® (p˂0.05, test Mann-Whithney).
Conclusion: These data confirm the statistically significant difference in PK and PD parameters of PEGylated and non-PEGylated interferon beta-1a in patients with RRMS. As expected, PEGylation of IFN-β1a can improve the dosing regimen reducing the frequency of administration compared to Avonex®. Morever the higher amplitude of neopterin elevation in PEG-IFN-β1a groups supports higher PD effects and, potentially, better efficacy of the pegylated product.
Disclosure: This study was sponsored by JSC BIOCAD.
A. Zinkina-Orikhan and Y. Linkova are employees for BIOCAD Company.