Subcutaneous Recombinant Interferon-β-1a (Rebif®)
Abstract Subcutaneous recombinant interferon-β-1a (Rebif®) 22 or 44μg three times weekly is a valuable option in the first-line treatment in patients with relapsing-remitting multiple sclerosis (RRMS). It has shown benefits on outcome measures related to relapses, progression of disability and magne...
Ausführliche Beschreibung
Autor*in: |
Murdoch, David [verfasserIn] Lyseng-Williamson, Katherine A. [verfasserIn] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2005 |
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Schlagwörter: |
Expand Disability Status Scale |
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Übergeordnetes Werk: |
Enthalten in: Drugs - Berlin [u.a.] : Springer, 1971, 65(2005), 9 vom: Juni, Seite 1295-1312 |
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Übergeordnetes Werk: |
volume:65 ; year:2005 ; number:9 ; month:06 ; pages:1295-1312 |
Links: |
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DOI / URN: |
10.2165/00003495-200565090-00010 |
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Katalog-ID: |
SPR033196575 |
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520 | |a Abstract Subcutaneous recombinant interferon-β-1a (Rebif®) 22 or 44μg three times weekly is a valuable option in the first-line treatment in patients with relapsing-remitting multiple sclerosis (RRMS). It has shown benefits on outcome measures related to relapses, progression of disability and magnetic resonance imaging (MRI) in clinical trials. A significant efficacy advantage for subcutaneous interferon-β-1a three times weekly over intramuscular interferon-β-1a 30μg once weekly was shown at 24 and 48 weeks. The most common adverse events are generally mild and clinically manageable. Considering both direct and indirect comparative clinical trial data, an assessment suggests that subcutaneous interferon-β-1a 44μg three times weekly has the best benefit-to-risk values of the available disease-modifying drugs used to treat RRMS. Pharmacological Properties Glycosylated recombinant interferon-β-1a has the same primary structure and biological effects in the body as endogenous human interferon-β. Immunomodulatory activity, the principal pharmacodynamic property of interferon-β-1a, most likely results from interferon-stimulated gene products mediating biological activities. The long-term clinical significance of the development of neutralising antibodies (NABs) to interferon-β-1a is currently unclear; therefore, it is recommended that treatment decisions are based on clinical efficacy and not on the presence of NABs alone. In healthy volunteers, subcutaneous interferon-β-1a has a long apparent elimination half-life and appears to accumulate after repeated doses. Therapeutic Efficacy In a randomised 2-year trial, subcutaneous interferon-β-1a 22 or 44μg three times weekly for 2 years was more effective than placebo as assessed by a number of clinical (e.g. relapse rate per patient, proportion of patients without clinical relapse and changes from baseline in Kurtzke Expanded Disability Status Scale [EDSS] scores) and MRI (total burden of disease and numbers of active lesions per patient per scan) endpoints. Significant dose-response effects in favour of the higher dosage were evident when the study period was extended for another 2 years. Extension data for a total follow-up period of 7–8 years in the original cohort showed sustained clinical benefits with subcutaneous interferon-β-1a therapy. In a 48-week comparative trial, patients randomised to subcutaneous interferon-β-1a 44μg three times weekly were more likely to remain free of relapses and have significantly more favourable measures of MRI lesion activity at weeks 24 and 48 weeks, and a longer time to first relapse, than those randomised to intramuscular interferon-β-1a 30μg once weekly. In the crossover extension phase (median treatment duration 34 weeks), clinical and MRI outcomes improved in patients who crossed over from treatment with intramuscular interferon-β-1a 30μg once weekly to subcutaneous interferon-β-1a 44μg three times weekly. Tolerability In clinical trials of subcutaneous interferon-β-1a, the most commonly reported adverse events (e.g. injection-site reactions, headache and influenza-like symptoms) were generally mild, manageable and reversible. Mild, asymptomatic and reversible haematological disorders and alterations in liver function tests may occur. A few patients experience serious effects on liver function. Subcutaneous interferon-β-1a 44μg three times weekly was associated with a significantly higher incidence of injection-site disorders and liver function or haematological abnormalities than intramuscular interferon-β-1a 30μg once weekly. No between-group differences were noted regarding the proportions of patients experiencing serious adverse events. Pharmacoeconomic and Other Considerations In an assessment that evaluated the four available RRMS disease-modifying treatments based on the numbers of patients needed to treat to obtain benefit or harm, subcutaneous interferon-β-1a 44μg three times weekly had the best benefit-to-risk values. Based on data from pivotal directly comparative trials, subcutaneous interferon-β-1a 44μg three times weekly had favourable benefit-to-risk values relative to subcutaneous interferon-β-1a 22μg three times weekly and intramuscular interferon-β-1a 30μg once weekly. Based on indirect comparative data from published clinical trials, subcutaneous interferon-β-1a appeared to have favourable efficacy values relative to interferon-β-1b every other day, and interferon-β formulations appeared to have favourable benefit-to-risk ratios relative to placebo and also subcutaneous glatiramer acetate 20gmg once daily. In pharmacoeconomic analyses from a healthcare payer perspective, subcutaneous interferon-β-1a 44μg three times weekly was predicted to be increasingly more cost effective than placebo over the mid-(10 years) and long-(20 years) term with regard to preventing EDSS-months of disability in the UK and France, and cost saving relative to intramuscular interferon-β-1a 30μg once weekly over 48 weeks in the US. | ||
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10.2165/00003495-200565090-00010 doi (DE-627)SPR033196575 (SPR)00003495-200565090-00010-e DE-627 ger DE-627 rakwb eng 610 ASE 44.40 bkl 44.38 bkl Murdoch, David verfasserin aut Subcutaneous Recombinant Interferon-β-1a (Rebif®) 2005 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Subcutaneous recombinant interferon-β-1a (Rebif®) 22 or 44μg three times weekly is a valuable option in the first-line treatment in patients with relapsing-remitting multiple sclerosis (RRMS). It has shown benefits on outcome measures related to relapses, progression of disability and magnetic resonance imaging (MRI) in clinical trials. A significant efficacy advantage for subcutaneous interferon-β-1a three times weekly over intramuscular interferon-β-1a 30μg once weekly was shown at 24 and 48 weeks. The most common adverse events are generally mild and clinically manageable. Considering both direct and indirect comparative clinical trial data, an assessment suggests that subcutaneous interferon-β-1a 44μg three times weekly has the best benefit-to-risk values of the available disease-modifying drugs used to treat RRMS. Pharmacological Properties Glycosylated recombinant interferon-β-1a has the same primary structure and biological effects in the body as endogenous human interferon-β. Immunomodulatory activity, the principal pharmacodynamic property of interferon-β-1a, most likely results from interferon-stimulated gene products mediating biological activities. The long-term clinical significance of the development of neutralising antibodies (NABs) to interferon-β-1a is currently unclear; therefore, it is recommended that treatment decisions are based on clinical efficacy and not on the presence of NABs alone. In healthy volunteers, subcutaneous interferon-β-1a has a long apparent elimination half-life and appears to accumulate after repeated doses. Therapeutic Efficacy In a randomised 2-year trial, subcutaneous interferon-β-1a 22 or 44μg three times weekly for 2 years was more effective than placebo as assessed by a number of clinical (e.g. relapse rate per patient, proportion of patients without clinical relapse and changes from baseline in Kurtzke Expanded Disability Status Scale [EDSS] scores) and MRI (total burden of disease and numbers of active lesions per patient per scan) endpoints. Significant dose-response effects in favour of the higher dosage were evident when the study period was extended for another 2 years. Extension data for a total follow-up period of 7–8 years in the original cohort showed sustained clinical benefits with subcutaneous interferon-β-1a therapy. In a 48-week comparative trial, patients randomised to subcutaneous interferon-β-1a 44μg three times weekly were more likely to remain free of relapses and have significantly more favourable measures of MRI lesion activity at weeks 24 and 48 weeks, and a longer time to first relapse, than those randomised to intramuscular interferon-β-1a 30μg once weekly. In the crossover extension phase (median treatment duration 34 weeks), clinical and MRI outcomes improved in patients who crossed over from treatment with intramuscular interferon-β-1a 30μg once weekly to subcutaneous interferon-β-1a 44μg three times weekly. Tolerability In clinical trials of subcutaneous interferon-β-1a, the most commonly reported adverse events (e.g. injection-site reactions, headache and influenza-like symptoms) were generally mild, manageable and reversible. Mild, asymptomatic and reversible haematological disorders and alterations in liver function tests may occur. A few patients experience serious effects on liver function. Subcutaneous interferon-β-1a 44μg three times weekly was associated with a significantly higher incidence of injection-site disorders and liver function or haematological abnormalities than intramuscular interferon-β-1a 30μg once weekly. No between-group differences were noted regarding the proportions of patients experiencing serious adverse events. Pharmacoeconomic and Other Considerations In an assessment that evaluated the four available RRMS disease-modifying treatments based on the numbers of patients needed to treat to obtain benefit or harm, subcutaneous interferon-β-1a 44μg three times weekly had the best benefit-to-risk values. Based on data from pivotal directly comparative trials, subcutaneous interferon-β-1a 44μg three times weekly had favourable benefit-to-risk values relative to subcutaneous interferon-β-1a 22μg three times weekly and intramuscular interferon-β-1a 30μg once weekly. Based on indirect comparative data from published clinical trials, subcutaneous interferon-β-1a appeared to have favourable efficacy values relative to interferon-β-1b every other day, and interferon-β formulations appeared to have favourable benefit-to-risk ratios relative to placebo and also subcutaneous glatiramer acetate 20gmg once daily. In pharmacoeconomic analyses from a healthcare payer perspective, subcutaneous interferon-β-1a 44μg three times weekly was predicted to be increasingly more cost effective than placebo over the mid-(10 years) and long-(20 years) term with regard to preventing EDSS-months of disability in the UK and France, and cost saving relative to intramuscular interferon-β-1a 30μg once weekly over 48 weeks in the US. Multiple Sclerosis (dpeaa)DE-He213 Expand Disability Status Scale (dpeaa)DE-He213 Expand Disability Status Scale Score (dpeaa)DE-He213 Annualise Relapse Rate (dpeaa)DE-He213 Magnetic Resonance Imaging Outcome (dpeaa)DE-He213 Lyseng-Williamson, Katherine A. verfasserin aut Enthalten in Drugs Berlin [u.a.] : Springer, 1971 65(2005), 9 vom: Juni, Seite 1295-1312 (DE-627)320609413 (DE-600)2021165-X 1179-1950 nnns volume:65 year:2005 number:9 month:06 pages:1295-1312 https://dx.doi.org/10.2165/00003495-200565090-00010 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_266 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.40 ASE 44.38 ASE AR 65 2005 9 06 1295-1312 |
spelling |
10.2165/00003495-200565090-00010 doi (DE-627)SPR033196575 (SPR)00003495-200565090-00010-e DE-627 ger DE-627 rakwb eng 610 ASE 44.40 bkl 44.38 bkl Murdoch, David verfasserin aut Subcutaneous Recombinant Interferon-β-1a (Rebif®) 2005 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Subcutaneous recombinant interferon-β-1a (Rebif®) 22 or 44μg three times weekly is a valuable option in the first-line treatment in patients with relapsing-remitting multiple sclerosis (RRMS). It has shown benefits on outcome measures related to relapses, progression of disability and magnetic resonance imaging (MRI) in clinical trials. A significant efficacy advantage for subcutaneous interferon-β-1a three times weekly over intramuscular interferon-β-1a 30μg once weekly was shown at 24 and 48 weeks. The most common adverse events are generally mild and clinically manageable. Considering both direct and indirect comparative clinical trial data, an assessment suggests that subcutaneous interferon-β-1a 44μg three times weekly has the best benefit-to-risk values of the available disease-modifying drugs used to treat RRMS. Pharmacological Properties Glycosylated recombinant interferon-β-1a has the same primary structure and biological effects in the body as endogenous human interferon-β. Immunomodulatory activity, the principal pharmacodynamic property of interferon-β-1a, most likely results from interferon-stimulated gene products mediating biological activities. The long-term clinical significance of the development of neutralising antibodies (NABs) to interferon-β-1a is currently unclear; therefore, it is recommended that treatment decisions are based on clinical efficacy and not on the presence of NABs alone. In healthy volunteers, subcutaneous interferon-β-1a has a long apparent elimination half-life and appears to accumulate after repeated doses. Therapeutic Efficacy In a randomised 2-year trial, subcutaneous interferon-β-1a 22 or 44μg three times weekly for 2 years was more effective than placebo as assessed by a number of clinical (e.g. relapse rate per patient, proportion of patients without clinical relapse and changes from baseline in Kurtzke Expanded Disability Status Scale [EDSS] scores) and MRI (total burden of disease and numbers of active lesions per patient per scan) endpoints. Significant dose-response effects in favour of the higher dosage were evident when the study period was extended for another 2 years. Extension data for a total follow-up period of 7–8 years in the original cohort showed sustained clinical benefits with subcutaneous interferon-β-1a therapy. In a 48-week comparative trial, patients randomised to subcutaneous interferon-β-1a 44μg three times weekly were more likely to remain free of relapses and have significantly more favourable measures of MRI lesion activity at weeks 24 and 48 weeks, and a longer time to first relapse, than those randomised to intramuscular interferon-β-1a 30μg once weekly. In the crossover extension phase (median treatment duration 34 weeks), clinical and MRI outcomes improved in patients who crossed over from treatment with intramuscular interferon-β-1a 30μg once weekly to subcutaneous interferon-β-1a 44μg three times weekly. Tolerability In clinical trials of subcutaneous interferon-β-1a, the most commonly reported adverse events (e.g. injection-site reactions, headache and influenza-like symptoms) were generally mild, manageable and reversible. Mild, asymptomatic and reversible haematological disorders and alterations in liver function tests may occur. A few patients experience serious effects on liver function. Subcutaneous interferon-β-1a 44μg three times weekly was associated with a significantly higher incidence of injection-site disorders and liver function or haematological abnormalities than intramuscular interferon-β-1a 30μg once weekly. No between-group differences were noted regarding the proportions of patients experiencing serious adverse events. Pharmacoeconomic and Other Considerations In an assessment that evaluated the four available RRMS disease-modifying treatments based on the numbers of patients needed to treat to obtain benefit or harm, subcutaneous interferon-β-1a 44μg three times weekly had the best benefit-to-risk values. Based on data from pivotal directly comparative trials, subcutaneous interferon-β-1a 44μg three times weekly had favourable benefit-to-risk values relative to subcutaneous interferon-β-1a 22μg three times weekly and intramuscular interferon-β-1a 30μg once weekly. Based on indirect comparative data from published clinical trials, subcutaneous interferon-β-1a appeared to have favourable efficacy values relative to interferon-β-1b every other day, and interferon-β formulations appeared to have favourable benefit-to-risk ratios relative to placebo and also subcutaneous glatiramer acetate 20gmg once daily. In pharmacoeconomic analyses from a healthcare payer perspective, subcutaneous interferon-β-1a 44μg three times weekly was predicted to be increasingly more cost effective than placebo over the mid-(10 years) and long-(20 years) term with regard to preventing EDSS-months of disability in the UK and France, and cost saving relative to intramuscular interferon-β-1a 30μg once weekly over 48 weeks in the US. Multiple Sclerosis (dpeaa)DE-He213 Expand Disability Status Scale (dpeaa)DE-He213 Expand Disability Status Scale Score (dpeaa)DE-He213 Annualise Relapse Rate (dpeaa)DE-He213 Magnetic Resonance Imaging Outcome (dpeaa)DE-He213 Lyseng-Williamson, Katherine A. verfasserin aut Enthalten in Drugs Berlin [u.a.] : Springer, 1971 65(2005), 9 vom: Juni, Seite 1295-1312 (DE-627)320609413 (DE-600)2021165-X 1179-1950 nnns volume:65 year:2005 number:9 month:06 pages:1295-1312 https://dx.doi.org/10.2165/00003495-200565090-00010 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_266 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.40 ASE 44.38 ASE AR 65 2005 9 06 1295-1312 |
allfields_unstemmed |
10.2165/00003495-200565090-00010 doi (DE-627)SPR033196575 (SPR)00003495-200565090-00010-e DE-627 ger DE-627 rakwb eng 610 ASE 44.40 bkl 44.38 bkl Murdoch, David verfasserin aut Subcutaneous Recombinant Interferon-β-1a (Rebif®) 2005 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Subcutaneous recombinant interferon-β-1a (Rebif®) 22 or 44μg three times weekly is a valuable option in the first-line treatment in patients with relapsing-remitting multiple sclerosis (RRMS). It has shown benefits on outcome measures related to relapses, progression of disability and magnetic resonance imaging (MRI) in clinical trials. A significant efficacy advantage for subcutaneous interferon-β-1a three times weekly over intramuscular interferon-β-1a 30μg once weekly was shown at 24 and 48 weeks. The most common adverse events are generally mild and clinically manageable. Considering both direct and indirect comparative clinical trial data, an assessment suggests that subcutaneous interferon-β-1a 44μg three times weekly has the best benefit-to-risk values of the available disease-modifying drugs used to treat RRMS. Pharmacological Properties Glycosylated recombinant interferon-β-1a has the same primary structure and biological effects in the body as endogenous human interferon-β. Immunomodulatory activity, the principal pharmacodynamic property of interferon-β-1a, most likely results from interferon-stimulated gene products mediating biological activities. The long-term clinical significance of the development of neutralising antibodies (NABs) to interferon-β-1a is currently unclear; therefore, it is recommended that treatment decisions are based on clinical efficacy and not on the presence of NABs alone. In healthy volunteers, subcutaneous interferon-β-1a has a long apparent elimination half-life and appears to accumulate after repeated doses. Therapeutic Efficacy In a randomised 2-year trial, subcutaneous interferon-β-1a 22 or 44μg three times weekly for 2 years was more effective than placebo as assessed by a number of clinical (e.g. relapse rate per patient, proportion of patients without clinical relapse and changes from baseline in Kurtzke Expanded Disability Status Scale [EDSS] scores) and MRI (total burden of disease and numbers of active lesions per patient per scan) endpoints. Significant dose-response effects in favour of the higher dosage were evident when the study period was extended for another 2 years. Extension data for a total follow-up period of 7–8 years in the original cohort showed sustained clinical benefits with subcutaneous interferon-β-1a therapy. In a 48-week comparative trial, patients randomised to subcutaneous interferon-β-1a 44μg three times weekly were more likely to remain free of relapses and have significantly more favourable measures of MRI lesion activity at weeks 24 and 48 weeks, and a longer time to first relapse, than those randomised to intramuscular interferon-β-1a 30μg once weekly. In the crossover extension phase (median treatment duration 34 weeks), clinical and MRI outcomes improved in patients who crossed over from treatment with intramuscular interferon-β-1a 30μg once weekly to subcutaneous interferon-β-1a 44μg three times weekly. Tolerability In clinical trials of subcutaneous interferon-β-1a, the most commonly reported adverse events (e.g. injection-site reactions, headache and influenza-like symptoms) were generally mild, manageable and reversible. Mild, asymptomatic and reversible haematological disorders and alterations in liver function tests may occur. A few patients experience serious effects on liver function. Subcutaneous interferon-β-1a 44μg three times weekly was associated with a significantly higher incidence of injection-site disorders and liver function or haematological abnormalities than intramuscular interferon-β-1a 30μg once weekly. No between-group differences were noted regarding the proportions of patients experiencing serious adverse events. Pharmacoeconomic and Other Considerations In an assessment that evaluated the four available RRMS disease-modifying treatments based on the numbers of patients needed to treat to obtain benefit or harm, subcutaneous interferon-β-1a 44μg three times weekly had the best benefit-to-risk values. Based on data from pivotal directly comparative trials, subcutaneous interferon-β-1a 44μg three times weekly had favourable benefit-to-risk values relative to subcutaneous interferon-β-1a 22μg three times weekly and intramuscular interferon-β-1a 30μg once weekly. Based on indirect comparative data from published clinical trials, subcutaneous interferon-β-1a appeared to have favourable efficacy values relative to interferon-β-1b every other day, and interferon-β formulations appeared to have favourable benefit-to-risk ratios relative to placebo and also subcutaneous glatiramer acetate 20gmg once daily. In pharmacoeconomic analyses from a healthcare payer perspective, subcutaneous interferon-β-1a 44μg three times weekly was predicted to be increasingly more cost effective than placebo over the mid-(10 years) and long-(20 years) term with regard to preventing EDSS-months of disability in the UK and France, and cost saving relative to intramuscular interferon-β-1a 30μg once weekly over 48 weeks in the US. Multiple Sclerosis (dpeaa)DE-He213 Expand Disability Status Scale (dpeaa)DE-He213 Expand Disability Status Scale Score (dpeaa)DE-He213 Annualise Relapse Rate (dpeaa)DE-He213 Magnetic Resonance Imaging Outcome (dpeaa)DE-He213 Lyseng-Williamson, Katherine A. verfasserin aut Enthalten in Drugs Berlin [u.a.] : Springer, 1971 65(2005), 9 vom: Juni, Seite 1295-1312 (DE-627)320609413 (DE-600)2021165-X 1179-1950 nnns volume:65 year:2005 number:9 month:06 pages:1295-1312 https://dx.doi.org/10.2165/00003495-200565090-00010 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_266 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.40 ASE 44.38 ASE AR 65 2005 9 06 1295-1312 |
allfieldsGer |
10.2165/00003495-200565090-00010 doi (DE-627)SPR033196575 (SPR)00003495-200565090-00010-e DE-627 ger DE-627 rakwb eng 610 ASE 44.40 bkl 44.38 bkl Murdoch, David verfasserin aut Subcutaneous Recombinant Interferon-β-1a (Rebif®) 2005 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Subcutaneous recombinant interferon-β-1a (Rebif®) 22 or 44μg three times weekly is a valuable option in the first-line treatment in patients with relapsing-remitting multiple sclerosis (RRMS). It has shown benefits on outcome measures related to relapses, progression of disability and magnetic resonance imaging (MRI) in clinical trials. A significant efficacy advantage for subcutaneous interferon-β-1a three times weekly over intramuscular interferon-β-1a 30μg once weekly was shown at 24 and 48 weeks. The most common adverse events are generally mild and clinically manageable. Considering both direct and indirect comparative clinical trial data, an assessment suggests that subcutaneous interferon-β-1a 44μg three times weekly has the best benefit-to-risk values of the available disease-modifying drugs used to treat RRMS. Pharmacological Properties Glycosylated recombinant interferon-β-1a has the same primary structure and biological effects in the body as endogenous human interferon-β. Immunomodulatory activity, the principal pharmacodynamic property of interferon-β-1a, most likely results from interferon-stimulated gene products mediating biological activities. The long-term clinical significance of the development of neutralising antibodies (NABs) to interferon-β-1a is currently unclear; therefore, it is recommended that treatment decisions are based on clinical efficacy and not on the presence of NABs alone. In healthy volunteers, subcutaneous interferon-β-1a has a long apparent elimination half-life and appears to accumulate after repeated doses. Therapeutic Efficacy In a randomised 2-year trial, subcutaneous interferon-β-1a 22 or 44μg three times weekly for 2 years was more effective than placebo as assessed by a number of clinical (e.g. relapse rate per patient, proportion of patients without clinical relapse and changes from baseline in Kurtzke Expanded Disability Status Scale [EDSS] scores) and MRI (total burden of disease and numbers of active lesions per patient per scan) endpoints. Significant dose-response effects in favour of the higher dosage were evident when the study period was extended for another 2 years. Extension data for a total follow-up period of 7–8 years in the original cohort showed sustained clinical benefits with subcutaneous interferon-β-1a therapy. In a 48-week comparative trial, patients randomised to subcutaneous interferon-β-1a 44μg three times weekly were more likely to remain free of relapses and have significantly more favourable measures of MRI lesion activity at weeks 24 and 48 weeks, and a longer time to first relapse, than those randomised to intramuscular interferon-β-1a 30μg once weekly. In the crossover extension phase (median treatment duration 34 weeks), clinical and MRI outcomes improved in patients who crossed over from treatment with intramuscular interferon-β-1a 30μg once weekly to subcutaneous interferon-β-1a 44μg three times weekly. Tolerability In clinical trials of subcutaneous interferon-β-1a, the most commonly reported adverse events (e.g. injection-site reactions, headache and influenza-like symptoms) were generally mild, manageable and reversible. Mild, asymptomatic and reversible haematological disorders and alterations in liver function tests may occur. A few patients experience serious effects on liver function. Subcutaneous interferon-β-1a 44μg three times weekly was associated with a significantly higher incidence of injection-site disorders and liver function or haematological abnormalities than intramuscular interferon-β-1a 30μg once weekly. No between-group differences were noted regarding the proportions of patients experiencing serious adverse events. Pharmacoeconomic and Other Considerations In an assessment that evaluated the four available RRMS disease-modifying treatments based on the numbers of patients needed to treat to obtain benefit or harm, subcutaneous interferon-β-1a 44μg three times weekly had the best benefit-to-risk values. Based on data from pivotal directly comparative trials, subcutaneous interferon-β-1a 44μg three times weekly had favourable benefit-to-risk values relative to subcutaneous interferon-β-1a 22μg three times weekly and intramuscular interferon-β-1a 30μg once weekly. Based on indirect comparative data from published clinical trials, subcutaneous interferon-β-1a appeared to have favourable efficacy values relative to interferon-β-1b every other day, and interferon-β formulations appeared to have favourable benefit-to-risk ratios relative to placebo and also subcutaneous glatiramer acetate 20gmg once daily. In pharmacoeconomic analyses from a healthcare payer perspective, subcutaneous interferon-β-1a 44μg three times weekly was predicted to be increasingly more cost effective than placebo over the mid-(10 years) and long-(20 years) term with regard to preventing EDSS-months of disability in the UK and France, and cost saving relative to intramuscular interferon-β-1a 30μg once weekly over 48 weeks in the US. Multiple Sclerosis (dpeaa)DE-He213 Expand Disability Status Scale (dpeaa)DE-He213 Expand Disability Status Scale Score (dpeaa)DE-He213 Annualise Relapse Rate (dpeaa)DE-He213 Magnetic Resonance Imaging Outcome (dpeaa)DE-He213 Lyseng-Williamson, Katherine A. verfasserin aut Enthalten in Drugs Berlin [u.a.] : Springer, 1971 65(2005), 9 vom: Juni, Seite 1295-1312 (DE-627)320609413 (DE-600)2021165-X 1179-1950 nnns volume:65 year:2005 number:9 month:06 pages:1295-1312 https://dx.doi.org/10.2165/00003495-200565090-00010 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_266 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.40 ASE 44.38 ASE AR 65 2005 9 06 1295-1312 |
allfieldsSound |
10.2165/00003495-200565090-00010 doi (DE-627)SPR033196575 (SPR)00003495-200565090-00010-e DE-627 ger DE-627 rakwb eng 610 ASE 44.40 bkl 44.38 bkl Murdoch, David verfasserin aut Subcutaneous Recombinant Interferon-β-1a (Rebif®) 2005 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Subcutaneous recombinant interferon-β-1a (Rebif®) 22 or 44μg three times weekly is a valuable option in the first-line treatment in patients with relapsing-remitting multiple sclerosis (RRMS). It has shown benefits on outcome measures related to relapses, progression of disability and magnetic resonance imaging (MRI) in clinical trials. A significant efficacy advantage for subcutaneous interferon-β-1a three times weekly over intramuscular interferon-β-1a 30μg once weekly was shown at 24 and 48 weeks. The most common adverse events are generally mild and clinically manageable. Considering both direct and indirect comparative clinical trial data, an assessment suggests that subcutaneous interferon-β-1a 44μg three times weekly has the best benefit-to-risk values of the available disease-modifying drugs used to treat RRMS. Pharmacological Properties Glycosylated recombinant interferon-β-1a has the same primary structure and biological effects in the body as endogenous human interferon-β. Immunomodulatory activity, the principal pharmacodynamic property of interferon-β-1a, most likely results from interferon-stimulated gene products mediating biological activities. The long-term clinical significance of the development of neutralising antibodies (NABs) to interferon-β-1a is currently unclear; therefore, it is recommended that treatment decisions are based on clinical efficacy and not on the presence of NABs alone. In healthy volunteers, subcutaneous interferon-β-1a has a long apparent elimination half-life and appears to accumulate after repeated doses. Therapeutic Efficacy In a randomised 2-year trial, subcutaneous interferon-β-1a 22 or 44μg three times weekly for 2 years was more effective than placebo as assessed by a number of clinical (e.g. relapse rate per patient, proportion of patients without clinical relapse and changes from baseline in Kurtzke Expanded Disability Status Scale [EDSS] scores) and MRI (total burden of disease and numbers of active lesions per patient per scan) endpoints. Significant dose-response effects in favour of the higher dosage were evident when the study period was extended for another 2 years. Extension data for a total follow-up period of 7–8 years in the original cohort showed sustained clinical benefits with subcutaneous interferon-β-1a therapy. In a 48-week comparative trial, patients randomised to subcutaneous interferon-β-1a 44μg three times weekly were more likely to remain free of relapses and have significantly more favourable measures of MRI lesion activity at weeks 24 and 48 weeks, and a longer time to first relapse, than those randomised to intramuscular interferon-β-1a 30μg once weekly. In the crossover extension phase (median treatment duration 34 weeks), clinical and MRI outcomes improved in patients who crossed over from treatment with intramuscular interferon-β-1a 30μg once weekly to subcutaneous interferon-β-1a 44μg three times weekly. Tolerability In clinical trials of subcutaneous interferon-β-1a, the most commonly reported adverse events (e.g. injection-site reactions, headache and influenza-like symptoms) were generally mild, manageable and reversible. Mild, asymptomatic and reversible haematological disorders and alterations in liver function tests may occur. A few patients experience serious effects on liver function. Subcutaneous interferon-β-1a 44μg three times weekly was associated with a significantly higher incidence of injection-site disorders and liver function or haematological abnormalities than intramuscular interferon-β-1a 30μg once weekly. No between-group differences were noted regarding the proportions of patients experiencing serious adverse events. Pharmacoeconomic and Other Considerations In an assessment that evaluated the four available RRMS disease-modifying treatments based on the numbers of patients needed to treat to obtain benefit or harm, subcutaneous interferon-β-1a 44μg three times weekly had the best benefit-to-risk values. Based on data from pivotal directly comparative trials, subcutaneous interferon-β-1a 44μg three times weekly had favourable benefit-to-risk values relative to subcutaneous interferon-β-1a 22μg three times weekly and intramuscular interferon-β-1a 30μg once weekly. Based on indirect comparative data from published clinical trials, subcutaneous interferon-β-1a appeared to have favourable efficacy values relative to interferon-β-1b every other day, and interferon-β formulations appeared to have favourable benefit-to-risk ratios relative to placebo and also subcutaneous glatiramer acetate 20gmg once daily. In pharmacoeconomic analyses from a healthcare payer perspective, subcutaneous interferon-β-1a 44μg three times weekly was predicted to be increasingly more cost effective than placebo over the mid-(10 years) and long-(20 years) term with regard to preventing EDSS-months of disability in the UK and France, and cost saving relative to intramuscular interferon-β-1a 30μg once weekly over 48 weeks in the US. Multiple Sclerosis (dpeaa)DE-He213 Expand Disability Status Scale (dpeaa)DE-He213 Expand Disability Status Scale Score (dpeaa)DE-He213 Annualise Relapse Rate (dpeaa)DE-He213 Magnetic Resonance Imaging Outcome (dpeaa)DE-He213 Lyseng-Williamson, Katherine A. verfasserin aut Enthalten in Drugs Berlin [u.a.] : Springer, 1971 65(2005), 9 vom: Juni, Seite 1295-1312 (DE-627)320609413 (DE-600)2021165-X 1179-1950 nnns volume:65 year:2005 number:9 month:06 pages:1295-1312 https://dx.doi.org/10.2165/00003495-200565090-00010 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_266 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.40 ASE 44.38 ASE AR 65 2005 9 06 1295-1312 |
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English |
source |
Enthalten in Drugs 65(2005), 9 vom: Juni, Seite 1295-1312 volume:65 year:2005 number:9 month:06 pages:1295-1312 |
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Enthalten in Drugs 65(2005), 9 vom: Juni, Seite 1295-1312 volume:65 year:2005 number:9 month:06 pages:1295-1312 |
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Multiple Sclerosis Expand Disability Status Scale Expand Disability Status Scale Score Annualise Relapse Rate Magnetic Resonance Imaging Outcome |
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Murdoch, David @@aut@@ Lyseng-Williamson, Katherine A. @@aut@@ |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR033196575</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230519190335.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201007s2005 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.2165/00003495-200565090-00010</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR033196575</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)00003495-200565090-00010-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="q">ASE</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">44.40</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">44.38</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Murdoch, David</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Subcutaneous Recombinant Interferon-β-1a (Rebif®)</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2005</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract Subcutaneous recombinant interferon-β-1a (Rebif®) 22 or 44μg three times weekly is a valuable option in the first-line treatment in patients with relapsing-remitting multiple sclerosis (RRMS). It has shown benefits on outcome measures related to relapses, progression of disability and magnetic resonance imaging (MRI) in clinical trials. A significant efficacy advantage for subcutaneous interferon-β-1a three times weekly over intramuscular interferon-β-1a 30μg once weekly was shown at 24 and 48 weeks. The most common adverse events are generally mild and clinically manageable. Considering both direct and indirect comparative clinical trial data, an assessment suggests that subcutaneous interferon-β-1a 44μg three times weekly has the best benefit-to-risk values of the available disease-modifying drugs used to treat RRMS. Pharmacological Properties Glycosylated recombinant interferon-β-1a has the same primary structure and biological effects in the body as endogenous human interferon-β. Immunomodulatory activity, the principal pharmacodynamic property of interferon-β-1a, most likely results from interferon-stimulated gene products mediating biological activities. The long-term clinical significance of the development of neutralising antibodies (NABs) to interferon-β-1a is currently unclear; therefore, it is recommended that treatment decisions are based on clinical efficacy and not on the presence of NABs alone. In healthy volunteers, subcutaneous interferon-β-1a has a long apparent elimination half-life and appears to accumulate after repeated doses. Therapeutic Efficacy In a randomised 2-year trial, subcutaneous interferon-β-1a 22 or 44μg three times weekly for 2 years was more effective than placebo as assessed by a number of clinical (e.g. relapse rate per patient, proportion of patients without clinical relapse and changes from baseline in Kurtzke Expanded Disability Status Scale [EDSS] scores) and MRI (total burden of disease and numbers of active lesions per patient per scan) endpoints. Significant dose-response effects in favour of the higher dosage were evident when the study period was extended for another 2 years. Extension data for a total follow-up period of 7–8 years in the original cohort showed sustained clinical benefits with subcutaneous interferon-β-1a therapy. In a 48-week comparative trial, patients randomised to subcutaneous interferon-β-1a 44μg three times weekly were more likely to remain free of relapses and have significantly more favourable measures of MRI lesion activity at weeks 24 and 48 weeks, and a longer time to first relapse, than those randomised to intramuscular interferon-β-1a 30μg once weekly. In the crossover extension phase (median treatment duration 34 weeks), clinical and MRI outcomes improved in patients who crossed over from treatment with intramuscular interferon-β-1a 30μg once weekly to subcutaneous interferon-β-1a 44μg three times weekly. Tolerability In clinical trials of subcutaneous interferon-β-1a, the most commonly reported adverse events (e.g. injection-site reactions, headache and influenza-like symptoms) were generally mild, manageable and reversible. Mild, asymptomatic and reversible haematological disorders and alterations in liver function tests may occur. A few patients experience serious effects on liver function. Subcutaneous interferon-β-1a 44μg three times weekly was associated with a significantly higher incidence of injection-site disorders and liver function or haematological abnormalities than intramuscular interferon-β-1a 30μg once weekly. No between-group differences were noted regarding the proportions of patients experiencing serious adverse events. Pharmacoeconomic and Other Considerations In an assessment that evaluated the four available RRMS disease-modifying treatments based on the numbers of patients needed to treat to obtain benefit or harm, subcutaneous interferon-β-1a 44μg three times weekly had the best benefit-to-risk values. Based on data from pivotal directly comparative trials, subcutaneous interferon-β-1a 44μg three times weekly had favourable benefit-to-risk values relative to subcutaneous interferon-β-1a 22μg three times weekly and intramuscular interferon-β-1a 30μg once weekly. Based on indirect comparative data from published clinical trials, subcutaneous interferon-β-1a appeared to have favourable efficacy values relative to interferon-β-1b every other day, and interferon-β formulations appeared to have favourable benefit-to-risk ratios relative to placebo and also subcutaneous glatiramer acetate 20gmg once daily. 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Murdoch, David |
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Murdoch, David ddc 610 bkl 44.40 bkl 44.38 misc Multiple Sclerosis misc Expand Disability Status Scale misc Expand Disability Status Scale Score misc Annualise Relapse Rate misc Magnetic Resonance Imaging Outcome Subcutaneous Recombinant Interferon-β-1a (Rebif®) |
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610 ASE 44.40 bkl 44.38 bkl Subcutaneous Recombinant Interferon-β-1a (Rebif®) Multiple Sclerosis (dpeaa)DE-He213 Expand Disability Status Scale (dpeaa)DE-He213 Expand Disability Status Scale Score (dpeaa)DE-He213 Annualise Relapse Rate (dpeaa)DE-He213 Magnetic Resonance Imaging Outcome (dpeaa)DE-He213 |
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ddc 610 bkl 44.40 bkl 44.38 misc Multiple Sclerosis misc Expand Disability Status Scale misc Expand Disability Status Scale Score misc Annualise Relapse Rate misc Magnetic Resonance Imaging Outcome |
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Subcutaneous Recombinant Interferon-β-1a (Rebif®) |
abstract |
Abstract Subcutaneous recombinant interferon-β-1a (Rebif®) 22 or 44μg three times weekly is a valuable option in the first-line treatment in patients with relapsing-remitting multiple sclerosis (RRMS). It has shown benefits on outcome measures related to relapses, progression of disability and magnetic resonance imaging (MRI) in clinical trials. A significant efficacy advantage for subcutaneous interferon-β-1a three times weekly over intramuscular interferon-β-1a 30μg once weekly was shown at 24 and 48 weeks. The most common adverse events are generally mild and clinically manageable. Considering both direct and indirect comparative clinical trial data, an assessment suggests that subcutaneous interferon-β-1a 44μg three times weekly has the best benefit-to-risk values of the available disease-modifying drugs used to treat RRMS. Pharmacological Properties Glycosylated recombinant interferon-β-1a has the same primary structure and biological effects in the body as endogenous human interferon-β. Immunomodulatory activity, the principal pharmacodynamic property of interferon-β-1a, most likely results from interferon-stimulated gene products mediating biological activities. The long-term clinical significance of the development of neutralising antibodies (NABs) to interferon-β-1a is currently unclear; therefore, it is recommended that treatment decisions are based on clinical efficacy and not on the presence of NABs alone. In healthy volunteers, subcutaneous interferon-β-1a has a long apparent elimination half-life and appears to accumulate after repeated doses. Therapeutic Efficacy In a randomised 2-year trial, subcutaneous interferon-β-1a 22 or 44μg three times weekly for 2 years was more effective than placebo as assessed by a number of clinical (e.g. relapse rate per patient, proportion of patients without clinical relapse and changes from baseline in Kurtzke Expanded Disability Status Scale [EDSS] scores) and MRI (total burden of disease and numbers of active lesions per patient per scan) endpoints. Significant dose-response effects in favour of the higher dosage were evident when the study period was extended for another 2 years. Extension data for a total follow-up period of 7–8 years in the original cohort showed sustained clinical benefits with subcutaneous interferon-β-1a therapy. In a 48-week comparative trial, patients randomised to subcutaneous interferon-β-1a 44μg three times weekly were more likely to remain free of relapses and have significantly more favourable measures of MRI lesion activity at weeks 24 and 48 weeks, and a longer time to first relapse, than those randomised to intramuscular interferon-β-1a 30μg once weekly. In the crossover extension phase (median treatment duration 34 weeks), clinical and MRI outcomes improved in patients who crossed over from treatment with intramuscular interferon-β-1a 30μg once weekly to subcutaneous interferon-β-1a 44μg three times weekly. Tolerability In clinical trials of subcutaneous interferon-β-1a, the most commonly reported adverse events (e.g. injection-site reactions, headache and influenza-like symptoms) were generally mild, manageable and reversible. Mild, asymptomatic and reversible haematological disorders and alterations in liver function tests may occur. A few patients experience serious effects on liver function. Subcutaneous interferon-β-1a 44μg three times weekly was associated with a significantly higher incidence of injection-site disorders and liver function or haematological abnormalities than intramuscular interferon-β-1a 30μg once weekly. No between-group differences were noted regarding the proportions of patients experiencing serious adverse events. Pharmacoeconomic and Other Considerations In an assessment that evaluated the four available RRMS disease-modifying treatments based on the numbers of patients needed to treat to obtain benefit or harm, subcutaneous interferon-β-1a 44μg three times weekly had the best benefit-to-risk values. Based on data from pivotal directly comparative trials, subcutaneous interferon-β-1a 44μg three times weekly had favourable benefit-to-risk values relative to subcutaneous interferon-β-1a 22μg three times weekly and intramuscular interferon-β-1a 30μg once weekly. Based on indirect comparative data from published clinical trials, subcutaneous interferon-β-1a appeared to have favourable efficacy values relative to interferon-β-1b every other day, and interferon-β formulations appeared to have favourable benefit-to-risk ratios relative to placebo and also subcutaneous glatiramer acetate 20gmg once daily. In pharmacoeconomic analyses from a healthcare payer perspective, subcutaneous interferon-β-1a 44μg three times weekly was predicted to be increasingly more cost effective than placebo over the mid-(10 years) and long-(20 years) term with regard to preventing EDSS-months of disability in the UK and France, and cost saving relative to intramuscular interferon-β-1a 30μg once weekly over 48 weeks in the US. |
abstractGer |
Abstract Subcutaneous recombinant interferon-β-1a (Rebif®) 22 or 44μg three times weekly is a valuable option in the first-line treatment in patients with relapsing-remitting multiple sclerosis (RRMS). It has shown benefits on outcome measures related to relapses, progression of disability and magnetic resonance imaging (MRI) in clinical trials. A significant efficacy advantage for subcutaneous interferon-β-1a three times weekly over intramuscular interferon-β-1a 30μg once weekly was shown at 24 and 48 weeks. The most common adverse events are generally mild and clinically manageable. Considering both direct and indirect comparative clinical trial data, an assessment suggests that subcutaneous interferon-β-1a 44μg three times weekly has the best benefit-to-risk values of the available disease-modifying drugs used to treat RRMS. Pharmacological Properties Glycosylated recombinant interferon-β-1a has the same primary structure and biological effects in the body as endogenous human interferon-β. Immunomodulatory activity, the principal pharmacodynamic property of interferon-β-1a, most likely results from interferon-stimulated gene products mediating biological activities. The long-term clinical significance of the development of neutralising antibodies (NABs) to interferon-β-1a is currently unclear; therefore, it is recommended that treatment decisions are based on clinical efficacy and not on the presence of NABs alone. In healthy volunteers, subcutaneous interferon-β-1a has a long apparent elimination half-life and appears to accumulate after repeated doses. Therapeutic Efficacy In a randomised 2-year trial, subcutaneous interferon-β-1a 22 or 44μg three times weekly for 2 years was more effective than placebo as assessed by a number of clinical (e.g. relapse rate per patient, proportion of patients without clinical relapse and changes from baseline in Kurtzke Expanded Disability Status Scale [EDSS] scores) and MRI (total burden of disease and numbers of active lesions per patient per scan) endpoints. Significant dose-response effects in favour of the higher dosage were evident when the study period was extended for another 2 years. Extension data for a total follow-up period of 7–8 years in the original cohort showed sustained clinical benefits with subcutaneous interferon-β-1a therapy. In a 48-week comparative trial, patients randomised to subcutaneous interferon-β-1a 44μg three times weekly were more likely to remain free of relapses and have significantly more favourable measures of MRI lesion activity at weeks 24 and 48 weeks, and a longer time to first relapse, than those randomised to intramuscular interferon-β-1a 30μg once weekly. In the crossover extension phase (median treatment duration 34 weeks), clinical and MRI outcomes improved in patients who crossed over from treatment with intramuscular interferon-β-1a 30μg once weekly to subcutaneous interferon-β-1a 44μg three times weekly. Tolerability In clinical trials of subcutaneous interferon-β-1a, the most commonly reported adverse events (e.g. injection-site reactions, headache and influenza-like symptoms) were generally mild, manageable and reversible. Mild, asymptomatic and reversible haematological disorders and alterations in liver function tests may occur. A few patients experience serious effects on liver function. Subcutaneous interferon-β-1a 44μg three times weekly was associated with a significantly higher incidence of injection-site disorders and liver function or haematological abnormalities than intramuscular interferon-β-1a 30μg once weekly. No between-group differences were noted regarding the proportions of patients experiencing serious adverse events. Pharmacoeconomic and Other Considerations In an assessment that evaluated the four available RRMS disease-modifying treatments based on the numbers of patients needed to treat to obtain benefit or harm, subcutaneous interferon-β-1a 44μg three times weekly had the best benefit-to-risk values. Based on data from pivotal directly comparative trials, subcutaneous interferon-β-1a 44μg three times weekly had favourable benefit-to-risk values relative to subcutaneous interferon-β-1a 22μg three times weekly and intramuscular interferon-β-1a 30μg once weekly. Based on indirect comparative data from published clinical trials, subcutaneous interferon-β-1a appeared to have favourable efficacy values relative to interferon-β-1b every other day, and interferon-β formulations appeared to have favourable benefit-to-risk ratios relative to placebo and also subcutaneous glatiramer acetate 20gmg once daily. In pharmacoeconomic analyses from a healthcare payer perspective, subcutaneous interferon-β-1a 44μg three times weekly was predicted to be increasingly more cost effective than placebo over the mid-(10 years) and long-(20 years) term with regard to preventing EDSS-months of disability in the UK and France, and cost saving relative to intramuscular interferon-β-1a 30μg once weekly over 48 weeks in the US. |
abstract_unstemmed |
Abstract Subcutaneous recombinant interferon-β-1a (Rebif®) 22 or 44μg three times weekly is a valuable option in the first-line treatment in patients with relapsing-remitting multiple sclerosis (RRMS). It has shown benefits on outcome measures related to relapses, progression of disability and magnetic resonance imaging (MRI) in clinical trials. A significant efficacy advantage for subcutaneous interferon-β-1a three times weekly over intramuscular interferon-β-1a 30μg once weekly was shown at 24 and 48 weeks. The most common adverse events are generally mild and clinically manageable. Considering both direct and indirect comparative clinical trial data, an assessment suggests that subcutaneous interferon-β-1a 44μg three times weekly has the best benefit-to-risk values of the available disease-modifying drugs used to treat RRMS. Pharmacological Properties Glycosylated recombinant interferon-β-1a has the same primary structure and biological effects in the body as endogenous human interferon-β. Immunomodulatory activity, the principal pharmacodynamic property of interferon-β-1a, most likely results from interferon-stimulated gene products mediating biological activities. The long-term clinical significance of the development of neutralising antibodies (NABs) to interferon-β-1a is currently unclear; therefore, it is recommended that treatment decisions are based on clinical efficacy and not on the presence of NABs alone. In healthy volunteers, subcutaneous interferon-β-1a has a long apparent elimination half-life and appears to accumulate after repeated doses. Therapeutic Efficacy In a randomised 2-year trial, subcutaneous interferon-β-1a 22 or 44μg three times weekly for 2 years was more effective than placebo as assessed by a number of clinical (e.g. relapse rate per patient, proportion of patients without clinical relapse and changes from baseline in Kurtzke Expanded Disability Status Scale [EDSS] scores) and MRI (total burden of disease and numbers of active lesions per patient per scan) endpoints. Significant dose-response effects in favour of the higher dosage were evident when the study period was extended for another 2 years. Extension data for a total follow-up period of 7–8 years in the original cohort showed sustained clinical benefits with subcutaneous interferon-β-1a therapy. In a 48-week comparative trial, patients randomised to subcutaneous interferon-β-1a 44μg three times weekly were more likely to remain free of relapses and have significantly more favourable measures of MRI lesion activity at weeks 24 and 48 weeks, and a longer time to first relapse, than those randomised to intramuscular interferon-β-1a 30μg once weekly. In the crossover extension phase (median treatment duration 34 weeks), clinical and MRI outcomes improved in patients who crossed over from treatment with intramuscular interferon-β-1a 30μg once weekly to subcutaneous interferon-β-1a 44μg three times weekly. Tolerability In clinical trials of subcutaneous interferon-β-1a, the most commonly reported adverse events (e.g. injection-site reactions, headache and influenza-like symptoms) were generally mild, manageable and reversible. Mild, asymptomatic and reversible haematological disorders and alterations in liver function tests may occur. A few patients experience serious effects on liver function. Subcutaneous interferon-β-1a 44μg three times weekly was associated with a significantly higher incidence of injection-site disorders and liver function or haematological abnormalities than intramuscular interferon-β-1a 30μg once weekly. No between-group differences were noted regarding the proportions of patients experiencing serious adverse events. Pharmacoeconomic and Other Considerations In an assessment that evaluated the four available RRMS disease-modifying treatments based on the numbers of patients needed to treat to obtain benefit or harm, subcutaneous interferon-β-1a 44μg three times weekly had the best benefit-to-risk values. Based on data from pivotal directly comparative trials, subcutaneous interferon-β-1a 44μg three times weekly had favourable benefit-to-risk values relative to subcutaneous interferon-β-1a 22μg three times weekly and intramuscular interferon-β-1a 30μg once weekly. Based on indirect comparative data from published clinical trials, subcutaneous interferon-β-1a appeared to have favourable efficacy values relative to interferon-β-1b every other day, and interferon-β formulations appeared to have favourable benefit-to-risk ratios relative to placebo and also subcutaneous glatiramer acetate 20gmg once daily. In pharmacoeconomic analyses from a healthcare payer perspective, subcutaneous interferon-β-1a 44μg three times weekly was predicted to be increasingly more cost effective than placebo over the mid-(10 years) and long-(20 years) term with regard to preventing EDSS-months of disability in the UK and France, and cost saving relative to intramuscular interferon-β-1a 30μg once weekly over 48 weeks in the US. |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR033196575</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230519190335.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201007s2005 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.2165/00003495-200565090-00010</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR033196575</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)00003495-200565090-00010-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="q">ASE</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">44.40</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">44.38</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Murdoch, David</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Subcutaneous Recombinant Interferon-β-1a (Rebif®)</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2005</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract Subcutaneous recombinant interferon-β-1a (Rebif®) 22 or 44μg three times weekly is a valuable option in the first-line treatment in patients with relapsing-remitting multiple sclerosis (RRMS). It has shown benefits on outcome measures related to relapses, progression of disability and magnetic resonance imaging (MRI) in clinical trials. A significant efficacy advantage for subcutaneous interferon-β-1a three times weekly over intramuscular interferon-β-1a 30μg once weekly was shown at 24 and 48 weeks. The most common adverse events are generally mild and clinically manageable. Considering both direct and indirect comparative clinical trial data, an assessment suggests that subcutaneous interferon-β-1a 44μg three times weekly has the best benefit-to-risk values of the available disease-modifying drugs used to treat RRMS. Pharmacological Properties Glycosylated recombinant interferon-β-1a has the same primary structure and biological effects in the body as endogenous human interferon-β. Immunomodulatory activity, the principal pharmacodynamic property of interferon-β-1a, most likely results from interferon-stimulated gene products mediating biological activities. The long-term clinical significance of the development of neutralising antibodies (NABs) to interferon-β-1a is currently unclear; therefore, it is recommended that treatment decisions are based on clinical efficacy and not on the presence of NABs alone. In healthy volunteers, subcutaneous interferon-β-1a has a long apparent elimination half-life and appears to accumulate after repeated doses. Therapeutic Efficacy In a randomised 2-year trial, subcutaneous interferon-β-1a 22 or 44μg three times weekly for 2 years was more effective than placebo as assessed by a number of clinical (e.g. relapse rate per patient, proportion of patients without clinical relapse and changes from baseline in Kurtzke Expanded Disability Status Scale [EDSS] scores) and MRI (total burden of disease and numbers of active lesions per patient per scan) endpoints. Significant dose-response effects in favour of the higher dosage were evident when the study period was extended for another 2 years. Extension data for a total follow-up period of 7–8 years in the original cohort showed sustained clinical benefits with subcutaneous interferon-β-1a therapy. In a 48-week comparative trial, patients randomised to subcutaneous interferon-β-1a 44μg three times weekly were more likely to remain free of relapses and have significantly more favourable measures of MRI lesion activity at weeks 24 and 48 weeks, and a longer time to first relapse, than those randomised to intramuscular interferon-β-1a 30μg once weekly. In the crossover extension phase (median treatment duration 34 weeks), clinical and MRI outcomes improved in patients who crossed over from treatment with intramuscular interferon-β-1a 30μg once weekly to subcutaneous interferon-β-1a 44μg three times weekly. Tolerability In clinical trials of subcutaneous interferon-β-1a, the most commonly reported adverse events (e.g. injection-site reactions, headache and influenza-like symptoms) were generally mild, manageable and reversible. Mild, asymptomatic and reversible haematological disorders and alterations in liver function tests may occur. A few patients experience serious effects on liver function. Subcutaneous interferon-β-1a 44μg three times weekly was associated with a significantly higher incidence of injection-site disorders and liver function or haematological abnormalities than intramuscular interferon-β-1a 30μg once weekly. No between-group differences were noted regarding the proportions of patients experiencing serious adverse events. Pharmacoeconomic and Other Considerations In an assessment that evaluated the four available RRMS disease-modifying treatments based on the numbers of patients needed to treat to obtain benefit or harm, subcutaneous interferon-β-1a 44μg three times weekly had the best benefit-to-risk values. Based on data from pivotal directly comparative trials, subcutaneous interferon-β-1a 44μg three times weekly had favourable benefit-to-risk values relative to subcutaneous interferon-β-1a 22μg three times weekly and intramuscular interferon-β-1a 30μg once weekly. Based on indirect comparative data from published clinical trials, subcutaneous interferon-β-1a appeared to have favourable efficacy values relative to interferon-β-1b every other day, and interferon-β formulations appeared to have favourable benefit-to-risk ratios relative to placebo and also subcutaneous glatiramer acetate 20gmg once daily. In pharmacoeconomic analyses from a healthcare payer perspective, subcutaneous interferon-β-1a 44μg three times weekly was predicted to be increasingly more cost effective than placebo over the mid-(10 years) and long-(20 years) term with regard to preventing EDSS-months of disability in the UK and France, and cost saving relative to intramuscular interferon-β-1a 30μg once weekly over 48 weeks in the US.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Multiple Sclerosis</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Expand Disability Status Scale</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Expand Disability Status Scale Score</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Annualise Relapse Rate</subfield><subfield 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