Eight-year immunogenicity and safety of interferon beta-1a-Avonex® treatment in patients with multiple sclerosis

Robert M. Herndon, Richard A. Rudick, Frederick E. Munschauer, Michele Mass, Andres M. Salazar, Michael E. Coats, Robert Labutta, John R. Richert, Stanley L. Cohan, Claude Genain, Donald Goodkin, Martin Toal, Katherine Riester

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

An open-label extension study of the phase III trial of intramuscular interferon beta-1a (IFNβ-1a-Avonex) was conducted to evaluate the immunogenicity and safety of IFNβ-1a-Avonex over six years in patients with relapsing multiple sclerosis (MS). Patients who participated in the pivotal phase III study were offered enrolment, entry was also open to patients who had not participated. All patients received IFNβ-1a-Avonex 30 μg intramuscularly once weekly for six years, for a treatment duration of up to eight years in patients who received IFNβ-1a-Avonex in the phase III trial. Serum levels of IFNβ antibodies were measured every six months using a screening enzyme-linked immunosorbent assay (ELISA) followed by an antiviral cytopathic effect assay to detect neutralizing antibodies (NAbs) in serum samples positive on ELISA. The incidence of adverse events and laboratory test results assessed safety. Of 382 total patients, 218 had participated in the phase III study (103 placebo, 115 IFNβ-1a-Avonex) and 164 had not participated; 24 of the 164 were IFNβ-naïve. At baseline, 281 patients were negative for IFNβ antibodies (NAb-). NAbs (titre≥20) developed at any time over six years in 5% of these patients. Of 140 patients who had been on IFNβ-1b-Betaseron, 49 were positive for NAbs (NAb+) at baseline; 11 of 115 who had been on IFNβ-1a-Avonex were NAb + at baseline. Thirty-nine of 49 patients who had been on Betaseron and were NAb + had titres 1000 seroconverted to NAb -, whether initially treated with IFNβ-1a-Avonex or -Betaseron. Adverse events were similar to those observed in the pivotal phase III trial. Results from this trial indicated that IFNβ-1a-Avonex was associated with a low incidence of NAbs and was well tolerated for up to eight years. Further, the results indicate that persistence of NAbs is dependent on titre and IFNβ product.

Original languageEnglish (US)
Pages (from-to)409-419
Number of pages11
JournalMultiple Sclerosis
Volume11
Issue number4
DOIs
StatePublished - Aug 2005

Fingerprint

Multiple Sclerosis
Safety
Neutralizing Antibodies
Therapeutics
Enzyme-Linked Immunosorbent Assay
Interferon beta-1a
Antibodies
Incidence
Serum
Antiviral Agents
Placebos

Keywords

  • Avonex
  • Extension study
  • Interferon beta-1a
  • Long-term safety
  • Multiple sclerosis
  • Neutralizing antibodies

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Herndon, R. M., Rudick, R. A., Munschauer, F. E., Mass, M., Salazar, A. M., Coats, M. E., ... Riester, K. (2005). Eight-year immunogenicity and safety of interferon beta-1a-Avonex® treatment in patients with multiple sclerosis. Multiple Sclerosis, 11(4), 409-419. https://doi.org/10.1191/1352458505ms1209oa

Eight-year immunogenicity and safety of interferon beta-1a-Avonex® treatment in patients with multiple sclerosis. / Herndon, Robert M.; Rudick, Richard A.; Munschauer, Frederick E.; Mass, Michele; Salazar, Andres M.; Coats, Michael E.; Labutta, Robert; Richert, John R.; Cohan, Stanley L.; Genain, Claude; Goodkin, Donald; Toal, Martin; Riester, Katherine.

In: Multiple Sclerosis, Vol. 11, No. 4, 08.2005, p. 409-419.

Research output: Contribution to journalArticle

Herndon, RM, Rudick, RA, Munschauer, FE, Mass, M, Salazar, AM, Coats, ME, Labutta, R, Richert, JR, Cohan, SL, Genain, C, Goodkin, D, Toal, M & Riester, K 2005, 'Eight-year immunogenicity and safety of interferon beta-1a-Avonex® treatment in patients with multiple sclerosis', Multiple Sclerosis, vol. 11, no. 4, pp. 409-419. https://doi.org/10.1191/1352458505ms1209oa
Herndon, Robert M. ; Rudick, Richard A. ; Munschauer, Frederick E. ; Mass, Michele ; Salazar, Andres M. ; Coats, Michael E. ; Labutta, Robert ; Richert, John R. ; Cohan, Stanley L. ; Genain, Claude ; Goodkin, Donald ; Toal, Martin ; Riester, Katherine. / Eight-year immunogenicity and safety of interferon beta-1a-Avonex® treatment in patients with multiple sclerosis. In: Multiple Sclerosis. 2005 ; Vol. 11, No. 4. pp. 409-419.
@article{d3b8c5caa0ad41829babd36161a5d1fd,
title = "Eight-year immunogenicity and safety of interferon beta-1a-Avonex{\circledR} treatment in patients with multiple sclerosis",
abstract = "An open-label extension study of the phase III trial of intramuscular interferon beta-1a (IFNβ-1a-Avonex) was conducted to evaluate the immunogenicity and safety of IFNβ-1a-Avonex over six years in patients with relapsing multiple sclerosis (MS). Patients who participated in the pivotal phase III study were offered enrolment, entry was also open to patients who had not participated. All patients received IFNβ-1a-Avonex 30 μg intramuscularly once weekly for six years, for a treatment duration of up to eight years in patients who received IFNβ-1a-Avonex in the phase III trial. Serum levels of IFNβ antibodies were measured every six months using a screening enzyme-linked immunosorbent assay (ELISA) followed by an antiviral cytopathic effect assay to detect neutralizing antibodies (NAbs) in serum samples positive on ELISA. The incidence of adverse events and laboratory test results assessed safety. Of 382 total patients, 218 had participated in the phase III study (103 placebo, 115 IFNβ-1a-Avonex) and 164 had not participated; 24 of the 164 were IFNβ-na{\"i}ve. At baseline, 281 patients were negative for IFNβ antibodies (NAb-). NAbs (titre≥20) developed at any time over six years in 5{\%} of these patients. Of 140 patients who had been on IFNβ-1b-Betaseron, 49 were positive for NAbs (NAb+) at baseline; 11 of 115 who had been on IFNβ-1a-Avonex were NAb + at baseline. Thirty-nine of 49 patients who had been on Betaseron and were NAb + had titres 1000 seroconverted to NAb -, whether initially treated with IFNβ-1a-Avonex or -Betaseron. Adverse events were similar to those observed in the pivotal phase III trial. Results from this trial indicated that IFNβ-1a-Avonex was associated with a low incidence of NAbs and was well tolerated for up to eight years. Further, the results indicate that persistence of NAbs is dependent on titre and IFNβ product.",
keywords = "Avonex, Extension study, Interferon beta-1a, Long-term safety, Multiple sclerosis, Neutralizing antibodies",
author = "Herndon, {Robert M.} and Rudick, {Richard A.} and Munschauer, {Frederick E.} and Michele Mass and Salazar, {Andres M.} and Coats, {Michael E.} and Robert Labutta and Richert, {John R.} and Cohan, {Stanley L.} and Claude Genain and Donald Goodkin and Martin Toal and Katherine Riester",
year = "2005",
month = "8",
doi = "10.1191/1352458505ms1209oa",
language = "English (US)",
volume = "11",
pages = "409--419",
journal = "Multiple Sclerosis",
issn = "1352-4585",
publisher = "SAGE Publications Ltd",
number = "4",

}

TY - JOUR

T1 - Eight-year immunogenicity and safety of interferon beta-1a-Avonex® treatment in patients with multiple sclerosis

AU - Herndon, Robert M.

AU - Rudick, Richard A.

AU - Munschauer, Frederick E.

AU - Mass, Michele

AU - Salazar, Andres M.

AU - Coats, Michael E.

AU - Labutta, Robert

AU - Richert, John R.

AU - Cohan, Stanley L.

AU - Genain, Claude

AU - Goodkin, Donald

AU - Toal, Martin

AU - Riester, Katherine

PY - 2005/8

Y1 - 2005/8

N2 - An open-label extension study of the phase III trial of intramuscular interferon beta-1a (IFNβ-1a-Avonex) was conducted to evaluate the immunogenicity and safety of IFNβ-1a-Avonex over six years in patients with relapsing multiple sclerosis (MS). Patients who participated in the pivotal phase III study were offered enrolment, entry was also open to patients who had not participated. All patients received IFNβ-1a-Avonex 30 μg intramuscularly once weekly for six years, for a treatment duration of up to eight years in patients who received IFNβ-1a-Avonex in the phase III trial. Serum levels of IFNβ antibodies were measured every six months using a screening enzyme-linked immunosorbent assay (ELISA) followed by an antiviral cytopathic effect assay to detect neutralizing antibodies (NAbs) in serum samples positive on ELISA. The incidence of adverse events and laboratory test results assessed safety. Of 382 total patients, 218 had participated in the phase III study (103 placebo, 115 IFNβ-1a-Avonex) and 164 had not participated; 24 of the 164 were IFNβ-naïve. At baseline, 281 patients were negative for IFNβ antibodies (NAb-). NAbs (titre≥20) developed at any time over six years in 5% of these patients. Of 140 patients who had been on IFNβ-1b-Betaseron, 49 were positive for NAbs (NAb+) at baseline; 11 of 115 who had been on IFNβ-1a-Avonex were NAb + at baseline. Thirty-nine of 49 patients who had been on Betaseron and were NAb + had titres 1000 seroconverted to NAb -, whether initially treated with IFNβ-1a-Avonex or -Betaseron. Adverse events were similar to those observed in the pivotal phase III trial. Results from this trial indicated that IFNβ-1a-Avonex was associated with a low incidence of NAbs and was well tolerated for up to eight years. Further, the results indicate that persistence of NAbs is dependent on titre and IFNβ product.

AB - An open-label extension study of the phase III trial of intramuscular interferon beta-1a (IFNβ-1a-Avonex) was conducted to evaluate the immunogenicity and safety of IFNβ-1a-Avonex over six years in patients with relapsing multiple sclerosis (MS). Patients who participated in the pivotal phase III study were offered enrolment, entry was also open to patients who had not participated. All patients received IFNβ-1a-Avonex 30 μg intramuscularly once weekly for six years, for a treatment duration of up to eight years in patients who received IFNβ-1a-Avonex in the phase III trial. Serum levels of IFNβ antibodies were measured every six months using a screening enzyme-linked immunosorbent assay (ELISA) followed by an antiviral cytopathic effect assay to detect neutralizing antibodies (NAbs) in serum samples positive on ELISA. The incidence of adverse events and laboratory test results assessed safety. Of 382 total patients, 218 had participated in the phase III study (103 placebo, 115 IFNβ-1a-Avonex) and 164 had not participated; 24 of the 164 were IFNβ-naïve. At baseline, 281 patients were negative for IFNβ antibodies (NAb-). NAbs (titre≥20) developed at any time over six years in 5% of these patients. Of 140 patients who had been on IFNβ-1b-Betaseron, 49 were positive for NAbs (NAb+) at baseline; 11 of 115 who had been on IFNβ-1a-Avonex were NAb + at baseline. Thirty-nine of 49 patients who had been on Betaseron and were NAb + had titres 1000 seroconverted to NAb -, whether initially treated with IFNβ-1a-Avonex or -Betaseron. Adverse events were similar to those observed in the pivotal phase III trial. Results from this trial indicated that IFNβ-1a-Avonex was associated with a low incidence of NAbs and was well tolerated for up to eight years. Further, the results indicate that persistence of NAbs is dependent on titre and IFNβ product.

KW - Avonex

KW - Extension study

KW - Interferon beta-1a

KW - Long-term safety

KW - Multiple sclerosis

KW - Neutralizing antibodies

UR - http://www.scopus.com/inward/record.url?scp=22144481998&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=22144481998&partnerID=8YFLogxK

U2 - 10.1191/1352458505ms1209oa

DO - 10.1191/1352458505ms1209oa

M3 - Article

C2 - 16042223

AN - SCOPUS:22144481998

VL - 11

SP - 409

EP - 419

JO - Multiple Sclerosis

JF - Multiple Sclerosis

SN - 1352-4585

IS - 4

ER -