PMID- 22046309 OWN - NLM STAT- MEDLINE DCOM- 20120326 LR - 20211020 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 6 IP - 10 DP - 2011 TI - Adverse events of interferon beta-1a: a prospective multi-centre international ICH-GCP-based CRO-supported external validation study in daily practice. PG - e26568 LID - 10.1371/journal.pone.0026568 [doi] LID - e26568 AB - BACKGROUND: Due to methodological shortcomings the available post-registration data on the adverse events (AEs) occurring in interferon beta-1a (INFb-1a)-treated patients fail to adequately validate phase III data and only partially inform on safety in daily practice. We assessed AEs in relapsing remitting multiple sclerosis (RRMS) patients treated with intramuscular (IM) INFb-1a in daily practice using data quality assurance measures similar to those in phase III trials. METHODS: A prospective, International Conference on Harmonization (ICH) - Good Clinical Practice (GCP)-based, clinical research organization (CRO)-supported study in 36 practices in the Netherlands, Belgium, the United Kingdom and Luxembourg. During 24 months after start of IM INFb-1a treatment 275 RRMS patients were assessed for AEs' severity (mild, moderate, severe) and relationship to treatment (not, unlikely, likely, definite). Data were compared with those reported in the pivotal phase III trial. FINDINGS: 75.3% of the patients experienced one or more AEs that were likely or definitely related to INFb-1a. Of all AEs 40.5% were likely or definitely treatment-related; 68.5% of these were mild, and 3% severe. 6.6% of the patients discontinued treatment because of an AE. Compared to the pivotal phase III trial, we found statistically significantly lower incidences for most of the common AEs: headache, muscle ache, fatigue, fever, chills, nausea. One patient died following two cerebral vascular events in study month 22, both AEs were assessed as not related to INFb-1a. CONCLUSION: Three out of four RRMS patients treated with IM INFb-1a in daily practice experience treatment-related AEs, most of these being mild. Our data externally validate the favorable phase III safety profile of IM INFb-1a and suggest that the real-life incidence of treatment-related AEs is less than reported in the pivotal phase III trial. Larger studies are needed to detect rare, potentially hazardous AEs of IM INFb-1a. FAU - Jongen, Peter Joseph AU - Jongen PJ AD - MS4 Research Institute, Nijmegen, The Netherlands. FAU - Sindic, Christian AU - Sindic C FAU - Sanders, Evert AU - Sanders E FAU - Hawkins, Stanley AU - Hawkins S FAU - Linssen, Wim AU - Linssen W FAU - van Munster, Erik AU - van Munster E FAU - Frequin, Stephan AU - Frequin S FAU - Borm, George AU - Borm G CN - Functional Composite and Quality of Life in Avonex-treated Relapsing Multiple Sclerosis Patients Study Group LA - eng PT - Clinical Trial PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't PT - Validation Study DEP - 20111025 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Adjuvants, Immunologic) RN - 77238-31-4 (Interferon-beta) RN - XRO4566Q4R (Interferon beta-1a) SB - IM CIN - Neurology. 2017 Nov 7;89(19):2022-2023. PMID: 29109136 MH - Adjuvants, Immunologic MH - Adult MH - Drug-Related Side Effects and Adverse Reactions MH - Europe MH - Humans MH - Incidence MH - Injections, Intramuscular MH - Interferon beta-1a MH - Interferon-beta/administration & dosage/*adverse effects MH - Multiple Sclerosis, Relapsing-Remitting/complications/*drug therapy MH - Treatment Outcome PMC - PMC3201962 COIS- Competing Interests: The authors have the following competing interests. This study was funded by Biogen-Idec. Dr. Jongen has received honoraria from Sanofi-Aventis, Teva, Merck-Serono, Novartis, Bayer-Schering, Biogen-Idec and Allergan for activities as speaker, advisory committee member, research support, or travel grants for conferences. Dr. Jongen had full access to all of the data in this study and takes complete responsibility for the integrity of the data and the accuracy of the data analysis. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials, as detailed online in the guide for authors. FIR - Driessen IR - Driessen FIR - Baard IR - Baard FIR - Frequin IR - Frequin FIR - Hintzen IR - Hintzen FIR - Hupperts IR - Hupperts FIR - Jongen IR - Jongen FIR - Linssen IR - Linssen FIR - Beyer, Mispelblom IR - Beyer M FIR - Moll IR - Moll FIR - van Munster IR - van Munster FIR - Den Bosch IR - Den Bosch FIR - Pratzsky IR - Pratzsky FIR - Sanders IR - Sanders FIR - Smits IR - Smits FIR - van Walbeek IR - van Walbeek FIR - Willems IR - Willems FIR - Witjes IR - Witjes FIR - van Zuilen IR - van Zuilen FIR - Bartholome IR - Bartholome FIR - Braeckveldt IR - Braeckveldt FIR - Van der Motte IR - Van der Motte FIR - Debruyne IR - Debruyne FIR - Decoo IR - Decoo FIR - Dedeyn IR - Dedeyn FIR - Engelborghs IR - Engelborghs FIR - Dupuis IR - Dupuis FIR - Jacquerye IR - Jacquerye FIR - Van de Gaer IR - Van de Gaer FIR - Guillaume IR - Guillaume FIR - Reznik IR - Reznik FIR - Harmant IR - Harmant FIR - D'Hooghe IR - D'Hooghe FIR - Klippel IR - Klippel FIR - Willems IR - Willems FIR - van Landegem IR - van Landegem FIR - Strauven IR - Strauven FIR - de Noordhout, Maertens IR - de Noordhout M FIR - Delavaux IR - Delavaux FIR - Nagels IR - Nagels FIR - Seeldrayers IR - Seeldrayers FIR - Vervonck IR - Vervonck FIR - Sindic IR - Sindic FIR - Goffette IR - Goffette FIR - El-Memar IR - El-Memar FIR - Hawkins IR - Hawkins FIR - de Diego IR - de Diego EDAT- 2011/11/03 06:00 MHDA- 2012/03/27 06:00 PMCR- 2011/10/25 CRDT- 2011/11/03 06:00 PHST- 2011/05/23 00:00 [received] PHST- 2011/09/29 00:00 [accepted] PHST- 2011/11/03 06:00 [entrez] PHST- 2011/11/03 06:00 [pubmed] PHST- 2012/03/27 06:00 [medline] PHST- 2011/10/25 00:00 [pmc-release] AID - PONE-D-11-09146 [pii] AID - 10.1371/journal.pone.0026568 [doi] PST - ppublish SO - PLoS One. 2011;6(10):e26568. doi: 10.1371/journal.pone.0026568. Epub 2011 Oct 25.