Abstract
Background
In clinical studies, treatment with subcutaneous interferon beta-1a (IFNβ-1a) has
been shown to reduce relapse rates and slow the progression of physical disability
in patients with relapsing forms of multiple sclerosis (MS). A formulation of subcutaneous
IFNβ-1a has been developed that is free of fetal bovine serum and human serum albumin.
Objective
To evaluate (a) the impact on quality of life (QoL) and treatment satisfaction of
transitioning from the original formulation of subcutaneous IFNβ-1a to the serum-free
formulation in patients with relapsing forms of MS; and (b) the impact of dose titration
versus non-titration during the transition on tolerability and patterns of analgesic
use. QoL was measured by the Multiple Sclerosis Treatment Concerns Questionnaire Global
Side Effects (GSE) score.
Methods
Patients who had received the original formulation of IFNβ-1a subcutaneously for ≥24
weeks were randomized to receive the serum-free formulation of IFNβ-1a 44 μg subcutaneously three times weekly for 12 weeks, with or without a dose titration
over a 4-week period. After week 12, patients continued to receive serum-free subcutaneous
IFNβ-1a during a safety extension phase until they completed between 84 and 112 weeks
of treatment. The primary endpoint was the percentage change from baseline to week
12 in GSE score in all patients.
Results
A total of 232 patients were randomized (titrated n=113; non-titrated n=119). The mean percent change (improvement) from baseline to week 12 in the GSE score
was 5.0% (p<0.001 for mean change in GSE score from baseline); this change was similar between
titrated and non-titrated patients and met criteria for non-inferiority to the original
formulation. Adverse event (AE) incidence and use of analgesics for the treatment
of flu-like symptoms (FLS) were less common in the titrated group. Few patients (<2%)
discontinued due to AEs during weeks 0 to 12.
Conclusion
Patients with relapsing forms of MS who transitioned from original-formulation subcutaneous
IFNβ-1a to serum-free subcutaneous IFNβ-1a had overall improved QoL scores at 12 weeks
of treatment. Titration during the transition resulted in a lower requirement for
analgesic treatment of FLS and fewer AEs.
Highlights
- Patients with relapsing MS were transitioned to serum-free subcutaneous IFNβ-1a.
- Patients were randomized to treatment either with or without a dose titration.
- Patients had overall improved quality of life scores at 12 weeks.
- Incidence of adverse events was lower in the titrated group.
- Titration reduced the requirement for analgesic treatment of flu-like symptoms.
Abbreviations:
AE (Adverse event), BDI-II (Beck Depression Inventory II), CI (Confidence interval), DMD (Disease-modifying drug), FLS (Flu-like symptoms), FSS (Fatigue Severity Scale), IFNβ-1a (Interferon beta-1a), ISRs (Injection-site reactions), ITT (Intent-to-treat), LOCF (Last observation carried forward), MRI (Magnetic resonance imaging), MSTCQ (Multiple Sclerosis Treatment Concerns Questionnaire), QoL (Quality of life), sc (Subcutaneous(ly)), SD (Standard deviation), SF-36 (Short Form-36), SF-MPQ (Short-Form McGill Pain Questionnaire), tiw (Three times weekly)Keywords
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Article info
Publication history
Accepted:
July 17,
2012
Received in revised form:
June 1,
2012
Received:
December 21,
2011
Footnotes
☆ClinicalTrials.gov identifier NCT00472797.
Identification
Copyright
© 2012 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
