Evaluation of Peginterferon Beta-1a Tolerability Profile: Gaining Consensus Using the Delphi Technique

Background: ADVANCE was a 2-year, double-blind, randomized, placebo-controlled study to evaluate the efficacy and safety of subcutaneous peginterferon beta-1a 125 mcg given every 2 or 4 weeks in patients with multiple sclerosis (MS).

Objectives:  To understand and characterize peginterferon beta-1a treatment-related flu-like symptoms (FLS) and injection site reactions (ISR) in patients with MS based on experiences in the ADVANCE study.

Methods:  ADVANCE investigators with ≥2 enrolled patients in the United States and ≥10 elsewhere were offered the opportunity to participate in a consensus-generating process based on the Delphi methodology. The development of two questionnaires was overseen by an independent steering committee (N=4). Questionnaire 1 (150 questions) was designed to better understand frequency, impact and management of FLS and ISR in MS patients treated with peginterferon beta-1a. After completion of the first questionnaire, questionnaire 2 (15 questions) was designed to clarify best practices and generate consensus recommendations for the management of these side effects.

Results:  Of the 84 investigators who met inclusion criteria, 50 agreed to participate; 30 completed questionnaire 1 and 29 completed questionnaire 2. The 30 participating investigators represented 374 patients from ADVANCE. 93% (28/30) of responders reported FLS and 97% (29/30) reported ISR in ≥1 of their patients. FLS were reported in a typical patient after every dose or most doses by 71% (20/28) of responders during 0-3 months of therapy vs 39% (11/28) of responders after >3 months of therapy. 90% (26/29) of responders agreed that flu-like symptoms generally last ≤24 hours following peginterferon beta-1a administration. ISR were reported in a typical patient after every dose or most doses by 69% (20/29) of responders during 0-3 months of therapy vs 45% (13/29) after >3 months. 97% of responders agreed that for most patients these side effects have only mild to moderate (FLS) or minimal (ISR) impact on activities of daily living during the first 3 months of treatment

Conclusions:  Survey responders indicated that the frequency and duration of FLS and ISR generally reduced after 3 months’ treatment and had minimal to moderate impact on activities of daily living. Overall, these results reflect substantive experience with peginterferon beta-1a and may have an impact on patient adherence to therapy and ultimately influence patient outcomes.