Application of the Delphi Technique for Evaluation of the Tolerability Profile of Pegylated Interferon Beta-1a

Background: The tolerability profile of multiple sclerosis (MS) treatments can have an impact on patient adherence and affect treatment outcome.  Common adverse events (AE) with investigational peginterferon beta-1a (PEG-IFN) are flu-like symptoms (FLS) and injection site reactions (ISR).

Objectives: Understand PEG-IFN related FLS and ISR and identify effective management strategies for these AEs.

Methods: ADVANCE is a 2-year, randomized, double-blind, placebo-controlled (year 1) phase III study evaluating the efficacy and safety of subcutaneous PEG-IFN 125 mcg every 2 (Q2W) or 4 (Q4W) weeks. Investigators with a minimum number of enrolled patients in ADVANCE were offered the opportunity to participate in a consensus-generating exercise to identify best practices for management of FLS and ISR using widely-accepted Delphi methodology.  A steering committee (n=4) was convened to oversee development of a questionnaire designed to better understand how investigators approached the management of FLS and ISR. A second questionnaire will be used to clarify best practices and generate consensus recommendations.

Results: Mean number (SD) of patients enrolled at these sites for Q2W and Q4W dosing was 4.5 (4.2) and 4.3 (4.2), respectively. Based on data from year 1 of ADVANCE, median time on PEG-IFN was 337 days for both Q2W and Q4W. The percentage of patients reporting FLS and ISR over 1 year for Q2W was 38.6% (59/153) and 64.1% (98/153), respectively and 44.7% (68/152) and 69.1% (105/152) for Q4W, respectively. In Year 1, 74.0% (94/127) of PEG-IFN patients experiencing FLS utilized symptomatic therapy for FLS; 6.4% (13/203) of PEG-IFN patients experiencing ISR utilized symptomatic therapy for ISR.  At these sites 2.0% (3/153) and 0.7% (1/153) of Q2W patients discontinued PEG-IFN owing to FLS and ISR, respectively, and 2.0% (3/152) and 1.3% (2/152) of Q4W patients discontinuing owing to FLS and ISR, respectively. Of the 83 eligible investigators, 36 from 13 countries agreed to participate. Results from both questionnaires will be reported.

Conclusions: Data regarding patients enrolled by investigators agreeing to participate in the Delphi project is representative of  the overall ADVANCE population. The recommendations of the panel based on the results of the Delphi process will reflect substantive experience with PEG-IFN, may have an impact on patient adherence to therapy and ultimately influence patient outcomes.

Study supported by Biogen Idec, Inc.