Peginterferon Beta-1a and Management Strategies for Flu-like Symptoms and Injection Site Reactions: Obtaining Recommendations Using the Delphi Technique

Background: Side effects, including flu-like symptoms (FLS) and injection site reactions (ISR), have been reported with interferon treatment. These side effects can impact patient adherence and thereby affect treatment outcome in patients with multiple sclerosis (MS).

Objectives:  To obtain consensus on the characteristics and management of FLS and ISR associated with peginterferon beta-1a treatment using Delphi methodology.

Methods:  ADVANCE was a double-blind, randomized, placebo-controlled study of subcutaneous peginterferon beta-1a 125 mcg given every 2 or 4 weeks in MS patients. Investigators of the ADVANCE study with a predefined number of enrolled patients (≥2 in US and ≥10 elsewhere) were offered the opportunity to participate in the Delphi process. An independent steering committee (n=4) oversaw the development of two questionnaires designed to better understand frequency, duration and impact of FLS and ISR and to generate consensus recommendations for management of these side effects.  An average rating (AR) of ≥2.7 based on Likert scale (1=strongly disagree, 2=disagree, 3=agree, 4=strongly agree) was defined as the response level for consensus.

Results: 29 investigators who had completed questionnaire 1 also completed questionnaire 2. Responders agreed that, for most patients, FLS typically last ≤24 hours (AR: 3.17) and have only mild to moderate impact on activities of daily living (AR: 3.34). Responders recommended that patients who begin treatment should be advised to take acetaminophen/NSAID (AR: 3.31) on a scheduled basis and change the timing of peginterferon beta-1a injection (AR: 3.28) to manage FLS. When asked about ISR associated with peginterferon beta-1a administration, responders agreed that, for most patients, ISR have only minimal impact on activities of daily living (AR: 3.48). Responders recommended that patients should be advised to rotate injection site (AR: 3.83), cool the injection site after injection (AR: 3.10) and administer peginterferon beta-1a at room temperature (AR: 3.41) to manage ISR. All responders agreed that patients beginning treatment should be educated on the characteristics and management of FLS and ISR.

Conclusions:  The two-part Delphi questionnaire was successful in obtaining consensus on the characteristics and management of FLS and ISR that can be associated with peginterferon beta-1a administration. Education should be provided to all patients before they begin treatment.