Effect of Phenylephrine on Injection Site Reactions in Multiple Sclerosis Patients Treated with Plegridy (peginterferon beta-1a)

Background: Injection site reactions (ISRs), including pain, swelling, and redness at the injection site, are common side effects of the interferon medications including peginterferon beta-1a (Plegridy), a subcutaneous disease-modifying therapy for relapsing Multiple Sclerosis (RMS). There is currently no standard protocol for managing ISRs.

Objectives: The primary endpoint of our study was to assess the effect of phenylephrine cream compared to no cream in reducing ISRs via the Site Reaction Diary (SRD). The secondary endpoint was to assess the effect of phenylephrine cream compared to no cream on the degree of burden of ISRs via the Multiple Sclerosis Treatment Concerns Questionnaire (MSTCQ).  

Methods: 32 patients with RMS were enrolled and randomized to one of two groups: 1) Phenylephrine group and 2) Non-treatment group. The Phenylephrine group applied the cream 2 hours post-Plegridy injection. The non-treatment group did not apply phenylephrine cream after the first full dose of Plegridy regardless of ISR development or timing. Patients were asked to record, on a portable device, the injection location, duration, and pain.

Results: Change scores in average injection site redness were used to calculate improvement in redness from baseline to post-cream. The SRD included a 0-4 Likert scale with 0 indicating no redness and 4 indicating completely unacceptable redness. While the reported redness for the Phenylephrine group decreased after cream application (M=-0.50, SD=0.71) compared to no change in the non-treatment group (M=0.00, SD=0.00), this group difference was not statistically significant (p=0.34). Change in MSTCQ scores was the secondary endpoint, with higher scores indicating a more bothersome ISR measured by ISR duration, frequency, and interference in daily activities. MSTCQ scores for the specific question, “How bothersome is the site reaction?” from Baseline to Day 29 decreased in the Phenylephrine group (M=-0.33, SD=0.61) and increased in the non-treatment group (M=0.38, SD=0.75). However, this change was not significant (p=0.24). Of note, the study was not powered to detect statistical significance, so the lack of significance should not be interpreted as lack of effectiveness.

Conclusions: Topical treatment with phenylephrine for the management of ISRs showed trends towards efficacy in this pilot study. More studies with larger sample sizes are needed to verify the safety and efficacy of this measure.