Low Risk of New Flu-like Symptoms in Patients Transitioning from Non-Pegylated to Pegylated Interferon Beta-1a and Mitigation with Scheduled Naproxen
Objectives: To evaluate the incidence and severity of FLS in patients with RMS transitioning from non-pegylated IFN treatment to peginterferon beta-1a and the impact of prophylactic naproxen treatment on FLS.
Methods: ALLOW was a Phase 3b open-label, randomized study in patients with RMS. Eligible patients had received a stable regimen of a non-pegylated IFN for ≥4 months immediately prior to screening; this was continued throughout a 4-week run-in period for evaluation of FLS (influenza-like illness, myalgia, pyrexia and/or asthenia) on that regimen, using the 12-point FLS-score (FLS-S). All patients then switched to peginterferon beta-1a, titrated to 125 mcg every 2 weeks, and were randomized (1:1) to continue their current FLS management or to commence a regimen of naproxen 500 mg twice daily, starting 24 hours before each dose of peginterferon beta-1a and continuing for 48 hours after, for the first 8 weeks of treatment. Patients could then switch to their preferred FLS-management regimen and were followed for a total of 48 weeks. New or worsening FLS was defined as an increase of ≥2.0 points in FLS-S over the run-in phase.
Results: In total, 201 patients were enrolled and received treatment. Interim analysis of the primary endpoint indicates that the majority of patients (89.6% [172/192]) did not experience new/worsening FLS during the first 8 weeks following transition to peginterferon beta-1a. The proportion of patients with new/worsening FLS was numerically lower on naproxen than continued existing FLS regimen (7.4% versus 13.3%; p=0.1871). Subgroup analysis suggested that patients transitioning from intramuscular IFN beta-1a (Avonex®) had a slightly higher incidence of new/worsening FLS (12.6%) compared with those transitioning from other IFN treatments (8.2%). FLS were predominantly mild or moderate. Only 2.5% [5/201] of dosed patients withdrew due to FLS. The most common AE overall was injection-site erythema (29.4%). Final analysis is ongoing; results will be presented at the meeting.
Conclusions: Risk of additional FLS when transitioning from non-pegylated IFN to peginterferon beta-1a is low; scheduled naproxen may be a beneficial prophylactic strategy.