Epub: Singer et al. Comparative injection-site pain and tolerability of subcutaneous serum-free formulation of interferonbeta-1a versus subcutaneous interferonbeta-1b: results of the randomized, multicenter, Phase IIIb REFORMS study. BMC Neurol. 2012 Dec 6;12(1):154.
BACKGROUND: In RRMSer, subcutaneous (sc) interferon (IFN)beta-1a and IFNbeta-1b have been shown to reduce relapse rates. A formulation of IFNbeta-1a has been produced without fetal bovine serum and without human serum albumin as an excipient (not currently approved for use in the US).
OBJECTIVES: To evaluate tolerability, injection-site redness, subject-reported satisfaction with therapy, and clinical safety and efficacy of the serum-free formulation of IFNbeta-1a versus IFNbeta-1b in IFNbeta-treatment-naive patients with RRMS. The objectives of the extension phase were to evaluate long-term safety and tolerability of IFNbeta-1a.
METHODS: This randomized, parallel-group, open-label study was conducted at 27 clinical sites in the US. Eligible patients aged 18-60 years were randomized to receive either IFNbeta-1a, titrated to 44 mug sc three times weekly (tiw) (n = 65), or IFNbeta-1b, titrated to 250 mug sc every other day (n = 64) over 12 weeks. Following this, all patients received IFNbeta-1a 44 mug tiw for 82-112 weeks. Primary endpoint was mean change in MSer-reported pain, as assessed by visual analog scale (VAS) diary pain score (from 0 mm [no pain] to 100 mm [worst possible pain]) at the injection site, from pre-injection to 30 min post-injection over the first 21 full-dose injections. Secondary assessments included proportion of patients pain-free as recorded by VAS diary and the Short-Form McGill Pain questionnaire VAS.
RESULTS: A total of 129 MSers were included in the intent-to-treat analysis. Mean (standard deviation) change in VAS diary pain score was not significantly different between groups, although numerically lower with IFNbeta-1a versus IFNbeta-1b from pre-injection to immediately post-injection (1.46 [2.93] vs. 4.63 [10.57] mm), 10 min post-injection (0.70 [1.89] vs. 1.89 [5.75] mm), and 30 min post-injection (0.67 [2.32] vs. 1.14 [4.94] mm). Proportion of MSers pain-free at all time periods post-injection was also not significantly different between groups. Adverse events were consistent with the known safety profiles of these treatments.
CONCLUSIONS: In IFNbeta-treatment-naive RRMSers, both the serum-free formulation of IFNbeta-1a and IFNbeta-1b treatments were generally accompanied by low-level injection-site pain and were well tolerated.Trial registration: ClinicalTrials.gov NCT00428584.
|A typical interferon-beta injection site reaction!|
“Surprised that Rebif New Formulation or RNF is not licensed in the US. RNF has improved local tolerability of IFNbeta-1a subcutaneously substantially. It is also slightly less immunogenic than the older formulation, hence lower NABs. The later may make it more effective and partially explain why MSers on it in the Alemtuzumab vs Rebif or CARE-MS 1&2 trials did better than expected.”
CoI: multiple, in particular I was the PI on the RNF programme in Europe.