From the Ectrims site:
http://www.akm.ch/ectrims2006/
Incidence and effects of neutralising antibodies in patients with multiple sclerosis treated with Avonex® or Rebif® in PROOF
T.J. Murray, A. Minagar for the PROOF Study Investigators
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Sustained benefits from interferon beta (IFNB) products used to treat relapsing multiple sclerosis (RMS) require adherence (affected by tolerability and convenience) and clinical efficacy, which can be reduced when neutralizing antibodies (NAbs) are present.
PROOF, a phase IV, retrospective and prospective, open-label study was conducted to evaluate the efficacy and tolerability of intramuscular (IM) IFNB-1a 30 mcg once weekly compared with subcutaneous (SC) IFNB-1a 44 mcg three times weekly in RMS patients.
The goal of this pre-specified endpoint was to determine the incidence of NAb formation and their effects on clinical and MRI endpoints. Prior to enrollment, subjects received IM or SC IFNB-1a for 12 to 24 months without switch or interruption and had an EDSS of 0.0-5.5.
NAbs were evaluated at study enrollment and month 6. 123 patients (n=59, IM; n=64, SC) were evaluated for NAbs. At study enrollment, 0% and 21% of patients treated with IM IFNB-1a and SC IFNB-1a were NAb+. Persistent NAbs (positive at month 0 and 6) were present in 19% of patients, all treated with SC IFNB-1a.
Compared with NAb- patients, NAb+ patients had significantly more new or enlarging T2 lesions (36.4% vs 59.3% with 0 lesions; p=0.003), total number of Gd+ lesions (54.5% vs 75.6% with 0 lesions; p=0.04), and trended towards a higher Gd+ lesion volume (0.31 vs 0.05, p=0.02 at month 0; 0.21 vs 0.04, p = 0.06 at month 6).
Disease progression (EDSS) from study enrollment to month 6 increased significantly more in NAb+ patients compared with NAb- patients (p=0.02).
Compared with patients treated with IM IFNB-1a, patients treated with SC IFNB-1a were more likely to have persistent NAb+ titers. NAb+ patients had significantly more signs of disease as shown by new or enlarging T2 lesions, total Gd+ lesions, and increased EDSS after 18 to 30 months on therapy.