Combination of IFNβ‐1a (Avonex®) and mycophenolate mofetil (Cellcept®) in multiple sclerosis

Abstract

To determine the safety of a combination of mycophenolate mofetil (Cellcept, MMF) and IFNbeta-1a (Avonex) in relapsing-remitting multiple sclerosis (RRMS) and to evaluate the effects of the combination on clinical and magnetic resonance imaging (MRI) measures of disease activity. Secondary objectives were clinical and MRI data. An open-label, single-centre study including 30 RRMS patients was performed. Inclusion criteria were patients expanded disability status scale (EDSS) score <6.0, treated by Avonex for at least 6 months, with at least two relapses during the previous 2 years and at least one during the previous 6 months. MMF at a progressive dose of 2 g per day orally was added to Avonex for a duration of 6 months. MRI data were obtained at baseline and at the end of the study. The pre-study annual relapse rate was 2.0 +/- 0.7 and the EDSS score at baseline was 2.9 +/- 1.3. Eleven patients had gadolinium (Gd)-enhanced lesions at baseline for a total number of 35 lesions. Two patients interrupted the combination, one after the first dose for personal reasons unrelated to the study and the other due to diarrhoea. A few of the patients also reported nausea and abdominal pains. Adverse events included benign infectious diseases, insomnia and dizziness. No significant biological abnormalities were noted. The annualized relapse rate was 0.57 +/- 0.3 at the end of the study (P < 0.001). The mean EDSS score was 2.6 +/- 1.5 and no Gd-enhanced lesions were detected on MRI at the end of the study. MMF and IFNbeta-1a (Avonex) combined therapy is safe and very well-tolerated. Clinical and MRI data suggest that this combination may be beneficial.

Role of Immunosuppressive Therapy for the Treatment of Multiple Sclerosis

“…Serious infections did not occur. Other studies have been consistent with this safety and tolerability profile [49][50][51]. Opportunistic infections, including PML have occurred in mycophenolate-treated solid organ transplant and lupus patients.…”

“…Seven patients had disease progression, while others were perceived as remaining stable in time. An open-label study in 30 active relapsing-remitting (RR) patients treated with a combination of IFN beta-1a and mycophenolate reported a reduction in relapse rate (2 to 0.57), improvement in mean EDSS (2.9 to 2.6), and absence of gadolinium enhancing lesions on MRI follow-up [51]. During the six month study, more relapses occurred in the first two months, suggesting some delay in drug effect.…”

Mycophenolate mofetil for relapsing-remitting multiple sclerosis

“…It is also increasingly being used in the treatment of autoimmune diseases such as MS because of its potential efficacy and safety (Etemadifar 2011;Frohman 2010;Remington 2010;Vermersch 2007). MMF is a prodrug of mycophenolic acid (MPA), a compound that was synthesised to improve the bioavailability of MPA.…”

Immunosuppressive Agents in Multiple Sclerosis

“…67,68 Interestingly, in an openlabel trial, the combination of mycophenolate mofetil with interferon-␤1a exhibited superior efficacy as compared to interferon-␤1a alone. 69 Controlled and larger studies are warranted. The precise immunological mechanism of action of mycophenolate mofetil remains elusive.…”