Novel and Emerging Treatments in Relapsing-Remitting MS
Novel and Emerging Treatments in Relapsing-Remitting MS
Ocrelizumab is a humanized mAb directed against CD20 that depletes circulating B-lymphocytes via antibody-mediated cytotoxicity. Ocrelizumab is closely related to rituximab, but binds to a distinct but overlapping epitope of CD20. It is postulated that ocrelizumab's reliance on antibody-mediated B-cell depletion may render it less immunogenic and more efficacious than rituximab in RRMS. Ocrelizumab is not yet approved for use in RRMS, but results from two phase III trials are expected, and approval may follow shortly thereafter.
The efficacy of ocrelizumab in RRMS has been demonstrated in a large, randomized, multicenter, double-blind, placebo-controlled phase II trial: A Study of the Efficacy and Safety of Ocrelizumab in Patients with RRMS. This study enrolled patients with RRMS (n = 220) in a 1 : 1:1 : 1 ratio to placebo, low-dose (600 mg) intravenous ocrelizumab in two doses, high-dose (2000 mg) intravenous ocrelizumab in two doses, or intramuscular IFNβ-1a (30 μg) once weekly.
The primary outcome measure was the number of gadolinium-enhancing T1 lesions on MRI-brain at prespecified time points. Secondary outcome measures included ARR, proportion of relapse-free patients, a variety of MRI-based measures, and safety.
At 24 weeks, the primary outcome measure of number of gadolinium-enhancing lesions was significantly lower in both ocrelizumab treatment arms in comparison to placebo (89% lower in 600 mg ocrelizumab arm, P < 0.0001; 96% lower in 2000 mg ocrelizumab arm, P < 0.0001). In addition, the ARR (a secondary outcome measure) in both ocrelizumab arms were significantly decreased versus placebo (ARR = 0.64 in placebo, 0.13 in ocrelizumab 600 mg, 0.17 in ocrelizumab 2000 mg, P = 0.0005 and 0.0014 for comparisons against placebo, respectively). Exploratory analyses showed significantly lower gadolinium-enhancing lesions in both ocrelizumab treatment arms in comparison to IFNβ-1a (both P-values < 0.0001)
Ocrelizumab
Ocrelizumab is a humanized mAb directed against CD20 that depletes circulating B-lymphocytes via antibody-mediated cytotoxicity. Ocrelizumab is closely related to rituximab, but binds to a distinct but overlapping epitope of CD20. It is postulated that ocrelizumab's reliance on antibody-mediated B-cell depletion may render it less immunogenic and more efficacious than rituximab in RRMS. Ocrelizumab is not yet approved for use in RRMS, but results from two phase III trials are expected, and approval may follow shortly thereafter.
The efficacy of ocrelizumab in RRMS has been demonstrated in a large, randomized, multicenter, double-blind, placebo-controlled phase II trial: A Study of the Efficacy and Safety of Ocrelizumab in Patients with RRMS. This study enrolled patients with RRMS (n = 220) in a 1 : 1:1 : 1 ratio to placebo, low-dose (600 mg) intravenous ocrelizumab in two doses, high-dose (2000 mg) intravenous ocrelizumab in two doses, or intramuscular IFNβ-1a (30 μg) once weekly.
The primary outcome measure was the number of gadolinium-enhancing T1 lesions on MRI-brain at prespecified time points. Secondary outcome measures included ARR, proportion of relapse-free patients, a variety of MRI-based measures, and safety.
At 24 weeks, the primary outcome measure of number of gadolinium-enhancing lesions was significantly lower in both ocrelizumab treatment arms in comparison to placebo (89% lower in 600 mg ocrelizumab arm, P < 0.0001; 96% lower in 2000 mg ocrelizumab arm, P < 0.0001). In addition, the ARR (a secondary outcome measure) in both ocrelizumab arms were significantly decreased versus placebo (ARR = 0.64 in placebo, 0.13 in ocrelizumab 600 mg, 0.17 in ocrelizumab 2000 mg, P = 0.0005 and 0.0014 for comparisons against placebo, respectively). Exploratory analyses showed significantly lower gadolinium-enhancing lesions in both ocrelizumab treatment arms in comparison to IFNβ-1a (both P-values < 0.0001)
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