Relapse rates and enhancing lesions in a phase II trial of natalizumab in multiple sclerosis

Abstract

There was a lower proportion of subjects with an on-study relapse in natalizumab-treated patients, particularly in those with a more active disease at study entry. Larger ongoing phase III studies will allow more definitive investigation of these preliminary subgroup findings.

Assessment: The use of natalizumab (Tysabri) for the treatment of multiple sclerosis (an evidence-based review)

“…In the large Phase III trial studying combination therapy, the SENTINEL Trial, 21 patients were at somewhat later disease duration and had breakthrough activity while on IFN␤-1a therapy. In the Phase II trial, which included both RRMS and SPMS patients, 15,17 the disability at baseline and disease duration were considerably greater (mean EDSS ϭ 4.2-4.4; mean duration ϭ 10.2-13.1 years). All three of these natalizumab trials 15,17,[20][21][22] showed a significant benefit of treatment (as evaluated by a relative-risk comparison) on both clinical and MRI measures of disease activity defined earlier (tables 2 and 3), with MRI activity being suppressed by 80 -90% and clinical activity being reduced by 50 -70%.…”

“…In the Phase II trial, which included both RRMS and SPMS patients, 15,17 the disability at baseline and disease duration were considerably greater (mean EDSS ϭ 4.2-4.4; mean duration ϭ 10.2-13.1 years). All three of these natalizumab trials 15,17,[20][21][22] showed a significant benefit of treatment (as evaluated by a relative-risk comparison) on both clinical and MRI measures of disease activity defined earlier (tables 2 and 3), with MRI activity being suppressed by 80 -90% and clinical activity being reduced by 50 -70%. In both of the 2-year Class I trials in which disease severity was measured, [20][21][22] there was a significant benefit of treatment on both clinical and MRI measures of disease severity defined earlier (tables 2 and 3).…”

“…Twelve articles, relating to five randomized controlled trials (RCTs), met our inclusion criteria. [12][13][14][15][16][17][18][19][20][21][22][23] In addition, a sixth RCT (the GLANCE trial comparing the combination of natalizumab and glatiramer acetate to glatiramer acetate alone) had sufficient data presented for classification. 24 Each panel member read each article and classified the level of evidence for the clinical trials according to the system used by the American Academy of Neurology for therapeutic interventions (available as supplemental data on the Neurology ® Web site at www.…”

“…16,18,26 Three additional RCTs studied both clinical and MRI outcomes. 17,19,[22][23][24] Two compared natalizumab to placebo 15,17,20,22 and the other studied the combination of natalizumab and IFN␤-1a (Avonex) 30 g per week IM compared to IFN␤-1a alone. 21 The dose of natalizumab varied somewhat among the six RCTs (table 1).…”

Neuroimmunotherapies Targeting T Cells: From Pathophysiology to Therapeutic Applications

“…Results from a randomized, double-blind, placebo-controlled, phase II study in 343 patients with RRMS showed that the highest dose of firategrast resulted in a significantly lower cumulative number of new gadolinium-enhancing lesions (49 %) [105]. However, experience from the phase II natalizumab trial reported a 92 % reduction [106], pointing towards a lower efficacy of firategrast than expected. Furthermore, none of the doses of firategrast resulted in a significantly lower frequency of relapses compared with placebo.…”