Saturday, 16 October 2010

ECTRIMS 2010 Update: Phase 2 Ocrelizumab Results in RRMS

Ocrelizumab (anti-CD20) that targets B-cells was given as two treatment cycles, 6 months apart, in a phase 2 study in relapsing-remitting MS. It reduced MRI activity by ~90% (median T1 Gd-lesions at wk 24: placebo 1.6, 600mg 0.0, 2000mg 0.0, Avonex 1.0; p<0.0001 vs placebo) and annualised relapse rate by up to 80% (ARR: placebo 0.61, 600mg 0.18 (RRR 80%), 2000mg 0.2 (RRR 72%), Avo 0.4). Importantly the overall adverse event profile looks good (AEs: placebo 70%, 600mg 61%, 2000mg 65%, Avonex 55%). Infusion reactions typically disappeared at the day 15 infusion and there were no opportunistic infections. Worryingly there was one death in the high dose Ocrelizumab group at 14 weeks, from "systemic inflammatory response syndrome". These very impressive results need to be tempered against the death that we must assume is due to Ocrelizumab. Nevertheless this study demonstrates the importance of B cells in the pathogenesis of MS; the latter needs further exploration and may ultimately lead to a safer and even more effective therapy.

Monday, 4 October 2010

Improvement in MS disability after Alemtuzumab

Treatment of early RRMS with Alemtuzumab reduces relapses and the accumulation of disability compared to interferon β. Remarkably PwMS treated with alemtuzumab experienced an improvement in disability at 6 months that was sustained for at least 3 years in comparison to those treated with interferon β.

Critics have poopooed this observation as the study was single-blinded and liable to unblinding; i.e. only the evaluating neurologist is blinded to what the study subject received in the study. Due to infusion reactions from Alemtuzumab it is not possible to do double-blinded studies with the agent; i.e. studies in which the evaluating neurologist and study subjects do no know what they have received.

In an additional analysis of the phase 2 trial data it appears that the participants with no clinical disease activity immediately before treatment, or any clinical or radiological disease activity during the study trial, were noted to improve after Alemtuzumab but not following interferon β treatment. This would suggest that disability improvement after Alemtuzumab may not simply be due to its anti-inflammatory effects.

This statement is subject to the same criticisms levelled at the whole study; but despite these criticisms this would be the first treatment in MS to offer such a benefit. No wonder PwMS are so excited about the prospect of receiving this therapy.

Preliminary experiments hint that Alemtuzumab stimulates white blood cells to produce growth factors that promote survival of nerve cells and enhanced oligodendrocyte (cells that produce myelin) function. This data will need to be replicated and shown to be relevant in patients treated with Alemtuzumab.

The implications of this research for PwMS cannot be overemphasised; at last a possible treatment with the potential to promote recovery.

Jones et al Brain. 2010 Aug;133(Pt 8):2232-47. Epub 2010 Jul 21.