Article of interest (13): Alemtuzumab does not stop disease progression in SPMS

Coles AJ, et al. The window of therapeutic opportunity in multiple sclerosis: evidence from monoclonal antibody therapy. J Neurol. 2006 Jan;253(1):98-108.

Background: From 1991-2002, 58 MSers were treated using the humanised monoclonal antibody, Alemtuzumab of Campath-1H, which causes prolonged T lymphocyte depletion. 

Results: Clinical and surrogate markers of inflammation were suppressed. In both the RR and SP stages of the illness, Alemtuzumab reduced the annual relapse rate (from 2.2 to 0.19 and from 0.7 to 0.001 respectively; both p < 0.001). Remarkably, MRI scans of SPMSers, treated with Alemtuzumab 7 years previously, showed no new lesion formation. However, despite these effects on inflammation, disability was differently affected depending on the phase of the disease. SPMSers showed sustained accumulation of disability due to uncontrolled progression marked by unrelenting cerebral atrophy, attributable to ongoing axonal loss. The rate of cerebral atrophy was greatest in MSers with established cerebral atrophy and highest inflammatory lesion burden before treatment (2.3 versus 0.7 ml/year; p = 0.04). In contrast, RRMSers disease showed an impressive reduction in disability at 6 months after Alemtuzumab (by a mean of 1.2 EDSS points) perhaps owing to a suppression of on-going inflammation in these MSers with unusually active disease. In addition, there was a further significant, albeit smaller, mean improvement in disability up to 36 months after treatment. 

Conclusion: The investigator's speculate that this represents the beneficial effects of early rescue of neurons and axons from a toxic inflammatory environment, and that prevention of demyelination will prevent long-term axonal degeneration. 

"The observation that powerful immune suppression or immune modulation does not prevent delayed disability progression and or brain atrophy in SPMS and PPMS is not unique to Alemtuzumab. This has also been observed with cyclophosphamide, mitoxantrone, bone marrow transplantation and rituximab. I have also seen it personally with natalizumab, i.e. MSers who are on the cusp of going into the SPMS when they start natalizumab still progress despite suppression of relapses and MI activity."

"This phenomenon is another example of a disconnect between inflammation and neurodegeneration."

"Although these drugs don't stop disability progression they may slow it down. This means that MSers on these drugs will not necessarily be aware of any therapeutic effect as their MS will continue to progress albeit at a slower rate. I covered this issue extensively in my talk at the MS Life meeting earlier this year in Manchester. The following are my slides to refresh your memories." 

DMT Update MS Life 2012 from gavingiovannoni

CoI: multiple

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