Barts-MS rose-tinted-odometer: ★★ (seeing blue)
When I state that the real MS is smouldering MS and that relapses and focal MRI activity are not the disease I really mean it.
PwMS who are NEDA-2, without relapses and with no new MRI lesions, but getting worse must have something going on in their brains and spinal cords. This is why we need to go beyond NEIDA (no evidence of inflammatory disease activity) as a treatment target in MS and focus on protecting the end-organ so that pwMS can have enough reserve to cope with normal ageing when they get older.
One example or ugly fact to illustrate the disconnect between inflammation (relapses and focal MRI activity) and the end-organ (brain volume loss) is the recent ofatumumab vs. teriflunomide trials.
Gd-enhancing lesions (↓~95%): Ofatumumab >>>> teriflunomide
New T-2 lesions (↓~83%): Ofatumumab >>> teriflunomide
Relapses (↓~55%): Ofatumumab >> teriflunomide
Disability progression (↓~33%): Ofatumumab > teriflunomide
Brain volume loss (↓~0%): Ofatumumab = teriflunomide
If ofatumumab is so much more effective as an anti-inflammatory than teriflunomide why doesn’t it protect the end-organ more than teriflunomide? I don’t know but is clear, at least to me, that there is something else going on that is driving the end-organ damage in MS that is not linked to focal inflammation. Could something about teriflunomide’s mode of action that is downstream of focal inflammation be telling us something fundamental about the cause of MS?
General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust.