Barts-MS rose-tinted-odometer: ★★★★★ (A blue sky and sunflower yellow Tuesday; #87CEEB #ffda03)
I bang on about treating-2-target beyond NEIDA (no evident inflammatory disease activity) and targeting the end-organ, i.e. to try and normalise brain volume loss (BVL). The aim is to get pwMS to old age with a healthy brain so that they can age normally. Who wants to be at risk of premature ageing and being demented earlier than you have to be?
When it comes to BVL, not all DMTs are made equal. At the top of the ladder are HSCT and alemtuzumab, then natalizumab. Behind these come the anti-CD20 therapies, the S1P modulators, cladribine, teriflunomide and the also-rans.
In the smallish real-life study below pwMS who have been on natalizumab for at least 2 years appear to lose brain volume at a similar rate as normal controls. I wonder what would happen over a longer period of time? Natalizumab is very effective but it does not necessarily get on top of smouldering MS, so some patients will be doing better than others. Don’t be lulled into a sense of security by the average effect; 50% of people do worse than average (median) and 50% of people do better than average (median).
Please be aware that BVL is complicated with many physiological (day-2-day), biological (age), disease factors(duration, level of disability, lesion load, comorbidities) and other Influences (e.g. genomic factors) affecting the brain volume and rate of BVL. Despite BVL not being assessed in routine clinical practice, it is one of the metrics that need to be taken into account when choosing your DMT. Just maybe BVL should be the most important factor to consider in terms of efficacy? What do you think?
Yes, the volume of your brain predicts disability outcomes, cognition and how well you will do in old age.
Alvarez et al. Brain atrophy rates in patients with multiple sclerosis on long term natalizumab resembles healthy controls. Mult Scler Relat Disord. 2021 Jul 24;55:103170.
Background: Clinically stable multiple sclerosis (MS) patients often have negligible inflammatory MRI changes. Brain atrophy may provide insight into subclinical disease progression. The objective was to compare brain atrophy rates in stable patients on long term natalizumab treatment vs. age and gender matched healthy non-MS controls (HC) prospectively over two-years examining brain volume, cognition, and patient reported outcomes (PROs).
Methods: MS patients treated with natalizumab for a minimum of 2 years, age 18-60 were recruited and compared with age- and gender-matched healthy controls (HC). Both groups were followed prospectively to obtain two years of consecutive magnetic resonance imaging, clinical and PRO data. Baseline normalized brain volume (NBV), yearly T2 lesion volume (T2LV), and percent brain volume change (PBVC) were measured using SIENAX, JIM 6.0, and SIENA respectively. Neuropsychological tests from the MACFIMS battery were selected to optimize assessments for impairments in the domains of information processing speed and memory. Patient reported outcomes (PROs) for domains of physical, mental and social quality of life were evaluated using the NeuroQol short forms.
Results: Forty-eight natalizumab and 62 HC completed all study visits. At baseline, unadjusted mean NBV (natalizumab=1508.80cm (Popescu et al., 2013) vs. HC=1539.23cm (Popescu et al., 2013); p=0.033) and median baseline T2LV (natalizumab=1724.62mm (Popescu et al., 2013) vs. HC=44.20mm (Popescu et al., 2013); p=<0.0001) were different. The mean PBVC at year 2, adjusted for gender and baseline age was -0.57% (CI: 0.7620, -0.3716) for natalizumab and -0.50% (-0.7208, -0.2831) for HC, but the difference between groups was not statistically significant (0.073%; p=0.62). Over the 2-year period, HC demonstrated mild improvements in some cognitive tests vs. natalizumab subjects. However, PROs were similar between the two groups.
Conclusion: Stable MS patients on natalizumab have similar brain volume loss as people who do not have MS, suggesting normalization of brain atrophy.
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 and are not meant to be interpreted as personal clinical advice.