Background
Methods
Results
Implications of brain volume loss in MS and unmet needs
Unmet Needs | |
---|---|
1. | Applicability of MRI volume measurement in clinical practice |
2. | Lack of large long-term prospective studies of clinical correlates with brain volume loss |
3. | Reliable assessments of cognitive impairment in MS |
4. | Validation of disease progression parameters with brain volume loss |
5. | Lack of pathological correlation with brain volume loss |
6. | Paucity of data on regional brain volume effect in MS |
7. | Targeting brain volume loss as one of the main outcome measure in clinical trials |
8. | Reproducible effectiveness of DMTs in phase III studies on cognitive impairment |
Assessment of brain volume in patients with MS
Advantages | |
Whole brain atrophy is easy to measure | |
Brain atrophy is a “summary measure” of the irreversible/destructive pathological process of MS | |
Whole brain atrophy is highly reproducible and sensitive to disease-related changes | |
Correlates with disability, cognitive impairment and fatigue | |
Disadvantages: | |
End-stage phenomenon | |
Pseudoatrophy effect (first 6–12 months) | |
Fluctuations: steroids, hydration | |
Co-morbidities: smoking, alcohol, high BMI, etc. | |
MRI technical confounding factors | |
Time consuming: reimbursement? | |
Not enough evidence to use atrophy measures to assess and predict individual treatment response |
Disease-modifying therapies effect on brain volume
Drug (REF.) | Changes in Brain Volume Loss | ||
---|---|---|---|
Year 0–1 | Year 1–2 | Year 0–2 | |
IFN-β-1a IM [33] | x | ✓ 55% reduction vs. placebo | x |
IFN-β-1a SC [34] | - | - | x |
- | - | - | |
x | ✓ | x | |
(Eur/Canadian GA trial) | 40% reduction vs. placebo (Eur/Canadian GA trial) | (Eur/Canadian GA trial) | |
8% reduction vs. sc IFN-β-1a (REGARD)+ | 22% reduction vs. sc IFN-β-1a (REGARD)+ | 13% reduction vs. IFN-β-1a (REGARD) | |
No sig. difference with GA +/− sc IFN-β-1b (BEYOND) | No sig. difference with GA +/−. sc IFN-β-1b (BEYOND) | No sig. difference with GA +/− sc IFN-β-1b (BEYOND | |
No sig. difference with GA +/− sc IFN-β-1a (COMBIRx) | No sig. difference with GA +/−. sc IFN-β-1a (COMBIRx) | No sig. difference with GA +/− sc IFN-β-1a (COMBIRx) | |
✓ | x (AFFIRM) | ||
40% increase vs. placebo (AFFIRM) | 44% reduction vs. placebo (AFFIRM) | ||
19% increase vs. placebo (SENTINEL) | x 23% reduction with Natalizumab+ IM IFN-β-1a vs. IM IFN-β-1a + placebo (SENTINEL) | x (SENTINEL) | |
Teriflunomide [42] | 37% reduction vs. placebo (TEMSO) | 31% reduction vs. placebo (TEMSO)- | X |
- | 21% reduction vs. placebo (DEFINE) Significant effect (DEFINE) ׇ (CONFIRM) | ✓21% reduction vs. placebo (DEFINE) × ‡ () | |
- | ✓ 24–42% reduction vs IFN-β-1a | ||
- | - | ✓ (ALLEGRO) 33% reduction vs placebo (BRAVO) 28–34% reduction vs placebo | |
Daclizumab [49] | ✓ | ✓ | - |
Significant effect (Week 0–24) 9% reduction vs IM IFN-β-1a | Significant effect (Week 24–96) 7% reduction vs IM IFN-β-1a | ||
✓ | ✓ | ✓ | |
23–40% reduction vs placebo | 28–45% reduction vs placebo | 33–35% reduction vs placebo | |
✓§ 45% reduction vs. IM IFN β-1a (TRANSFORMS) | - | - |
New emerging strategies in MS
Cognitive assessment consensus
How? | SDMT | BICAMS | PASAT | WLG | CDT |
9 | 3 | 4 | 1 | 4 | |
In Whom? | RIS | CIS | RRMS | SPMS | |
7 | 8 | 12 | 8 | ||
When? | Initial | 3–6 months | 12 months | ||
2 | 1 | 12 | |||
Where? | Office | Home | Waiting area | ||
12 | 1 | 0 | |||
Who? | Physician | Nurse | Assistant | Automated | |
1 | 10 | 4 | 3 |
Brain volume assessment consensus
How? | SIENA | SIENAx | BPF | VBM | |
12 | 4 | ||||
In Whom? | RIS | CIS | RRMS | SPMS | |
7 | 11 | 12 | 4 | ||
When? | Initial | 3–6 months | Anytime with MRI acquisition | 6–12 months | Annual |
3 | 2 | 11 | 1 | ||
Who? | Neurologist | Radiologist | MRI Technician | Independent | |
1 | 12 | 1 |