Can disease-modifying therapies (DMTs) be initiated in patients with multiple sclerosis based on Magnetic Resonance Imaging (MRI) findings?

Can DMTs Be Initiated Based on MRI Findings Alone in Multiple Sclerosis?

Yes, disease-modifying therapies can and should be initiated based on MRI findings in multiple sclerosis, particularly in clinically isolated syndrome (CIS) and when MRI demonstrates subclinical disease activity, as MRI is highly sensitive for detecting MS pathology and predicting disease progression.

MRI as a Basis for DMT Initiation

In Clinically Isolated Syndrome (CIS)

• Glatiramer acetate and interferon β-1a are more effective than placebo in decreasing risk of conversion to MS in patients with CIS 1
• Cladribine, immunoglobulins, interferon β-1a 30 μg intramuscular weekly, interferon β-1b subcutaneous alternate day, and teriflunomide are probably more effective than placebo in decreasing risk of conversion to MS 1
• In patients with a first clinical event consistent with acute demyelination occurring within 90 days with 2 or more T2 lesions at least 3 mm in diameter characteristic of MS, DMT initiation is appropriate 2
• The proportion of patients free of relapse was significantly greater in teriflunomide-treated groups (70.5% for 7 mg and 72.2% for 14 mg) compared to placebo (61.7%) in CIS patients 2

In Established Relapsing-Remitting MS

• Brain MRI is very sensitive for monitoring disease activity and treatment efficacy, with parameters related to image acquisition relatively easy to standardize 3
• Contrast-enhanced T1-weighted sequences are recommended to detect acute inflammation, though demonstration of active (new or enlarging) T2 lesions can deliver sufficient information about subclinical disease activity and disease progression 3
• MRI brain volume measures have been used in randomized clinical trials to monitor effects of disease-modifying therapies, and baseline atrophy and high rates of subsequent volume loss are associated with cognitive impairment, fatigue, and disability progression over the long term 3

MRI Criteria for Treatment Escalation

Specific Thresholds for Action

• In clinically stable patients on low-to-moderate-efficacy DMT (interferon β, glatiramer acetate, teriflunomide, or dimethyl fumarate), escalation of DMT based on isolated MRI activity decreased risk of further relapse when at least 2 new T2 lesions occurred 4
• Patients who continued first-line DMT had a 3-fold increased risk of relapse given 2 new T2 lesions (HR 3.2) and a 4-fold increased risk given ≥3 new T2 lesions (HR 4.0) 4
• Escalation of DMT lowered the risk of relapse in patients with 2 new T2 lesions by approximately 80% (HR 0.2) and with ≥3 new T2 lesions by 70% (HR 0.3) 4
• In case of only 1 new T2 lesion, the increased risk of relapse and treatment effect did not reach statistical significance 4

High-Efficacy DMT Considerations

• High-efficacy DMTs (natalizumab, ocrelizumab, ofatumumab, alemtuzumab, cladribine) should be considered as first-line treatment for patients with markers of aggressive MS disease, including rapid MRI progression 5
• Current evidence favors early escalation and induction treatment strategies over traditional stepped approaches for patients with highly active disease 5
• For patients with relapsing-remitting MS who experienced a relapse on interferon-β or glatiramer acetate, alemtuzumab is more effective than interferon β-1a 44 μg subcutaneous 3 times per week in reducing the annualized relapse rate 1

MRI Monitoring Protocol

Baseline and Follow-Up Imaging

• Brain MRI should be performed on the same MRI system using the same imaging protocol as the reference (baseline) scan 3
• Regular brain MRI scans are essential for monitoring disease progression, and follow-up scans should include contrast-enhanced T1-weighted and T2-weighted sequences 6
• MRI surveillance should be conducted every 3-4 months for highly active disease or recent treatment change, then every 6 months in the first year, then annually if stable 5

Key MRI Markers

• Contrast-enhancing lesions and active T2 lesions measure acute MS-related inflammation 3
• Chronic T1 hypointense lesions ('black holes') that persist longer than 6 months may hold promise for predicting disability progression and monitoring remyelination 3
• Brain volume changes are an important measure of tissue damage in MS patients and are associated with cognitive impairment, fatigue, and disability progression 7

Critical Pitfalls to Avoid

Pseudoatrophy Effect

• Anti-inflammatory drugs can cause excessive decrease in brain volume within the first 6-12 months of treatment due to resolution of inflammation and edema, which should not be mistaken for disease progression 7
• This phenomenon is called pseudoatrophy and seems to be directly associated with the resolution of ongoing white matter inflammation induced at the time of treatment initiation 3
• To identify pseudoatrophy during treatment, brain volume should be measured every 3-6 months 3

Spinal Cord Imaging Limitations

• Serial spinal cord imaging for detection of new focal lesions might add little to brain imaging for monitoring of disease activity and progression 3
• Most spinal cord lesions are clinically symptomatic, and a strong relationship exists between development of new lesions in the brain and spinal cord 3
• The relevance of spinal cord imaging for routine follow-up seems rather limited 3

Treatment Delay Risks

• Do not delay high-efficacy DMT initiation in patients with aggressive MS based on MRI findings while waiting for clinical relapses to occur 5
• Avoid inappropriate washout periods between different DMTs that can lead to complications from carryover effects or disease reactivation 7