Table 4: Studies demonstrating the effects of disease modifying therapies on measures of gray matter pathology.

StudyMethodNumber of patientsDurationRelevant findings

Zivadinov et al. 2007 [96]Nonrandomized.
Intramuscular IFN beta-1a versus untreated patients
54 RRMS3 yearsIFN beta-1-a slows the rate of gray matter atrophy compared to untreated patients.
Nakamura et al. 2010 [97]Randomized.
Intramuscular IFN beta-1a versus placebo
131 RRMS2 yearsIFN beta-1a slows the rate of gray matter atrophy compared to placebo.
Bendfeldt et al. 2010 [98]Nonrandomized.
Subcutaneous IFN beta-1a versus intramuscular IFN beta-1a versus untreated patients
86 RRMS2 yearsIFN beta-1a reduced gray matter atrophy rates, while glatiramer acetate did not.
Progression of regional gray matter volume loss differs between patients treated with different immunomodulatory agents.
Calabrese et al. 2012 [99]Randomized.
Subcutaneous IFN beta-1a versus intramuscular IFN beta-1a versus glatiramer acetate
141 RRMS2 yearsEffect of subcutaneous IFN beta-1a in preventing new cortical lesions was higher compared to both intramuscular IFN beta-1a and glatiramer acetate.
Gray matter fraction decrease did not differ significantly among treatment groups.
Rinaldi et al. 2012 [100]Nonrandomized.
Natalizumab versus other IMAs (subcutaneous IFN beta-1a, intramuscular IFN beta-1a, or glatiramer acetate)
120 RRMS2 yearsNatalizumab treatment results in greater decreases in the rate of accumulation of cortical lesions and the progression of cortical atrophy as compared to other immunomodulatory agents.