Effect of Teriflunomide and Dimethyl Fumarate on Cortical Atrophy and Leptomeningeal Inflammation in Multiple Sclerosis: A Retrospective, Observational, Case-Control Pilot Study
Abstract
:1. Introduction
2. Methods
2.1. Study Design and Subjects
2.2. MRI Acquisition and Analyses
2.3. MRI Analyses
2.3.1. Brain Volume Analyses
2.3.2. LMCE Detection
2.3.3. Lesion Activity
2.4. Endpoints
2.5. Statistical Analysis
3. Results
3.1. Demographic, Clinical, and MRI Differences at Baseline between the Two Treatment Groups
3.2. Clinical Characteristics between the Two Treatment Groups over the Follow-Up
3.3. Differences in Percentage Brain Volume Changes between the Two Treatment Groups
3.4. Differences in the Frequency and Number of Leptomeningeal Contrast Enhancement Foci between the Two Treatment Groups
3.5. Differences in the MRI Lesion Activity Measures between the Two Treatment Groups
4. Discussion
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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TFM (n = 60) | DMF (n = 60) | p-Value | |
---|---|---|---|
Age, mean (SD) | 50.9 (8) | 50.8 (7.5) | 0.879 |
Age onset, mean (SD) | 33.5 (10.2) | 33.8 (9.7) | 0.869 |
Disease duration, mean (SD) | 16.3 (8.6) | 15.6 (9.6) | 0.674 |
Sex, n (%) | 0.820 | ||
Female | 47 (78.3) | 49 (81.7) | |
Male | 13 (21.7) | 11 (18.3) | |
BMI, mean (SD) | 27.2 (5.9) | 28.8 (6.1) | 0.171 |
Race, n (%) | 0.606 | ||
Caucasian | 45 (75) | 47 (78.3) | |
African-American | 7 (11.7) | 10 (16.7) | |
Hispanic | 8 (13.3) | 3 (5) | |
EDSS at baseline, median (IQR) | 3.0 (2.5–3.5) | 2.75 (2.0–3.5) | 0.377 |
Relapse rate in previous 12 months, mean (SD) | 0.28 (0.49) | 0.38 (0.66) | 0.351 |
Relapse rate in previous 24 months, mean (SD) | 0.38 (0.66) | 0.35 (0.63) | 0.779 |
DMT previous 12 months, n (%) | 0.144 | ||
Interferon-beta 1a | 18 (30) | 23 (38.3) | |
Glatiramer acetate | 9 (15) | 9 (15) | |
Natalizumab | 15 (25) | 11 (18.3) | |
Oral | 4 (6.7) | 0 (0) | |
Other | 0 (0) | 3 (5) | |
No treatment | 14 (23.3) | 14 (23.3) |
Lesion Measures | TFM (n = 60) | DMF (n = 60) | p-Value |
---|---|---|---|
T2 LN, mean (SD) | 25.5 (15.6) | 23 (15.3) | 0.393 |
T2 LV, mean (SD) | 15.3 (14.9) | 12.5 (9.7) | 0.226 |
T1 LN, mean (SD) | 12.1 (10.9) | 11.2 (8.9) | 0.647 |
T1 LV, mean (SD) | 4.6 (6.3) | 2.8 (3.3) | 0.062 |
Gd positivity, n (%) | 10 (16.7) | 13 (21.7) | 0.626 |
Gd LN, mean (SD) | 0.3 (1.4) | 0.3 (0.8) | 0.979 |
Gd LV, mean (SD) | 0.2 (0.08) | 0.05 (0.14) | 0.230 |
LMCE * | |||
Positivity, n (%) | 4 (10.3) | 8 (16.7) | 0.389 |
Number, mean (SD) sum | 0.07 (0.3) 4 | 0.14 (0.3) 8 | 0.718 |
LMCE ** | |||
Positivity, n (%) | 4 (13.8) | 7 (19.4) | 0.742 |
Number, mean (SD) sum | 0.06 (0.3) 4 | 0.1 (0.3) 7 | 0.684 |
Brain Volume Measures | |||
BPV, mean (SD) | 1480.3 (91.9) | 1476.3 (83) | 0.804 |
GMV, mean (SD) | 724.5 (66.9) | 725.8 (50) | 0.907 |
WMV, mean (SD) | 755.8 (52.8) | 750.5 (48.3) | 0.572 |
LVV, mean (SD) | 48.8 (18.1) | 48.3 (19.8) | 0.842 |
CV, mean (SD) | 573.5 (56.6) | 578.7 (41) | 0.573 |
Thalamus volume, mean (SD) | 19 (2.6) | 18.7 (2.4) | 0.432 |
DGM volume, mean (SD) | 55.9 (6.6) | 55.5 (6) | 0.748 |
TFM (n = 48) * | DMF (n = 46) * | p-Value | |
---|---|---|---|
Cessation of original DMT | 0.214 | ||
0–12 months, n (%) | 0 (0) | 3 (5) | |
12–24 months, n (%) | 12 (20) | 11 (18.3) | |
EDSS at 12 months, median (IQR) | 3.5 (2.5–4.0) | 3.0 (2.0–4.0) | 0.377 |
EDSS at 24 months, median (IQR) | 3.5 (3.0–4.4) | 3.0 (2.0–4.0) | 0.339 |
EDSS absolute change between 0–12 months, mean (SD) | 0.1 (1) | 0 (0.7) | 0.342 |
EDSS absolute change between 12–24 months, mean (SD) | 0.1 (0.9) | 0.2 (0.5) | 0.626 |
EDSS absolute change between 0–24 months, mean (SD) | 0.2 (1) | 0.2 (0.8) | 0.722 |
Relapse rate between 0–12 months, mean (SD) sum | 0.25 (0.4) 13 | 0.21 (0.5) 13 | 0.683 |
Relapse rate between 12–24 months, mean (SD) sum | 0.1 (0.3) 6 | 0.15 (0.4) 9 | 0.412 |
Annualized relapse rate between 0–24 months, mean (SD) sum | 0.17 (0.4) 19 | 0.18 (0.5) 22 | 0.890 |
DMT after cessation of original treatment, n (%) | 0.950 | ||
Interferon beta-1a | 7 (11.7) | 7 (11.7) | |
Glatiramer acetate | 3 (5) | 3 (5) | |
Natalizumab | 2 (3.3) | 4 (12.5) |
0–12 Months | 12–24 Months | 0–24 Months | |||||||
---|---|---|---|---|---|---|---|---|---|
TFM (n = 60) | DMF (n = 57) | p-Value | TFM (n = 48) | DMF (n = 46) | p-Value | TFM (n = 48) | DMF (n = 46) | p-Value | |
PBVC | −0.73 (1.4) | −0.92 (1.5) | 0.496 | −1.08 (1.2) | −1.4 (1.7) | 0.351 | −1.45 (1.5) | −2.07 (1.7) | 0.077 |
PGMVC | −0.24 (3.9) | −1.71 (3) | 0.044 | −075 (5.1) | −1.33 (4.1) | 0.605 | −0.44 (5.2) | −3.12 (4.3) | 0.015 |
PWMVC | −1.72 (4.7) | −1.19 (4.1) | 0.565 | −2.87 (5.1) | −2.24 (5.1) | 0.618 | −4.88 (4.8) | −4.17 (5.1) | 0.550 |
PLVVC | 1.40 (5.2) | 3.56 (5.7) | 0.05 | 3.07 (7.5) | 2.25 (6.9) | 0.620 | 3.85 (10.2) | 6.26 (8.7) | 0.245 |
PCVC | −0.29 (4) | −1.48 (3.2) | 0.115 | −0.79 (3.9) | −1.6 (3.3) | 0.358 | −0.20 (4.3) | −2.94 (3.9) | 0.004 |
PTVC | −0.83 (4) | −1.20 (3.3) | 0.624 | −0.44 (5) | −1.1 (4.1) | 0.531 | −1.18 (5.5) | −1.87 (5) | 0.556 |
PDGMVC | −0.5 (3.8) | −0.91 (3.2) | 0.557 | −0.34 (5.4) | −1.03 (4.4) | 0.538 | −1.0 (5.6) | −1.7 (4.2) | 0.515 |
0–12 Months | 12–24 Months | 0–24 Months | |||||||
---|---|---|---|---|---|---|---|---|---|
TFM (n = 60) | DMF (n = 57) | p-Value | TFM (n = 48) | DMF (n = 46) | p-Value | TFM (n = 48) | DMF (n = 46) | p-Value | |
No. of new/enlarging T2 lesions, mean (SD) | 0.1 (0.5) | 0.1 (0.2) | 0.121 | 0.1 (0.2) | 0.1 (0.4) | 0.367 | 0.2 (0.6) | 0.2 (0.6) | 0.945 |
Change in absolute T2-LV, mean (SD) | 0.3 (1.5) | 0.2 (0.8) | 0.620 | −0.4 (1.9) | −0.2 (1.3) | 0.598 | −0.1 (2.4) | −0.1 (1.5) | 0.990 |
No. of new/enlarging T1 lesions, mean (SD) | 0.1 (0.4) | 0.06 (0.3) | 0.309 | 0.06 (0.2) | 0.08 (0.3) | 0.720 | 0.23 (0.6) | 0.18 (0.5) | 0.593 |
Change in absolute T1-LV, mean (SD) | 0.04 (0.5) | 0.005 (0.3) | 0.169 | 0.08 (0.6) | 0.1 (0.7) | 0.175 | 0.1 (0.7) | 0.13 (0.7) | 0.821 |
Gd positivity, n (%) | 3 (5) | 2 (3.3) | 0.690 | 2 (4.2) | 3 (6.5) | 0.611 | 3 (6.3) | 4 (8.7) | 0.651 |
Change in Gd-LV, mean (SD) | 0.06 (0.3) | −0.04 (0.2) | 0.151 | −0.06 (0.7) | 0.06 (0.3) | 0.205 | −0.01 (0.1) | −0.01 (0.1) | 0.495 |
LMCE positivity *, n (%) | 2 (5.7) | 6 (12.8) | 0.157 | 3 (10) | 5 (12.5) | 0.998 | 3 (10) | 7 (17.5) | 0.375 |
LMCE No. *, mean (SD) | 0.04 (0.2) | 0.1 (0.3) | 0.109 | 0.07 (0.3) | 0.1 (0.3) | 0.424 | 0.1 (0.5) | 0.2 (0.7) | 0.216 |
LMCE positivity **, n (%) | 2 (6.9) | 5 (13.9) | 0.140 | 3 (13) | 5 (16.7) | 0.991 | 3 (13) | 6 (20) | 0.715 |
LMCE No. **, mean (SD) | 0.04 (0.1) | 0.08 (0.2) | 0.211 | 0.09 (0.3) | 0.1 (0.2) | 0.375 | 0.09 (0.4) | 0.2 (0.6) | 0.199 |
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Zivadinov, R.; Bergsland, N.; Carl, E.; Ramasamy, D.P.; Hagemeier, J.; Dwyer, M.G.; Lizarraga, A.A.; Kolb, C.; Hojnacki, D.; Weinstock-Guttman, B. Effect of Teriflunomide and Dimethyl Fumarate on Cortical Atrophy and Leptomeningeal Inflammation in Multiple Sclerosis: A Retrospective, Observational, Case-Control Pilot Study. J. Clin. Med. 2019, 8, 344. https://doi.org/10.3390/jcm8030344
Zivadinov R, Bergsland N, Carl E, Ramasamy DP, Hagemeier J, Dwyer MG, Lizarraga AA, Kolb C, Hojnacki D, Weinstock-Guttman B. Effect of Teriflunomide and Dimethyl Fumarate on Cortical Atrophy and Leptomeningeal Inflammation in Multiple Sclerosis: A Retrospective, Observational, Case-Control Pilot Study. Journal of Clinical Medicine. 2019; 8(3):344. https://doi.org/10.3390/jcm8030344
Chicago/Turabian StyleZivadinov, Robert, Niels Bergsland, Ellen Carl, Deepa P. Ramasamy, Jesper Hagemeier, Michael G. Dwyer, Alexis A. Lizarraga, Channa Kolb, David Hojnacki, and Bianca Weinstock-Guttman. 2019. "Effect of Teriflunomide and Dimethyl Fumarate on Cortical Atrophy and Leptomeningeal Inflammation in Multiple Sclerosis: A Retrospective, Observational, Case-Control Pilot Study" Journal of Clinical Medicine 8, no. 3: 344. https://doi.org/10.3390/jcm8030344