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Immunological and short-term brain volume changes in relapsing forms of multiple sclerosis treated with interferon beta-1a subcutaneously three times weekly: an open-label two-arm trial.

Dwyer MG, Zivadinov R, Tao Y, Zhang X, Kennedy C, Bergsland N, Ramasamy DP, Durfee J, Hojnacki D, Weinstock-Guttman B, Hayward B, Dangond F, Markovic-Plese S - BMC Neurol (2015)

Bottom Line: Interferon β-1a 44 μg SC tiw in 23 patients with RRMS resulted in significant reductions in whole brain and gray matter tissue volume early in the treatment course (baseline to 3 months; mean change; -0.95%; P = 0.030, -1.52%; P = 0.004, respectively), suggesting a short-term treatment-induced pseudoatrophy effect.From baseline to 6 months, there were significant correlations observed between decreased T- cell expression of IL-17 F and decreased whole brain and brain tissue-specific volume.These findings are consistent with the interpretation of the pseudoatrophy effect as resolution of inflammation following treatment initiation with interferon β-1a 44 μg SC tiw, rather than disease-related tissue loss.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Buffalo Neuroimaging Analysis Center, State University of New York at Buffalo, 100 High St, Buffalo, NY, 14203, USA. mgdwyer@bnac.net.

ABSTRACT

Background: Brain volume atrophy is observed in relapsing-remitting multiple sclerosis (RRMS).

Methods: Brain volume changes were evaluated in 23 patients with RRMS treated with interferon β-1a 44 μg given subcutaneously (SC) three times a week (tiw) and 15 healthy controls. Percentages of whole brain and tissue-specific volume change were measured from baseline (0 months) to 3 months, from 3 to 6 months, and from baseline to 6 months using SIENAX Multi Time Point (SX-MTP) algorithms. Immunological status of patients was also determined and correlations between subsets of T cells and changes in brain volume were assessed.

Results: Interferon β-1a 44 μg SC tiw in 23 patients with RRMS resulted in significant reductions in whole brain and gray matter tissue volume early in the treatment course (baseline to 3 months; mean change; -0.95%; P = 0.030, -1.52%; P = 0.004, respectively), suggesting a short-term treatment-induced pseudoatrophy effect. From baseline to 6 months, there were significant correlations observed between decreased T- cell expression of IL-17 F and decreased whole brain and brain tissue-specific volume.

Conclusions: These findings are consistent with the interpretation of the pseudoatrophy effect as resolution of inflammation following treatment initiation with interferon β-1a 44 μg SC tiw, rather than disease-related tissue loss.

Trial registration: ClinicalTrials.gov; NCT01085318.

No MeSH data available.


Related in: MedlinePlus

Gray matter volume changes in RRMS patients and HCs. Percent change in GM volume in RRMS patients treated with IFN β-1a SC tiw and in HCs was assessed. P-values were for the difference from zero within groups from the Wilcoxon signed-rank test. P-values in parentheses are those remaining significant after Holm–Bonferroni correction for multiple comparisons. *P < 0.05. **P < 0.01. ***P < 0.001. In the box plots, the bold line represents the median; the boxes represent the middle 50 % of data; the top and bottom of the box represent the third and first quartiles; the open circles are outliers. The whisker lines above and below the boxes represent the largest and smallest values that are not considered to be outliers. Means are denoted by a ‘+’ sign. GM gray matter; HC healthy control; IFN interferon; RRMS relapsing–remitting multiple sclerosis; SC subcutaneously; tiw three times weekly
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Fig2: Gray matter volume changes in RRMS patients and HCs. Percent change in GM volume in RRMS patients treated with IFN β-1a SC tiw and in HCs was assessed. P-values were for the difference from zero within groups from the Wilcoxon signed-rank test. P-values in parentheses are those remaining significant after Holm–Bonferroni correction for multiple comparisons. *P < 0.05. **P < 0.01. ***P < 0.001. In the box plots, the bold line represents the median; the boxes represent the middle 50 % of data; the top and bottom of the box represent the third and first quartiles; the open circles are outliers. The whisker lines above and below the boxes represent the largest and smallest values that are not considered to be outliers. Means are denoted by a ‘+’ sign. GM gray matter; HC healthy control; IFN interferon; RRMS relapsing–remitting multiple sclerosis; SC subcutaneously; tiw three times weekly

Mentions: GM volume analysis is shown in Table 1 and Fig. 2. The pattern for GM was similar to that of whole brain. In patients, the mean (SD) change from baseline to 3 months in GM volume was –1.52 % (2.41; P = 0.004 and after adjusting for multiple comparisons, P = 0.029), –0.46 % (3.11; P = 0.176) from 3 to 6 months, and –1.66 % (1.84; P < 0.001 and after adjusting for multiple comparisons, P = 0.002) from baseline to 6 months. There were no significant differences observed for the HCs: mean change from baseline to 3 months was 0.01 % (SD 2.42; P = 0.934), –0.60 % (2.19; P = 0.426) from 3 to 6 months, and –0.51 % (2.47; P = 0.268) from baseline to 6 months.Fig. 2


Immunological and short-term brain volume changes in relapsing forms of multiple sclerosis treated with interferon beta-1a subcutaneously three times weekly: an open-label two-arm trial.

Dwyer MG, Zivadinov R, Tao Y, Zhang X, Kennedy C, Bergsland N, Ramasamy DP, Durfee J, Hojnacki D, Weinstock-Guttman B, Hayward B, Dangond F, Markovic-Plese S - BMC Neurol (2015)

Gray matter volume changes in RRMS patients and HCs. Percent change in GM volume in RRMS patients treated with IFN β-1a SC tiw and in HCs was assessed. P-values were for the difference from zero within groups from the Wilcoxon signed-rank test. P-values in parentheses are those remaining significant after Holm–Bonferroni correction for multiple comparisons. *P < 0.05. **P < 0.01. ***P < 0.001. In the box plots, the bold line represents the median; the boxes represent the middle 50 % of data; the top and bottom of the box represent the third and first quartiles; the open circles are outliers. The whisker lines above and below the boxes represent the largest and smallest values that are not considered to be outliers. Means are denoted by a ‘+’ sign. GM gray matter; HC healthy control; IFN interferon; RRMS relapsing–remitting multiple sclerosis; SC subcutaneously; tiw three times weekly
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4642690&req=5

Fig2: Gray matter volume changes in RRMS patients and HCs. Percent change in GM volume in RRMS patients treated with IFN β-1a SC tiw and in HCs was assessed. P-values were for the difference from zero within groups from the Wilcoxon signed-rank test. P-values in parentheses are those remaining significant after Holm–Bonferroni correction for multiple comparisons. *P < 0.05. **P < 0.01. ***P < 0.001. In the box plots, the bold line represents the median; the boxes represent the middle 50 % of data; the top and bottom of the box represent the third and first quartiles; the open circles are outliers. The whisker lines above and below the boxes represent the largest and smallest values that are not considered to be outliers. Means are denoted by a ‘+’ sign. GM gray matter; HC healthy control; IFN interferon; RRMS relapsing–remitting multiple sclerosis; SC subcutaneously; tiw three times weekly
Mentions: GM volume analysis is shown in Table 1 and Fig. 2. The pattern for GM was similar to that of whole brain. In patients, the mean (SD) change from baseline to 3 months in GM volume was –1.52 % (2.41; P = 0.004 and after adjusting for multiple comparisons, P = 0.029), –0.46 % (3.11; P = 0.176) from 3 to 6 months, and –1.66 % (1.84; P < 0.001 and after adjusting for multiple comparisons, P = 0.002) from baseline to 6 months. There were no significant differences observed for the HCs: mean change from baseline to 3 months was 0.01 % (SD 2.42; P = 0.934), –0.60 % (2.19; P = 0.426) from 3 to 6 months, and –0.51 % (2.47; P = 0.268) from baseline to 6 months.Fig. 2

Bottom Line: Interferon β-1a 44 μg SC tiw in 23 patients with RRMS resulted in significant reductions in whole brain and gray matter tissue volume early in the treatment course (baseline to 3 months; mean change; -0.95%; P = 0.030, -1.52%; P = 0.004, respectively), suggesting a short-term treatment-induced pseudoatrophy effect.From baseline to 6 months, there were significant correlations observed between decreased T- cell expression of IL-17 F and decreased whole brain and brain tissue-specific volume.These findings are consistent with the interpretation of the pseudoatrophy effect as resolution of inflammation following treatment initiation with interferon β-1a 44 μg SC tiw, rather than disease-related tissue loss.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Buffalo Neuroimaging Analysis Center, State University of New York at Buffalo, 100 High St, Buffalo, NY, 14203, USA. mgdwyer@bnac.net.

ABSTRACT

Background: Brain volume atrophy is observed in relapsing-remitting multiple sclerosis (RRMS).

Methods: Brain volume changes were evaluated in 23 patients with RRMS treated with interferon β-1a 44 μg given subcutaneously (SC) three times a week (tiw) and 15 healthy controls. Percentages of whole brain and tissue-specific volume change were measured from baseline (0 months) to 3 months, from 3 to 6 months, and from baseline to 6 months using SIENAX Multi Time Point (SX-MTP) algorithms. Immunological status of patients was also determined and correlations between subsets of T cells and changes in brain volume were assessed.

Results: Interferon β-1a 44 μg SC tiw in 23 patients with RRMS resulted in significant reductions in whole brain and gray matter tissue volume early in the treatment course (baseline to 3 months; mean change; -0.95%; P = 0.030, -1.52%; P = 0.004, respectively), suggesting a short-term treatment-induced pseudoatrophy effect. From baseline to 6 months, there were significant correlations observed between decreased T- cell expression of IL-17 F and decreased whole brain and brain tissue-specific volume.

Conclusions: These findings are consistent with the interpretation of the pseudoatrophy effect as resolution of inflammation following treatment initiation with interferon β-1a 44 μg SC tiw, rather than disease-related tissue loss.

Trial registration: ClinicalTrials.gov; NCT01085318.

No MeSH data available.


Related in: MedlinePlus