Autoimmune Comorbidities Are Associated with Brain Injury in Multiple Sclerosis

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Table 1:

Demographic and clinical characteristics of patients with MS with and without comorbidities^{^a}

	Total Patients with MS (N = 815)	Patients with MS with Comorbidities (n = 241)	Patients with MS without Comorbidities (n = 574)	P Value^{^b}
Females (No.) (%)	626 (76.8)	201 (83.4)	425 (74.0)	.300
Age (yr) (mean) (SD)	45.7 (10.3)	46.3 (10.4)	45 (10.2)	.082
Disease duration (yr) (mean) (SD)	13.1 (9.4)	13.3 (10)	12.8 (8.8)	.452
EDSS (median) (IQR)	2.5 (1.5–6.0)	2.5 (1.5–5.5)	2.5 (2.0–6.0)	.732
MS subtype (No.) (%)
RR	554 (67.9)	157 (65.1)	397 (69.2)	.120
SP	227 (27.9)	77 (32.0)	150 (26.1)
PP	34 (4.2)	7 (2.9)	27 (4.7)
DMT use (No.) (%)	598 (73.4)	175 (72.6)	423 (73.7)	.900
DMT months (mean) (SD)	48.9 (35.2)	48.8 (35.2)	49 (39.2)	.942

Note:—RR indicates relapsing-remitting; SP, secondary-progressive; PP, primary-progressive; DMT, disease-modifying therapy; IQR, interquartile range.
↵a Demographic and clinical characteristics were tested using the χ², Student t, and Mann-Whitney rank sum tests.
↵b P values refer to analyses between patients with MS with and without comorbidities.

Table 2:

Demographic and clinical characteristics of patients with MS with comorbidities, according to their specific comorbidity type

Disease	Females (No.) (%)	Age (yr) (Mean) (SD)	DD (yr) (Mean) (SD)	EDSS (Median) (IQR)	MS Subtype (No.) (%)					DMT Use (No.) (%)	DMT Months (Mean) (SD)
Disease	Females (No.) (%)	Age (yr) (Mean) (SD)	DD (yr) (Mean) (SD)	EDSS (Median) (IQR)	RR	SP		PP		DMT Use (No.) (%)	DMT Months (Mean) (SD)
Asthma (n = 41)	38 (92.7)	45.2 (8.8)	12.4 (10.0)	2.5 (1.5–5.0)	32 (78)		7 (17.1)		2 (4.9)	32 (78.0)	51.7 (40.7)
Crohn disease (n = 1)	1 (100)	53	16	3.0	0 (0)		1 (100)		0 (0)	1 (100)	60
Diabetes mellitus type 1 (n = 3)	2 (66.6)	36.3 (4.7)	6.7 (4.2)	2.3 (1.5–2.5)	2 (66.7)		1 (33.3)		0 (0)	0 (0.0)	0 (0)
Diabetes mellitus type 2 (n = 40)	28 (70.0)	49.3 (8.7)	14.5 (9.9)	5.5 (2.0–5.0)	23 (57.5)		16 (40)		1 (2.5)	29 (72.5)	50.9 (40.7)
Myasthenia gravis (n = 1)	1 (100)	47	12	6.5	0 (0)		1 (100)		0 (0)	1 (100)	24
Psoriasis (n = 33)	23 (69.7)	50.4 (9.1)	15.9 (10)	3.0 (2.0–5.5)	21 (63.6)		11 (33.3)		1 (3.1)	24 (72.7)	63.7 (34.2)
Rheumatoid arthritis (n = 22)	17 (77.3)	51.8 (9.1)	16.4 (11.8)	3.0 (1.5–5.5)	13 (59.1)		8 (36.4)		1 (4.5)	17 (77.2)	58.4 (31.4)
SLE (n = 3)	2 (66.6)	50 (3)	15.7 (1.5)	4.0 (4.0–5.0)	0 (0)		3 (100)		0 (0)	3 (100)	50.3 (24.6)
Thyroid disease (n = 97)	89 (91.8)	46.6 (10.6)	14.6 (11.1)	2.5 (1.5–5.5)	66 (68.0)		29 (29.9)		2 (2.1)	68 (70.1)	46.5 (35.2)

Note:—SLE indicates systemic lupus erythematosus; DD, disease duration; RR, relapsing-remitting; SP, secondary-progressive; PP, primary-progressive; DMT, disease-modifying therapy; IQR, interquartile range.

Table 3:

Primary and secondary MRI outcomes in patients with MS with and without comorbidities^{^a}

	Patients with MS with Comorbidities (n = 241)	Patients with MS without Comorbidities (n = 574)	P Value
Primary MRI outcomes
T2-LV	15.7 (15.5)	15.3 (18.2)	.943
T1-LV	2.8 (4.7)	2.6 (4.7)	.955
Gd-LV	0.08 (0.3)	0.1 (0.4)	.992
NBV	1451.1 (97.3)	1481 (86.4)	<.001^{^b}
MTR-NABT	34.1 (5.1)	35.3 (5)	.01^{^b}
Secondary MRI outcomes
NGMV	722.8 (86.9)	747.9 (81.5)	.01^{^b}
NWMV	728.3 (86.7)	732.6 (64)	.311
NCV	537.1 (67.3)	557.6 (62.8)	<.001^{^b}
NLVV	47.5 (20.6)	45.3 (20.5)	.528
MTR-NAGM	31.1 (5.5)	32.3 (5.1)	.045^{^b}
MTR-NAWM	37.1 (5.3)	38.1 (4.9)	.105
MTR-T2-LV	32.3 (4.8)	32.8 (5.1)	.650
MD × 10³	1.26 (0.29)	1.22 (0.22)	.136

Note:—Gd indicates gadolinium; NWMV, normalized white matter volume; NLVV, normalized lateral ventricle volume; NAGM, normal-appearing gray matter; NBV, normalized brain volume; NGMV, normalized gray matter volume; NCV, normalized cortical volume; NAWM, normal appearing-white matter.
↵a The data are expressed as mean and SD. Volumes are expressed in milliliters. MTR values are expressed as percentage units. MD is expressed as mm²/s. Analysis of covariance, adjusted for age, sex, MS subtype, disability status, and use and duration of disease-modifying treatment, was used to explore the difference between patients with MS with and without comorbidities. The Benjamini-Hochberg correction was used to minimize the false discovery rate.
↵b Corrected P value < .05 was significant.

Table 4:

Primary and secondary MRI outcomes in patients with MS with specific comorbidities^{^a}

	Patients with MS without Comorbidities (n = 574)	Patients with MS with Asthma (n = 41)	Patients with MS with Diabetes Mellitus Type 2 (n = 40)	Patients with MS with Psoriasis (n = 33)	Patients with MS with Rheumatoid Arthritis (n = 22)	Patients with MS with Thyroid Disease (n = 97)
Primary MRI outcomes
T2-LV	15.3 (18.2)	12.9 (14.2)	19.3 (17)	17.2 (18.1)	17.1 (19.1)	12.9 (14.2)
T1-LV	2.6 (4.7)	2.2 (2.7)	2.9 (3.5)	3.5 (5.2)	3.4 (5.9)	2.2 (4)
Gd-LV	0.1 (0.4)	0.08 (0.1)	0.1 (0.05)	0.04 (0.1)	0.1 (0.2)	0.08 (0.2)
NBV	1481 (86.4)	1490.6 (90.5)	1434.4 (89)^{^b}	1394.3 (105)^{^c}	1461.2 (91.9)	1454.3 (87.3)^{^b}
MTR-NABT	35.3 (5)	36.4 (3.7)	35.1 (4.5)	33.1 (4.7)^{^b}	33 (4.6)	33.8 (5.7)
Secondary MRI outcomes
NGMV	747.9 (81.5)	NA	708.2 (58.9)^{^b}	694.4 (89)^{^d}	NA	722.9 (68.5)^{^b}
NWMV	732.6 (64)	NA	726.3 (58.9)	699.8 (84)^{^b}	NA	731.3 (52.9)
NCV	557.6 (62.8)	NA	522.8 ((53.7)^{^d}	516.2 (91)^{^d}	NA	537.9 (52.7)^{^b}
NLVV	45.3 (20.5)	NA	52.5 (21.5)	50.7 (20.8)	NA	45.5 (21.3)
MTR-NAGM	32.3 (5.1)	NA	32 (4.3)	30.1 (4.7)	NA	30.8 (6.2)
MTR-NAWM	38.1 (4.9)	NA	38.2 (4.3)	36.2 (5.6)	NA	36.7 (5.9)
MTR-T2-LV	32.8 (5.1)	NA	32.9 (4.6)	32.1 (4.4)	NA	32.7 (5.2)
MD × 10³	1.22 (0.22)	NA	1.32 (0.37)^{^d}	1.25 (0.13)	NA	1.23 (0.31)

Note:—NA indicates not available; NBV, normalized brain volume; Gd, gadolinium; NGMV, normalized gray matter volume; NWMV, normalized white matter volume; NCV, normalized cortical volume; NLVV, normalized lateral ventricle volume.
↵a The data are expressed as mean and SD. Volumes are expressed in milliliters. MTR values are expressed as percentage units. MD is expressed as mm²/s. Because there were only a few subjects with systemic lupus erythematosus (n = 3), type 1 diabetes mellitus (n = 3), Crohn disease (n = 1), and myasthenia gravis (n = 1), they were excluded from MRI analyses. Because no significant MRI primary outcome differences in patients with MS with asthma and rheumatoid arthritis, compared with patients with MS without any comorbidities, were found, no comparison of secondary MRI outcomes was performed for these comorbidities (NA). Analysis of covariance, adjusted for age, sex, MS subtype, disability status, and use and duration of disease-modifying treatment, was used to explore the difference between patients with MS with specific comorbidities compared with patients with MS without any comorbidities. The Benjamini-Hochberg correction was used to minimize the false discovery rate, and corrected P values < .05 were considered significant.
↵b P < .05 shows significant differences of specific comorbidities compared with patients with MS without any comorbidities.
↵c P < .001.
↵d P < .01.