Medication use in a large international sample of people with multiple sclerosis: associations with quality of life, relapse rate and disability

Figures & data

Table 1. Number (%) of people with MS currently taking each medication, duration and number (%) previously taking each medication

Class of medication	Medication name	Number currently taking	Time taken (years)**				Number previously taking
		n = 2276	< 1 year	1–10 years	10+ years	Missing	n = 2276
First generation DMDs	Glatiramer acetate	488 (21.4)	125 (25.6)	321 (65.8)	25 (5.1)	17 (3.5)	345 (15.2)
	Interferons	433 (19.0)	100 (23.1)	266 (61.4)	51 (11.8)	16 (3.7)	570 (25.0)
Second generation DMDs	Natalizumab	132 (5.8)	56 (42.4)	70 (53.0)	1 (0.8)	5 (3.8)	77 (3.4)
	Alemtuzumab	2 (0.1)	2 (100)	0 (0)	0 (0)	0 (0)	3 (0.1)
	Daclizumab	1 (0.1)	1 (100)	0 (0)	0 (0)	0 (0)	2 (0.1)
	Rituximab	2 (0.1)	1 (50.0)	1 (50.0)	0 (0)	0 (0)	5 (0.2)
	Fingolimod	94 (4.1)	71 (75.5)	22 (23.4)	0 (0)	1 (1.1)	25 (1.1)
	Dimethyl fumarate	22 (1.0)	9 (40.9)	11 (50.0)	0 (0)	2 (9.1)	7 (0.3)
	Teriflunomide	4 (0.2)	0 (0)	3 (75.0)	0 (0)	1 (25.0)	0 (0)
	Cladribine	2 (0.1)	2 (100)	0 (0)	0 (0)	0 (0)	0 (0)
	Laquinimod	3 (0.1)	0 (0)	3 (0.1)	0 (0)	0 (0)	2 (0.1)
General immunosuppressants	Azathioprine	7 (0.3)	6 (85.7)	1 (14.3)	0 (0)	0 (0)	22 (1.0)
	Cyclophosphamide	1 (0.1)	1 (100)	0 (0)	0 (0)	0 (0)	14 (0.6)
	Methotrexate	5 (0.2)	2 (40.0)	3 (60.0)	0 (0)	0 (0)	26 (1.1)
	Mitoxantrone	4 (0.2)	3 (75.0)	0 (0)	0 (0)	1 (25.0)	45 (2.0)
	Mycophenolate	5 (0.2)	2 (40.0)	3 (60.0)	0 (0)	0 (0)	3 (0.1)
Steroids	Adrenocorticotropic hormone (ACTH)	9 (0.4)	2 (22.2)	0 (0)	0 (0)	7 (77.8)	28 (1.2)
	Prednisolone	144 (6.3)	99 (68.7)	15 (10.4)	7 (4.9)	23 (16.0)	756 (33.2)
Others	Immunoglobulins	5 (0.2)	1 (20.0)	4 (80.0)	0 (0)	0 (0)	23 (1.0)
	Plasmapheresis	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	11 (0.5)
	LDN	163 (7.2)	44 (27.0)	111 (68.1)	3 (1.8)	5 (3.1)	67 (2.9)
	Minocycline	16 (0.7)	9 (56.2)	7 (43.8)	0 (0)	0 (0)	13 (0.6)
	Baclofen	242 (10.6)	57 (23.6)	147 (60.7)	29 (12.0)	9 (3.7)	127 (5.6)
	Fampridine	80 (3.5)	40 (50.0)	36 (45.0)	1 (1.2)	3 (3.8)	36 (1.6)

DMD: disease-modifying drug; Low-dose naltrexone; MS: multiple sclerosis.

* Data for time taking medication not provided by respondent

** Denominator is variable based on number currently taking specific medication.

Table 2. Medications taken by disease type

Class of medication	Medication name	RRMS	PPMS	SPMS	PRMS	BMS	Unknown MS type	Missing	Total
First generation DMDS	Glatiramer acetate	384 (78.7)	10 (2.0)	6 (1.2)	6 (1.2)	8 (1.6)	52 (10.7)	22 (4.5)	488 (100)
	Interferons	338 (78.1)	7 (1.6)	5 (1.2)	5 (1.2)	8 (1.8)	44 (10.2)	26 (6.0)	433 (100)
Second generation DMDs	Natalizumab	103 (78.0)	6 (4.5)	7 (5.3)	7 (5.3)	0 (0)	8 (6.0)	1 (0.8)	132 (100)
	Alemtuzumab	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	2 (0.0)	2 (100)
	Daclizumab	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	1 (100)	1 (100)
	Rituximab	2 (100.0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	2 (100)
	Fingolimod	67 (71.3)	6 (6.4)	1 (1.1)	1 (1.1)	1 (1.1)	8 (8.5)	10 (10.6)	94 (100)
	Dimethyl fumarate	11 (50.0)	1 (4.5)	1 (4.5)	1 (4.5)	1 (4.5)	3 (27.2)	4 (18.2)	22 (100)
	Teriflunomide	3 (75.0)	0 (0)	0 (0)	0 (0)	0 (0)	1 (25.0)	0 (0)	4 (100)
	Cladribine	1 (50.0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	1 (50.0)	2 (100)
	Laquinimod	3 (100.0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	3 (100)
General immunosuppressants	Azathioprine	1 (14.3)	1 (14.3)	0 (0)	0 (0)	0 (0)	1 (14.3)	4 (57.1)	7 (100)
	Cyclophosphamide	0 (0)	1 (100.0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	1 (100)
	Methotrexate	3 (60.0)	1 (20.0)	0 (0)	1 (20.0)	0 (0)	0 (0)	0 (0)	5 (100)
	Mitoxantrone	1 (25.0)	1 (25.0)	0 (0)	0 (0)	0 (0)	1 (25.0)	1 (25.0)	4 (100)
	Mycophenolate	1 (20.0)	2 (40.0)	0 (0)	1 (20.0)	1 (20.0)	0 (0)	0 (0)	5 (100)
Steroids	Adrenocorticotropic hormone (ACTH)	3 (33.3)	1 (1.1)	1 (1.1)	0 (0)	0 (0)	3 (33.3)	1 (1.1)	9 (100)
	Prednisolone	94 (65.3)	12 (8.3)	3 (2.1)	3 (2.1	3 (2.1)	19 (13.2)	10 (6.9)	144 (100)
Others	Immunoglobulins	2 (40.0)	2 (40.0)	0 (0)	0 (0)	0 (0)	0 (0)	1 (20.0)	5 (100)
	Plasmapheresis	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (100)
	LDN	72 (44.2)	23 (14.1)	3 (1.8)	3 (1.8)	1 (0.6)	26 (3.7)	35 (21.5)	163 (100)
	Minocycline	11 (68.8)	1 (6.3)	0 (0)	0 (0)	0 (0)	4 (25.0)	0 (0)	16 (100)
	Baclofen	91 (37.6)	38 (15.7)	12 (5.0)	12 (5.0)	2 (0.8)	25 (10.3)	62 (0.1)	242 (100)
	Fampridine	30 (37.5)	11 (13.8)	5 (6.3)	5 (6.3)	0 (0)	14 (17.5)	15 (18.8)	80 (100)

DMD: disease-modifying drug; RRMS: relapsing-remitting MS; PPMS: primary progressive MS; SPMS: secondary progressive MS; PRMS: progressive relapsing MS; BMS: benign MS; LDN: low-dose naltrexone.

* Data for type of MS not provided by respondent.

Table 3. Number of participants taking other over the counter, prescription and herbal agents by complaint for which taken (n = 2276)

Condition	Over the counter	Prescription	Herbal	Total participants taking a treatment
Pain	462 (20.3)	389 (17.1)	66 (2.9)	826 (36.3)
Headaches	650 (28.6)	195 (8.6)	40 (1.8)	817 (35.9)
Depression	9 (0.4)	502 (22.1)	69 (3.0)	556 (25.0)
Sleep difficulties	131 (5.8)	292 (12.8)	170 (7.5)	552 (24.3)
Spasticity	32 (1.4)	363 (15.9)	76 (3.3)	453 (19.9)
Fatigue	48 (2.1)	236 (10.4)	134 (5.9)	401 (17.6)
Bladder problems	27 (1.2)	306 (13.6)	74 (3.3)	391 (17.2)
Anxiety	11 (0.5)	258 (11.3)	99 (4.3)	358 (15.7)
Bowel problems	128 (5.6)	102 (4.5)	85 (3.7)	290 (12.7)
Other	33 (1.4)	121 (5.3)	78 (3.4)	215 (9.4)

Values in brackets refer to the percentage of participants overall taking that category of agent for a particular complaint

* Many were taking agents from more than one category.

Table 4. HRQOL composites and subscores by use of a single DMD or not

HRQOL composite/subscore	Single DMD or no DMD	n	Mean HRQOL	SD	P
Overall QOL subscore	No DMD	1104	66.8	19.4	0.472
	DMD	1081	67.4	18.7
Physical health composite	No DMD	919	59.0	22.1	0.403
	DMD	958	59.8	20.8
Mental health composite	No DMD	1078	68.2	21.0	0.011
	DMD	1061	65.9	21.6
Physical health subscore	No DMD	1125	56.4	34.9	0.000
	DMD	1096	64.0	31.1
Role limitations physical subscore	No DMD	1123	44.3	43.3	0.049
	DMD	1092	47.9	43.5
Role limitations emotional subscore	No DMD	1117	69.7	41.0	0.373
	DMD	1080	68.1	41.3
Pain subscore	No DMD	1129	72.0	26.2	0.985
	DMD	1090	72.0	26.1
Emotional wellbeing subscore	No DMD	1132	70.1	18.2	0.001
	DMD	1098	67.4	19.1
Energy subscore	No DMD	1132	44.5	23.1	0.121
	DMD	1098	43.0	22.0
Health perception subscore	No DMD	1130	57.2	23.4	0.082
	DMD	1097	55.5	21.9
Social function subscore	No DMD	1094	69.0	24.9	0.118
	DMD	1067	70.6	23.2
Cognitive function subscore	No DMD	1132	68.2	26.3	0.002
	DMD	1098	64.6	27.3
Health distress subscore	No DMD	1130	61.8	27.0	0.009
	DMD	1098	58.8	27.3
Sexual function subscore	No DMD	976	65.4	31.3	0.113
	DMD	999	67.6	30.0

HRQOL: health-related quality of life; DMD: disease-modifying drug.

* Data are for respondents taking one DMD only. Bold denotes statistically significant.

Figure 1. Health-related quality of life (HRQOL) by individual DMDs, all other DMDs and no DMD use

Figure 2. Health-related quality of life (HRQOL) for low-dose naltrexone (LDN), all other DMDs and no DMD use^*

Table 5. HRQOL composites and subscores comparing each of the four most frequently used DMDs against no DMD use

HRQOL composite/subscore	DMD used	n =	Mean HRQOL	SD	P	Pairwise comparisons*
Physical health composite	1. Natalizumab only	107	54.9	20.9	0.002	3 vs 1, P = 0.001
	2. Fingolimod only	71	55.8	20.5		3 vs 2, P = 0.012
	3. Glatiramer only	408	62.8	20.8		3 vs 4, P = 0.014
	4. Interferons only	351	59.0	20.7		3 vs 5, P = 0.003
	5. No DMD	919	59.0	22.1
Mental health composite	1. Natalizumab only	118	64.5	21.4	0.012	5 vs 2, P = 0.027
	2. Fingolimod only	85	62.9	20.6		5 vs 4, P = 0.007
	3. Glatiramer only	450	67.8	21.7		3 vs 4, P = 0.045
	4. Interferons only	384	64.8	21.7
	5. No DMD	1078	68.2	21.0
Physical health subscore	1.Natalizumab only	122	56.6	32.7	< 0.001	3 vs 1, P < 0.001
	2. Fingolimod only	86	55.8	33.6		3 vs 2, P = 0.001
	3. Glatiramer only	463	68.6	30.0		3 vs 4, P = 0.013
	4. Interferons only	401	63.1	30.5		3 vs 5, P < 0.001
	5. No DMD	1125	56.4	34.9		4 vs 5, P < 0.001
Role limitations physical subscore	1. Natalizumab only	119	43.1	43.8	0.023	3 vs 1, P = 0.044
	2. Fingolimod only	86	44.2	42.1		3 vs 4, P = 0.034
	3. Glatiramer only	463	52.0	43.8		3 vs 5, P = 0.001
	4. Interferons only	400	45.8	43.1
	5. No DMD	1123	44.3	43.3
Pain subscore	1. Natalizumab only	121	70.4	27.9	0.003	3 vs 2, P = 0.001
	2. Fingolimod only	85	65.6	27.4		3 vs 4, P = 0.003
	3. Glatiramer only	463	75.5	24.8		3 vs 5, P = 0.017
	4. Interferons only	397	70.1	26.2		2 vs 5, P = 0.029
	5. No DMD	1129	72.0	26.2
Emotional wellbeing subscore	1. Natalizumab only	122	67.1	19.4	0.006	4 vs 5, P < 0.001
	2. Fingolimod only	86	67.6	18.7
	3. Glatiramer only	464	68.6	19.0
	4. Interferons only	402	66.3	19.0
	5. No DMD	1132	70.1	18.2
Health perception subscore	1. Natalizumab only	122	54.8	23.5	0.017	3 vs 2, P = 0.005
	2. Fingolimod only	86	50.3	19.3		3 vs 4, P = 0.047
	3. Glatiramer only	464	57.8	22.3		5 vs 2, P = 0.007
	4. Interferons only	401	54.7	21.4
	5. No DMD	1130	57.2	23.4
Social function subscore	1. Natalizumab only	117	66.7	22.8	0.005	3 vs 1, P = 0.006
	2. Fingolimod only	83	68.1	22.6		3 vs 4, P = 0.008
	3. Glatiramer only	455	73.6	22.6		3 vs 5, P = 0.001
	4. Interferons only	388	69.1	24.0
	5. No DMD	1094	69.0	24.9
Cognitive function subscore	1.Natalizumab only	122	63.4	27.9	0.008	5 vs 2, P = 0.004
	2. Fingolimod only	86	59.5	29.1		5 vs 4, P = 0.038
	3. Glatiramer only	464	65.5	27.2
	4. Interferons only	402	65.0	27.2
	5. No DMD	1132	68.2	26.3
Health distress subscore	1.Natalizumab only	122	56.8	28.0	0.033	4 vs 5, P = 0.027
	2. Fingolimod only	86	55.6	27.5
	3. Glatiramer only	464	61.0	27.6
	4. Interferons only	402	58.3	26.8
	5. No DMD	1130	61.8	27.0
Sexual function subscore	1. Natalizumab only	113	64.2	31.5	0.033	3 vs 2, P = 0.035
	2. Fingolimod only	74	62.4	29.2		3 vs 4, P = 0.039
	3. Glatiramer only	422	70.5	29.4		3 vs 5, P = 0.004
	4. Interferons only	369	66.0	30.2
	5. No DMD	976	65.4	31.3

Only domains with significant differences are shown.

HRQOL: health-related quality of life; DMD: disease-modifying drug.

* Pairwise comparison with bonferroni adjustment applied, significant differences only shown. Bold denotes statistically significant.

Table 6. Number and percentage of PwMS in each major disability category by DMD use and polypharmacy

		Level of disability (PDDS)
		Normal/some n (%)	Moderate n (%)	Major n (%)	Total n (%)	P
DMD use	Yes	674 (61.6)	355 (32.4)	66 (6.0)	1095 (100)	< 0.001
	No	557 (49.2)	410 (36.2)	166 (14.7)	1133 (100)
	Total	1231 (55.3)	765 (34.3)	232 (10.4)	2228 (100)
Polypharmacy	Yes	107 (31.6)	165 (48.7)	67 (19.8)	339 (100%)	< 0.001
	No	1160 (59.2)	628 (32.0)	173 (8.8)	1961 (100%)
	Total	1267 (55.1)	793 (34.5)	240 (10.4)	2300 (100)
Polypharmacy among subsample with DMD use	Yes	48 (41.4)	56 (48.3)	12 (10.3)	116 (100.0)	< 0.001
	No	393 (64.3)	185 (30.3)	33 (5.4)	611 (100.0)
	Total	441 (60.7)	241 (33.1)	45 (6.2)	727 (100.0)
Polypharmacy among subsample without DMD use	Yes	38 (24.7)	70 (45.5)	46 (29.9)	154 (100.0)	< 0.001
	No	519 (53.0)	340 (34.7%)	120 (12.3%)	979 (100.0)
	Total	557 (49.2)	410 (36.2)	166 (14.7)	1133 (100.0)

DMD: disease-modifying drug; PDDS: patient-determined disease steps; PwMS: people with multiple sclerosis.

* Bold faces denote significantly over-represented as determined by standardized adjusted residuals.

† Denotes significantly under-represented as determined by standardized adjusted residuals.