Can a physician predict the clinical response to first-line immunomodulatory treatment in relapsing–remitting multiple sclerosis?

Figures & data

Table 1 Baseline data of all patients and groups according to the type of immunomodulatory treatment (IMT)

	Total	IFN beta-1b	GA	IFN beta-1a IM	IFN beta-1a SC	P (ANOVA)
Number	81	21	26	27	7
Females	51	14	18	15	4
Mean IMT duration (months)	54 ± 33	80 ± 33	52 ± 36	38 ± 20	40 ± 13	< 0.0001
Age ± SD at initiation of IMT (years)	35.3 ± 8.3	36.0 ± 8	36.2 ± 8.3	32.2 ± 7.1	41.6 ± 9.8	0.037
Time between onset and diagnosis of MS (years)	4 ± 3.8	2.8 ± 2	5.0 ± 5.1	2.9 ± 2.7	8.1 ± 3.3	0.0017
Time between diagnosis and initiation of IMT (years)	3.8 ± 3.4	4.5 ± 4.4	4.1 ± 3.3	2.9 ± 2.8	3.6 ± 2.6	NS
Prior 2-year relapses	2.4 ± 1.3	3.0 ± 1.1	2.0 ± 1.7	2.5 ± 1.1	2.1 ± 0.9	NS
Mean baseline EDSS score	2.8 ± 1.4	3.4 ± 1.3	3.1 ± 1.6	2.1 ± 1.0	2.6 ± 1.1	0.011

Abbreviations: IFN, interferon; GA, glatiramer acetate; IM, intramuscular; SC, subcutaneous; ANOVA, analysis of variance; SD, standard deviation; MS, multiple sclerosis; NS, not significant; EDSS, Expanded Disability Status Scale.

Figure 1 Distribution of EDSS score at baseline in groups with different immunomodulatory agents.

Abbreviations: EDSS, Expanded Disability Status Scale; INF, interferon; GA, glatiramer acetate.

Figure 2 Effect of treatment on relapse numbers in the groups according to the type of immunomodulatory treatment (IMT).

Table 2 Effect of treatment on EDSS progression in patient subgroups according to the length of continuous immunomodulatory treatment (IMT)

	Total	IFN beta-1b	GA	IFN beta-1a IM	IFN beta-1a SC	P (ANOVA)
Patients
2, 4, and >6 years’ IMT, respectively	78, 75, 29	20, 20, 16	24, 21, 7	27, 27, 6	7, 7, 0
EDSS 2 years’ IMT	2.9 ± 1.6	3.3 ± 1.7	3.3 ± 1.8	2.1 ± 1.1	2.9 ± 1.1	0.025
EDSS 4 years’ IMT	3.0 ± 1.8	3.8 ± 1.8	3.5 ± 2.2	2.1 ± 1.1	2.9 ± 1.1	0.003
EDSS > 6 years’ IMT	4.0 ± 2.2	4.5 ± 2.1	4.6 ± 2.1	1.9 ± 1.4	NA	0.025
EDSS change from baseline at 2 years’ IMT	0.1 ± 0.7	−0.1 ± 0.8	0.3 ± 0.8	0.0 ± 0.5	0.4 ± 0.6	NS
EDSS change from baseline at 4 years’ IMT	0.3 ± 0.9	0.4 ± 1.1	0.6 ± 1.1	−0.1 ± 0.6	0.3 ± 0.5	NS
EDSS change from baseline over 6 years’ IMT	0.9 ± 1.3	1.1 ± 1.5	1.1 ± 1.1	0.2 ± 0.9	NA	0.003

Abbreviations: IFN, interferon; GA, glatiramer acetate; IM, intramuscular; SC, subcutaneous; ANOVA, analysis of variance; NA, not applicable; NS, not significant; EDSS, Expanded Disability Status Scale.

Figure 3 Sustained efficacy of longer than 6 years’ immunomodulatory treatment on disability.

Notes: Patients treated with IFN beta-1a intramuscularly had the smallest Expanded Disability Status Scale (EDSS) score at baseline and 2, 4, and more than 6 years’ treatment (P = 0.011, 0.025, 0.003, and 0.025 respectively).

Table 3 Baseline data of patients and treatment response in the groups according to clinical presentation at onset of multiple sclerosis (MS)

	Unifocal symptom (n = 46)	Multifocal symptoms (n = 35)
Time between onset and diagnosis of MS (years ± SD)	3.9 ± 3.5	4.1 ± 4.4
Time between diagnosis and initiation of IMT (years ± SD)	3.4 ± 2.7	4.2 ± 4.2
Age ± SD at initiation of IMT (years)	35.3 ± 2.8	35.2 ± 8.5
Prior 2-year relapses	2.3 ± 0	2.5 ± 0.7
Relapses in first 2 years’ IMT	0.5 ± 0	0.7 ± 2.8
Mean baseline EDSS score (± SD)	2.6 ± 2.1	3.0 ± 0.3
Mean IMT duration (months ± SD)	59 ± 35	47 ± 30
Final duration of disorder with IMT	12.3 ± 5.8	12.2 ± 7.3
Final EDSS on IMT	3.1 ± 2.0	3.6 ± 2.1
EDSS on >6 years’ IMT	3.8 (n = 18)	4.3 (n = 11)

Abbreviations: IMT, immunomodulatory treatment; SD, standard deviation; EDSS, Expanded Disability Status Scale.

Table 4 Long-term effect of immunomodulatory treatment (IMT) on EDSS change in the groups according to short-term response to IMT by relapse numbers

	Responders (n = 58)	Nonresponders (n = 8)	Partial responders (n = 15)	P
Time between onset and diagnosis of MS (years)	3.9 ± 8.1	4.8 ± 6.0	3.9 ± 7.4	NS
Time between diagnosis and initiation of IMT (years)	3.3 ± 3.5	5.6 ± 1.1	4.6 ± 0	NS
Mean IMT duration (months)	55 ± 33	42 ± 28	57 ± 36	NS
Final duration of disorder	11.8 ± 8.5	13.8 ± 8.1	13.1 ± 6.7	NS
Final EDSS score on IMT	3.0 ± 2.0	4.6 ± 2.4	4.0 ± 1.6	0.032
Age ± SD at initiation of IMT (years)	35.8 ± 13.4	34.9 ± 7.8	33.6 ± 2.1	NS
Prior 2-year relapses	2.5 ± 0.7	2.1 ± 1.4	2.5 ± 0.7	NS
Relapses in first 2 years’ IMT	0.2 ± 0	1.9 ± 1.4	1.5 ± 0.7	<0.0001
Mean baseline EDSS score	2.6 ± 0.7	3.1 ± 1.8	3.2 ± 0.7	NS
EDSS score, 2 years’ IMT	2.5 ± 0.4	3.7 ± 2.1	3.7 ± 0.7	0.015
EDSS score, 4 years’ IMT	2.6 ± 0.4	4.3 ± 0.7	3.9 ± 0.4	0.016
EDSS score, >6 years’ IMT	3.6 ± 0.4 (n = 21)	7.5 (n = 1)	4.9 (n = 7)	NS

Abbreviations: SD, standard deviation; MS, multiple sclerosis; NS, not significant; EDSS, Expanded Disability Status Scale.

Table 5 Incidences of side effects of immunomodulatory drugs

	IFN beta-1b (n = 21)	GA (n = 26)	IFN beta-1a IM (n = 27)	IFN beta-1a SC (n = 7)
Injectionsite reaction	6	3	0	1
Lipoatrophy	2	1	0	1
Flu-like symptoms	6	0	5	3

Abbreviations: IFN, interferon; GA, glatiramer acetate; IM, intramuscular; SC, subcutaneous.