J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website https://jocmr.elmerjournals.com

Original Article

Volume 18, Number 5, May 2026, pages 301-312

Optimizing Rituximab Maintenance Therapy: Outcomes of Extended-Interval Dosing in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder

↓ Figure 1. Flowchart demonstrating patients that were included and excluded in the study. *Three AQP4-IgG-seropositive NMOSD patients receiving rituximab were not recruited in the study because they had received rituximab at intervals shorter than 24 weeks due to persistently elevated CD19 levels 24 weeks after each infusion. AQP4-IgG+ NMOSD: aquaporin-4 immunoglobulin G seropositive neuromyelitis optica spectrum disorder.

↓ Figure 2. Annualized relapse rate pre- and post-treatment. (a) Multiple sclerosis. (b) AQP4-IgG-seropositive neuromyelitis optica spectrum disorder. AQP4-IgG: aquaporin-4 immunoglobulin G.

↓ Figure 3. Kaplan–Meier curve demonstrating the proportion of relapse-free patients at the cutpoint of 32 weeks. (a) Multiple sclerosis. (b) AQP4-IgG-seropositive neuromyelitis optica spectrum disorder. CI: confidence interval; AQP4-IgG: aquaporin-4 immunoglobulin G.

↓ Figure 4. Kaplan–Meier curve demonstrating the proportion of relapse-free in treatment-naive and treatment-experienced patients. (a) Multiple sclerosis. (b) AQP4-IgG-seropositive neuromyelitis optica spectrum disorder. AQP4-IgG: aquaporin-4 immunoglobulin G.

↓ **Table 1.** Baseline Characteristics of Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder
	Total (n = 87)	MS (n = 43)	NMOSD (n = 44)
^aData are presented as mean ± standard deviation. ^bData are presented as median (IQR). ^cInitial dosing interval refers to the dosing interval of the first cycle immediately after induction. NMOSD: neuromyelitis optica spectrum disorder; MS: multiple sclerosis; RTX: rituximab; SD: standard deviation; IQR: interquartile range.
Female sex	68 (78.2)	31 (72.1)	37 (84.1)
Age at onset (years)^a	33.99 ± 15.52	26.63 ± 10.48	41.35 ± 16.33
Age at RTX initiation (years)^a	39.28 ± 15.11	32.34 ± 10.98	46.23 ± 15.59
Age at enrolment (years)^a	43.56 ± 15.47	36.28 ± 11.26	50.83 ± 15.79
Duration since onset to RTX initiation (years)^b	3.28 (0.76–8.04)	5.10 (1.49–8.05)	2.18 (0.62–7.70)
Treatment status, n (%)
Treatment-naive	27 (31.0)	13 (30.2)	14 (31.8)
Treatment-experienced	60 (69.0)	30 (69.8)	30 (68.2)
Azathioprine	50 (57.5)	23 (53.5)	27 (61.4)
Mycophenolate	29 (33.3)	11 (25.6)	18 (40.9)
Methotrexate	1 (1.1)	1 (2.3)	0 (0.0)
Mitoxantrone	1 (1.1)	0 (0.0)	1 (2.3)
Cyclophosphamide	1 (1.1)	0 (0.0)	1 (2.3)
Interferon-beta	3 (3.4)	2 (4.7)	1 (2.3)
Teriflunomide	2 (2.3)	2 (4.7)	0 (0.0)
Fingolimod	1 (1.1)	1 (2.3)	0 (0.0)
RTX indication, n (%)
Treatment ineffectiveness	45 (75.0)	23 (76.7)	22 (73.3)
Treatment adverse effects	15 (25.0)	7 (23.3)	8 (26.7)
RTX regimen
Initial dosing interval (weeks)^c
Mean ± SD	31.98 ± 8.01	30.98 ± 6.85	32.95 ± 8.97
Median (IQR)	27.71 (26.57–37.43)	27.71 (26.43–34.29)	28.00 (26.61–39.07)
Mean dosing interval (weeks)
Mean ± SD	33.25 ± 7.04	32.61 ± 4.87	33.87 ± 8.67
Median (IQR)	30.38 (28.57–36.67)	32.25 (29.03–35.89)	29.44 (27.87–40.92)
RTX duration (years)
Mean ± SD	4.52 ± 1.96	4.10 ± 1.42	4.92 ± 2.32
Median (IQR)	4.34 (3.10–5.51)	4.32 (2.81–5.46)	4.45 (3.16–5.52)

↓ Table 1. Baseline Characteristics of Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder

Total (n = 87)

MS (n = 43)

NMOSD (n = 44)

^aData are presented as mean ± standard deviation. ^bData are presented as median (IQR). ^cInitial dosing interval refers to the dosing interval of the first cycle immediately after induction. NMOSD: neuromyelitis optica spectrum disorder; MS: multiple sclerosis; RTX: rituximab; SD: standard deviation; IQR: interquartile range.

Female sex

68 (78.2)

31 (72.1)

37 (84.1)

Age at onset (years)^a

33.99 ± 15.52

26.63 ± 10.48

41.35 ± 16.33

Age at RTX initiation (years)^a

39.28 ± 15.11

32.34 ± 10.98

46.23 ± 15.59

Age at enrolment (years)^a

43.56 ± 15.47

36.28 ± 11.26

50.83 ± 15.79

Duration since onset to RTX initiation (years)^b

3.28 (0.76–8.04)

5.10 (1.49–8.05)

2.18 (0.62–7.70)

Treatment status, n (%)

Treatment-naive

27 (31.0)

13 (30.2)

14 (31.8)

Treatment-experienced

60 (69.0)

30 (69.8)

30 (68.2)

Azathioprine

50 (57.5)

23 (53.5)

27 (61.4)

Mycophenolate

29 (33.3)

11 (25.6)

18 (40.9)

Methotrexate

1 (1.1)

1 (2.3)

0 (0.0)

Mitoxantrone

1 (1.1)

0 (0.0)

1 (2.3)

Cyclophosphamide

1 (1.1)

0 (0.0)

1 (2.3)

Interferon-beta

3 (3.4)

2 (4.7)

1 (2.3)

Teriflunomide

2 (2.3)

2 (4.7)

0 (0.0)

Fingolimod

1 (1.1)

1 (2.3)

0 (0.0)

RTX indication, n (%)

Treatment ineffectiveness

45 (75.0)

23 (76.7)

22 (73.3)

Treatment adverse effects

15 (25.0)

7 (23.3)

8 (26.7)

RTX regimen

Initial dosing interval (weeks)^c

Mean ± SD

31.98 ± 8.01

30.98 ± 6.85

32.95 ± 8.97

Median (IQR)

27.71 (26.57–37.43)

27.71 (26.43–34.29)

28.00 (26.61–39.07)

Mean dosing interval (weeks)

Mean ± SD

33.25 ± 7.04

32.61 ± 4.87

33.87 ± 8.67

Median (IQR)

30.38 (28.57–36.67)

32.25 (29.03–35.89)

29.44 (27.87–40.92)

RTX duration (years)

Mean ± SD

4.52 ± 1.96

4.10 ± 1.42

4.92 ± 2.32

Median (IQR)

4.34 (3.10–5.51)

4.32 (2.81–5.46)

4.45 (3.16–5.52)

↓ **Table 2.** Disease Activity and Disability Outcomes of Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder
Efficacy outcomes	Total (n = 87)	MS (n = 43)	NMOSD (n = 44)
^aData are presented as median (IQR). NMOSD: neuromyelitis optica spectrum disorder; EDSS: EDSS: Expanded Disability Status Scale; Gd: gadolinium-enhanced; MS: multiple sclerosis; RTX: rituximab; T2w: T2-weighted; IQR: interquartile range.
Relapse
Number of relapses	11 (12.6)	4 (9.3)	7 (15.9)
Relapses within 6 months after RTX, n (%)	4 (4.6)	0 (0)	4 (9.1)
Time to first relapse after RTX (years)^a	1.12 (0.27–1.60)	1.44 (1.18–2.02)	0.45 (0.20–0.87)
EDSS
EDSS before RTX^a	4.0 (2.0–5.8)	2.0 (0.0–4.5)	4.5 (4.0–6.5)
EDSS after RTX^a	2.0 (0.0–4.0)	0.0 (0.0–2.0)	4.0 (2.0–5.0)
EDSS change^a	1.0 (0.0–2.0)	0.0 (0.0–2.0)	1.0 (0.0–2.9)
Radiological activity, n (%)
New T2w lesions	0/40 (0.0)	0/26 (0.0)	0/14 (0.0)
New Gd lesions	0/40 (0.0)	0/26 (0.0)	0/14 (0.0)
Safety outcomes, n (%)
RTX adverse effects	33 (37.9)	14 (32.6)	19 (43.2)
Infusion-related	14 (16.1)	7 (16.3)	7 (15.9)
Infection	18 (20.7)	6 (14.0)	12 (27.3)
Leukopenia	5 (5.7)	2 (4.7)	3 (6.8)
Hypogammaglobulinemia	1/27 (3.7)	0/12 (0.0)	1/15 (6.7)

↓ Table 2. Disease Activity and Disability Outcomes of Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder

Efficacy outcomes

Total (n = 87)

MS (n = 43)

NMOSD (n = 44)

^aData are presented as median (IQR). NMOSD: neuromyelitis optica spectrum disorder; EDSS: EDSS: Expanded Disability Status Scale; Gd: gadolinium-enhanced; MS: multiple sclerosis; RTX: rituximab; T2w: T2-weighted; IQR: interquartile range.

Relapse

Number of relapses

11 (12.6)

4 (9.3)

7 (15.9)

Relapses within 6 months after RTX, n (%)

4 (4.6)

0 (0)

4 (9.1)

Time to first relapse after RTX (years)^a

1.12 (0.27–1.60)

1.44 (1.18–2.02)

0.45 (0.20–0.87)

EDSS

EDSS before RTX^a

4.0 (2.0–5.8)

2.0 (0.0–4.5)

4.5 (4.0–6.5)

EDSS after RTX^a

2.0 (0.0–4.0)

0.0 (0.0–2.0)

4.0 (2.0–5.0)

EDSS change^a

1.0 (0.0–2.0)

0.0 (0.0–2.0)

1.0 (0.0–2.9)

Radiological activity, n (%)

New T2w lesions

0/40 (0.0)

0/26 (0.0)

0/14 (0.0)

New Gd lesions

0/40 (0.0)

0/26 (0.0)

0/14 (0.0)

Safety outcomes, n (%)

RTX adverse effects

33 (37.9)

14 (32.6)

19 (43.2)

Infusion-related

14 (16.1)

7 (16.3)

7 (15.9)

Infection

18 (20.7)

6 (14.0)

12 (27.3)

Leukopenia

5 (5.7)

2 (4.7)

3 (6.8)

Hypogammaglobulinemia

1/27 (3.7)

0/12 (0.0)

1/15 (6.7)

↓ **Table 3.** Comparison of Clinical and Laboratory Outcomes Between Pre- and Post-RTX
	Pre-RTX	Post-RTX	P value
All data are presented as median (interquartile range). NMOSD: neuromyelitis optica spectrum disorder; ARR: annualized relapse rate; CD19: cluster of differentiation 19; EDSS: Expanded Disability Status Scale; MS: multiple sclerosis; RTX: rituximab.
MS (n = 43)
Number of relapses (times)	3 (2–4)	0 (0–0)	< 0.001
ARR (times/year)	0.55 (0.47–0.84)	0.00 (0.00–0.00)	< 0.001
EDSS	2.0 (0.0–4.5)	0.0 (0.0–2.0)	0.006
%CD19	13.58 (9.11–18.25)	1.45 (0.95–2.56)	< 0.001
NMOSD (n = 44)
Number of relapses (times)	3 (2–6)	0 (0–0)	< 0.001
ARR (times/year)	1.15 (0.54–1.72)	0.00 (0.00–0.00)	< 0.001
EDSS	4.5 (4.0–6.5)	4.0 (2.0–5.0)	< 0.001
%CD19	15.14 (12.25–23.38)	2.08 (0.89–5.39)	< 0.001

↓ Table 3. Comparison of Clinical and Laboratory Outcomes Between Pre- and Post-RTX

Pre-RTX

Post-RTX

P value

All data are presented as median (interquartile range). NMOSD: neuromyelitis optica spectrum disorder; ARR: annualized relapse rate; CD19: cluster of differentiation 19; EDSS: Expanded Disability Status Scale; MS: multiple sclerosis; RTX: rituximab.

MS (n = 43)

Number of relapses (times)

3 (2–4)

0 (0–0)

< 0.001

ARR (times/year)

0.55 (0.47–0.84)

0.00 (0.00–0.00)

< 0.001

EDSS

2.0 (0.0–4.5)

0.0 (0.0–2.0)

0.006

%CD19

13.58 (9.11–18.25)

1.45 (0.95–2.56)

< 0.001

NMOSD (n = 44)

Number of relapses (times)

3 (2–6)

0 (0–0)

< 0.001

ARR (times/year)

1.15 (0.54–1.72)

0.00 (0.00–0.00)

< 0.001

EDSS

4.5 (4.0–6.5)

4.0 (2.0–5.0)

< 0.001

%CD19

15.14 (12.25–23.38)

2.08 (0.89–5.39)

< 0.001

↓ **Table 4.** Subgroup Analysis in Patients With and Without Other Treatments Prior to RTX
	Pre-RTX	Post-RTX	P value
All data are presented as median (interquartile range). NMOSD: neuromyelitis optica spectrum disorder; EDSS: Expanded Disability Status Scale; MS: multiple sclerosis; RTX: rituximab.
MS
Treatment-naive (n = 13)
Number of relapses (time)	2 (1–3)	0 (0–0)	0.001
EDSS	2.0 (0.0–4.8)	0.0 (0.0–2.0)	0.012
Treatment-experienced (n = 27)
Number of relapses (time)	3 (2–5)	0 (0–0)	< 0.001
EDSS	2.0 (0.0–4.0)	2.0 (0.0–3.0)	0.106
NMOSD
Treatment-naive (n = 10)
Number of relapses (time)	1 (1–2)	0 (0–0)	0.001
EDSS	4.5 (2.8–6.0)	2.0 (0.8–5.1)	0.011
Treatment-experienced (n = 24)
Number of relapses (time)	4 (2–8)	0 (0–1)	< 0.001
EDSS	4.5 (4.0–6.5)	4.0 (2.1–4.0)	0.005

↓ Table 4. Subgroup Analysis in Patients With and Without Other Treatments Prior to RTX

Pre-RTX

Post-RTX

P value

All data are presented as median (interquartile range). NMOSD: neuromyelitis optica spectrum disorder; EDSS: Expanded Disability Status Scale; MS: multiple sclerosis; RTX: rituximab.

Treatment-naive (n = 13)

Number of relapses (time)

2 (1–3)

0 (0–0)

0.001

EDSS

2.0 (0.0–4.8)

0.0 (0.0–2.0)

0.012

Treatment-experienced (n = 27)

Number of relapses (time)

3 (2–5)

0 (0–0)

< 0.001

EDSS

2.0 (0.0–4.0)

2.0 (0.0–3.0)

0.106

NMOSD

Treatment-naive (n = 10)

Number of relapses (time)

1 (1–2)

0 (0–0)

0.001

EDSS

4.5 (2.8–6.0)

2.0 (0.8–5.1)

0.011

Treatment-experienced (n = 24)

Number of relapses (time)

4 (2–8)

0 (0–1)

< 0.001

EDSS

4.5 (4.0–6.5)

4.0 (2.1–4.0)

0.005