Satralizumab treatment in adults with aquaporin-4 immunoglobulin G-seropositive neuromyelitis optica spectrum disorder in clinical practice

Abstract

Background

Satralizumab is approved for aquaporin-4 immunoglobulin G-positive (AQP4-IgG⁺) neuromyelitis optica spectrum disorder (NMOSD), but real-world data are limited. This case series aimed to describe real-world experiences with satralizumab in adults with AQP4-IgG⁺ NMOSD.

Methods

Case information for patients with AQP4-IgG⁺ NMOSD who received satralizumab for ≥6 months was obtained from US healthcare providers over 28 months. Patient characteristics, examination findings, diagnostic tests, treatment responses, and adverse events were recorded.

Results

Of 43 patients, 88% were female and 44% self-identified as Black. Median age was 54 (range, 20–82) years, and time since confirmed NMOSD diagnosis was 8 (1–18) years. Reasons for satralizumab initiation included intolerance/safety concerns with existing therapy (30%), new diagnosis (26%), and inadequate disease control (21%). The median duration of satralizumab treatment was 31 (range, 7–104) months, during which three patients (7%) had radiographically confirmed relapses and 15 (35%) experienced a related adverse event. At data cutoff, 35 patients (81%) were receiving satralizumab.

Conclusion

Satralizumab was effective and well tolerated in patients with NMOSD, including those who switched from previous treatments due to inadequate disease control and/or intolerance. These real-world outcomes align with long-term safety and efficacy findings from the Phase III SAkura trials.

Keywords

Neuromyelitis optica case studies satralizumab monoclonal antibodies treatment switches

Introduction

Neuromyelitis optica spectrum disorder (NMOSD), an autoimmune disease characterized by central nervous system inflammation affecting the optic nerves and spinal cord, leads to vision loss, motor and sensory impairment, and permanent neurological disability.¹ Worldwide, NMOSD prevalence is estimated at 0.34 to 10 per 100,000 adults and ≤0.22 per 100,000 children but is higher in women and varies by geography, race, and ethnicity.² Pathogenic anti-aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) are present in the majority of patients with NMOSD.¹ Patients with AQP4-IgG-seropositive (AQP4-IgG⁺) NMOSD are more often female and have more severe clinical attacks.^3,4

NMOSD management involves treatment of acute attacks and long-term maintenance to prevent future relapses.⁵ Before 2019, only off-label therapies were available to prevent NMOSD relapses, including monoclonal antibodies (mAbs; e.g. rituximab, tocilizumab) and immunosuppressant therapies (ISTs; e.g. oral corticosteroids, azathioprine, mycophenolate mofetil (MMF)).⁶ Several mAbs are now approved for AQP4-IgG⁺ NMOSD, including eculizumab⁷ and ravulizumab,⁸ which target C5 complement protein, and inebilizumab,⁹ which targets CD19 B-cell antigen.¹⁰

Additionally, satralizumab, a subcutaneously administered, humanized IgG2 mAb targeting the interleukin 6 (IL-6) receptor,¹⁰ was developed specifically for AQP4-IgG⁺ NMOSD and approved for adults by the US Food and Drug Administration (FDA) in 2020.¹¹ IL-6 participates in NMOSD pathophysiology via T- and B-cell activation and AQP4-IgG autoantibody secretion.^12–15 Inhibition of membrane-bound and soluble IL-6 receptors by satralizumab suppresses lymphocyte activation and central nervous system injury associated with IL-6.^1,13,16,17 Satralizumab has demonstrated long-term safety and efficacy in placebo-controlled Phase III trials (SAkuraSky (NCT02028884) and SAkuraStar (NCT02073279)).^17,18

Patients with NMOSD commonly switch treatments due to reasons including relapses, intolerance of current therapies, preference for different routes of administration, or changes in insurance coverage. Since FDA-approved therapies for NMOSD are now available, transitions are made from both off-label therapies like rituximab and other approved treatments. These shifts underscore a broader need to understand the implications of moving directly between therapies without washout periods that are standard in clinical trials. Clinical trials often mandate washout periods of 3–6 months^17–20 to ensure that observed effects are attributable solely to the study drug and not influenced by interactions with or withdrawal effects from previous medications. However, these washout periods can be unrepresentative of real-world clinical practice, especially for patients at high risk of relapse. Furthermore, clinical trials often impose age and comorbidity restrictions, which may not capture the full spectrum of patient populations encountered in routine practice.

The objective of this case series is to highlight the real-world experiences of US patients with NMOSD who have received satralizumab either as an initial preventive treatment or after switching from an approved or off-label therapy. This analysis aims to provide critical insights into efficacy and safety in a real-world setting, thereby addressing the practical gaps left by controlled clinical trials.

Patients and methods

Cases were identified by US healthcare providers from academic centers, specialized neuroimmunology clinics, and private neurology groups, who were instructed to include all eligible patients within their practice who had a diagnosis of AQP4-IgG⁺ NMOSD according to the 2015 international panel criteria,²¹ confirmed detection of AQP4-IgG (by cell-based assay, fluorescence-activated cell sorting, or enzyme-linked immunosorbent assay) and received satralizumab. Inclusion criteria required ≥6 months of continuous satralizumab treatment at the time of physician-reported data submission. Data were collected between April 1, 2022 and July 31, 2024 (data cutoff). Observation time on satralizumab varied by patient and was defined as the period from treatment initiation to either treatment discontinuation or the time of data submission, whichever came first. No requirements were imposed regarding elapsed time between discontinuing a maintenance treatment and initiating satralizumab. All patients who met the study criteria were included, regardless of clinical outcomes, adverse events (AEs) or patient experiences. Patients saw their physicians as part of their typical care, and physicians reported on any clinical findings available. There were no formal study visits or prespecified study outcomes.

Cases where patients discontinued rituximab and eculizumab and initiated satralizumab cases have been partially described^22,23 but the current report provides information on additional months of follow up for patients with these treatment switches. Moreover, this report provides a comprehensive overview of all cases shared by practicing physicians to date, including patients who were previously treatment naive or had received other preventative treatments, including ISTs or tocilizumab, prior to starting satralizumab.

Satralizumab was administered subcutaneously per label instructions: 120-mg loading doses every 2 weeks for three administrations, then 120-mg maintenance doses every 4 weeks.¹¹ Patient characteristics, examination findings (including Expanded Disability Status Scale (EDSS) score or estimated EDSS score), diagnostic test results, AEs, and treatment responses were recorded. Radiographically confirmed relapse was defined as a clinical worsening of neurological symptoms supported by magnetic resonance imaging (MRI) findings of new or enhancing lesions. Events of relapse symptoms that were not counted as radiographically confirmed relapses due to a lack of MRI evidence were qualitatively described. Descriptive statistics were used to summarize patient characteristics and clinical outcomes.

Ethical review and approval were not required for this retrospective, observational study. All patients provided written consent for the publication of their case information.

Results

Demographic and clinical characteristics

Of 43 patients included (38 women; 5 men), the median age was 54 (range, 20–82) years; 44% of patients self-identified as Black and 49% as White (Table 1). Overall, 35% of patients had coexisting autoimmune comorbidities, most commonly hypothyroidism, myasthenia gravis, Sjögren syndrome, and systemic lupus erythematosus (SLE; n = 3 for each). One treatment-naive patient (TN4) had coexisting high myelin oligodendrocyte glycoprotein antibody titer (1:100) along with AQP4-IgG positivity, and overlapping clinical features of both disorders.

Table 1.

Demographic and clinical characteristics of patients with AQP4-IgG⁺ NMOSD who received satralizumab.

	All patients(N = 43)
Age, median (range), years^a	54 (20–82)
Sex, n (%)
Female	38 (88.4)
Male	5 (11.6)
Race, n (%)
Asian/Pacific Islander	2 (4.7)
Black/African American	19 (44.2)
Multiracial	1 (2.3)
White	21 (48.8)
Autoimmune comorbidities, n (%)^b,c	15 (34.9)
Hypothyroidism	3 (7.0)
Myasthenia gravis	3 (7.0)
Sjögren syndrome	3 (7.0)
SLE	3 (7.0)
Other^d	4 (9.3)
Duration of NMOSD, median (range), years	10 (1–33)
Time since NMOSD diagnosis, median (range), years	8 (1–18)
NMOSD phenotype, n (%)^e
Cerebral	1 (2.3)
ON	10 (23.3)
ON + cerebral	1 (2.3)
ON + TM	17 (39.5)
TM	13 (30.2)
TM + cerebral	1 (2.3)
EDSS score before satralizumab, mean (SD)^f,g	4.3 (2.2)
Preventive treatments before satralizumab, n (%)
Azathioprine	6 (14.0)
Cyclophosphamide	2 (4.7)
Glatiramer acetate	2 (4.7)
Leflunomide	1 (2.3)
Methotrexate	1 (2.3)
Mitoxantrone	2 (4.7)
MMF	9 (20.9)
Oral prednisone^h	6 (14.0)
Tocilizumab	2 (4.7)
Rituximab	26 (60.5)
Eculizumab	5 (11.6)
Last preventive treatment before transition to satralizumab, n (%)
Immunosuppressive therapy	6 (14.0)
Tocilizumab	2 (4.7)
Rituximab	20 (46.5)
Eculizumab	5 (11.6)
None (treatment naive)	10 (23.3)
Duration of satralizumab treatment, median (range), months	31 (7–104)
Type of satralizumab therapy as of cutoff, n (%)ⁱ
Combination therapy	3 (7.0)
Monotherapy	40 (93.0)

AQP4-IgG, aquaporin-4 immunoglobulin G; EDSS, Expanded Disability Status Scale; MMF, mycophenolate mofetil; NMOSD, neuromyelitis optica spectrum disorder; ON, optic neuritis; SLE, systemic lupus erythematosus; TM, transverse myelitis.

Age at data cutoff.

Includes comorbid and previous autoimmune disorders.

Not mutually exclusive.

Includes autoimmune lymphocytic colitis, immune-mediated thrombocytopenia, Kawasaki disease, and rheumatoid arthritis.

Experienced by patients at any time in their disease course.

EDSS or estimated EDSS score provided.

EDSS or estimated EDSS scores available for 41 patients.

Does not include short-term corticosteroid taper or bridging corticosteroids.

Type of therapy at data cutoff or discontinuation date.

The median times from symptom onset and confirmed NMOSD diagnosis were 10 (range, 1–33) and 8 (1–18) years, respectively, both measured until the data cutoff date. The most frequent NMOSD disease phenotypes were optic neuritis (ON) combined with transverse myelitis (TM) (40%), TM alone (30%), and ON alone (23%) (Table 1). The mean EDSS or estimated EDSS score before receiving satralizumab was 4.3 (SD, 2.2).

Twenty patients switched from rituximab (RTX), five switched from eculizumab (ECU), and two switched from tocilizumab (TCZ). Ten patients received no preventive NMOSD treatment (TN), and six received ISTs (IST) as the only preventive treatment before switching to satralizumab. Four patients were initially misdiagnosed and treated with multiple sclerosis disease-modifying therapies (glatiramer acetate or mitoxantrone). Twenty patients received an average of 1.4 ISTs before initiating satralizumab, indicating that some received more than one. The most common ISTs used were azathioprine and MMF. Overall, 26 patients (60%) received rituximab at any time before satralizumab; of those with available treatment dates (n = 24), the median duration of rituximab treatment was 52 (range, 1–162) months. Of the 20 patients who transitioned from rituximab to satralizumab (with or without concomitant IST), the median time between discontinuation of rituximab and initiation of satralizumab was 11 (range, 2–72).²³ Of the five patients who transitioned from eculizumab to satralizumab, the median duration of eculizumab treatment was 10 (range, 5–22) months, and the interval between eculizumab discontinuation and satralizumab initiation ranged from 2 to 17 weeks.²² All patients received acute therapy with corticosteroids and plasma exchange at the time of relapse prior to starting satralizumab.

The primary reported reasons for satralizumab initiation were intolerance/safety concerns with previous treatment (30%), initial treatment after a new diagnosis (26%) and inadequate disease control (per radiographically confirmed relapses or patient reports) with previous treatment (21%)) (Figure 1). Twelve patients switched from rituximab to satralizumab due to intolerance, of whom seven (58%) experienced hypogammaglobulinemia and recurrent infections.²³

Figure 1.

Reasons for initiation of satralizumab for (a) all patients and patients whose treatment was switched from (b) IST, (c) rituximab, (d) eculizumab, and (e) tocilizumab. ECU, eculizumab; FDA, Food and Drug Administration; IST, immunosuppressant therapy; NMOSD, neuromyelitis optica spectrum disorder; ROA, route of administration; RTX, rituximab; TCZ, tocilizumab. ^aInadequate disease control was defined as radiographically confirmed relapses and patient-reported outcomes. ^bFor IST switch, other was desire to taper immunosuppressants (n = 1); for RTX switch, other was lack of insurance coverage (n = 2) and recommendation for FDA-approved treatment (n = 1); for TCZ switch, other was shortage of TCZ during the COVID-19 pandemic (n = 2). ^cThe patient previously received ISTs for multiple sclerosis before diagnosis of NMOSD.

Satralizumab treatment

At data cutoff, 39% had received satralizumab for >36 months (Figure 2). Median duration of satralizumab treatment was 31 (range, 7–104) months, including 36.5 (16–104) months among patients who switched from rituximab²³ and 30 (7–45) months among those who did not. Nine patients (21%) received bridging corticosteroids for 3–6 months during satralizumab initiation. At data cutoff, 35 patients (81%) were still receiving satralizumab, two were receiving concurrent MMF and one was receiving as-needed oral prednisone for SLE symptoms. Six patients discontinued satralizumab: two (TN3 and TN7) due to radiologically confirmed relapses after 30 and 25 months, respectively; two (RTX5 and ECU3) due to insurance reasons after 25 and 37 months; one (RTX7) due to persistent asymptomatic neutropenia after 24 months; and one (RTX14) due to patient-reported right-sided weakness after 19 months (however, this event was not classified as a relapse due to lack of objective evidence such as radiographic confirmation of new lesions).²³

Figure 2.

Duration of satralizumab treatment.

Relapses before and after initiation of satralizumab

Most patients (72%) had ≥1 radiographically confirmed relapse before initiating satralizumab (Figure 3), including 80% of patients who switched from rituximab and 65% of those who did not. Eleven had radiologically confirmed relapse(s) while receiving preventive treatment: three while receiving ISTs and eight while receiving rituximab (three had delayed rituximab dosing, due to infections (n = 2) or lack of follow-up (n = 1)). No radiologically confirmed relapses occurred among patients receiving eculizumab. One patient (ECU4) experienced ON symptoms while receiving eculizumab, but this possible relapse was not confirmed with objective measures. Median time between the initial attack or closest relapse and satralizumab initiation was 29 (range, 1–215) months.

Figure 3.

Timeline of NMOSD treatments and radiographically confirmed relapses. ECU, eculizumab; IST, immunosuppressant therapy; MMF, mycophenolate mofetil; NMOSD, neuromyelitis optica spectrum disorder; RTX, rituximab; TN, treatment naive. ^aSmall x's denote brief durations (<2 months) of the treatment of the corresponding color (most exact dates are unknown). ^bReceived rituximab as a preventative treatment before satralizumab, but timing was not specified. ^cPatient data were unavailable after September 30, 2023. ^dExact dates of four radiographically confirmed relapses early in the course of disease are unknown. ^ePatient data were unavailable after January 31, 2024. ^fCalculated by dividing elapsed days by 30.

Forty patients (93%) were free from radiographically confirmed relapses while receiving satralizumab, including 100% of patients who switched from rituximab and 87% of those who did not. Three treatment-naive patients (TN3, TN7, and TN10) had a total of four radiographically confirmed relapses while receiving satralizumab. One radiographically confirmed relapse occurred during the early treatment period at 1 month in TN10, who received bridging corticosteroids. TN3 also received bridging corticosteroids and experienced a radiographically confirmed relapse 31 months after satralizumab initiation TN7, who did not receive bridging corticosteroids, had two radiographically confirmed relapses after 23 and 26 months. TN7 also experienced an event of relapse symptoms after 18 months, but MRI did not indicate relapse. RTX1, who received bridging corticosteroids, also had two episodes of relapse symptoms at 5 and 44 months after satralizumab initiation but did not undergo confirmatory radiographic testing. TN3 and TN7 discontinued satralizumab due to inadequate disease control, and TN10 and RTX1 continued satralizumab for 30 and 44 months, respectively, without further relapses.

Based on clinical observations and patient report forms provided by physicians, patients were clinically stable or improved while receiving satralizumab, with three patients reporting improved vision. TN1 reported improvement from blindness in both eyes to 20/50 (right) and 20/100 (left) after 1 month of satralizumab treatment, then reported 20/50 and 20/70 after 8 months. TN4 reported improved vision from “counting fingers” to 20/40. TN8 reported improvement from blindness in the left eye to seeing outlines of objects. Of 20 patients who started satralizumab after myelitis attacks, 15 reported improved motor function after satralizumab treatment. Improvements were reported by patients and, in some cases, corroborated by physician assessments, including changes in gait, strength, or EDSS scores. All patients had received corticosteroids and/or plasmapheresis at the time of acute attack.

Adverse events

Fifteen patients (35%) experienced AEs that the treating physician attributed to satralizumab (Table 2), including six patients who switched from rituximab (30%) and nine who did not (39%). The most common related AEs were hyperlipidemia (12%), asymptomatic leukopenia (9%), and asymptomatic neutropenia (7%). RTX1 developed hyperlipidemia requiring statin therapy,²³ and TCZ1 had worsening of preexisting hyperlipidemia, requiring an increase in statin dosage. RTX9 experienced lymphopenia after 22 months of satralizumab treatment, and the satralizumab dosing interval was extended to every 5 weeks. ECU1 experienced episodes of neutropenia 2 months and 1 year after satralizumab initiation, leading to temporary interruption (one dose on each occasion).²²

Table 2.

Safety data with satralizumab in patients with NMOSD.

	All patients(N = 43)
Adverse events attributed to satralizumab by practicing physician, n (%)^a,b
Hyperlipidemia	5 (11.6)
Leukopenia	4 (9.3)
Neutropenia	3 (7.0)
Elevated liver function test results (ALT, AST)	2 (4.7)
Lymphopenia	2 (4.7)
Other^c	6 (14.0)
Adverse events related to satralizumab leading to permanent discontinuations, n (%)^a,d	2 (4.7)
Adverse events deemed unrelated to satralizumab, n (%)^a
Infection^e	8 (18.6)
Hypogammaglobulinemia	4 (9.3)
Anemia	3 (7.0)
Hyperlipidemia	3 (7.0)
Low immunoglobulin M	2 (4.7)
Other^f	8 (18.6)

ALT, alanine aminotransferase; AST, aspartate aminotransferase; NMOSD, neuromyelitis optica spectrum disorder.

Classification of adverse events considered related or unrelated to satralizumab were based on the opinion of the healthcare provider.

All adverse events were reported to US Food and Drug Administration as required.

Included contact dermatitis and postinflammatory hypopigmentation (n = 1), nasal congestion and sore throat (n = 1), right-sided weakness (n = 1), thrombocytopenia (n = 2), and transient abdominal bloating (n = 1).

One patient permanently discontinued satralizumab due to asymptomatic neutropenia (which transiently resolved after discontinuation of satralizumab but then recurred), and one patient permanently discontinued due to right-sided weakness (with no objective documentation, so this event was not considered a relapse).

Included recurrent/chronic urinary tract infection (n = 2), recurrent ear infection (n = 1), recurrent bacterial or fungal vaginal infection (n = 1), herpes zoster (n = 1), meningococcus (n = 1), and methicillin-resistant Staphylococcus aureus (n = 1) and Escherichia coli (n = 1) infections. In some cases, an individual experienced multiple infection types; some infections were not specified.

Included chronic styes, chronic headache, acute sepsis (fatal), cervical cancer (fatal) and leukopenia, macrocytosis, nonalcoholic steatohepatitis, and stage 1 lung adenocarcinoma (all n = 1).

Two patients had AEs that led to permanent discontinuation of satralizumab: RTX7 due to asymptomatic neutropenia after 24 months (resolving <5 months after discontinuation and after discontinuation of MMF) and RTX14 due to right-sided weakness (not classified as a relapse) after 19 months. RTX14 reported that the weakness improved after satralizumab discontinuation.²³

Overall, 22 patients (51%) had AEs that treating physicians deemed unrelated to satralizumab, including 10 patients who switched from rituximab (50%) and 12 who did not (52%). There were three fatalities. IST4 had dementia and severe peripheral vascular disease before receiving satralizumab, did not report any AEs related to satralizumab and died 7 months after initiating satralizumab due to complications of vascular disease. RTX14 experienced chronic meningococcus urinary tract infection while receiving eculizumab (initiated 8 months after satralizumab discontinuation), which was managed prophylactically with daily penicillin, but suddenly developed Escherichia coli sepsis and died. ECU4 received satralizumab for 11 months with no AEs; however, the patient died 2 months after discontinuation of satralizumab due to stage IV cervical cancer.

Treatment after satralizumab discontinuation

All three patients who discontinued satralizumab due to inadequate disease control or AEs transitioned to another FDA-approved NMOSD treatment. TN3 received inebilizumab while TN7 and RTX14 received eculizumab. TN3 and TN7 had no relapses in their 10 and 3 months of inebilizumab and eculizumab treatment, respectively. RTX14 experienced two relapses between discontinuing satralizumab and initiating eculizumab, then continued eculizumab treatment for approximately 9 months without any further NMOSD relapses until their death from sepsis. RTX5 switched from satralizumab to inebilizumab for insurance reasons but was planning to reinitiate satralizumab prior to being lost to follow-up.

Discussion

This retrospective case series of 43 US patients with AQP4-IgG⁺ NMOSD who received satralizumab provides valuable insights into the real-world safety and effectiveness of satralizumab. A comprehensive and heterogenous picture of the patient population receiving satralizumab in everyday practice was achieved partially through inclusion of treatment-naive patients and those who received prior off-label or approved NMOSD therapies and partially through longer-term data that built on previous accounts of patients switching to satralizumab from rituximab and eculizumab.^22,23 Time from NMOSD diagnosis ranged from 1 to 18 years, and approximately three-quarters of patients switched to satralizumab after receiving treatment with an IST, eculizumab, tocilizumab, or rituximab. Primary reasons for satralizumab initiation were intolerance/safety concerns with previous treatments and new NMOSD diagnoses. Satralizumab had a favorable safety profile after other therapies without washout periods, which may be reassuring to clinicians and relevant to daily practice. Over two-thirds of patients continued treatment for >24 months, with 81% still receiving satralizumab at data cutoff. Most patients (93%) were free from radiographically confirmed relapses while receiving satralizumab.

Varied treatment journeys before receiving satralizumab were captured. Many patients were diagnosed before approved treatments for NMOSD became available; consequently, almost two-thirds of patients received rituximab as a preventive treatment. NMOSD treatment switches may occur due to insurance policies, route of administration preferences, AEs, or lack of efficacy,²⁴ which is consistent with our findings.

Most patients had a radiographically confirmed relapse before satralizumab initiation, and one-quarter had a radiographically confirmed relapse while receiving preventive treatment before satralizumab. Only three treatment-naive patients experienced radiographically confirmed relapses while receiving satralizumab, two of whom transitioned to another FDA-approved NMOSD therapy. Our observations are consistent with findings from two randomized, Phase III, double-blind placebo-controlled trials, which demonstrated that satralizumab (alone or combined with IST) significantly reduced relapse risk in patients with NMOSD.^17,18 The efficacy and safety of satralizumab, as demonstrated in long-term studies, including the open-label extension, were sustained for up to 8.9 years in adults with AQP4-IgG⁺ NMOSD.^25–27

Although prior treatments could have prolonged effects that overlap with satralizumab initiation,²³ beneficial outcomes were observed regardless of treatment histories or time elapsed between other therapies and satralizumab. Rituximab depletes B cells, and immunoprotection from rituximab may have potentially persisted into the satralizumab treatment period. However, only 4 of 20 patients initiated satralizumab within 6 months of discontinuing rituximab, which is the average time after which B-cell repletion is expected. There were no notable differences in efficacy or safety outcomes with satralizumab treatment when qualitatively comparing patients who received rituximab with those who did not have prior B-cell depletion.

The onset of action of preventive therapies is a critical consideration in NMOSD management due to the risk of early relapses and long-term disability. In this case series, two of nine patients who received bridging corticosteroids had radiographically confirmed relapses whereas only 1 of 34 patients without bridging corticosteroids had a radiographically confirmed relapse. These findings suggest that satralizumab may exert clinically meaningful effects early in the treatment course, contributing to relapse prevention even in the absence of bridging corticosteroids. Notably, no head-to-head trials have been conducted to systematically evaluate the onset of action of satralizumab compared with other FDA-approved therapies for NMOSD, such as eculizumab and inebilizumab. As a result, the clinical significance of early efficacy differences between these agents—and the role of bridging corticosteroids—remains an open question that warrants further investigation.

Three patients treated with satralizumab reported notable vision improvements. TN1 experienced a remarkable recovery from bilateral blindness to measurable visual acuity within 1 month of treatment initiation. To our knowledge, this is the first real-world evidence reporting significant recovery from blindness in one or both eyes in an NMOSD patient with an FDA-approved maintenance therapy. Observations that NMOSD relapses are strongly associated with worsening vision²⁸ underscore the relevance of these findings and the importance of effective relapse prevention in NMOSD management. Although the improvement in vision cannot be solely attributed to satralizumab in those patients, IL-6 inhibition via satralizumab may facilitate vision recovery by reducing inflammation, modulating autoimmune responses, and promoting conditions conducive to neural repair and may have significant value in managing visual disability in NMOSD. Importantly, prior to starting satralizumab, some patients in our case series received acute treatment with corticosteroids and plasma exchange, which may have also contributed to these outcomes. Further research in larger cohorts is needed to confirm these effects.

The most common AEs were mild, asymptomatic laboratory abnormalities, particularly hyperlipidemia, and asymptomatic leukopenia. Most AEs occurred within the first 6 months following satralizumab initiation. Infections were rare and generally mild in severity, except in one patient who died from E. coli sepsis. AEs led to permanent satralizumab discontinuation in two patients. RTX7 discontinued satralizumab due to asymptomatic neutropenia,²³ but given several confounding factors in their medical and treatment history (e.g. leukemia, SLE), satralizumab discontinuation was primarily precautionary. RTX14 discontinued satralizumab after 19 months due to perceived right-sided weakness, which was considered an AE as there was no objective documentation of relapse.²³

Up to 30% of patients with NMOSD have concomitant autoimmune disease.²⁹ Consistently, one-third of patients documented here had current or past history of comorbid autoimmune disease, including hypothyroidism, myasthenia gravis, Sjögren syndrome, and SLE. In a pooled analysis of the SAkura studies, satralizumab had a comparable efficacy and safety profile in patients with concomitant autoimmune diseases versus the overall study population.³⁰

Although our methodology prioritized broad inclusion of treatment settings and patient experiences, some degree of selection bias may exist due to retrospective data collection and differences in uptake of satralizumab among providers and specialists. Patients receiving care in clinical practice may differ from those included in clinical trials, with longer disease durations, multiple previous and concomitant therapies, no recent history of disease relapse, and distinct demographic characteristics. Patients in this case series were 20–82 years old, with confirmed NMOSD disease duration of 1–33 years, and almost half were Black/African American. Historically, Black/African American and Hispanic/Latino patients have been underrepresented in clinical research, including NMOSD trials. In two of five key clinical trials for NMOSD, race was not reported^17,19; when it was, White patients accounted for the majority of the study population.^18,20,31 Hispanic/Latino ethnicity was reported in only one trial and ranged from 16 to 29% depending on treatment group.³¹ Black/African American populations have higher prevalence of NMOSD,³² and higher mortality has been reported in individuals with NMOSD of African versus European ancestry.³³ In addition, non-White patients have been reported to have a younger age of onset and more severe disease, including more frequent brain symptoms or MRI abnormalities, than White patients.³⁴ Thus, it is essential to understand the effect of NMOSD treatments across all racial and ethnic groups. In our real-world study, satralizumab had a favorable efficacy and safety profile across all racial and ethnic groups, suggesting that satralizumab could benefit a wider range of patients than those included in more controlled clinical trial environments.

Limitations are characteristic of a retrospective case series, including partially missing data and lack of a control group. Duration, dose, and frequency of previous treatments prior to satralizumab were not uniform among patients. Thus, the comparison of the number of relapses before and after satralizumab should be interpreted with caution. Relapse classification in this study required radiographic confirmation on MRI, which may have led to underrecognition of relapses that solely presented with clinical symptoms without new imaging findings. However, such instances were infrequent and, when present, were documented qualitatively as possible relapses, suggesting that any underestimation of relapse frequency was likely minimal. Finally, comparison to other FDA-approved therapies cannot be made based on these data. Nonetheless, this case series offers valuable real-world insights into the use of satralizumab in patients with AQP4-IgG⁺ NMOSD, complementing existing clinical trial evidence with observations from routine clinical practice.

Conclusion

In this retrospective case series, satralizumab was effective and well tolerated in patients with NMOSD in real-world clinical practice, either as an initial NMOSD treatment or after a switch from another preventive therapy. Most patients were free from radiographically confirmed relapses after initiating satralizumab, and no major safety events were reported. These outcomes align with the long-term efficacy and safety outcomes of satralizumab in Phase III SAkura clinical trials.

Footnotes

Acknowledgments

We would like to thank the patients who participated in this case series, as well as Noore Ali, Lisa Aquillano, Cecilia Ciarlo, Vanessa Di Felice, Jasmin Graziano, Idan Hannawa, Katie Kidder, Ken Linsky, Kerri Lucia, Amy Neal, Jessica Priest, Jugena Smith, Kaylan Fenton, and Lynn Wheeler for their assistance in obtaining case information. Third-party writing and editorial assistance were provided by Nicola Gillespie, DVM, CMPP and Emma Bouck, PhD, of Nucleus Global, and was funded by Genentech, Inc.

Consent for publication

All patients provided written informed consent for the publication of their case information.

Data availability

Anonymized records for individual patients across more than one data source external to Roche cannot, and should not, be linked due to a potential increase in risk of patient re-identification. For up-to-date details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see .

Declaration of conflicting interests

The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: H. Abboud: consultant for Alexion, Alpine Pharma, Biogen, Bristol Myers Squibb, Cycle Pharma, Genentech, Inc., Horizon/Amgen, and TG Therapeutics; research support from Bristol Myers Squibb, Genentech, Inc., the Guthy-Jackson Charitable Foundation, Novartis, Sanofi-Genzyme, and UCB; editorial board member of the Neurology Journal; and royalties from UpToDate. B. Steingo: honoraria/speaker fees and research fees from Biogen, Bristol Myers Squibb, EMD Serono, Genentech, Inc. (advisory board), Janssen, Novartis, and Sanofi. D. Vargas: nothing to disclose. J. Patel: nothing to disclose. M.A. Willis: consultant for Genentech, Inc.; speaker for Alexion; and research support from Alexion. Y. Mao-Draayer: consultant fees and/or grant support from Acorda, Bayer, Biogen Idec, Celgene/Bristol Myers Squibb, EMD Serono, F. Hoffmann-La Roche Ltd/Genentech, Inc., Janssen, Novartis, Questor, Sanofi-Genzyme, and Teva Neuroscience; grant support from Chugai, Genentech, Inc., National Institute of Allergy and Infectious Diseases Autoimmune Center of Excellence (UM1-AI110557-05, UM1 AI144298-01), Novartis, Patient-Centered Outcomes Research Institute, and Sanofi-Genzyme. D. Khaitov: speaker for Biogen. J. Avila Ornelas: consultant and speaker for Alexion, Banner Pharmaceuticals, Biogen, EMD Serono, and Horizon. A. Subei: speakers bureau for Alexion, Amgen, Biogen, Bristol Myers Squibb, EMD Serono, and TG Therapeutics; and research fees from Novartis and Sanofi. C. Reed: speaker fees/honoraria from Biogen, Bristol Myers Squibb (advisory boards and speaker training), and EMD Serono. W.S. Baek: speakers bureau for AbbVie Pharmaceuticals. M. Tsai: nothing to disclose. A. Kim: nothing to disclose. A.Z. Obeidat: compensation for speaking, advisory boards or steering committees from Alexion Pharmaceuticals, Amgen, AstraZeneca, Banner Life Sciences, BD Biosciences, Biogen, Biologix Solutions, Bristol Myers Squibb, Celgene, EMD Serono, GW Pharmaceuticals, Horizon Therapeutics, Jazz Pharmaceuticals, Merck, Novartis, Roche-Genentech, Sandoz, Sanofi-Genzyme, TG Therapeutics, and Viela Bio. K. Pandey: consultant for Bristol Myers Squibb, Genentech, Inc., and Sanofi Genzyme; compensation for serving on speakers bureaus for Biogen, Bristol Myers Squibb, Genentech, Inc., Horizon Therapeutics, and Sanofi-Genzyme; and institutional research support from National Institutes of Health and Consortium of Multiple Sclerosis Centers. M. Levy: consultant for Alexion, AstraZeneca Rare Disease, Genentech/Roche/Chugai, and Viela Bio; and consulting fees from Mitsubishi, Quest Diagnostics, and UCB Pharmaceuticals. N. Molazadeh: institutional research support from Genentech, Inc. R.K. Shin: compensation as a consultant or speaker for Alexion, Biogen, Bristol Myers Squibb, EMD Serono, Genentech, Horizon, Novartis, Sanofi Genzyme, and TG Therapeutics. R.S. Romero: consultant for Alexion, Bristol Myers Squibb, Genentech, Inc., Horizon, and Viela Bio. R. Walch, P. Goulette, J. Coté, and R. Pace: consultants for Alexion, Bristol Myers Squibb, Genentech/Roche, Horizon, and Sanofi; speakers bureau for Alexion, Biogen, Bristol Myers Squibb, EMD Serono, and Horizon; and institutional research support from EMD Serono, Genentech/Roche, Novartis, Sanofi, and TG Therapeutics. B. Sengul: advisory boards for EMD Serono, Genentech, Inc. and Horizon; compensation for speakers bureaus for Biogen and EMD Serono; and steering committee for EMD Serono. B. Osborne: speakers bureau for Alexion and Amgen; advisory boards for Alexion, Amgen, Genentech, Inc., and TG Therapeutics; and royalties from UptoDate. A. Mahadeen: nothing to disclose. L. Ferayorni and S. Gholizadeh: employment with Genentech, Inc., and shareholders in F. Hoffmann-La Roche Ltd.

Ethical considerations

Ethical review and approval were not required for this retrospective, observational study.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This case series was funded by F. Hoffmann-La Roche Ltd and Genentech, Inc.

ORCID iDs

Hesham Abboud

Mary Alissa Willis

Jose Avila Ornelas

Ahmed Z. Obeidat

Michael Levy

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