F. Hoffmann-La Roche Ltd

Author Of 1 Presentation

Neuromyelitis Optica and Anti-MOG Disease Oral Presentation

FC01.03 - Effect of satralizumab on relapse severity in neuromyelitis optica spectrum disorder (NMOSD): results from the Phase III SAkura studies

Speakers
Presentation Number
FC01.03
Presentation Topic
Neuromyelitis Optica and Anti-MOG Disease
Lecture Time
13:24 - 13:36

Abstract

Background

NMOSD is an autoimmune disorder characterized by acute, unpredictable relapses that result in accumulating disability. Satralizumab, a humanized, monoclonal recycling antibody that targets the interleukin-6 receptor, reduced relapse frequency and had a favourable safety profile vs placebo in two randomized, phase 3 clinical trials: SAkuraSky (satralizumab in combination with baseline immunosuppressants; NCT02028884), and SAkuraStar (satralizumab monotherapy; NCT02073279).

Objectives

To assess the impact of satralizumab on relapse severity in patients with NMOSD.

Methods

Patients in the SAkura studies received satralizumab 120mg or placebo at Weeks 0, 2, 4, and Q4W thereafter. This analysis was performed using data from the pooled intention-to-treat population across the double-blind periods of both studies. We assessed the severity of protocol-defined relapses (PDRs) by comparing patients’ Expanded Disability Status Scale (EDSS) score at PDR vs their score prior to relapse (last scheduled study visit). A similar analysis on optic neuritis PDRs was performed using visual Functional Systems Score (FSS). A PDR was categorised as severe if it resulted in a change of ≥2 points on the EDSS or visual FSS (optic neuritis analysis). Kaplan-Meier analyses were performed to assess time to first severe PDR. Additionally, the number of patients receiving acute therapy for any relapse was compared between treatment groups.

Results

Overall, 178 patients were included in the analyses. In the satralizumab group, 27 of 104 patients (26%) experienced a PDR vs 34 of 74 patients (46%) in the placebo group. The proportion of PDRs that were severe was lower in patients receiving satralizumab vs placebo (5 of 27 events [19%] vs 12 of 34 events [35%]). Similarly, the proportion of optic neuritis PDRs that were severe was lower in patients receiving satralizumab vs placebo (2 of 8 events [25%] vs 5 of 13 events [39%]). Across all patients, there was a 79% reduction in severe PDR risk with satralizumab vs placebo (hazard ratio [95% CI]; 0.21 [0.07–0.61]; p=0.002). A lower proportion of patients receiving satralizumab were prescribed acute relapse therapy vs placebo (38% vs 58%; odds ratio [95% CI] 0.46 [0.25–0.86], p=0.015).

Conclusions

Patients treated with satralizumab had a lower risk of severe relapse, and were less likely to receive acute relapse therapy compared with placebo. The number of patients with severe PDRs was low, so results should be interpreted with caution.

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Author Of 3 Presentations

Neuromyelitis Optica and Anti-MOG Disease Poster Presentation

P0711 - Efficacy of satralizumab in neuromyelitis optica spectrum disorder (NMOSD): Results from open-label extension periods of SAkuraSky and SAkuraStar (ID 1319)

Speakers
Presentation Number
P0711
Presentation Topic
Neuromyelitis Optica and Anti-MOG Disease

Abstract

Background

Satralizumab, a humanized, monoclonal recycling antibody that targets the interleukin-6 receptor, reduced patients’ risk of NMOSD relapse in the double-blind (DB) periods of two randomized, phase 3 clinical trials in NMOSD: SAkuraSky (satralizumab in combination with baseline immunosuppressants; NCT02028884), and SAkuraStar (satralizumab monotherapy; NCT02073279).

Objectives

To assess the efficacy of satralizumab over a longer period of treatment, using data from the SAkura studies’ open-label extension (OLE) periods.

Methods

Patients entering SAkuraSky/Star were randomized to receive satralizumab 120mg or placebo at Weeks 0, 2, 4, and Q4W thereafter. After completing the DB period or experiencing a relapse, patients could enter the OLE period (same satralizumab dosing as DB period). The primary endpoint of both studies was time to first protocol-defined relapse (PDR) in the DB period, adjudicated by a Clinical Endpoint Committee (CEC). In this analysis, which includes OLE data (CEC adjudication unavailable), we assessed time to first investigator-reported PDR (any relapse considered by the investigator to meet PDR criteria) in the combined DB+OLE periods, using a pooled population from both studies.

Results

Overall, 179 patients were randomized to treatment (satralizumab n=105; placebo n=74), of whom 166 received ≥1 dose of satralizumab in the combined DB+OLE period. The median (range) satralizumab exposure in the DB period was 96.1 (8–224) weeks, and in the combined DB+OLE was 131.9 (13–276) weeks.

In the combined DB+OLE, patients originally randomized to satralizumab had a 51% lower risk of investigator-reported PDR vs those originally randomized to placebo (HR [95% CI] 0.49 [0.31–0.79]; P=0.002); the risk reduction was more pronounced in AQP4-IgG seropositive patients (66% risk reduction; HR [95% CI] 0.34 [0.19–0.62]; P<0.001). Patients who switched from placebo to satralizumab upon entry into the OLE period were included in the placebo group for this analysis, which likely reduced the observed treatment difference between satralizumab and placebo compared with the DB period.

No patients randomized to satralizumab withdrew from the OLE period due to a relapse, vs four patients who were originally randomized to placebo. The safety profile of satralizumab in the OLE was consistent with the DB period.

Conclusions

Across the DB and OLE periods of the SAkura studies, patients randomized to satralizumab had a significantly reduced risk of relapse vs placebo.

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Neuromyelitis Optica and Anti-MOG Disease Poster Presentation

P0754 - Satralizumab in first incident treatment-naïve AQP4-IgG seropositive NMOSD patients enrolled to SAkuraStar: a case series (ID 1371)

Speakers
Presentation Number
P0754
Presentation Topic
Neuromyelitis Optica and Anti-MOG Disease

Abstract

Background

Patients with neuromyelitis optica spectrum disorder (NMOSD) may experience severe disability after their incident (first) attack, with disability accumulating with subsequent relapses. Satralizumab, a humanized monoclonal antibody that inhibits the interleukin-6 receptor, reduced relapse frequency and had a favorable safety profile vs placebo in two randomized, placebo-controlled, phase 3 clinical trials in patients with NMOSD: SAkuraSky (satralizumab in combination with baseline immunosuppressants; NCT02028884), and SAkuraStar (satralizumab monotherapy; NCT02073279).

Objectives

To review a case series of treatment-naïve, aquaporin-4-IgG seropositive (AQP4-IgG+) NMOSD patients who enrolled in SAkuraStar following their incident attack.

Methods

All instances of investigator-reported relapse were assessed in six treatment-naïve, AQP4-IgG+ NMOSD patients enrolled in SAkuraStar after their first attack. Relapses that met protocol-defined relapse (PDR) criteria are specified. Patients who experienced a PDR or remained in SAkuraStar when the double-blind period ended were eligible to enter the open-label extension (OLE). Expanded Disability Status Scale (EDSS) scores were recorded at regular intervals and at relapse.

Results

Of the six enrolled patients, two were randomized to placebo, and four to satralizumab. Demographic characteristics in these six patients were generally consistent with the overall SAkuraStar population. One of the two patients who received placebo experienced a PDR on Study Day 21, with a 1.5-point increase in EDSS score, and fully recovered to pre-relapse EDSS score. Two of the four patients who received satralizumab experienced a relapse. The first patient experienced a PDR on Study Day 214, with a 1-point increase in EDSS, and the second patient experienced a relapse (not meeting PDR criteria) on Study Day 458, with a 0.5-point increase in EDSS score. Both patients fully recovered to pre-relapse EDSS score.

Five of six patients continued in the ongoing OLE, and no further relapses were reported (up to March 2020). Safety outcomes were consistent with the overall SAkuraStar safety population.

Conclusions

Treatment-naïve AQP4-IgG+ patients enrolled in SAkuraStar after their incident attack and randomized to placebo experienced a relapse earlier than those randomized to satralizumab. All patients fully recovered to pre-relapse EDSS score. Interpretation is limited due to the small sample size.

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Patient-Reported Outcomes and Quality of Life Poster Presentation

P1046 - Psychometric validation of the Expanded Disability Status Scale in neuromyelitis optica spectrum disorder (ID 1392)

Speakers
Presentation Number
P1046
Presentation Topic
Patient-Reported Outcomes and Quality of Life

Abstract

Background

The Expanded Disability Status Scale (EDSS) is an established measure of disability in multiple sclerosis (MS). Due to similarities in the clinical presentations of MS and neuromyelitis optica spectrum disorder (NMOSD), the EDSS is also widely used to assess disability in NMOSD but has yet to be validated for this purpose.

Objectives

To establish the psychometric reliability, validity, and responsiveness of the EDSS in NMOSD patients.

Methods

Analyses were conducted in a pooled population of NMOSD patients (N=178) from the phase 3 SAkuraSky (NCT02028884) and SAkuraStar (NCT02073279) studies. EDSS was assessed at regular intervals. Reliability was evaluated using standardized Cronbach’s α and test/re-test reliability. Convergent validity was assessed by comparison with the EuroQol Visual Analog Scale (EQ-VAS) and relevant outputs from the Short Form-36 (SF-36) health survey (Physical Functioning [PF], Role-functioning Physical [RP], and Physical Component Summary [PCS] domain scores). Discriminant validity was assessed against the Visual Analogue Scale for Pain (VAS-pain), and non-physical domains of the SF-36 (Vitality [VT], Mental Health [MH], Role-Emotional [RE], and Mental Component Score [MCS]). Criterion validity was assessed by comparison with the modified Rankin Scale (mRS). Responsiveness of the EDSS to changes in health status was assessed through a relative validity (RV) comparison of EDSS scores in patients who experienced an investigator-reported clinical relapse vs those without.

Results

Cronbach’s α coefficient was >0.6, suggesting reasonable internal consistency (α=0.67). The test/retest reliability coefficient was α=0.91, with scores >0.70 representing reasonable reliability. Assessment of convergent validity revealed moderate-to-strong correlations between EDSS and other measures of physical functioning (EQ-VAS, rs0.53; SF-36 PF, rs0.61; SF-36 RP, rs0.58; SF-36 PCS, rs0.60). The EDSS showed strong discriminant validity against VAS-pain and non-physical SF-36 domains (VAS-pain, rs 0.31; SF-36 VT, rs0.35; SF-36 MH, rs0.27; SF-36 RE, rs0.37; SF-36 MCS, rs –0.25). Strong criterion validity was observed in relation to the mRS (rs 0.68). The EDSS was found to be responsive to investigator-reported relapses (F-statistic=36.64, p<0.0001; RV=1.0).

Conclusions

The EDSS demonstrated reliability, validity, and responsiveness as a measure of disability in patients with NMOSD. Further studies to corroborate these findings are warranted.

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