Roche Product Development Medical Affairs (PDMA) Genentech

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

P0759 - Treatment patterns in patients with neuromyelitis optica spectrum disorder (ID 1400)

Abstract

Background

Many patients with neuromyelitis optica spectrum disorder (NMOSD) are managed using off-label immunosuppressants for relapse prevention, and treatment guidelines are based on small, often uncontrolled, studies with low levels of evidence.

Objectives

To assess real-world treatment patterns in patients with NMOSD.

Methods

Based on the global NMOBase cohort, patients diagnosed with NMOSD between 2006–2019 per the international 2015 consensus criteria and with ≥2 Expanded Disability Status Scale scores recorded at different visits were included in the study population. The aquaporin-4 autoantibody (AQP4-IgG) serostatus was determined mainly by cell-based assay; treatment sequence for maintenance therapies was assessed in seropositive (AQP4-IgG+) patients only. The date of biomarker testing was used as a proxy for diagnosis date and served as the baseline for the observational period.

Results

The study population included 334 NMOSD patients tested for AQP4-IgG serostatus. Among them, 301 (90.1%) were AQP4-IgG+. Mean age was 45.3 years; 84.1% were women and 51.8% (n=156) came from Europe. Two thirds had ≥5 visits recorded in NMObase, and the mean observational period was 4.8 years. Five treatment lines (1L–5L) were observed, with only 1.3% of the AQP4-IgG+ cohort (n=4) progressing to the last line. At baseline, the most common therapy was azathioprine (23.6%) followed by rituximab (5.3%), and 65.4% (n=197) were not prescribed any disease-modifying therapy (DMT). The median time between the test date and initiation of DMT was 3.2 months, although 25% of patients waited >10 months. Most AQP4-IgG+ patients (66.4%; n=200) progressed beyond 1L. The most frequent treatments at 2L were rituximab (43.5%) and azathioprine (41.0%). The proportion receiving rituximab, the predominant therapy beyond 2L, remained stable at 3L (48.1%; n=25) and 4L (46.7%; n=7). Across all treatment lines, there were anecdotal reports of use of DMT indicated for multiple sclerosis (MS) (e.g., betaferon), possibly reflecting old clinical practice. A large proportion (83.4%) received corticosteroids, either as acute relapse- or maintenance- therapy, along their treatment pathway.

Conclusions

Based on data collected before recent drug approvals, the main treatment options included off-label drugs and a few MS DMTs. A quarter of patients did not initiate NMOSD DMTs for >10 months from diagnosis. Newly approved therapies might partly address this unmet need, at least for AQP4-IgG+ patients.

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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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