Author Of 1 Presentation
FC01.03 - Effect of satralizumab on relapse severity in neuromyelitis optica spectrum disorder (NMOSD): results from the Phase III SAkura studies
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).
To assess the impact of satralizumab on relapse severity in patients with NMOSD.
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.
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).
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.
Author Of 1 Presentation
P1046 - Psychometric validation of the Expanded Disability Status Scale in neuromyelitis optica spectrum disorder (ID 1392)
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.
To establish the psychometric reliability, validity, and responsiveness of the EDSS in NMOSD patients.
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.
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, rs –0.53; SF-36 PF, rs –0.61; SF-36 RP, rs –0.58; SF-36 PCS, rs –0.60). The EDSS showed strong discriminant validity against VAS-pain and non-physical SF-36 domains (VAS-pain, rs 0.31; SF-36 VT, rs –0.35; SF-36 MH, rs –0.27; SF-36 RE, rs –0.37; 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).
The EDSS demonstrated reliability, validity, and responsiveness as a measure of disability in patients with NMOSD. Further studies to corroborate these findings are warranted.