Author Of 3 Presentations
P0718 - Impact of relapse on disability and quality of life in patients with neuromyelitis optica spectrum disorder: findings from the Phase 3 PREVENT study (ID 701)
Abstract
Background
Neuromyelitis optica spectrum disorder (NMOSD) is a rare, inflammatory disorder associated with relapse activity that may lead to poor recovery. The phase 3 PREVENT study was a randomized controlled trial with an open-label extension (OLE) that evaluated the efficacy of eculizumab in patients with aquaporin-4 immunoglobulin G-positive (AQP4-IgG+) NMOSD. Patients on eculizumab had a significantly lower risk of adjudicated relapse versus patients on placebo and reported improved health-related quality of life (HRQoL). Additional analyses on the impact of relapses on disease progression can provide a basis for the strategic treatment of patients with NMOSD.
Objectives
A post hoc analysis of data from the PREVENT study and its OLE assessed the impact of relapses on disability and HRQoL in patients with AQP4-IgG+ NMOSD.
Methods
Neurological disability was measured via the Expanded Disability Status Scale (EDSS). HRQoL was assessed using the Physical Component Summary (PCS) and Mental Component Summary (MCS) of the 36-Item Short-Form Health Survey (SF-36). Changes in mean scores and the proportion of patients having clinically meaningful worsening (SF-36: 5-point decrease; EDSS: ≥2-point increase if the baseline score was 0, ≥1-point increase if the baseline score was 1 to 5, and ≥0.5-point increase if the baseline score was ≥5.5) from prerelapse to 30, 90, and 120 days post relapse were analysed.
Results
Overall, 27 patients were identified as having ≥1 adjudicated relapse. Compared with prerelapse measures, mean SF-36 PCS and MCS scores were significantly worse at 30 days post relapse, the mean EDSS score was significantly worse at 90 days post relapse, and the mean score for the SF-36 MCS was significantly worse at 120 days post relapse. Between 30 and 90 days post relapse, the proportion of patients with clinically meaningful worsening increased by 7%, 8%, and 11% for the EDSS, SF-36 PCS, and SF-36 MCS, respectively. Between 90 and 120 days post relapse, the proportion of patients decreased by 11% for the EDSS to reach 30%, and increased only by 4% for both the SF-36 PCS and SF-36 MCS to reach 31% and 50%, respectively, suggesting a stabilization of the relapse symptoms.
Conclusions
In the PREVENT study and its OLE, patients with AQP4-IgG+ NMOSD had significant, sustained (120 days) worsening of disability and HRQoL outcomes following adjudicated relapses. One-quarter to one-half of relapsing patients experienced stable, clinically meaningful worsening.
P0727 - Long-term efficacy and safety of eculizumab in AQP4+ neuromyelitis optica spectrum disorder (ID 555)
Abstract
Background
Neuromyelitis optica spectrum disorder (NMOSD) relapses can cause significant and irreversible neurologic disability. In PREVENT, eculizumab reduced the risk of relapse in patients with aquaporin-4 immunoglobulin G-positive (AQP4+) NMOSD by 94.2% vs placebo (hazard ratio 0.058; 95% confidence interval [CI]: 0.017–0.197; p < 0.0001) and adjudicated annualized relapse rate (ARR) for eculizumab was 0.02. The rate of adverse events (AEs)/100 patient-years (PY) was 749.3 for eculizumab and 1160.9 for placebo.
Objectives
To present the long-term efficacy and safety of eculizumab in patients with AQP4+ NMOSD during PREVENT (NCT01892345) and its ongoing open-label extension (OLE; NCT02003144).
Methods
During PREVENT, adults with AQP4+ NMOSD received eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo with/without concomitant immunosuppressive therapy (IST). Patients who completed PREVENT could enroll in the OLE to receive eculizumab. Eculizumab safety and efficacy data from PREVENT and its OLE (interim data cut, July 31, 2019) were combined for this analysis.
Results
Overall, 137 patients received eculizumab, and were observed for a median (range) of 133.29 (5.1– 276.9) weeks, for a combined total of 362.3 PY. The estimated percentage of patients who were relapse free at 192 weeks (3.7 years) was 94.4% (95% CI: 88.6–97.3). The adjudicated ARR was 0.025 (95% CI: 0.013–0.048) and the annualized relapse-related hospitalization rate (ARRHR) was 0.03/PY (95% CI: 0.017–0.055). Rates of AEs and serious AEs (SAEs)/100 PY were 732.5 and 33.7, respectively. Common AEs included headache (29.2%) and upper respiratory tract infection (27.7%). Common SAEs, excluding NMOSD relapses, were pneumonia (3.6%), urinary tract infection (2.9%) and acute cholecystitis (2.9%). One patient died during PREVENT (pulmonary empyema) and one patient developed a disseminated Neisseria gonorrhoeae infection. In all, 25/137 patients (18.2%) developed a serious infection vs 6/47 (12.8%) receiving placebo in PREVENT. No patient had a meningococcal infection. During the OLE, 50/119 patients (42%) changed concomitant IST; most patients (44/50) stopped or decreased concomitant IST dose.
Conclusions
During PREVENT and its OLE, the percentage of relapse-free patients remained high (94%) through 192 weeks. Eculizumab was well tolerated and AEs were consistent with the safety profile established in other indications. ARRHR was low and many patients were able to reduce or stop concomitant IST.
P0752 - Safety of eculizumab in NMOSD and MG – analysis of the phase 3 studies PREVENT and REGAIN and their extensions (ID 554)
Abstract
Background
Aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4+ NMOSD) and acetylcholine receptor antibody-positive generalized myasthenia gravis (AChR+ gMG) are neurological disorders with complement involvement. Eculizumab (a terminal complement inhibitor) demonstrated efficacy in reducing relapse risk and in eliciting clinical improvements during the phase 3, randomized, double-blind PREVENT and REGAIN studies and their open-label extensions (OLEs) (NCT01892345/NCT02003144 [interim data, July 2019] and NCT01997229/NCT02301624) previously published.
Objectives
To compare infection rates in patients with AQP4+ NMOSD or AChR+ gMG receiving eculizumab or placebo with or without concomitant immunosuppressive therapy (IST) during PREVENT, REGAIN and their OLEs.
Methods
Patients were randomized to eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo. Concomitant ISTs, excluding rituximab, were permitted. Post hoc analysis was performed to examine rates of infections in these studies and for subgroups determined by number of ISTs received at baseline.
Results
Rates/100 patient-years (PY) and types of infection were similar in eculizumab and placebo groups. In patients with NMOSD, rates/100 PY and % (n/N), respectively, were: no IST: 176.1, 80.0% (28/35) vs 192.2, 61.5% (8/13); 1 IST: 171.5, 81.8% (45/55) vs 154.1, 63.6% (14/22); 2 ISTs: 186.7, 85.1% (40/47) vs 238.2, 83.3% (10/12). For patients with gMG, rates/100 PY and % (n/N), respectively, were: no IST: 236.8, 100.0% (2/2) vs 305.6, 50.0% (1/2); 1 IST: 228.8, 82.9% (34/41) vs 253.1, 50.0% (9/18); 2 ISTs: 170.5, 91.0% (71/78) vs 192.5, 58.5% (24/41); ≥ 3 ISTs: 97.5, 50.0% (1/2) vs 100.1, 50.0% (1/2). In patients with NMOSD or gMG receiving eculizumab vs placebo, serious infection rates/100 PY and % (n/N), respectively, were: no IST: 2.3, 5.7% (2/35) vs 8.0, 7.7% (1/13) and none observed (0/2 vs 0/2); 1 IST: 11.2, 16.4% (9/55) vs 7.0, 9.1% (2/22) and 16.2, 24.4% (10/41) vs 34.5, 5.6% (1/18); 2 ISTs, 14.8, 29.8% (14/47) vs 47.6, 25.0% (3/12) and 13.4, 21.8% (17/78) vs 24.1, 12.2% (5/41); ≥ 3 ISTs (gMG only), 13.9, 50.0% (1/2) vs 0.0, 0.0% (0/2). One patient with gMG (2 ISTs) had meningococcal meningitis that resolved with antibiotics and eculizumab was resumed.
Conclusions
In AQP4+ NMOSD and AChR+ gMG, infection rates/100 PY were similar in eculizumab and placebo groups, regardless of concomitant IST. Infection rates/100 PY were consistent with the established safety profile of eculizumab.