Author Of 2 Presentations
P0310 - Cladribine tablets in patients with RRMS and active SPMS after suboptimal response to prior DMD (MASTER-2 and CLICK-MS): initial baseline demographics (ID 129)
Abstract
Background
Although the efficacy and safety of cladribine tablets (CT) 10 mg (3.5 mg/kg cumulative dose over 2 years [yrs]) have been shown in patients (pts) with relapsing forms of multiple sclerosis (MS) in Phase 3 trials, real world data are limited.
Objectives
To examine real-world effectiveness, safety, and pt reported outcomes (PROs) in pts with relapsing-remitting MS (RRMS) and active secondary progressive MS (SPMS) who transition to CT after suboptimal response to prior disease-modifying drugs (DMDs).
Methods
MASTER-2 and CLICK-MS are single arm, observational, 30-month (mo), Phase 4 trials in the US (Timeline: 2019–2023). Eligible pts are adults with RRMS or active SPMS, with suboptimal response to an oral/infusion (MASTER-2) or injectable (CLICK-MS) DMD, meeting criteria for CT 3.5 mg/kg treatment (US Prescribing Information). The primary outcome is 24-mo annualized relapse rate (ARR). Key secondary outcomes are PROs, treatment adherence and satisfaction, ARR in prior 24 mos, MS treatment pattern prior to transition and follow-up if CT are discontinued, and adverse events (AEs). Planned enrollment per study is 200 pts across 50 sites.
Results
Pt enrollment is ongoing for both trials. As of May 2020, 52 pts (mean [standard deviation {SD}] age: 50 [10.6] yrs; 75% female) have baseline data available in MASTER-2 (data not shown for CLICK-MS). Mean (SD) time since diagnosis was 11.8 (7.71) yrs. Most recent DMDs used included teriflunomide (23.1%), dimethyl fumarate (23.1%), fingolimod (19.2%), ocrelizumab (13.5%), natalizumab (9.6%) and alemtuzumab (1.9%). Sixteen pts had 21 relapses within 24 mos prior to enrollment (mean [SD] ARR: 0.21 [0.351]). Mean (SD) baseline PRO scores before starting CT were 50.7 (25.11) for 14-Item Treatment Satisfaction Questionnaire for Medication (Global Satisfaction), 50.0 (9.57) and 41.4 (11.56) for 36-Item Short Form Health Survey (mental and physical component summaries, respectively), 1.4 (1.71) for Beck-Depression Inventory-Fast Screen, 8.9 (4.79) for the Fatigue Impact Scale, and 2.7 (2.31) for Patient Determined Disability Steps scale. Thirty-six treatment emergent AEs (2 serious, but unrelated) were seen in 12 pts in 9.97 pt-yrs to date. Additional MASTER-2 and CLICK-MS pt baseline data will be shown in the presentation.
Conclusions
These studies will report real-world effectiveness and safety data of cladribine tablets in pts with RRMS and active SPMS with suboptimal response to prior oral, infusion, or injectable DMDs.
P0753 - Safety of satralizumab based on pooled data from phase 3 studies in patients with neuromyelitis optica spectrum disorder (ID 1375)
Abstract
Background
Interleukin-6 (IL-6) is implicated in the immunopathology of neuromyelitis optica spectrum disorder (NMOSD). Satralizumab, a humanized recycling monoclonal antibody that inhibits the IL-6 receptor, demonstrated a reduction in NMOSD relapse risk in two phase 3 studies: SAkuraSky (satralizumab in combination with baseline immunosuppressants; NCT02028884), and SAkuraStar (satralizumab monotherapy; NCT02073279).
Objectives
To evaluate the safety of satralizumab vs placebo in a pooled population of NMOSD patients from the SAkura studies, including the latest data from the open-label extension (OLE) period of the studies.
Methods
SAkuraStar and SAkuraSky are randomized studies comprising a double-blind (DB) period (satralizumab 120mg Q4W vs placebo) followed by an OLE period (satralizumab only). The combined DB and extension period was defined as the overall satralizumab treatment (OST) period (cut-off: 7 Jun 2019). Safety was evaluated in the DB and OST periods and reported as adverse event (AE) rates per 100 patient-years (PY).
Results
The pooled DB population included 178 patients (satralizumab, n=104; placebo, n=74), and 166 patients received satralizumab in the OST. Median duration of safety observation with satralizumab was 96.1 weeks in the DB period and 131.9 weeks in the OST period. Rates of AEs and serious AEs were comparable between satralizumab and placebo groups in the DB period (AEs: 478.49 vs 506.51 events/100PY, respectively; serious AEs: 14.97 vs 17.98 events/100PY, respectively), and were consistent in the OST period. In the DB period, four patients (3.8%) in the satralizumab group and five (6.8%) in the placebo group discontinued treatment due to AEs. Serious infection rates were comparable between the satralizumab and placebo groups in the DB period (4.13 vs 6.99 events/100PY) and remained stable in the OST (3.88 events/100PY). No opportunistic infections were observed in the satralizumab group. The injection-related reaction (IRR) rate was higher with satralizumab vs placebo in the DB period (17.03 vs 8.99 events/100PY); IRRs were mostly mild-to-moderate and did not lead to treatment discontinuation. Laboratory abnormalities were in line with those expected with IL-6 receptor antagonists in the DB and OST period. No deaths or anaphylactic reactions were reported.
Conclusions
In NMOSD patients, satralizumab was well tolerated and showed a favorable safety profile. Results from the OST period were consistent with the DB period.