Five Years of Ublituximab in Relapsing Multiple Sclerosis: Additional Results from Open-label Extension of ULTIMATE I and II Studies
Bruce Cree1, Edward Fox2, Hans-Peter Hartung3, Enrique Alvarez4, Peiqing Qian5, Sibyl Wray6, Derrick Robertson7, Deren Huang8, Krzysztof Selmaj9, Daniel Wynn10, Koby Mok2, Yanzhi Hsu2, Yihuan Xu2, Chris Rowland2, Karthik Bodhinathan2, Peter Sportelli2, Jackie Parker2, Hari Miskin2, Lawrence Steinman11
1UCSF, Multiple Sclerosis Center, 2TG Therapeutics, 3Heinrich Heine University Medical Faculty, 4University of Colorado, 5Swedish Medical Center, 6Hope Neurology, 7University of South Florida, 8Licking Memorial Hospital, 9University of Warmia and Mazury, 10Consultants in Neurology, Ltd., 11Stanford Medicine
Objective:
To evaluate the long-term clinical efficacy and safety of ublituximab.
Background:
In ULTIMATE I and II studies, ublituximab (UBL) demonstrated significant reduction in disease activity vs. teriflunomide (TER) over 2 years. Results from additional 3 years of open label extension (OLE) are presented.
Design/Methods:
After 2 years in double-blind period (DBP), RMS patients, either continued UBL treatment, or switched from TER to UBL (TER-UBL). Adjusted annualized relapse rates (ARR) were analyzed using generalized estimating equations and 24-week confirmed disability progression (CDP), confirmed disability improvement (CDI), were estimated by Kaplan-Meier method and Cox regression model.
Results:
Upon completion of DBP, over 85% of patients entered OLE (UBL, N=422; TER-UBL, N=429), and over 70% stayed on UBL treatment at OLE Year 3. Patients switching from TER to UBL experienced significant reduction in ARR at 1 year post switch [-58.4%; 0.182 vs 0.076; RR (95% CI): 0.416 ( 0.289, 0.599), P<0.0001] which continued to drop to 0.048 and 0.045 for OLE Years 2 and 3, respectively. Patients continuing UBL saw further reductions in ARR [0.053, 0.032, and 0.020 for OLE Years 1, 2, and 3 respectively]. CDP 24 at year 5 was 8.0% in UBL vs 14.3% in TER-UBL patients [HR (95% CI): 0.612 (0.414, 0.904); P=0.0126]. CDI 24 at year 5 was 17.0% in UBL vs 12.2% in TER-UBL patients [1.472 (1.048, 2.067); P=0.0249]. IgG and IgM levels remained stable and above LLN for patients on UBL for 5 years [mean (SD), 8.1 (2.23) g/L and 0.7 (0.66) g/L, respectively]. Overall, adverse events were consistent with established safety profile.
Conclusions:
UBL treatment for 5 years provided MS patients with sustained clinical benefit versus switching after 2 years of TER, with 1 relapse every 50 years of treatment, and significant benefits on disability progression. Results confirm early UBL initiation confers long-term benefits.
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