2025 American Academy of Neurology Abstract Website

Lawrence Steinman¹, Edward Fox², Hans-Peter Hartung³, Enrique Alvarez⁴, Peiqing Qian⁵, Sibyl Wray⁶, Derrick Robertson⁷, Krzysztof Selmaj⁸, Daniel Wynn⁹, Koby Mok², Yanzhi Hsu², Yihuan Xu², Chris Rowland², Karthik Bodhinathan², Peter Sportelli², Jackie Parker², Hari Miskin², Bruce Cree¹⁰
¹Stanford Medicine, ²TG Therapeutics, ³Heinrich Heine University Medical Faculty, ⁴University of Colorado, ⁵Swedish Medical Center, ⁶Hope Neurology, ⁷University of South Florida, ⁸University of Warmia and Mazury, ⁹Consultants in Neurology, Ltd., ¹⁰UCSF, Multiple Sclerosis Center

Objective:

To evaluate the immunological safety profile of prolonged UBL treatment.

Background:

UBL provides sustained clinical benefit over five years of treatment. Immunoglobulin and infection profile with prolonged UBL treatment are presented.

Design/Methods:

After 2 years in double-blind period, RMS patients either continued UBL treatment, or switched from teriflunomide to UBL during open-label extension. At 5 years, mean serum Ig levels were calculated. LLN thresholds were (g/L): 5.65 (IgG), 0.4 (IgM), 0.7 (IgA). Severity of hypogammaglobulinemia (g/L) were classified as mild: <5.65 to ≥ 4.0, moderate: <4.0 to ≥ 2.0, severe: <2.0 for IgG, and mild: <0.4 to ≥ 0.36, moderate: <0.36 g/L to ≥ 0.2, and severe: <0.2 for IgM.

Results:

Mean serum IgG and IgM levels remained stable and above LLN after continuous UBL treatment for 5 years [mean (SD), 8.1 (2.23) g/L and 0.7 (0.66) g/L, respectively]. At year 5, IgG drops were limited and mild (12.6%) to moderate (0.3%), none were severe, and IgM were mild (4.9%), moderate (18.9%) or severe (11.2%). Rates of SI per 100 patient-years and 95% CI for UBL-treated patients <LLN or ≥LLN were 3.26 (2.10, 5.05) and 2.44 (1.94, 3.07]) for IgM, 2.92 (0.94, 9.06) and 2.57 (2.09, 3.16) for IgG, and 3.66 (1.37, 9.76) and 2.55 (2.07, 3.13) for IgA respectively, indicating no significant difference in the incidence of SI regardless of Ig levels above or below LLN. The rate of SIs occurring within 1 month of <LLN or ≥LLN Ig evaluation did not differ, further supporting lack of relationship between decreases in Ig below LLN and SI.

Conclusions:

Mean Ig levels remained stable and above LLN at year 5, and no association between decreased immunoglobulins and risk of SI was observed. Thus, UBL confers a benefit risk balance suitable for long-term clinical management of RMS.