Early Plasma GFAP Lowering Predicts Reduced Disability Worsening Risk in Progressive MS

Jens Kuhle, MD, PhD

Data from a recent study suggest that lowering plasma glial fibrillary acidic protein (pGFAP) early leads to a reduced risk of disability worsening in patients with secondary progressive multiple sclerosis (SPMS) treated with siponimod (Mayzent; Novartis).

These findings were presented virtually by Jens Kuhle, MD, PhD, head, MS Center, and senior physician, University Hospital Basel, at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, February 25-27.

“In the EXPAND study (NCT01665144), siponimod significantly reduced the risk of disability progression in patients with SPMS compared with placebo. pGFAP and plasma neurofilament light chain (pNfL) correlated with disease activity and have shown utility as markers of disability and treatment response in SPMS. The predictive value of the change in these blood biomarker levels during the early stage of treatment for disability worsening has not been investigated,” Kuhle and colleagues wrote.

The researchers conducted a post-hoc analysis from the EXPAND core study in order to assess the value of the changes in pGFAP and pNfL levels from baseline to 3 months in predicting disability worsening in patients with SPMS treated with siponimod or placebo.

READ MORE: African American Patients Have Higher MS Disability Scores Than Hispanic, Caucasian Patients

They quantified pGFAP and pNfL levels at baseline and 3 months in patients with SPMS using Single Molecule Array technology and quantified disability via the expanded disability status scale (EDSS). They used Cox regression models adjusted for age, gender, disease duration at baseline and relapses in the 24 months before study initiation, and EDSS score at 3 months to analyze the impact of change in pNfL and pGFAP levels.

Altogether, samples from 1453 of 1651 randomized patients were analyzed. In patients treated with siponimod with pFGAP levels over 75 pg/mL, a decrease in pGFAP levels after 3 months was associated with a reduced risk of disability worsening. Time to 1-point sustained EDSS worsening had a hazard ratio (HR) of 0.68 (P = .0543) and time to 3-month confirmed disability worsening (3mCDW) had an HR of 0.66 (P = .0053). Time to sustained EDSS score of 7 had an HR of 0.79 (P = .4470) from month 3 to end of study.

None of these associations were seen in patients treated with placebo. The HR of time to 1-point sustained EDSS worsening was 1.19 (P = .5193), the HR of time to 3mCDW was 1.03 (P = .8691), and the HR of time to sustained EDSS score of 7 was 1.48 (P = .3580).

Kuhle and colleagues analyzed pNfL similarly and saw that a decrease from baseline to 3 months was only associated with a slightly decreased risk of disability worsening in siponimod-treated patients with baseline pNfL levels over 20 pg/mL. The HR for time to 1-point sustained EDSS worsening was 0.97 (P = .8926), the HR for time to 3mCDW was 0.91 (P = .5249), and the HR for time to sustained EDSS score of 7 was 0.64 (P = .1610). Similar trends were seen in pNfL associations in patients treated with placebo, unlike the findings in pGFAP.

“This is the first study that supports an association of the early lowering in pGFAP levels and a reduced risk of disability worsening in patients with progressive MS under disease-modifying treatment. Results underscore the utility of pGFAP as treatment response and prognostic marker in SPMS,” Kuhle and colleagues concluded.

For more coverage of ACTRIMS Forum 2021, click here.

REFERENCES

1. Akinsanya J, Absinta M, Dargah-zade N, et al. Toward the use of paramagnetic rim lesions in proof-of-concept clinical trials for treating chronic inflammation in multiple sclerosis. Presented at ACTRIMS Annual Forum; February 25-27, 2021. Poster P126.