Sustained benefits with ocrelizumab in relapsing-remitting MS

Patients with relapsing-remitting multiple sclerosis (RRMS) who have suboptimal response to disease-modifying therapies (DMTs) experienced low disease activity after switching to ocrelizumab, according to interim results of the LIBERTO study.

“Almost 60 percent of patients had no evidence of disease activity (NEDA) after 3 years, EDSS* remained stable, [and] relapse rate very low with minimal variation over 3 years,” presented study author Professor Patrick Vermersch from the University of Lille, Lille, France, at AAN 2022.

Participants were 680 patients aged 18–55 years with RRMS for <10 years initially enrolled in the phase IIIb, multicentre, open-label CASTING study. The patients had a suboptimal response after treatment with one or two DMTs for ≥6 months and an EDSS score of 0–4 at screening. They received intravenous (IV) ocrelizumab (two 300 mg infusions on days 1 and 15 followed by single 600 mg infusions Q24W) for a 96-week treatment period. MRI rebaselining was carried out at week 8. At the end of the CASTING study, 439 patients considered to have a positive risk-benefit ratio, according to their neurologist, were enrolled in the follow-up long-term LIBERTO study where they continued IV ocrelizumab 600 mg Q24W.

Over the 3-year period, 59.4 percent of patients had NEDA, defined as an absence of protocol-defined relapses, 24-week confirmed disability progression (CDP), and contrast-enhancing T1-weighted lesion (T1w-CEL) and new/enlarging T2-weighted lesions (N/E T2w-L). [AAN 2022, poster number P5.4-003]

Between baseline and year 1 (CASTING year 1), 82.6 percent of patients had NEDA, while 87.0 percent had NEDA between year 1 and 2 (CASTING year 2) and 82.5 percent between year 2 and 3 (LIBERTO year 1).

Overall, 68.1 percent had no evidence of clinical activity and 86.6 percent had no evidence of MRI activity. Lack of clinical activity was noted in 86.9, 90.2, and 84.2 percent between baseline and year 1, year 1–2, and year 2–3, respectively. Lack of MRI activity was noted in 93.7, 95.9, and 98.2 percent of patients in those respective time periods.

Looking at the individual components of the NEDA composite, 78.1 percent had no 24-week CDP, 96.6 percent had no T1w-CEL, 84.7 percent had no relapses, and 86.6 percent had no N/E T2w-L.

EDSS score was a mean 2.09 at CASTING baseline and 2.16 at year 3. Annualized relapse rates were low throughout the study period at 0.07, 0.05, and 0.05 at years 1, 2, and 3, respectively.

Adverse events (AEs) were reported by 92.3 percent of patients in the LIBERTO study, though these were primarily of mild or moderate severity (79 percent of grade 1–2). The most common AEs (>10 percent of patients) were infusion-related reactions (44.2 percent), nasopharyngitis (28.5 percent), headache (22.6 percent), influenza (18.2 percent), and urinary tract infections (UTIs; 14.8 percent). Almost 72 percent of patients experienced infections. Serious AEs were reported in 8.4 percent, with the most common (>1 patient) being sinusitis and UTIs (0.7 and 0.5 percent, respectively). Eleven patients had serious infections. Malignancies occurred in three patients. There were four AE-related discontinuations (0.9 percent). The one documented death occurred during the CASTING study.

No new safety signals were observed, said Vermersch.

“Patients with RRMS often experience disease activity despite receiving a DMT,” he said. Although prior studies have shown significant benefits on clinical and MRI outcomes in patients with relapsing and primary progressive MS, data on the efficacy and safety of ocrelizumab in patients with a suboptimal response to DMTs remain limited, he continued. [N Engl J Med 2017;376:221-234; N Engl J Med 2017;376:209-220]

“[This study showed that] patients with a suboptimal response to one or two prior DMTs who switched to ocrelizumab had consistently low disease activity over 3 years, based on clinical and MRI measures,” Vermersch concluded.