Ocrelizumab Shows Similar Safety Among Older, More Disabled Patients With MS

Ellen S. Lathi, MD

For patients with multiple sclerosis (MS) who have higher baseline levels of disability and those who are older, treatment with ocrelizumab (Ocrevus; Genentech) does not appear to be associated with a higher rate of adverse events (AEs), according to the real-world results of ACAPELLA, a single-center, prospective study.

Presented in a poster at the 2021 Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC), October 25-28, the data show that those with an Expanded Disability Status Scale (EDSS) score of 6 or higher (n = 82) had a slightly higher rate of urinary tract infections, but no increased incidence of infections (45%; n = 37) or Herpes simplex virus (HSV) 1 or 2 (5%; n = 4) compared with the overall population of 354 patients (Infections: 36% [n = 126]; HSV-1 or HSV-2: 8% [n = 28]). Similar results were observed for the group aged 55 years and older (n = 134) for rates of both HSV-1 and 2 (7%; n = 28) and overall moderate infections (37%; n = 49).

All told, 5% (n = 17) of the cohort experienced serious infection that required hospitalization, though no correlations with age or disability were observed in this group. The older and more disabled group reported serious infection at a rate of 6% (n = 3), while those with only more disability and those who were older reported rates of 7% (n = 6) and 2% (n = 8), respectively.

“Ocrelizumab and other anti-CD20 antibodies generally have an excellent safety profile. Concerns have been raised about the potential for increased risk of infection, hypogammaglobulinemia, and malignancy with long-term use,” Ellen S. Lathi, MD, codirector, Elliot Lewis Center for Multiple Sclerosis Care, and colleagues wrote. “Although our hypothesis was that older and/or more disabled patients might have higher rates of AEs, thus far in our cohort of 354 patients treated with [ocrelizumab] for up to 4 years, this was not observed.”

Study coauthor Elizabeth Douglas, MPH, clinical research director, Elliot Center for MS, told NeurologyLive that "in older and/or more disabled patients, there was a trend toward higher risk for UTI, but no increased risk for other infections or malignancy."

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For the combined group of those aged 55 years and older with an EDSS score of 6 or greater (n = 48), rates of moderate infection and HSV-1/2 were 44% (n = 21) and 8% (n = 4), respectively. Zoster was not present for any individuals in the EDSS of 6 or greater group nor the combined group of those aged 55 years and older with an EDSS of 6 or greater, though the group over the aged of 55 years experienced a similarly low rate (2%; n = 3) compared with the overall group (3%; n = 9).

Overall, the majority of patients (53%; n = 188) in the study were on at least their fifth cycle of ocrelizumab treatment, equating to 24 months of therapy. Additionally, 41% (n = 144) had completed their sixth cycle, or 30 months, and 5% (n = 30) were on their seventh cycle, or 36 months of therapy.

Of the total patient population, 64.1% (n = 227) had relapsing MS and 35.8% (n = 127) had progressive disease, with respective mean ages of 44 years and 56 years, and respective mean EDSS scores of 2.5 and 5.0­­­­. The total cohort had a mean age of 48 years, with a mean EDSS score of 3.5.

“Six patients developed malignancies of different types,” Lathi et al wrote, adding that “in our study, malignancies occurred at a rate similar to that observed in the general MS population. These incidences were reported as grade II estrogen/progesterone receptor-positive ductal carcinoma in situ (n = 1), stage T2b adenocarcinoma of the prostate (n = 1), stage IIIb colon cancer (n = 2), colorectal cancer met to the liver (n = 1), and squamous cell carcinoma of the neck (n = 1). The majority of these patients—save for 1 with stage IIIb colon cancer—were at least 3 months past their most recent dose.

Incidences of breakthrough disease, defined as clinical relapse and/or new MRI activity, were also low (3%; n = 12), as were rates of mild to moderate post-infusion symptoms or prolonged malaise (6%; n = 22). None of the post-infusion symptoms were deemed related to early B-cell reconstitution.

“The ACAPELLA trial is a prospective, observational study that includes those patients who would fall outside of the parameters specified in clinical trials,” Lathi and colleagues wrote. “In addition to AEs, ACAPELLA substudies are evaluating the impact of [ocrelizumab] on immunoglobulin levels, CD19 reconstitution, and JC virus antibody titers. Interim data analyses occur on a biyearly basis and findings will be reported annually.”

REFERENCE
Douglas EA, Jungquist RMM, Bouley AJ, Katz JD, Lathi ES. Real-world experience with ocrelizumab, year four data. Presented at CMSC 2021; October 25-28, 2021.