Ocrevus Reduces MS Relapse Risk, But Linked to More Hospitalizations
Ocrevus (ocrelizumab) reduces relapse risk and slows disability progression in multiple sclerosis (MS) but also is associated with higher hospitalization rates in older people with relapsing forms of the disease, a new observational study reports.
Hospitalizations — which occurred mainly due to urinary tract infections — were more frequent in adults ages 55 and older than in those below that age, the study found.
“Although patients older than 55 were not at higher risk of having an infection, the number of hospitalisations in older patients in our [study] due to an infection is concerning,” the researchers wrote.
“Given these … observations, we recommend that the patient’s age and level of disability should be taken into account when considering the use of ocrelizumab [Ocrevus] and should prompt very close monitoring when it is employed in older and more disabled patients,” they wrote.
Marketed by Genentech, Ocrevus is an anti-CD20 monoclonal antibody that binds to CD-20-expressing mature B-cells, immune cells associated with MS and subsequent disability. Results from three Phase 3 trials showed that Ocrevus significantly reduces relapse risk and slows disability progression.
However, the selection criteria for these trials required the exclusion of many potential participants due to age, underlying conditions, or the use of other, simultaneous medications. Thus, while Ocrevus is indicated for use in people with relapsing MS and PPMS who did not meet clinical trial inclusion criteria, its efficacy may be different in these patients.
Moreover, since people older than 55 were excluded from the Phase 3 trials testing Ocrevus, the risk of infection and other adverse events more commonly seen in older patients is not clear.
To address this gap, a team of researchers in Oregon sought to investigate Ocrevus’ efficacy and adverse event rates in a general population of people with relapsing MS — relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) with relapses — and PPMS.
The study’s goal “is to determine whether use of ocrelizumab in a general MS population, which met U.S. Food and Drug Administration (FDA) prescribing indications for the treatment of MS, would reveal differences in clinical outcomes, especially their risk profile, when compared with that observed in controlled trials,” the researchers wrote.
The team used data collected from adults with MS enrolled in the Providence Ocrelizumab Registry (POR). All were prescribed Ocrevus between March 2017 and February 2020.
Adverse events, including infections and hospitalizations, and the patients’ annualized relapse rate (ARR) were evaluated. The researchers also examined disability progression using the Expanded Disability Scale Score (EDSS), and brain MRI data.
A total of 355 participants were enrolled in the study. The vast majority (90.5%) were white, and 71.9% were female. Among those in the study, 78.3% had relapsing MS, while 13.2% had SPMS (with no relapses), and 8.5% had PPMS. The mean age of the group was 51.8 years, and the mean duration of disease was 12 years for relapsing MS, 18.7 years for SPMS, and 12.7 years for PPMS.
The participants had taken Ocrevus for a median duration of 23.6 months, and 85% of them had been re-evaluated at least four times after starting Ocrevus.
A total of 32.9% of participants experienced infusion reactions after the first course of Ocrevus, which was very close to the 32.2% who had such reactions in the clinical trials. In this study, the percentage of patients experiencing reactions was reduced to 12.7% after subsequent courses, the data show.
“In terms of safety, infusing reaction rates in the POR cohort did not significantly differ from those observed in the prior phase III clinical trials, the first course having the highest rate followed by a stepwise decline with subsequent ocrelizumab infusions,” the researchers wrote.
Respiratory infections, which affected 40.1% of patients, and urinary tract infections, occurring in 33.1% of participants, were other common adverse events. Interestingly, there was no significant difference in infection rates between patients younger than 55 and those older than that age (68.5% vs. 67.5%).
However, it was “concerning” that hospitalizations — mainly due to urinary tract infections — occurred more frequently in people ages 55 and older, the researchers said.
“Infections resulting in hospitalisation are a concern, especially in older and disabled patients,” they wrote.
Notably, of those hospitalized, 69.2% were older than 55, and their mean EDSS was 5.7 — indicating disability severe enough to preclude full daily activities.
Given the findings, the researchers issued a recommendation that a patient’s age and level of disability should be taken into account in prescribing Ocrevus. The investigators also called for prompt and close monitoring of the infusion therapy when it is given to older and more disabled patients.
Ocrevus-prescribing guidelines in Europe and the U.S. have been updated to include an association between reduced antibody levels and the risk of severe infection. However, in participants who had their antibody levels measured, the risk of infection was similar in people with high and low antibody levels, suggesting that no link exists between antibody levels and infection risk.
The team noted, however, that participants in the study had used Ocrevus for just less than two years, so a longer observation period may be needed to support the association between antibody levels and infection risk as indicated by prescribing guidelines.
In terms of efficacy, Ocrevus was found to effectively reduce relapse rates among relapsing MS patients, with the participants exhibiting an ARR of 0.09, compared with 0.34 at two years (24 months) before starting treatment. The reduced ARR rates were similar to those observed in clinical trials, the researchers said.
A total of 43 patients (12.1%) stopped using Ocrevus after a median duration of 10.8 months — 24 due to side effects, 15 due to relapse or clinical progression, and four due to death. The highest relapse rates were observed in patients transitioning from Tysabri (natalizumab), but the team noted that “the rate of relapse [seen] was not significantly higher than that of the other [disease-modifying therapies],” they wrote.
Post-treatment brain MRI scans were done for 81.9% of the participants who had undergone such scans before starting Ocrevus. Among these participants, 90% had stable MRI results and the median EDSS remained unchanged for all patients at 12 months.
While the researchers noted limitations of their study’s registry design, they concluded that it “provides valuable information concerning the use of [Ocrevus] in a large community-based MS centre and may assist in future decision-making regarding selection and management of patients who are potential candidates for [Ocrevus] therapy.”
The team emphasized that “only 12.1% of patients have discontinued ocrelizumab.”