Ocrevus, rituximab may not slow disability progression in PPMS
Anti-CD20 therapies appear to be ineffective in real-world study
Anti-CD20 therapies like Ocrevus (ocrelizumab) and rituximab appear to be ineffective at slowing disability progression in people with primary progressive multiple sclerosis (PPMS), a form of the disease characterized by symptoms that steadily worsen over time, according to data from a real-world study in France.
The study, “Anti-CD20 Therapies in Drug-Naive Patients With Primary Progressive Multiple Sclerosis A Multicenter Real-Life Study,” was published in Neurology, a journal of the American Academy of Neurology (AAN).
“Anti-CD20 therapies are widely prescribed, in part because there are few alternate treatments” for PPMS, Laure Michel, MD, PhD, who led the study from Rennes University in France, said in an AAN press release. “However, our study suggests they may not slow disability from worsening for people with primary progressive MS [multiple sclerosis].”
Importantly, the smaller number of patients treated with Ocrevus in this study — most received rituximab — calls for caution when interpreting the results for this PPMS-approved therapy, the researchers noted.
Nevertheless, the findings draw attention to ongoing research efforts to determine the best strategies to treat PPMS, balancing potential benefits with risks like serious infections and other side effects.
“Medications for MS can be expensive and come with risks of side effects” Michel said. “Our results indicate that there should be a constant evaluation of MS therapies to determine if the benefits outweigh the risks for people with primary progressive MS.”
Analyzing disability progression data on treated vs. untreated PPMS patients
Primary progressive multiple sclerosis is a type of MS that progresses slowly and steadily from its onset, without clear periods of recovery or relapse — when symptoms worsen suddenly or new ones appear. Treatment options for PPMS are limited and often fail to slow disability progression.
Both Ocrevus and rituximab are designed to promote the death of B-cells, the immune cells that produce the self-reactive antibodies thought to drive MS-related neurodegeneration. These therapies work by targeting the CD20 protein found at the cells’ surface. This is believed to reduce the autoimmune attacks that drive the disease, thereby easing symptoms of MS and potentially slowing its progression.
Ocrevus is the only approved therapy for PPMS, and is also cleared for use in relapsing forms of MS. Rituximab, approved to treat certain blood cancers and some autoimmune diseases, is not approved for any type of MS, but is often used off-label for treating the condition.
Now, Michel and other researchers sought to evaluate how well Ocrevus and rituximab slow disability progression in people with PPMS. The team used data from patients enrolled in the French MS registry.
Specifically, the researchers analyzed data from January 2016 through June 2021 from patients who had not received disease-modifying therapies for at least two previous years, nor previously received anti-CD20 therapies or immunosuppressive agents with long-lasting effects.
Of the 1,184 patients included in the study, 426 (36%) received anti-CD20 therapies during the timeframe and were dubbed the treated group. Meanwhile, the remaining 758 (64%) were not given such therapies and were known as the untreated group. In the treated group, 295 were given rituximab and 131 received Ocrevus.
The treated patients were a median of 6.7 years younger (51.9 vs. 58.6 years) and had shorter disease duration (5.1 vs. 8.4 years) than untreated patients. A greater proportion of treated patients had active disease within the two years before the study’s start (54.5% vs. 27.8%).
Results support need for ‘constant evaluation’ of anti-CD20 therapies
The main goal of the analysis was to compare the time it took for patients in either group to experience confirmed disability progression, or CDP, defined as an increase in the Expanded Disability Status Scale (EDSS) score lasting at least three months.
The results, adjusted for potential influencing factors, showed no significant difference in the time to CDP between the anti-CD20 treated group (3.71 years) and the untreated group (3.87 years).
At two years, a slightly greater proportion of anti-CD20 treated patients were found to have confirmed disability progression (28.2% vs. 25.4%), but this difference was also not statistically significant.
When comparing data from the 131 Ocrevus-treated patients and 262 untreated patients entering the study after 2018 — the year Ocrevus was approved in France — there were again no significant group differences in terms of time to CDP or the proportion of patients with this outcome at two years.
In the study, most treated PPMS patients received rituximab, “and even if the subgroup analysis on [Ocrevus-treated] patients does not suggest a significant effect of [Ocrevus] on progression, the limited number of patients in this subgroup ([number] = 131) limits the interpretation,” the researchers wrote.
Secondary measures such as the number of relapses, time to first relapse, and disease activity based on brain MRI scans were also similar between the anti-CD20-treated and untreated groups. However, the rate of serious infections was about twice as high in treated patients as in untreated patients, the data showed.
We showed that in a real-life setting, the time to first CDP was not different between anti-CD20-treated patients with PPMS and untreated patients and that treated patients present a high risk of serious infections.
Additional statistical analysis showed that factors like sex — specifically being male — and a longer disease duration significantly increased the likelihood of disability progression among these PPMS patients.
“We showed that in a real-life setting, the time to first CDP [confirmed disability progression] was not different between anti-CD20-treated patients with PPMS and untreated patients and that treated patients present a high risk of serious infections,” the team wrote.
The researchers stressed that their study was retrospective, or looked back in time, and primarily included individuals treated with rituximab.
Nonetheless, the team concluded: “Our results indicate that there should be a constant evaluation of all available data to ascertain the best risk/benefit ratio for patients with PPMS” treated with anti-CD20 therapies.
About the Author
