Older Patients With MS Face Additional Risks With Ocrelizumab Treatment

Evan Luxenberg, MD

Data from a recent study suggest that patients with multiple sclerosis (MS) over 55 years of age face additional risks while on ocrelizumab compared to patients under 55 years of age.¹ 

These findings were presented virtually by Evan Luxenberg, MD, resident, University of Washington, at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2021, February 25-27.

"Ocrelizumab is a B-Cell depleting humanized monoclonal antibody FDA-approved for treatment of relapsing-remitting multiple sclerosis (RRMS) and primary progressive multiple sclerosis (PPMS). In the pivotal trials for both [relapsing-remitting] MS and [primary progressive] MS, patients [older than] 55 years were excluded. In clinical practice, though, many patients receive ocrelizumab therapy beyond this age cutoff. Here, we are reporting on our single-center cohort experience in this subset of patients,” Luxenberg and colleagues wrote.

Luxenberg and colleagues conducted a retrospective analysis of all ocrelizumab-treated patients infused at the University of Washington MS Center’s infusion suite in order to assess clinical and laboratory parameters in patients over the age of 55 years. They reviewed clinic notes, emergency department visits, admissions, outside hospital encounters, and internal and external laboratory results via the electronic medical record. They also searched for instances of infection, pneumonia, and influenza among other adverse events.

A total of 335 patients received ocrelizumab at the center since March 2017. Of these patients, 59 (17,6%) were above the age of 55, with ages ranging from 56 to 84 years old. Specifically, 30 (50.8%) were 56 to 60 years old, 12 (20.3%) were 61 to 65 years old, 10 (16.9%) were 66 to 70 years old, and 7 (11.9%) were over 70 years old. Of patients over 55 years of age, 28 (47.5%) were women.

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Luxenberg and colleagues found that 14 patients over 55 years of age stopped ocrelizumab treatment. This decision was made due to MS progression in 5 patients, repeated or severe infections in 5 patients, including 1 with fatal pneumonia, unfavorable risk-to-benefit ratio in 2 patients, worsening psoriasis in 1 patient, and autologous stem cell transplant in 1 patient. Prolonged B-cell depletion up to over 1.5 years after last ocrelizumab infusion was observed in individual patients over the age of 70 years, although post-discontinuation CD19 data is limited so far.

“Our data highlight some of the risks in the aged population on ocrelizumab and emphasize the need to study this population to guide more well-informed conversations about the risks and benefits of this treatment, "Luxenberg and colleagues concluded.

An additional, unrelated study presented at ACTRIMS also investigated ocrelizumab and its use in older patients with MS. Samantha Epstein, MD, resident, New York Presbyterian Columbia University Medical Center, presented a study that showed that investigated tolerance of ocrelizumab in patients with primary progressive MS or secondary progressive MS over 55 years of age.² 

Epstein and colleagues found that over the 2 years prior to anti-CD20 therapy, 58% (n = 14) of patients remained stable, and 41% (n = 10) experienced confirmed disability progression (CDP). After ocrelizumab treatment, 71% (n = 17) remained stable and 29% (n = 7) experienced CDP. There was no significant difference between CDP (P = .54) or change in EDSS (P = .09) between groups. 

Each group had 75% (n = 12) of patients with a stable timed 25-foot walk test (T25FW), and 25% (n = 4) with over a 20% increase in T25FW. At least 1 documented infection was seen in 16 patients (29%) on ocrelizumab, compared to 10 patients (18%) prior to anti-CD20 (P = .26). A severe infusion-related reaction was reported. 

Patients in the control group experienced lip swelling (n = 1, with teriflunomide), flushing/GI distress (n = 2, with DMF; n = 1, with fingolimod), flu-like symptoms (n = 1, with IFN), and a malignant skin growth (n = 1). were reported. No patients on ocrelizumab had neoplasms diagnosed.

“We found no difference in 2-year clinical endpoints for patients while on ocrelizumab compared to prior to anti-CD20 therapy; though, there was a trend toward decreased CDP on ocrelizumab that our study was not sufficiently powered to evaluate. Ocrelizumab was generally well tolerated. Larger trials are needed,” Epstein and colleagues concluded.

Alana Jones, MD-PhD graduate student, University of Alabama at Birmingham, presented another study that clarified characteristics of patients receiving ocrelizumab at a tertiary referral MS center. The study found that African American patients with MS switched to ocrelizumab at a younger age than Caucasian patients. AA patients with RMS (mean, 43.2 years) and PPMS (mean, 55.9 years) were younger than Caucasian patients with RMS (mean, 45.8 years) and PPMS (59.2 years), despite similar disease duration in both groups.³

Jones and colleagues saw that patients with PPMS had a mean age of 58.5 years while patients with RMS were significantly younger, with a mean age of 44.8 years (P ≤.05). They also had a longer duration of disease (mean, 16.5 years) compared to patients with RMS (mean, 11.3 years). No difference was found in the mean number of DMTs prior to ocrelizumab treatment.

Physician rationales for switch to ocrelizumab change were mostly due to suboptimal response (overall, 46.2%; RMS, 41.5%; PPMS, 56.3%; P ≤.05). Patient rationales for requesting treatment change were mostly due to adverse effects (overall, 22.1%; RMS, 29.6%; PPMS, 6.3%; P ≤.05) and personal choice/convenience (overall, 29.1%; RMS, 26.0%; PPMS, 37%; P ≤.05).

For more coverage of ACTRIMS Forum 2021, click here.

REFERENCES

1. Luxenberg E, von Geldern G, Wundes A. Analysis of ocrelizumab treatment in aged patients at an academic MS center. Presented at ACTRIMS Annual Forum; February 25-27, 2021. Poster P069.
2. Epstein S, Fong KT, Levine L, et al. Evaluation of ocrelizumab in older progressive multiple sclerosis patients. Presented at ACTRIMS Annual Forum; February 25-27, 2021. Poster P073. 
3. Manouvakhova O, Jones A, Bashir K. Observations regarding ocrelizumab use at a tertiary referral MS center. Presented at ACTRIMS Annual Forum; February 25-27, 2021. Poster P076.