Switching to Ocrevus or Kesimpta doesn’t alter either’s effectiveness
Researchers did see link between changing anti-CD20 therapy and IgG declines
Switching between CD20-targeting antibodies Ocrevus (ocrelizumab) and Kesimpta (ofatumumab) doesn’t affect either’s effectiveness at lowering disease activity and slowing disability progression in people with multiple sclerosis (MS), a real-world study in Germany shows.
Researchers did see a link between switching and a faster, continuous decrease of immunoglobulin G (IgG), a class of antibodies that contribute to disease development.
“Our observation of increased loss of IgG warrants further validation, but may indicate niche-specific immunological effects of [Kesimpta] and [Ocrevus],” the study’s researchers wrote. The study, “Disease outcomes following lateral switch among different CD20-antibodies in active multiple sclerosis,” was published in the Multiple Sclerosis Journal.
MS occurs when the immune system attacks the myelin sheath, a protective layer around nerve fibers that helps ensure electrical signals are efficiently sent from one nerve cell to another. The loss of myelin leads to progressive nerve fiber degeneration and MS symptoms.
Anti-CD20 therapies, such as Ocrevus and Kesimpta, are well-established disease-modifying therapies for relapsing forms of MS. They work by targeting the CD20 protein on the surface of B-cells, which are immune cells responsible for producing self-reactive antibodies that drive MS and other autoimmune diseases, leading to their death. Both treatments are similarly effective at reducing MS activity and disability progression. Ocrevus is given as an infusion into a vein once every six months, while Kesimpta is given monthly as an injection under the skin and can be self-administered.
Switching from one anti-CD20 therapy to another
“However, there are no data on whether lateral switches between both substances affect treatment effectiveness or safety,” wrote researchers in Germany, who compared the clinical outcomes of those who started with Ocrevus or Kesimpta and switched to the other during follow-up against those who stayed on their first treatment. Those who switched were generally older and had a shorter disease duration.
Among those who started with Ocrevus, 38 switched to Kesimpta, while 149 remained on Ocrevus and served as controls. Those in the control group were treated for a mean of 28 months, while those in the switch group were treated for 38.2 months, or about 3 years. Reasons for switching included patient preference, infusion-related reactions, and adverse events. The median time between the last Ocrevus dose and the first dose of Kesimpta was 186 days, or about six months.
Twenty-four patients who started with Kesimpta switched to Ocrevus and were treated for a mean of 23.7 months, and 83 controls remained on Kesimpta for a mean of 19.3 months. A reason for switching to Ocrevus was active disease or injection-site reactions. Ocrevus was started at a median of 31 days after the last Kesimpta dose.
During a follow-up, 20.9% of those who started on Ocrevus had a relapse, with no significant differences seen between switchers and controls. Similarly, no significant differences between the groups were seen regarding new or enlarging inflammatory lesions and confirmed disease worsening.
For those on Kesimpta, 17.8% had a relapse during follow-up (14.5% of controls vs. 29.2% of switchers), with similar effects seen in the two groups regarding new/enlarging inflammatory lesions and confirmed disease worsening.
Regardless of whether patients started with Ocrevus or Kesimpta, they saw a rapid and sustained reduction of B-cell levels.
IgG levels showed an initial decline in both controls and switchers after treatment started. However, while IgG levels stabilized in those who stuck with their first therapy, they continued declining in those who switched and became significantly lower in both groups — at 30 months among those who switched to Kesimpta, and at 24 months among those who switched to Ocrevus.
The most frequent adverse events included injection/infusion-site reactions, infections in the urinary and upper respiratory tract, and low levels of antibodies. Itch, rash, fatigue, headache, reflux disease, and menstrual cycle disturbances were also reported.
Wrote the researchers: “Clinical effectiveness remained stable following the switch, but we observed an association between switching and accelerated IgG decline.” They said more research to help “elucidate niche-specific effects of [B-cell targeting therapies in relapsing] MS” was warranted.
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