Subcutaneous Ofatumumab Shows Reduced Injection Reactions in Multiple Sclerosis

Ofatumumab (Kesimpta) should be considered a manageable therapeutic approach for patients with multiple sclerosis (MS), according to a recent study published in Frontiers in Neurology that compared the drug’s injective-related reactions (IRRs) with that of ocrelizumab (Ocrevus). This intervention is not risk-free; however, close monitoring of patients remains important for future data to demonstrate its long-term safety profile.¹

In 2017, the FDA approved ocrelizumab for adult patients seeking treatment for primary progressive MS (PPMS) and other relapsing forms of the disease.² This therapy is delivered intravenously, and its approval marked the first drug approval indicated for PPMS. Although patients who were administered ocrelizumab had reduced rates of relapse and disability progression, the treatment is associated with multiple IRRs, including hives, low blood pressure, fever, headache, shortness of breath, throat swelling, accelerated heartbeat, upper and lower respiratory tract infection, and more.

The primary ofatumumab injection reaction is typically development of a fever | image credit: Trsakaoe - stock.adobe.com

Ofatumumab was approved for various relapsing forms of MS in 2021.¹ This drug differs from ocrelizumab because it is a recombinant human anti-CD20 monoclonal antibody (mAb) and is administered subcutaneously without the need for a premedication. As the present authors wrote, this intervention was specifically created to minimize certain adverse events (AEs) like IRRs; subcutaneous delivery helps reduce the risk of these events because it allows the body to absorb the medication in a slower, more controlled manner. Ofatumumab has been demonstrated to reduce the chances of experiencing an IRR, but some patients have reported generally mild or moderate post-treatment AEs such as fever, headache, pain, fatigue, and more.

With both of these options in mind, Scavone et al conducted a study to assess and compare the IRR characteristics associated with ofatumumab and ocrelizumab to paint a clearer picture for patients and clinicians considering these treatment avenues.

Data were collected from EudraVigilance (EV), a European spontaneous reporting system database. Between 2021 and 2023, information regarding Individual Case Safety Reports (ICSRs)—that reported on IRRs after treatment with ofatumumab or ocrelizumab— was gathered.

In total, the researchers retrieved 860 ICSRs where there was suspicion of ofatumumab (n = 441; 51%) or ocrelizumab (n = 419; 49%) treatment. Among these patients, 73% of those who experienced IRRs related to ocrelizumab were between 18 and 64 years of age; however, the age group was not specified for those with IRRs following ofatumumab. The authors noted no discernable, significant differences were observed regarding ICSRs in either treatment group.

For those who received ofatumumab, flu-like illness and symptoms were the most prevalent reported events, whereas ocrelizumab was more commonly associated with anaphylactic and infusion-related reactions. The analysis found that premedication drugs had also been administered in 148 of the reported ICSRs (131 with ocrelizumab, 17 with ofatumumab). The presence of premedication drugs in cases of ICSR was often found in those who experienced infusion-related reactions (57%) and pyrexia (30.2%).

“The analysis of data reported in the EV database showed a similar number of ICSRs reporting IRRs following ofatumumab and ocrelizumab treatments, although few differences were noted in terms of IRRs’ signs and symptoms,” the authors wrote. “Thus, although a risk of ofatumumab-induced IRRs cannot be excluded, it should be considered as manageable considering that the drug seems to be mostly associated with the occurrence of fever.”

References

1. Scavone C, Anatriello A, Baccari I, et al. Comparison of injective related reactions following ofatumumab and ocrelizumab in patients with multiple sclerosis: Data from the European spontaneous reporting system. Front Neuro. 2024;15. doi:10.3389/fneur.2024.1383910

2. FDA approves new drug to treat multiple sclerosis. FDA. News release. March 29, 2017. Accessed June 28, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treat-multiple-sclerosis#:~:text=On%20March%2028%2C%20the%20U.S.,by%20the%20FDA%20for%20PPMS