ECTRIMS 2021 Ofatumumab latest research progress

On October 13-15, 2021, the 37th European Committee for Multiple Sclerosis Treatment and Research (ECTRIMS 2021) will be held online
.

The exploration of effective and safe disease modification treatments is still the focus of research in the field of multiple sclerosis (MS), and it is also a hot topic in this conference
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Ofatumumab is a precisely targeted B-cell therapy that has been approved for the treatment of patients with relapsing multiple sclerosis (RMS) in the United States, the European Union, Canada, and Japan
.

The latest research progress of ofatumumab was updated in this meeting
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Ofatumumab treatment reduces the activation of microglia in patients with RMS in the early stage: Interim results of the study are announced 1 Microglia are immune cells of the central nervous system, and their excessive activation is related to the pathogenesis of MS
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In order to explore the early effects of ofatumumab treatment on microglia activity in patients with RMS, Professor Tarun Singhal and others conducted a 9-month study and released the interim analysis results at the ECTRIMS meeting
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A total of 10 patients with RMS were included in the study.
[F-18]PBR06 PET was used to determine the effect of ofatumumab on the activation of microglia in patients with RMS, as well as peripheral blood CD19 counts and clinical evaluation indicators
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The results of the interim analysis showed that the average glial cell activity load (CGM-GALP) was significantly lower than the baseline at the 3rd month (p<0.
05) (n=5)
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The absolute count and percentage of CD19+ cells decreased significantly on the 5th day, and the level of clearance was maintained during 3 months
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Fusion PET/MRI imaging showed that the TSPO signal of RMS patients decreased within 3 months after the initiation of ofatumumab treatment
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The results of this study suggest that the decrease in CGM microglia activation after 3 months of ofatuzumab treatment is related to the rapid clearance of B cells on day 5, indicating that B cell clearance treatment indirectly regulates the downstream effects of microglia activation in RMS patients
.

Network meta-analysis: disease-modifying treatment drugs (DMT), comparison of the efficacy of reducing recurrence 2 Randomized controlled trials evaluating the efficacy of different DMT are usually limited to comparison with placebo or single active control drugs, through network meta-analysis (Network Meta-analysis) , NMA) method, which can indirectly compare the efficacy of new treatment methods relative to other DMT
.

By searching biomedical databases (including Embase, MEDLINE, and Cochrane Central Register) and related conferences and health technology assessment agencies’ websites, all randomized controlled trials of adult RMS patients with DMT as of December 2019 were included.
The selection criteria is that the duration of the study needs to be in 48 weeks and above, and the annual recurrence rate was included in the study endpoint
.

NMA network analysis included 33 randomized controlled trials of 20 treatment options (including placebo).
The results showed that compared with placebo, the order of efficacy in reducing ARR was alemtuzumab (rate ratio [RR]: 0.
28, 95% confidence interval [CRI] 0.
21-0.
34), ofatumumab (RR: 0.
30, 95% CRI 0.
23-0.
39), natalizumab (RR: 0.
32, 95% CRI 0.
24-0.
41) and Austrian Renibizumab (RR: 0.
33, 95% CRI 0.
25–0.
43)
.

In the newer approved DMT (after 2020), Ofatumumab is superior to Ozamod (0.
5mg, 1.
0mg) and ponesimod
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Therefore, of the recently approved and previously approved DMT, ofatumumab is an efficient treatment option that can significantly reduce the risk of recurrence in patients with RMS
.

3.
5-year long-term follow-up safety data of Ofatumumab treatment, IgG levels are stable, and the incidence of serious infections is low.
3ASCLEPIOS Phase 3 study showed that RMS patients received ofatumumab for 96 weeks, with an average serum immunoglobulin G (IgG) The level was similar to the baseline level, and there was no correlation between the serum IgG/IgM level and the risk of infection
.

Heinz Wiendl et al.
conducted a long-term study to evaluate the effect of ofatumumab treatment on serum IgG/ The impact of IgM levels and assess the risk of serious infections
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A total of 1969 patients were enrolled in the study, and they were divided into a long-term treatment group (continuous use of ofatumumab in the core and extended studies; N=1292) and a drug conversion group (teriflunomide converted to ofatumumab; N =677)
.

The results of the study showed that the average serum IgG of ofatumumab remained stable during 3.
5 years of treatment, and the average serum IgM level remained within the reference range over time
.

In addition, in the long-term group, IgG levels in all quartiles remained similar to baseline values, IgM levels decreased over time, and the average level remained within the reference range
.

In terms of the incidence of infection, the total incidence of serious infections after 3.
5 years of ofatumumab treatment is relatively low
.

The long-term follow-up IgG level remained stable, and the average IgM level remained above LLN (total patients and four groups according to the baseline level).
The long-term follow-up data showed that the average IgG level remained stable for 3.
5 years and the average IgM level remained stable after the 3.
5-year treatment of ofatumumab Within the reference range
.

Decline in Ig level is not related to the risk of serious infection
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The results of ofatumumab treatment for 3.
5 years are consistent with the core clinical phase 3 study data
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Listen to the voices of doctors and patients: Six months after Ofatumumab was approved by the FDA, MS doctors’ comments on social media 4 The effectiveness and safety of Ofatumumab are in the ASCLEPIOS I&II Phase III clinical trial It was confirmed and approved by the US FDA for the treatment of RMS patients in August 2020
.

In order to further understand the views of patients, medical staff, etc.
of Ofatumumab in the US for 6 months, Mitzi Williams et al.
conducted a social media listening study (Social Media listening), the researcher We searched on social media platforms with "multiple sclerosis" and different therapies as keywords, and analyzed the social media conversations of patients, medical staff, and MS associations/organizations within 6 months of the launch of Ofatumumab
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The results of the social listening study show that of DMT, ofatumumab received the most positive feedback due to its tolerability, efficacy and convenience
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The biggest advantage of ofattumumab is the route of administration, efficacy and safety
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In addition, the most common reasons for switching to ofatumumab treatment are flexibility, convenience and home administration, curative effect/recurrence and reduced lesion activity, fewer side effects experienced/better safety and administration The process is simple
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   Expert comment on expert profileProfessor Guan Yangtai, chief physician/professor, doctoral supervisor, director of the Department of Neurology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Chairman, Chinese Medical Biotechnology Association, Neural Repair and Regeneration Branch Chairman, Chinese Medical Doctor Association, Neurologist Branch Standing Committee Member, China Member of the Standing Committee of the Neuroprosthetics Committee of the Chinese Medical Doctor Association Leader of the Neuroimmunology Group of the Neurology Branch of the Chinese Medical Association Team Deputy Leader Shanghai Leading Talents, Excellent Academic Leaders, and Medical Leaders With the continuous development of medicine, there are more and more types of DMT drugs with different mechanisms of action, efficacy, safety and convenience
.

The latest ofatumumab data released at the ECTRIMS conference has been supplemented in addition to the core clinical research ASCLEPIOS
.

Microglia play a variety of functions in the process of neuroinflammation.
In recent years, studies have found that activated microglia are the direct targets of MS treatment and may help inhibit neurodegeneration
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An interim analysis of a prospective study of ofatumumab showed that 3 months of treatment can reduce the activation of microglia, and we look forward to further analysis of biomarkers (especially neurodegeneration markers) and clinical efficacy
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DMT drugs require long-term administration.
The long-term follow-up results of the 3.
5-year ALITHIOS study of Ofatumumab are consistent with the core phase data.
The overall incidence of infection is low, which reflects the long-term safety and efficacy guarantee for patients
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Through the survey and feedback of MS doctors and patients in the marketed countries, the confidence of Ofatumumab as the preferred treatment for relapsing multiple sclerosis has been strengthened
.

References: 1.
Singhal T.
, et al.
Early efficacy of ofatumumab on microglial activity in patients with relapsing forms of multiple sclerosis: Interim analysis of a 9-month study.
ECTRIMS 2021.
2.
Stoneman D.
et.
al.
Relapse reduction by disease-modifying therapies for relapsing multiple sclerosis: A network meta‑analysis.
ECTRIMS 20213.
Wienhl H.
, et al.
Effect of ofatumumab on serum immunoglobulin levels and infection risk in patients with relapsing multiple sclerosis over 3.
5 years.
ECTRIMS 2021.
4.
Williams M .
, et al.
Evaluating perceptions of ofatumumab in multiple sclerosis via social media listening --Early 6 Months post approval data.
ECTRIMS 2021.