Ofatumumab: A Comprehensive Guide for Patients with Relapsing Multiple Sclerosis

Table of Contents

• Introduction: Understanding Multiple Sclerosis and Treatment Options
• How Ofatumumab Works in the Body
• Clinical Trial Results: How Effective Is Ofatumumab?
• Side Effects and Safety Profile
• Special Safety Concerns
• Dosage and Administration
• Conclusion: Is Ofatumumab Right For You?
• Source Information

Introduction: Understanding Multiple Sclerosis and Treatment Options

Multiple sclerosis (MS) is a chronic neurological condition that affects approximately 2.8 million people worldwide, with women being up to three times more likely to develop the disease than men. While MS currently has no cure, treatments that modify the disease course can significantly reduce relapses (flare-ups of symptoms) and slow disability progression.

For patients with relapsing forms of MS—including clinically isolated syndrome, relapsing-remitting MS, and secondary progressive MS with active disease—preventing relapses is crucial. Research has shown that B cells, a type of immune cell, play a key role in driving MS inflammation and damage. Ofatumumab (marketed as Kesimpta®) represents a new approach to treatment as the first B-cell-targeting therapy that patients can self-administer at home after proper training.

This article provides a comprehensive look at ofatumumab based on extensive clinical research, including two major phase III trials called ASCLEPIOS I and II that compared this medication against teriflunomide, an established oral MS treatment. Understanding how this medication works, its benefits, and potential side effects can help patients make informed decisions about their treatment options.

How Ofatumumab Works in the Body

Ofatumumab is a fully human monoclonal antibody that specifically targets CD20, a protein found on the surface of B cells. By binding to this protein, ofatumumab effectively depletes these immune cells through two main mechanisms: complement-mediated cytotoxicity (triggering the immune system to destroy the cells) and antibody-dependent cell-mediated cytotoxicity (recruiting other immune cells to eliminate B cells).

The medication demonstrates rapid and sustained action against B cells. Clinical trials showed that:

• 84.6% of patients had B cell counts below 10 cells/μL by day 14 of treatment
• 94% of patients maintained B cell counts below 10 cells/μL at week 4
• This profound B cell depletion was sustained for up to 120 weeks (over 2 years) with continued monthly treatment

Unlike some other B-cell therapies, ofatumumab allows for relatively rapid recovery after treatment stops. The median time for B cells to return to normal levels after discontinuing ofatumumab was 24.6 weeks (approximately 6 months), according to clinical trial data.

Researchers also measured neurofilament light chain (NfL), a biomarker that indicates nerve damage in MS. Patients receiving ofatumumab showed significant reductions in NfL levels—from an average of 13.3 pg/mL at baseline to 6.8-6.9 pg/mL after 24 months of treatment—compared to those taking teriflunomide (9.0 pg/mL). This reduction suggests ofatumumab effectively reduces the nerve damage associated with MS progression.

Clinical Trial Results: How Effective Is Ofatumumab?

The approval of ofatumumab was based on two identical phase III clinical trials (ASCLEPIOS I and II) that together enrolled 1,882 adults aged 18-55 with relapsing forms of MS. These were rigorous studies designed to compare monthly subcutaneous ofatumumab injections against daily oral teriflunomide tablets.

Patient characteristics across both trials were well-balanced: average age was 38 years, 68% were female, 89% were white, 94% had relapsing-remitting MS, and 40% had never received any previous disease-modifying therapy. The average Expanded Disability Status Scale (EDSS) score was 2.9 at baseline, indicating mild to moderate disability.

Relapse Reduction
The primary measure of effectiveness was the annualized relapse rate (how many relapses patients experienced per year). Ofatumumab demonstrated superior efficacy:

• ASCLEPIOS I: 0.11 relapses/year with ofatumumab vs. 0.22 with teriflunomide (51% reduction)
• ASCLEPIOS II: 0.10 relapses/year with ofatumumab vs. 0.25 with teriflunomide (58% reduction)

These results were statistically highly significant (p<0.001), meaning there's less than a 0.1% chance they occurred by random chance.

MRI Lesion Activity
Ofatumumab dramatically reduced evidence of disease activity on MRI scans:

• Gadolinium-enhancing T1 lesions (indicating active inflammation): 97% reduction in ASCLEPIOS I and 94% reduction in ASCLEPIOS II compared to teriflunomide
• New or enlarging T2 lesions (indicating disease burden): 82% reduction in ASCLEPIOS I and 85% reduction in ASCLEPIOS II compared to teriflunomide

Disability Progression
Ofatumumab significantly slowed disability worsening compared to teriflunomide:

• 34% reduction in risk of 3-month confirmed disability progression (10.9% vs. 15.0% of patients)
• 32% reduction in risk of 6-month confirmed disability progression (8.1% vs. 12.0% of patients)

These disability benefits were statistically significant (p=0.002 for 3-month and p=0.01 for 6-month disability progression). The study found no significant difference between treatments in terms of disability improvement or brain volume loss.

Benefits for Newly Diagnosed Patients
A separate analysis focused on 615 patients who were newly diagnosed (within 3 years) and had not received previous MS treatments. Ofatumumab showed similarly strong benefits in this group, reducing relapse rates and disability progression compared to teriflunomide.

Side Effects and Safety Profile

Ofatumumab demonstrated a generally manageable safety profile in clinical trials. In the pooled data from both phase III studies:

• 83.6% of ofatumumab patients experienced adverse events compared to 84.2% of teriflunomide patients
• 9.1% of ofatumumab patients experienced serious adverse events compared to 7.9% of teriflunomide patients
• 5.7% of ofatumumab patients discontinued treatment due to side effects compared to 5.2% of teriflunomide patients

The most common side effects occurring in at least 10% of patients receiving ofatumumab included:

• Injection-related reactions (20.6%)
• Nasopharyngitis (common cold symptoms) (18%)
• Headache (13.3%)
• Injection-site reactions (10.9%)
• Upper respiratory tract infections (10.3%)
• Urinary tract infections (10.3%)

Most injection-site reactions were mild to moderate and included redness, pain, itching, and swelling. Using preventive medications like pain relievers, antihistamines, or steroids did not significantly reduce the frequency of these reactions.

Special Safety Concerns

Researchers paid special attention to several potential safety issues with ofatumumab treatment:

Infections
Infections occurred at similar rates between treatment groups (51.6% with ofatumumab vs. 52.7% with teriflunomide). Serious infections were slightly more common with ofatumumab (2.5% vs. 1.8%), leading to temporary treatment interruption in 1.2% of patients and discontinuation in 0.2%.

Immunoglobulin Levels
Ofatumumab treatment reduced immunoglobulin M (IgM) levels by 30.9% after 48 weeks and 38.8% after 96 weeks. Approximately 14.3% of patients developed IgM levels below the normal range. However, this reduction was not associated with an increased risk of infections. Immunoglobulin G (IgG) levels actually increased slightly (4.3% at 48 weeks).

Long-term data from the ALITHIOS trial (following patients for up to 3.5 years) showed that changes in immunoglobulin levels did not increase the risk of serious infections, which occurred at a rate of 1.39 per 100 patient-years.

Injection-Related Reactions
Systemic injection-related reactions (affecting the whole body rather than just the injection site) occurred more frequently with ofatumumab than with placebo injections given to the teriflunomide group. These reactions were most common with the first injection (14.4% of patients) and decreased to less than 3% from the third injection onward. Most were mild to moderate and included:

• Fever
• Headache
• Muscle pain (myalgia)
• Chills
• Fatigue

Only two patients (0.2%) experienced severe injection reactions, and only one patient discontinued treatment after the first injection due to this side effect.

Malignancy Risk
No increased cancer risk was observed with ofatumumab compared to teriflunomide (0.5% vs. 0.4% of patients).

Dosage and Administration

Ofatumumab is approved in the United States, European Union, Japan, and other countries for treating relapsing forms of MS in adults. The medication comes in a pre-filled auto-injector pen or syringe (Sensoready®) containing 20 mg/0.4 mL of medication for subcutaneous injection into the abdomen, thigh, or outer upper arm.

The recommended dosing schedule is:

1. Initial dose: 20 mg on day 1
2. Second dose: 20 mg on day 7
3. Third dose: 20 mg on day 14
4. Maintenance dosing: 20 mg once monthly starting from day 28

The first injection should be administered under the guidance of a healthcare professional who can provide proper training on self-injection technique. Ofatumumab is contraindicated in patients with severe active infections, known active malignancies, or those who are severely immunocompromised. In the United States, patients with active hepatitis B virus infection should not receive ofatumumab.

Conclusion: Is Ofatumumab Right For You?

Ofatumumab represents a significant advancement in MS treatment as the first B-cell therapy that patients can self-administer at home. The clinical trial data demonstrate superior efficacy compared to teriflunomide in reducing relapse rates, MRI lesion activity, and disability progression.

The convenience of monthly self-injection offers advantages over treatments that require intravenous infusion at medical facilities. While injection-related reactions and infections are common side effects, they are generally manageable and decrease in frequency after the initial doses.

As with any MS treatment, the decision to use ofatumumab should be made in consultation with your healthcare provider, considering your specific disease characteristics, treatment history, and personal preferences. The medication may be particularly suitable for patients seeking effective disease control with the convenience of at-home administration.

Source Information

Original Article: Ofatumumab: A Review in Relapsing Forms of Multiple Sclerosis
Authors: Connie Kang, Hannah A. Blair
Publication: Drugs (2022) 82:55–62
Note: This patient-friendly article is based on peer-reviewed research originally published in a scientific journal. It maintains all key findings, data points, and conclusions from the original research while translating the information into more accessible language for patients.