What are the potential side effects of Kesimpta (ofatumumab) in a patient with relapsing multiple sclerosis?

Side Effects of Kesimpta (Ofatumumab) in Relapsing Multiple Sclerosis

Kesimpta has a generally manageable tolerability profile with injection-related reactions and infections being the most clinically significant adverse events, though most are mild to moderate in severity. 1, 2

Most Common Adverse Events

Upper respiratory tract infections are the most frequent side effect, occurring in 39% of patients compared to 38% with teriflunomide, including nasopharyngitis, sinusitis, pharyngitis, and influenza. 1, 2

Injection-related reactions (systemic) affect 21% of patients, with the highest incidence occurring after the first injection (14.4%), decreasing substantially with subsequent injections (4.4% with second injection, less than 3% thereafter). 1, 3

• The most common systemic injection symptoms include fever, headache, myalgia, chills, and fatigue (each occurring in ≥2% of patients). 1
• 99.8% of injection-related reactions are mild to moderate in severity, with only 0.2% being serious and no life-threatening reactions reported. 1, 3
• Pre-medication with steroids or non-steroidal agents does not substantially reduce the incidence or severity of injection-related reactions. 3

Local injection-site reactions occur in 11% of patients, presenting as erythema, pain, itching, and swelling—all mild to moderate in severity. 1

Headache affects 13% of patients (versus 12% with teriflunomide), and notably increases over time from 10% to 26% with prolonged treatment. 1, 4

Serious Infections

Serious infections occur in 2.5% of patients, which is slightly higher than the 1.8% seen with teriflunomide. 5

• Urinary tract infections affect 10% of patients. 1
• Back pain occurs in 8% of patients. 1

Progressive multifocal leukoencephalopathy (PML) is a rare but serious risk, presenting with progressive weakness on one side of the body, loss of coordination, vision problems, and changes in thinking, memory, and personality. 1

Hepatitis B virus (HBV) reactivation can occur, potentially causing serious liver problems including liver failure or death—patients must be screened before initiating therapy and monitored during and after treatment. 1

Immunologic Effects

Decreased immunoglobulin M (IgM) levels occur in 7.7% of patients (versus 3.1% with teriflunomide), leading to treatment discontinuation in 3.4% of cases. 1

• In 14.3% of patients, IgM levels decrease below 0.34 g/L. 1
• No decline in IgG levels was observed at study end, with a 4.3% decrease at 48 weeks but a 2.2% increase by 96 weeks. 1
• There is no apparent association between decreased immunoglobulin levels and increased risk of serious infections after 3.5 years of treatment. 2
• Quantitative serum immunoglobulin monitoring is required during treatment, especially in patients with opportunistic or recurrent infections. 6, 1

Long-Term Tolerability Considerations

With prolonged treatment, limb pain increases from 5% to 26% of patients, though overall quality of life improves subjectively. 4

The safety profile remains consistent during continuous use or after switching from other therapies, with no new safety signals emerging over 18 months of follow-up. 3

Critical Contraindications and Precautions

Kesimpta is absolutely contraindicated in patients with active hepatitis B infection or those who have had life-threatening injection-related reactions to ofatumumab. 1

Live or live-attenuated vaccines must be completed at least 4 weeks before starting Kesimpta and are contraindicated during treatment until B-cell recovery occurs. 1

Effective contraception is required during treatment and for 6 months after the last dose due to potential fetal harm from B-cell lymphopenia and reduced antibody response in exposed offspring. 1

Clinical Management Pitfalls

Treatment must be delayed if active infection is present until the infection resolves, as concurrent immunosuppression increases infection risk. 1

Consider discontinuing therapy if serious opportunistic infections or recurrent infections develop in patients with low immunoglobulin levels, or if prolonged hypogammaglobulinemia requires intravenous immunoglobulin replacement. 1

Patients switching from other immunosuppressive therapies have increased infection risk, requiring careful timing and monitoring during the transition period. 1