Kesimpta (Ofatumumab) Side Effects and New Lesion Reduction in Relapsing Multiple Sclerosis
Kesimpta demonstrates exceptional efficacy in suppressing new MRI lesions, with 94-98% reduction in T1 gadolinium-enhancing lesions and 82-85% reduction in new or enlarging T2 lesions compared to teriflunomide, while maintaining a generally manageable safety profile dominated by injection-related reactions that diminish rapidly after the first dose. 1
MRI Lesion Activity Outcomes
New Lesion Suppression:
- T1 gadolinium-enhancing lesions: Mean of 0.01-0.03 lesions per scan with Kesimpta versus 0.46-0.52 with teriflunomide, representing a 94-98% relative reduction 1
- New or enlarging T2 lesions: 0.64-0.72 lesions per year with Kesimpta versus 4.00-4.16 with teriflunomide, representing an 82-85% relative reduction 1
- These dramatic reductions in lesion activity translate to superior clinical outcomes, with 78% of patients achieving NEDA-3 (no relapses, no disability progression, no new MRI lesions) at 5 years versus only 3% with teriflunomide 2
Side Effect Profile
Injection-Related Reactions (Most Common)
Systemic injection-related reactions occur in 21% of Kesimpta patients versus 15% with teriflunomide, but critically, 99.8% are mild to moderate in severity 1:
- First injection: 14.4% incidence (highest risk period) 1
- Second injection: 4.4% incidence 1
- Third and subsequent injections: <3% incidence 1
- Most frequent symptoms (≥2%): fever, headache, myalgia, chills, and fatigue 1
- Only 0.2% experienced serious injection-related reactions; no life-threatening reactions occurred 1
Local injection-site reactions occur in 11% of patients, all mild to moderate, with symptoms including erythema, pain, itching, and swelling 1
Infections
- Upper respiratory tract infections: 39% with Kesimpta versus 38% with teriflunomide 1
- Urinary tract infections: 10% with Kesimpta versus 8% with teriflunomide 1
- Overall infection rate: 51.6% versus 52.7% with teriflunomide 3
- Serious infections: 2.5% versus 1.8% with teriflunomide 3
- Real-world data through 4 years shows no new safety signals and no increased infection tendency 4, 3
Immunoglobulin Changes
IgM reduction is the most clinically relevant laboratory abnormality:
- Decreased IgM reported in 7.7% of Kesimpta patients versus 3.1% with teriflunomide 1
- 14.3% of patients had IgM levels fall below 0.34 g/L 1
- Critical finding: No apparent association between IgM or IgG changes and risk of serious infections after 3.5 years of treatment 5
- IgG showed initial 4.3% decrease at 48 weeks but increased 2.2% by 96 weeks 1
- Treatment discontinuation due to low immunoglobulins occurred in 3.4% of patients 1
Other Common Adverse Events (≥5% and Greater Than Teriflunomide)
Clinical Efficacy Context
The side effect profile must be weighed against superior efficacy outcomes 1:
- Annualized relapse rate: 0.10-0.11 with Kesimpta versus 0.22-0.25 with teriflunomide (51-58% reduction)
- 3-month confirmed disability progression: 10.9% versus 15.0% (34.3% relative risk reduction)
- Real-world data confirms only one relapse event observed during 9.8 months mean treatment duration 4
Important Safety Monitoring
Required monitoring includes 1:
- Quantitative serum immunoglobulin levels during treatment, especially in patients with opportunistic or recurrent infections
- Hepatitis B screening before initiation (risk of reactivation)
- Signs of progressive multifocal leukoencephalopathy (PML), though not reported with subcutaneous Kesimpta, has occurred with higher intravenous doses in other conditions 1
Practical Considerations
- Self-administration: 87% of patients found handling "very easy" in real-world use 4
- DMT-naïve use: Increasingly used as first-line therapy (58.4% of patients at 9 months post-FDA approval were DMT-naïve) 6
- Contraception required: Effective contraception needed during treatment and for 6 months after last dose due to fetal risk 1
- Live vaccines contraindicated during treatment and until B-cell recovery 1
The benefit-risk profile strongly favors Kesimpta, with dramatic lesion suppression and manageable, predominantly mild-to-moderate side effects that decrease substantially after initial dosing 1, 5, 3.