What are the considerations for treating a patient with relapsing multiple sclerosis and a history of post-operative spinal cord injury at the level of C7-T1 with Kesimpta (ofatumumab)?

Ofatumumab (Kesimpta) in Relapsing MS with Prior C7-T1 Spinal Cord Injury

Direct Recommendation

Ofatumumab can be safely used in patients with relapsing multiple sclerosis who have a history of post-operative spinal cord injury at C7-T1, as there are no specific contraindications for this population, and the drug demonstrates superior efficacy with a manageable safety profile in relapsing MS. 1, 2

Clinical Rationale

Disease Activity Assessment

• Confirm active relapsing-remitting MS with MRI monitoring using gadolinium enhancement and T2-weighted sequences to document inflammatory activity. 3, 4
• In relapsing-remitting MS, approximately 80% of new lesions show gadolinium enhancement, indicating active blood-brain barrier breakdown and inflammation. 3, 5
• The presence of gadolinium-enhancing lesions supports the use of high-efficacy disease-modifying therapy like ofatumumab. 4

Spinal Cord Injury Considerations

• The C7-T1 spinal cord injury history does not contraindicate ofatumumab use, as the drug's mechanism targets B-cell depletion systemically rather than affecting spinal cord structural integrity. 2
• While spinal cord MRI monitoring is more time-consuming and not routinely recommended in MS treatment trials, brain MRI remains the primary monitoring tool. 3
• The prior surgical intervention and stable post-operative status should be documented, but does not alter ofatumumab eligibility. 3

Ofatumumab-Specific Benefits for This Patient

Efficacy Profile

• Ofatumumab demonstrates superior efficacy versus teriflunomide with annualized relapse rates of 0.05, reduction in gadolinium-enhancing lesions to 0.01 lesions/scan, and 78.8% of patients achieving no evidence of disease activity over 4 years. 6
• The drug achieves rapid and sustained near-complete B-cell depletion through subcutaneous administration of 20 mg monthly (after initial weekly loading at weeks 0,1, and 2). 2
• Efficacy is maintained regardless of body weight, race, or prior disease-modifying therapy exposure. 2

Safety and Tolerability

• The most common adverse events are infections (58.35% overall), nasopharyngitis, headache, upper respiratory tract infections, and urinary tract infections, all generally manageable. 1, 7, 6
• Injection-related reactions occur in 24.7% of patients, with 99.2% being mild to moderate in severity, predominantly after the first injection. 8
• No pre-medication is required, and systemic injection-related reactions are minimized by the low 20 mg dose and stepwise initial dosing regimen. 2, 8
• Serious infection incidence remains low (2.5%), with no opportunistic infections or progressive multifocal leukoencephalopathy identified in up to 3.5 years of exposure. 7

Immunoglobulin Monitoring

• Mean serum IgG levels remain stable during treatment, while IgM levels decrease but stay above the lower limit of normal in most patients. 7
• Decreased immunoglobulin levels are not associated with increased risk of serious infections. 7
• The fully human nature of ofatumumab results in low immunogenicity, with only 2 of 914 patients developing anti-drug antibodies in phase 3 trials. 2

Practical Implementation

Dosing Regimen

• Administer ofatumumab 20 mg subcutaneously at weeks 0,1, and 2 for initial B-cell depletion, followed by 20 mg monthly maintenance dosing. 2, 6
• Self-administration at home using pre-filled syringe or autoinjector pen is feasible and does not require healthcare facility visits. 2, 8

Monitoring Protocol

• Perform baseline brain MRI with gadolinium enhancement, then repeat at 3-6 months after initiating therapy to assess treatment response. 9
• For active disease, conduct MRI every 6 months for the first 1-2 years, transitioning to annual MRI if disease stabilizes. 9
• Use consistent MRI protocols with T2-weighted sequences and gadolinium enhancement to monitor new lesion development. 3, 9
• Document disability using Expanded Disability Status Scale (EDSS) scoring at regular intervals. 4

Key Monitoring Parameters

• Monitor for infections, particularly upper respiratory and urinary tract infections, which are the most common adverse events. 1, 6
• Assess for injection-related reactions, especially after the first three doses, though severity is typically mild to moderate. 8
• Check immunoglobulin levels periodically, though routine monitoring is not mandated given the lack of association between decreased levels and serious infections. 7

Critical Pitfalls to Avoid

• Do not withhold ofatumumab based solely on prior spinal cord surgery, as there is no mechanistic interaction between B-cell depletion and structural spinal cord pathology. 2
• Do not routinely use pre-medication with steroids or NSAIDs, as this does not substantially reduce injection-related reaction incidence or severity. 8
• Do not rely on spinal cord MRI for routine monitoring, as brain MRI is more practical and informative for assessing MS disease activity. 3
• Do not delay treatment initiation due to concerns about long-term safety, as 4-year data demonstrate no new safety signals and sustained efficacy. 6