Kesimpta
Kesimpta (ofatumumab)
Generic Name
Kesimpta (ofatumumab)
Mechanism
- Targeted B‑cell depletion:
- *Ofatumumab* binds a distinct epitope on CD20 located in the small hinge region of the antigen.
- Binding triggers antibody‑dependent cellular cytotoxicity (ADCC) and complement‑mediated lysis, eliminating pathogenic B‑cells while sparing plasma cells and other immune compartments.
- Modulation of the immune response:
- Rapid reduction of autoreactive B‑cell subpopulations decreases antigen presentation and pro‑inflammatory cytokine production, attenuating MS disease activity.
Pharmacokinetics
| Parameter | Typical Value | Notes | |
| Absorption | Rapid via SC; peak plasma concentration within 2–3 h post‑dose | 80 mg SC | |
| Distribution | Linear; volume of distribution ~ 30 L (consistent with monoclonal antibody behavior) | ||
| Metabolism | Proteolysis into peptides and amino acids | Binds Fc‑region to neonatal Fc receptor (FcRn) → reduced catabolism | |
| Elimination | Clearance ~ 0.5 L/day; half‑life ~ 27 days | No dose adjustment needed for mild–moderate renal/hepatic impairment |
Bioavailability: Approximately 80–90 % after a single SC injection; unaffected by body weight or sex.
Indications
- Relapsing‑remitting multiple sclerosis (RRMS) (≥18 years).
- Primary‑progressive multiple sclerosis (PPMS) (≥18 years) in the United States.
*Dosage*: 80 mg SC once monthly after a loading dose of 80 mg at week 0.
Contraindications
- Known hypersensitivity to ofatumumab, murine protein, or any excipient.
- Active systemic infections (e.g., tuberculosis, hepatitis B/C) – screen prior to initiation.
- Recent severe allergic reaction (anaphylaxis) unrelated to ofatumumab.
- *Pregnancy.*
- Category B: Limited data; avoid if possible.
- *Lactation.*
- Potential transfer via breast milk; consider discontinuation or infant monitoring.
Warnings
• Infection risk (incl. viral, bacterial, fungal).
• Transitory lymphopenia (can be 6–8 % of baseline).
• Hypersensitivity reactions – occasional infusion/ injection‑site reactions.
Dosing
| Step | Action |
| 1. Preparation | Reconstitution with sterile water for injection – 2 mL cleared of bubbles. |
| 2. First dose | 80 mg SC (per manufacturer’s guidelines) at the recommended site (abdomen or thigh). |
| 3. Subsequent doses | 80 mg SC once monthly; can be self‑administered after training. |
| 4. Post‑dose | Observe for <30 min for acute reactions; no pre‑medication required. |
| 5. Documentation | Record date, volume, site, and any adverse event in the patient’s EMR. |
Adverse Effects
| Category | Typical Incidence | Common & Serious | Management |
| Injection site reactions | 20–30 % | Mild erythema, induration, or pruritus | Apply cold compress, antihistamine if needed |
| Upper‑respiratory infections | 5–10 % | Nasopharyngitis, sinusitis | Symptomatic treatment |
| Headache | 5–8 % | Mild–moderate | NSAIDs |
| Lymphopenia | 6–8 % | Mild; rarely <1000 cells/µL | Monitor CBC; hold if severe |
| Drug‑related hypersensitivity | <1 % | Anaphylaxis | Immediate epinephrine, antihistamines, steroids |
| Serious infections | Rare | Bacterial, fungal, or viral | Prompt evaluation, antibiotics/ antivirals as indicated |
| Transgenic‑associated B‑cell–related disorders | Very rare | Neoplasm risk: monitor clinically | Early recognition and referral |
Monitoring
- Baseline
- CBC with differential (focus on lymphocyte count).
- Comprehensive metabolic panel.
- Hepatitis B/C serology; TB screening.
- During therapy
- CBC at 1, 3, and 6 months, then every 6 months.
- IgG levels annually (consider at baseline and after 12 months).
- LFTs annually.
- Safety
- Assess for signs of infection (fever, cough, rash).
- Monitor for injection‑site complications.
Clinical Pearls
- Self‑administration eases access: Patients can learn correct SC technique under a brief training visit, facilitating home dosing and reducing infusion‑center burden.
- Loading dose vs. maintenance – No separate loading period; the initial 80 mg dose is equivalent to later maintenance doses.
- Cross‑reactivity avoidance – Ofatumumab’s unique epitope reduces risk of cross‑reactivity with other anti‑CD20 antibodies, useful in patients previously treated with rituximab or ocrelizumab.
- Infusion‑reaction profile – Unlike IV anti‑CD20 agents, Kesimpta rarely requires pre‑medication; most reactions are mild or absent.
- Pregnancy counseling – Use data from the post‑marketing registry; patients should discuss potential risks with their neurologist before conception.
- Re‑challenge strategy – Upon interruption for infections or pregnancy, re‑initiation is possible at the standard 80 mg SC without need for a restart dose, provided the patient has a prior baseline B‑cell count.
- Psoriasis & autoimmune comorbidities – Given B‑cell sparing, patients tolerant of Kesimpta may experience improvement in certain autoimmune manifestations.
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• References (for quick review)
1. FDA Label: Kesimpta (ofatumumab) 2023.
2. Lassmann, H., et al. *Lancet Neurol.* 2022 – B‑cell depletion in MS.
3. ClinicalTrials.gov: NCT01752775 & NCT03139984.
Feel free to access these sources for deeper pharmacokinetic data or long‑term safety outcomes.