Generic Name

Tepezza

Mechanism

Tepezza works by inhibiting IGF‑1R, thereby interrupting the cross‑talk between IGF‑1R and the thyrotropin‑receptor on orbital fibroblasts.
* ↓ Orbital fibroblast activation → reduces inflammation and adipogenesis.
* ↓ Cytokine production (IL‑6, IL‑1β, TNF‑α) → limits edema and proptosis.
* ↓ TGF‑β signaling → decreases collagen deposition and fibrosis.
Result: marked improvement in proptosis, diplopia, and inflammatory signs of active TAO.

Pharmacokinetics

• Route: Intravenous infusion (2‑3 h).
• Half‑life: ~11 days (steady‑state).
• Cmax: ~70 μg/ml after the 10 mg/kg loading dose.
• Clearance: Linear, 0.05 ml/kg/hr (approx.).
• Volume of distribution: ~4 l (blood‑centric).
• Protein binding: ~90 % (predominantly to serum IgG).
• Metabolism: Proteolytic catabolism into peptides.
• Excretion: Renal (minimal), primarily via catabolism.

Indications

• Active, moderate‑to‑severe TAO (proptosis >3 mm change, diplopia, and inflammatory signs).
• Adult patients who are euthyroid or who have stable thyrotoxicosis/thyroiditis.

Contraindications

• Hypersensitivity to teprotumumab, any excipient, or any monoclonal antibody.
• Severe uncontrolled diabetes mellitus (due to risk of hyperglycemia).
• Active serious infection or optic neuropathy.
• Pregnancy & lactation: Category B; use only if benefits outweigh risks.
• Concurrent treatment with investigational IGF‑1R agents is contraindicated.

Warnings
• Risk of dysgeusia, hearing loss, and ocular surface disease.
• Monitor for serious infusion‑related reactions (anaphylaxis).
• Possible worsening of glycemic control; screen and monitor glucose.

Dosing

• Total of 8 infusions (≈6 months).
• Begin infusion with a baseline CBC, CMP, fasting glucose, audiometry, and ophthalmologic exam.
• Adjust dosing for body weight; max per infusion 1 g.

Adverse Effects

Common (≥10 %)
• Dysgeusia (taste disturbance)
• Dry eye/lacrimal dysfunction
• Fatigue
• Musculoskeletal pain
• Headache

Serious (≥1 %)
• Hyperglycemia (requires insulin or oral agents)
• Hearing loss (sensorineural) – audiogram monitoring
• Optic neuropathy – visual acuity & field testing
• Infusion reactions (anaphylaxis, hypotension)
• Peripheral edema

Monitoring

• Pre‑infusion: weight, BMI, fasting glucose, vital signs.
• During infusion: BP, HR, oxygen saturation, temperature.
• Post‑infusion: DSME; baseline labs re‑checked 1 week after cycle 1.
• Monthly: CBC, CMP, fasting glucose, audiometry, ophthalmic exam (visual acuity, proptosis measurement).
• At any time: immediate evaluation for signs of infection or severe allergic reaction.

Clinical Pearls

• Baseline euthyroidism is crucial; uncontrolled thyrotoxicosis worsens TAO and can confound response.
• Early initiation (during active inflammation) yields maximal improvement in proptosis and diplopia.
• Concomitant steroids? Use short‑course systemic steroids only if refractory; avoid prolonged steroids as they can diminish tepezza efficacy.
• Diabetes management: Initiate or intensify glucose‑lowering therapy before and during treatment.
• Audiologic surveillance: Because 15–20 % of patients report hearing changes, baseline and every‑3‑month audiograms are recommended.
• Patient education: Counsel patients on strict adherence, reporting of taste changes, and ocular symptoms promptly.

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• Key Takeaway: Tepezza offers a disease‑modifying option for moderate‑to‑severe, active TAO. Proper patient selection, vigilant monitoring, and proactive management of metabolic and auditory side effects are essential for optimal outcomes.