During treatment with Tividnofusp alfa, various side effects may occur, involving hypersensitivity reactions, infusion-related reactions, hematologic abnormalities, and renal injury.

I. Common Adverse Reactions

1. Infusion-Related Reactions

(1) May occur during the infusion or within 24 hours after completion, with some cases appearing 2 hours or later after the infusion ends.

(2) Symptoms include chills, fever, flushing, urticaria, rash, cough, vomiting, diarrhea, abdominal pain, headache, irritability, etc.

(3) More common in patients who have not previously received enzyme replacement therapy, but the frequency tends to decrease with extended treatment duration.

(4) Infusion-related reactions may still occur even with premedication.

2. Infectious Reactions

(1) Upper respiratory tract infection is a common adverse event during treatment.

(2) Ear infections (including otitis media, acute otitis media, and otitis externa) have also been reported.

3. Systemic Reactions

(1) Fever is relatively common.

(2) Gastrointestinal symptoms such as vomiting, diarrhea, and constipation have been reported.

(3) Rash, rhinorrhea, nasal congestion, and other allergy‑ or mucosal‑related symptoms may be seen.

(4) Non‑specific manifestations such as falls, headache, and skin abrasions are also present.

II. Serious Adverse Reactions

1. Hypersensitivity Reactions and Anaphylactic Shock

(1) May occur early in treatment or suddenly after long‑term use.

(2) Symptoms include tachycardia, hypotension, wheezing, vomiting, urticaria, swelling of the lips and tongue, etc.

(3) If anaphylactic shock occurs, the infusion must be stopped immediately and emergency treatment with epinephrine should be administered.

(4) Before re‑administration, the premedication regimen, infusion rate, or dose reduction should be reassessed.

2. Anemia

(1) A decrease in hemoglobin may occur within weeks to months after starting treatment, and may persist for up to one year in some patients.

(2) Patients with pre‑existing anemia are more susceptible.

(3) Most patients recover gradually over time; management includes iron supplementation.

(4) Patients and caregivers should be advised to watch for signs of anemia such as fatigue and pallor.

3. Membranous Nephropathy

(1) Biopsy‑proven steroid‑refractory membranous nephropathy with renal immune complex deposition has been reported.

(2) Serum creatinine and urine protein/creatinine ratio should be monitored during treatment.

(3) If suspected, diagnostic evaluation and timely intervention are required.

(4) After confirmation, the benefit of continued therapy versus the potential risk of renal injury should be weighed.

III. Special Population Considerations

1. Patients with Impaired Cardiopulmonary Function

(1) Patients with Hunter syndrome may already have insufficient cardiopulmonary reserve.

(2) Infusion‑related reactions may exacerbate these risks and lead to serious complications.

(3) Such patients require close monitoring of vital signs and clinical symptoms after administration.

2. Patients Previously Treated with Other Enzyme Replacement Therapies

(1) Antibodies generated against other IDS enzyme replacement therapies are expected to cross‑react with this product.

(2) The immune response after administration is primarily directed against the IDS component of the drug, not the Fc fragment.

(3) Antibody titers typically peak at around 13 weeks of treatment and gradually decline after 24 weeks.

3. Pediatric and Elderly Patients

(1) Safety and efficacy in children weighing less than 5 kg have not been established.

(2) Clinical trial data for elderly patients (aged 65 years and older) are lacking; use with caution.