Natalizumab is primarily used in the treatment of patients with relapsing multiple sclerosis to reduce the frequency of clinical attacks. As an α4-integrin inhibitor, it exerts its therapeutic effect by blocking leukocyte migration. Various side effects may occur during the use of this biological agent, and some of them can be quite severe.

What Are the Side Effects of Natalizumab?

Systemic Reactions

Clinical data show that approximately 35% of patients may experience headache, 24% may have fatigue, 15% report joint pain, 7% may develop allergic reactions, and 4% may feel chest discomfort.

About 3% of patients may experience local bleeding and chills, while 2% may have syncope.

Infection-Related Reactions

Approximately 18% of patients may develop urinary tract infections, 15% may have lower respiratory tract infections, 9% report gastroenteritis, 8% of female patients may experience vaginitis, and 5% may have tonsillitis.

These infections are mostly upper respiratory tract infections, influenza, and urinary tract infections.

Psychiatric and Neurological Reactions

Approximately 17% of patients may experience depressive symptoms, including 0.5% who may have suicidal ideation.

3% of patients may develop tremors.

Gastrointestinal Reactions

About 10% of patients report abdominal discomfort, and 5% may have abnormal liver function test results.

Severe Side Effects of Natalizumab That Require Vigilance

Hypersensitivity Reactions

Natalizumab may cause severe hypersensitivity reactions, including anaphylaxis (incidence < 1%).

These reactions usually occur within 2 hours after the start of infusion, and symptoms may include urticaria, dizziness, fever, rash, chills, pruritus, nausea, flushing, hypotension, dyspnea, and chest pain.

Once a hypersensitivity reaction occurs, the infusion should be stopped immediately and appropriate treatment initiated. Such patients should not receive Natalizumab again.

Progressive Multifocal Leukoencephalopathy (PML)

Natalizumab is associated with an increased risk of progressive multifocal leukoencephalopathy (PML), a rare but severe brain infection.

This disease, caused by the JC virus, can lead to severe disability or death and requires special vigilance.

Severe Infections

In clinical studies, the incidence of severe infections in patients treated with Natalizumab was 2.1%. The most common type was pneumonia (0.6%).

Although most patients did not discontinue treatment during the infection period, immunocompromised patients may face a higher risk of infection.

Hepatobiliary System Issues

Approximately 0.8% of patients may develop cholelithiasis, which is also one of the severe adverse reactions requiring attention.

Hematological Effects

Natalizumab increases the number of circulating leukocytes (including lymphocytes, monocytes, basophils, and eosinophils) but has no effect on the number of neutrophils.

This effect is usually reversible within 16 weeks after drug discontinuation.

Precautions for Natalizumab Administration

Administration in Special Populations

Pregnant women (Category C): Animal studies have shown that high doses may affect the fetus, while data in humans are limited. The use of Natalizumab in pregnant women requires weighing the benefits and risks, and consideration should be given to discontinuing the drug.

Lactating women: It is not yet clear whether the drug is excreted in breast milk. A cautious decision should be made on whether to continue breastfeeding or the medication.

Children: The efficacy of Natalizumab in patients under 18 years of age has not been studied, and its use is not recommended.

Elderly patients: Clinical study data are insufficient, so careful evaluation is required.

Immune-Related Precautions

Approximately 10% of patients develop antibodies against Natalizumab, among which 6% are persistently positive.

Positive antibodies may reduce the efficacy of the drug and increase the risk of infusion reactions.

Antibody testing should be performed regularly during treatment (e.g., once every 12 weeks).

Laboratory Monitoring

During treatment, regular complete blood count monitoring should be conducted, with attention to changes in lymphocytes, monocytes, and other cell types.

Patients with abnormal liver function also need enhanced monitoring.