Infliximab Side Effects
The most common side effects of infliximab are upper respiratory tract infections, headache, and elevated liver enzymes, but serious adverse events including severe infections (particularly tuberculosis), infusion reactions, malignancies, and hepatotoxicity require vigilant monitoring and appropriate screening. 1, 2
Common Side Effects
The most frequently reported adverse events include 1:
- Upper respiratory tract infections (most common)
- Headache
- Elevated hepatic transaminases (usually transient and asymptomatic)
- Cough
- Stomach pain
- Nausea
Serious Adverse Events Requiring Immediate Attention
Infections (Most Critical Concern)
Infections represent the most common serious adverse event, with approximately a twofold increased risk. 3
Tuberculosis (TB):
- Incidence reported as 103 per 100,000 patient-years for infliximab (higher than etanercept at 39 per 100,000) 1
- Greater likelihood of extrapulmonary involvement compared to other TNF antagonists 3
- Reactivation typically occurs after 3+ infusions (median 12 weeks) 3
- Mandatory TB screening before initiation - patients with positive skin tests who received prophylaxis did not develop TB 4
Opportunistic infections include 1:
- Atypical mycobacteria
- Histoplasmosis, coccidioidomycosis, blastomycosis
- Pneumocystis pneumonia
- Candidiasis and aspergillosis
- Herpes zoster
Critical pitfall: Anti-TNF therapy should not be started in the presence of active infection and must be discontinued if serious infection develops 3.
Infusion Reactions
Acute infusion reactions occur in 3-22% of patients with diverse symptoms 1, 2:
- Occur during or within 2 hours of infusion
- Symptoms: fever, chills, chest pain, dyspnea, nausea, rash, itching, blood pressure changes
- Rarely: anaphylactic shock
- Risk increases with antibody development to infliximab
Delayed hypersensitivity reactions (3-12 days post-infusion) 5:
- Myalgias, arthralgias, fever, rash, pruritus
- Facial/hand/lip edema, dysphagia, urticaria
- Sore throat, headache
Protective factors to minimize reactions 5:
- Concomitant immunomodulators or corticosteroids
- Proper 0,2,6-week induction regimen
- Maintenance dosing every 8 weeks or less
- Avoiding long intervals between infusions
Malignancies
Increased skin cancer risk 1:
- Non-melanoma skin cancer: HR 1.7 (95% CI 1.3-2.2)
- Melanoma: HR 2.6 (95% CI 1.0-6.7)
- Regular comprehensive dermatological assessment mandatory
- Hepatosplenic T-cell lymphoma reported (often fatal)
- Primarily in adolescent/young adult males with Crohn's disease
- All cases occurred with concomitant azathioprine or 6-mercaptopurine
- Standardized incidence ratio for lymphoma: 2.98 in RA trials (95% CI 1.89-4.47) 1
Contraindications for malignancy history 1:
- Avoid if current or recent malignancy unless diagnosed/treated >5 years ago OR high likelihood of cure
- Relative contraindication: >200 PUVA or >350 UVB treatments, especially if followed by ciclosporin
Hepatotoxicity
Liver injury ranges from transient elevation to severe hepatitis 1:
- Transaminase elevations are common and usually asymptomatic
- Rare cases of severe hepatitis and acute liver failure requiring transplantation or resulting in death
- Monitor for jaundice, dark urine, right upper quadrant pain, severe fatigue 2
Cardiovascular Events
Heart failure exacerbation 3, 2:
- ATTACH trial showed increased risk of death/hospitalization with 10 mg/kg dose in NYHA class III-IV heart failure
- Contraindicated in moderate-to-severe heart failure
- Numerous postmarketing reports of worsening heart failure
Acute cardiovascular events (within 24 hours of infusion) 2:
- Heart attack, low blood flow to heart, abnormal heart rhythm
- Stroke reported within 24 hours
- Symptoms: chest pain, arm pain, shortness of breath, palpitations
Hematologic Reactions
Blood cell abnormalities 2:
- Leukopenia, neutropenia, anemia
- Body may not produce enough infection-fighting or clotting cells
- Monitor for persistent fever, easy bruising/bleeding, pallor
Neurologic Reactions
- Demyelinating disorders (occur with lesser frequency than other TNF antagonists)
- Symptoms: vision changes, numbness/tingling, seizures, limb weakness
- Stroke within 24 hours of infusion
Autoimmune Reactions
- Rare but documented
- Symptoms: chest pain, shortness of breath, joint pain, facial/arm rash worsening in sun
- Generally resolves 6 weeks to 14 months after discontinuation 3
- Development of anti-nuclear antibodies and anti-dsDNA antibodies more common than clinical lupus
New or worsening psoriasis 2:
- Paradoxical psoriasiform eruptions in 20% of patients 4
- Red scaly patches or pus-filled raised bumps
Monitoring Requirements
Pre-treatment screening mandatory 3, 2:
- TB testing (skin test or IGRA)
- Hepatitis B serology
- Assessment for active infections
- Malignancy history evaluation
- Cardiac function if heart disease history
During treatment 3:
- Monitor for infection signs continuously
- Regular dermatological assessment for skin cancers
- Liver function tests
- Temperature monitoring
- Avoid live vaccines 3, 2
Special Populations
Pediatric patients show different side effect profiles 2:
- More frequent: anemia, leukopenia, flushing, viral infections, neutropenia, bone fractures, bacterial infections, allergic respiratory reactions
- Higher infection rates in children with ulcerative colitis compared to adults
Concomitant steroid use is the only independent risk factor for infections (OR 2.69,95% CI 1.18-6.12) 4.
Long-term Safety Profile
A 14-year cohort study showed no significant difference in serious adverse events between infliximab-treated patients (13%) and controls (19%) (OR 1.33,95% CI 0.56-3.00) 4. No difference in mortality, malignancies, or overall infection rates was observed in this long-term follow-up, suggesting acceptable safety with proper screening and monitoring.
Human antichimeric antibodies develop in approximately 13% of patients, increasing subsequent infusion reaction risk 6.