What are the potential side effects of Infliximab (a monoclonal antibody) in patients with autoimmune diseases such as rheumatoid arthritis, Crohn's disease, and ulcerative colitis?

Infliximab Side Effects

Infliximab carries significant risks including serious infections (particularly tuberculosis reactivation), infusion reactions, hepatotoxicity, and potential malignancy, requiring mandatory pre-treatment screening and ongoing monitoring throughout therapy. 1, 2

Major Categories of Adverse Effects

Infections (Most Common Serious Complication)

• Infection risk is approximately twofold higher compared to baseline, representing the most common reason for serious adverse events across all clinical trials 1
• Serious infections include pneumonia, bronchitis, sepsis, cellulitis, systemic fungal infections, and herpes zoster 1
• In clinical trials, infections occurred in 56% of pediatric Crohn's disease patients and 50% of adult patients 2
• Tuberculosis reactivation is a critical concern, with historical rates as high as 1,893 cases per 100,000 patient-years before screening protocols were implemented 1
• Two active tuberculosis cases were reported in psoriasis studies at 6 weeks and 34 weeks after starting infliximab 2

Infusion-Related Reactions

• Infusion reactions occur in approximately 18% of infliximab-treated patients compared to 5% of placebo patients 2
• Reactions are defined as adverse events occurring during infusion or within 1 hour after infusion 2
• Common symptoms include fever, chills, nausea, dyspnea, flushing, headache, and rash 2, 3
• Serious infusion reactions occur in <1% of patients and include anaphylaxis, convulsions, erythematous rash, and hypotension 2
• Approximately 3% of patients discontinue infliximab due to infusion reactions 2
• Patients who develop antibodies to infliximab are two-to-three-fold more likely to experience infusion reactions 2

Delayed Hypersensitivity Reactions

• Serum sickness or serum sickness-like reactions occur in approximately 1% of patients (15/1,373 in psoriasis studies) 2
• Delayed reactions occur 3-12 days after infusion and include myalgias, arthralgias, fever, rash, pruritus, facial/hand/lip edema, dysphagia, urticaria, sore throat, and headache 3
• Six patients in psoriasis studies required hospitalization due to fever, severe myalgia, arthralgia, swollen joints, and immobility 2

Hepatotoxicity

• Transient, asymptomatic elevation in liver transaminases is the most common manifestation 1
• Rare cases of severe hepatitis and acute liver failure resulting in transplantation or death have been reported 1
• Elevated ALT levels (>3× upper limit of normal) occurred in varying frequencies across conditions: rheumatoid arthritis (4%), Crohn's disease (5%), ulcerative colitis (2%), ankylosing spondylitis (10%), psoriatic arthritis (7%), and plaque psoriasis (8%) 2

Malignancy Risk

• Non-melanoma skin cancers (NMSC) were diagnosed in 7 of 1,123 patients receiving infliximab compared to 0 of 334 placebo patients in psoriasis studies 2
• Lymphoma risk exists, though the exact incidence remains unclear from available data 4
• Concomitant use with azathioprine or 6-mercaptopurine increases risk of hepatosplenic T-cell lymphoma 1

Autoimmune Phenomena

• Treatment may result in formation of autoantibodies and development of lupus-like syndrome 2
• Development of antinuclear antibodies or anti-ds-DNA has been described, though clinical lupus-like syndrome is rare 3
• Treatment should be discontinued if lupus-like symptoms develop 2

Mandatory Pre-Treatment Screening Requirements

Before initiating infliximab, the following screening is mandatory: 1

• Tuberculosis screening (PPD or interferon-gamma release assay)
• Hepatitis B and C serology
• Complete blood count (CBC)
• Liver function tests
• Assessment for active infections
• History of malignancy and cardiovascular disease

Ongoing Monitoring Requirements

Throughout treatment, patients require: 1

• Periodic history and physical examination with temperature monitoring
• Consideration of yearly PPD testing
• Periodic CBC and liver function tests
• Monitoring for viral hepatitis reactivation
• High index of suspicion for tuberculosis even after prophylaxis

Common Adverse Reactions (≥5% Incidence)

Based on pooled data from 4,779 adult patients, the most frequent adverse reactions include: 2

• Upper respiratory tract infection (32%)
• Nausea (21%)
• Headache (18%)
• Sinusitis (14%)
• Pharyngitis, coughing, diarrhea (12% each)
• Abdominal pain, dyspepsia, rash (10%)
• Fatigue, bronchitis (9-10%)
• Arthralgia, urinary tract infection (8%)
• Fever, hypertension, pruritus (7%)

Pediatric-Specific Considerations

Pediatric patients experience some unique adverse reaction patterns: 2

• Anemia (11%), leukopenia (9%), flushing (9%), viral infection (8%), neutropenia (7%), bone fracture (7%), bacterial infection (6%), and respiratory tract allergic reactions (6%) occurred more commonly in pediatric Crohn's disease patients
• Infections were more frequent with every 8-week dosing (74%) versus every 12-week dosing (38%)
• Pneumonia occurred in 3 pediatric patients
• Herpes zoster occurred in 2 patients in the every 8-week maintenance group

Critical Contraindications and Precautions

• Live vaccines are contraindicated during infliximab therapy and for at least 6 months in infants exposed in utero 2
• Fatal disseminated BCG infection has been reported in an infant who received BCG vaccine after in utero exposure 2
• Avoid in patients with active viral hepatitis; exercise great caution with hepatitis C 1
• Concurrent use with abatacept is not recommended due to increased infection risk without added benefit 2
• Care must be taken when switching between biologics due to overlapping biological activity increasing infection risk 2

Risk Mitigation Strategies

Protective factors that minimize adverse reactions include: 3

• Concomitant administration of immunomodulators (particularly methotrexate) or corticosteroids
• Starting with proper 0,2,6-week induction regimen
• Maintenance dosing every 8 weeks or less
• Avoiding long periods between infusions

Concomitant immunosuppressant use reduces both antibody formation and infusion reaction frequency 2

Patient Education Requirements

Patients must be instructed to: 1

• Check temperature frequently
• Report signs of infection immediately
• Report shortness of breath or breathing changes
• Understand the risk of serious infections including tuberculosis