Table 3.
Main adverse events reported in association with anti-tumour necrosis factor use in children with rheumatic diseases 17–19, 26, 28–30, 46, 70, 123–127
| AE category | Generic anti-TNF AEs | Etanercept | Adalimumab | Infliximab |
|---|---|---|---|---|
| Musculoskeletal | Arthritis flare, arthralgia | MAS, sarcoidosis, aseptic necrosis (femoral head), vasculitic rash, osteoporosis | Elevated CPK, myositis, back pain, muscle spasms | MAS |
| Haematological | – | Pancytopenia, lymphadenopathy, epistaxis | Neutropenia, leucopenia | – |
| Gastrointestinal and/or renal | Vomiting | CD, UC, aspecific bowel inflammation, biliary calculosis, nausea, abdominal pain, weight loss or gain, anorexia, oral apthosis, proctorrhagia | Increased ALT and AST, appendicitis, abdominal pain, gastroduodenitis, gastrointestinal bleeding | Persistent macroscopic haematuria |
| Cardiorespiratory | Hypertension | Cough, chest pain, asthma, tachycardia, extrasystolia | Chest pain | Cough |
| Infectious | Upper respiratory tract infections, pneumonia, CMV, gastrointestinal infection, soft tissue infections | Urosepsis, pyelonephritis, meningoencephalitis, appendicular abscess, prosthetic hip infection, EBV, recurrent urinary tract infections, dental infections, otitis | Tuberculosis, herpes zoster, herpes simplex, streptococcal infection, urinary tract infection, pharyngitis, Clostridum difficile | Tuberculosis, candidiasis (vaginal and oral), herpes zoster, varicella zoster, viral thyroiditis, histoplasmosis, pharyngitis, bronchiolitis |
| Autoimmune and/or immunological | Injection-site or infusion reactions | New onset of JSLE, Takayasu's arteritis, dermatomyositis, DM, alopecia, new auto-antibodies, autoimmune hepatitis | Lupus-like syndrome, injection-site reaction, new antibodies to ADA, DM | Infusion reactions*, newly induced auto-antibodies, development of antibodies to infliximab |
| Ophthalmological | – | Uveitis, blurred vision | Keratitis | Uveitis |
| Neurological | Headache | Demyelinating retrobulbar neuritis, neuropathy, epileptic insult, hearing loss, vertigo, dysaesthesia, insomnia | ‘Sporadic seizure’, dizziness, syncope | Irritability, paraesthesia |
| Psychiatric | – | Depression, personality disorder, emotional lability, panic attacks, anxiety, agitation, concentration disorder, hallucinations, aggression | – | Psychoses, depression, panic attacks, anxiety, hyperactivity |
| Oncological | – | Lymphomas, thyroid carcinoma, yolk-sac tumour | Lymphomas | – |
| Gynaecological | – | Ovarian cyst, endometriosis, irregular/painful menses | Menorrhagia | – |
| Dermatological | New-onset psoriasis | Skin ulcer, hair loss, pruritic/urticarial rash, pityriasis, onychodystrophy, coccygeal cyst, eczema | Granuloma annulare, excoriation, purpura | Urticaria |
| Deaths | – | – | Four deaths† | Two deaths‡ |
Abbreviations are as follows: ADA, adalimumab; AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CD, Crohn's disease; CMV, cytomegalovirus; CPK, creatinine phosphokinase; DM, diabetes mellitus; EBV, Epstein–Barr virus; JSLE, juvenile-onset systemic lupus erythematosus; MAS, macrophage activation syndrome; TNF, tumour necrosis factor; UC, ulcerative colitis.
Reported infusion reactions to infliximab include anaphylaxis, vomiting, fever, headache, hypotension, abdominal pain, coughing, face oedema, rash, urticaria, chills, fatigue, sleepiness and insomnia.
Described by the FDA US Healthcare AE Reporting System.
Deaths described in Table 2.