MABs / Side effects
Common side effects of MAB treatment
- Infusion reactions:
- immediate response during infusion
(not unique to antibodies; seen particularly with cancer chemotherapy drugs)- symptoms include:
- Cardiovascular: chest pain, hypo- or hypertension, tachy- or bradycardia, arrhythmia, edema, ischemia or infarction, cardiac arrest
- Respiratory: cough, dyspnea, nasal congestion, rhinitis, sneezing, wheezing, bronchospasm, edema, cyanosis, acute respiratory distress syndrome
- CNS: headache, dizziness, consfusion, loss of consciousness, anxiety, sense of impending doom
- Skin: rash, pruritis, urticaria, flushing, local or diffuse erythema, conjunctival erythema
- Endocrine: rigors, diaphoresis, fever, generalized feeling of warmth
- GI: nausea, vomiting, metalic taste, diarrhea, abdominal cramping, bloating
- Urinary: incontinence, renal impairment
- Genital: uterine cramping
- Musculoskeletal: arthralgias, myalgias, fatigue
- symptoms include:
- 2 types (symptoms are similar for both types, and are typically managed by slowing the infusion and by administration of antihistamines and other procedures common to management of type I hypersensitivity reactions):
- typical IgE mediated type I hypersensitivity reaction
- occurs within minutes (10-12 hours maximum)
- increased severity and quicker response with repeated exposure
- cytokine release due to Fc region recruitment of immune effector cells (esp. granulocytes that release cytokines, obviously!)
- occurs during the first few hours after infusion
- worse on 1st infusion, often decreases in severity with subsequent exposures
- typical IgE mediated type I hypersensitivity reaction
- immediate response during infusion
- Type III hypersensitivity reactions –
deposition of antigen/antibody complexes in tissues, leading to general malaise, and (ultimately) serum sickness
- HAMA (human anti-mouse antibody) response produces severe hypersensitivity reactions that result in kidney damage characteristic of serum sickness
- antibodies differ significantly in the degree of HAMA, depending upon the amount of mouse protein they contain (mouse > chimeric > humanised > human)
- there is some thought that some aspects of infusion reactions can be explained by the fact that most people have had some prior exposure to mouse proteins
- Cytokine release syndrome:
- observed particularly with anti-T cell antibodies that can directly activate the T cell receptor before triggering destruction of lymphocytes)
- can result in a "cytokine storm", a kind of positive feedback loop where cytokine release recruits more effector cells that release more cytokines, etc.
- shaking chills, fever, arthralgia, diarrhea, vomiting, hypotension and respiratory distress
- Infections (Reference)
- especially when antibodies that decrease immune system function are coadministered with other immunosuppressive agents
- reactivation of tuberculosis (particularly problematic for TNFα inhibitors)
- standard is to test for TB (Mantoux test, chest x-ray) before starting any MAB drug treatment regimen
- standard is to test for TB (Mantoux test, chest x-ray) before starting any MAB drug treatment regimen
- Unknown effects on immunization, carcinogenesis, mutagenesis, impairment of fertility, pregnancy, nursing infants (human IgG is secreted in milk)
- administration of anti-TNFα agents (e.g., infliximab, entanercept) has recently been shown to be associated with increases in congenital abnormalities
- it is unknown whether this is due to TNF-alpha inhibition (see also THALIDOMIDE), or more general characteristics of the antibody/fusion protein
- administration of anti-TNFα agents (e.g., infliximab, entanercept) has recently been shown to be associated with increases in congenital abnormalities