Immunomodulators: Names and Classifications
Immunomodulators are medications that modify the immune system's function and include corticosteroids, thiopurines, methotrexate, calcineurin inhibitors, anti-TNF agents, and other biologics. 1
Major Classes of Immunomodulators
Corticosteroids
- Prednisone, prednisolone, methylprednisolone, dexamethasone
- Mechanism: Broad anti-inflammatory effects
- Note: A total daily dose equivalent to ≥20 mg of prednisolone for ≥2 weeks is associated with increased risk of infections 1
Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs)
- Thiopurines: Azathioprine, 6-mercaptopurine
- Methotrexate
- Mycophenolate mofetil (MMF)
- Calcineurin inhibitors: Cyclosporine, tacrolimus
- Others: Cyclophosphamide, sulfasalazine, hydroxychloroquine 1
Biologic Disease-Modifying Anti-Rheumatic Drugs (bDMARDs)
TNF Inhibitors
- Infliximab (monoclonal antibody)
- Adalimumab (monoclonal antibody)
- Etanercept (soluble receptor) 2
- Certolizumab (PEGylated Fab fragment)
- Golimumab (monoclonal antibody) 1
Anti-Cytokine/Cytokine Receptor Agents
- Anti-IL-6 receptor: Tocilizumab, sarilumab
- Anti-IL-4Ra: Dupilumab
- Anti-IL-17A: Secukinumab, ixekizumab
- Anti-IL-23a: Guselkumab
- Anti-IL-12/IL-23: Ustekinumab 1
B-Cell Targeting Agents
- Anti-CD20 monoclonal antibodies: Rituximab, obinutuzumab, ocrelizumab 1
- Note: These agents demonstrate the weakest response to COVID-19 vaccination 3
T-Cell Targeting Agents
- Anti-CTLA-4: Abatacept
- Anti-CD52: Alemtuzumab
- Anti-thymocyte globulin therapy 1
Gut-Specific Immunosuppressants
- Vedolizumab (integrin antagonist that binds to α4β7 integrin) 1
Targeted Synthetic DMARDs
- Janus kinase (JAK) inhibitors: Tofacitinib, baricitinib 1
Other Immunomodulators
Clinical Applications
Inflammatory Bowel Disease
- Commonly used: Corticosteroids, thiopurines, methotrexate, anti-TNF agents 1
- For steroid-refractory colitis: Infliximab (particularly effective) 1
- Gut-specific option: Vedolizumab for GI inflammation 1
Immune-Related Adverse Events (irAEs) from Cancer Immunotherapy
- First-line: Corticosteroids
- For steroid-refractory irAEs: TNF inhibitors (particularly for colitis and inflammatory arthritis) 1
- Personalized anti-cytokine strategies may:
- Reduce symptom duration and hospitalization
- Enable rapid resumption of cancer immunotherapy
- Provide more targeted approach than corticosteroids 1
Primary Immunodeficiency Disorders
- IVIG is standard of care for patients with impaired antibody production 4
- Recommended dosage: 400-600 mg/kg every 3-4 weeks 4
Important Considerations
Infection Risk
- All immunomodulators compromise the patient's immune response to varying degrees 1
- Risk factors for opportunistic infections include:
- Combination immunomodulator therapy
- Malnutrition
- Comorbidities
- Advanced age 1
Vaccination
- Live vaccines should be deferred for 11 months after receiving high-dose IVIG 4
- Inactivated vaccines are not routinely administered during immunoglobulin therapy for patients with major antibody deficiencies 4
Monitoring
- Regular monitoring of appropriate laboratory parameters based on specific agent
- For IVIG: Monitor IgG trough levels at least yearly 4
- For other immunomodulators: Monitor for specific toxicities (e.g., hepatotoxicity, bone marrow suppression)
The selection of an appropriate immunomodulator depends on the specific disease being treated, the patient's comorbidities, and the risk-benefit profile of each agent. Understanding the mechanisms of action and potential adverse effects of these medications is crucial for optimal patient management.