Immunosuppressants use heterogeneous mechanisms of action to suppress the body's cell-mediated and humoral immune response. They may be used as transplant rejection prophylaxis or to treat autoimmune disorders such as lupus, psoriasis, and rheumatoid arthritis. Commonly used immunosuppressants include cyclosporine A, tacrolimus, glucocorticoids, methotrexate, and biological agents (e.g., rituximab). A common side effect of immunosuppressants is an increased susceptibility to infection and malignancy.
are discussed in detail in another article.
- Immunosuppressants are a heterogeneous class of drugs used to suppress the body's cell-mediated and humoral immune response via lymphocyte inhibition.
- The most common indications include transplant rejection prophylaxis and the treatment of autoimmune disorders such as lupus, psoriasis, and rheumatoid arthritis.
- It is common practice to use a combination of different immunosuppressive drugs to maximize their immunosuppressive effect and minimize their side effects.
- A common side effect of long-term immunosuppressants use is an increased susceptibility to infection and malignancy.
|Overview of immunosuppressants|
|Immunosuppressant class||Common drugs||Mechanism of action||Suppression of cell-mediated immune response||Suppression of humoral immune response||Indications||Adverse effects|
|Glucocorticoids||Prednisolone, hydrocortisone, dexamethasone|| || || || |
|Cyclosporine A|| || || |
|Tacrolimus (also FK-506 or fujimycin)|| || |
|mTOR inhibitors||Sirolimus (also known as rapamycin)|| || |
|Purine analog|| |
| || || |
|IMDH/IMPDH inhibitors||Mycophenolate mofetil|| || |
|Other cytostatic and antiproliferative agents|||| || || |
| || |
|Protein drugs||Antibodies|| || || || |
|Other biological proteins|
✓ = Definite suppression
(✓) = Probable suppression (inconclusive research currently)
– = No suppression
- Biological agents are recombinant proteins that intervene in immunological processes.
- Used in autoimmune diseases and malignancies
- Although complex and costly, they can significantly improve the success of treatment in some cases.
- The naming of antibodies follows a certain classification scheme:
- The suffix "-mab": indicates "monoclonal antibody."
- Second to last syllable: describes the origin (e.g., "xi"=chimeric, "u"=human)
- Third to last syllable: denotes the target (e.g., li(m)=immune system)
|Overview of biologics|
| || |
|Rituximab|| || |
|Cetuximab|| || || |
|Palivizumab|| || |
|Secukinumab|| || |
|Brodalumab|| || || |
|Vedolizumab|| || |
| || |
|Omalizumab|| || |
|Abciximab|| || |
|Trastuzumab|| || |
|Eculizumab|| || |
|Denosumab|| || |
|Alemtuzumab|| || |
|Guselkumab|| || |
- Calcineurin inhibitors become even more neurotoxic and nephrotoxic when combined; for this reason, they should never be coadministered.
- Because of their neurotoxicity, patients receiving higher doses and those who have decreased renal function should be closely monitored.
- Gingival hyperplasia
- Hypertrichosis and hirsutism
- Diabetogenic effect (particularly after organ transplantation), which can lead to:
- Increase in malignancies and infectious diseases (e.g., increase in the risk of squamous cell carcinoma by 50% in patients who are on simultaneous treatment with PUVA during psoriasis treatment)
- Nausea and diarrhea
Tacrolimus (FK506) 
- Nephrotoxicity: monitor for oliguria
- Neurotoxicity (more severe compared to cyclosporin)
- Diabetogenic effect (more severe compared to cyclosporin A) ; 
- Hair loss
- Nausea and diarrhea
- Abdominal discomfort
- Pancytopenia; (leukopenia, macrocytic anemia, thrombocytopenia): exacerbated by interaction with allopurinol, since it inhibits xanthine oxidase, which is responsible for the degradation of 6-mercaptopurine
- Malignancies, including , , , (rare)
- Nausea, vomiting, and dose-related diarrhea
- Acute pancreatitis
mTOR inhibitors (sirolimus, everolimus) 
- Insulin resistance
- No nephrotoxicity
- Infection (e.g., respiratory or urinary tract)
- Peripheral edema
To remember that sirolimus can cause pancytopenia, think “Sir, don't forget your pants!”
- Infection; (e.g., respiratory or urinary tract), especially with CMV
- Vomiting and diarrhea
- Comparatively low neurotoxicity and nephrotoxicity
- Peripheral edema
- Back pain
- Bone marrow suppression: pancytopenia and/or macrocytic anemia
- Mucositis (particularly stomatitis, enteritis), susceptibility to infection
- Gastrointestinal side effects (e.g., nausea and vomiting)
- Pulmonary fibrosis and toxicity
- Hair loss
- Increased risk of lymphoproliferative disorders
Salvage therapy (leucovorin rescue therapy) 
- The side effects of methotrexate can be reduced by administering salvage therapy.
- Salvage therapy involves the administration of folic acid and folinic acid (active folic acid = leucovorin = calcium folinate).
Biologics (e.g., daclizumab) 
General side effects
- Rash, dermatitis
- Formation of anti-drug antibodies (especially for adalimumab and infliximab): can manifest with a decrease in clinical response (e.g., recurrence of symptoms), low drug levels, and/or allergic reactions.
- Flu-like symptoms
- ↑ ALT, ↑ AST
- Infections (e.g., nasopharyngitis)
- Gastrointestinal symptoms (e.g., diarrhea)
- Leukocytosis or leukopenia, thrombocytopenia, anemia
- Rituximab and natalizumab: reactivation of a latent JC virus infection, resulting in )
- Cetuximab and panitumumab: : general side effects (especially rash, diarrhea, ↑ ALT, ↑ AST)
- Trastuzumab: dilated cardiomyopathy (reversible in most cases)
- TNF-α inhibitors
- Alemtuzumab: ↑ risk of developing autoimmune conditions (e.g., ITP) and infections
- Nivolumab, pembrolizumab, and cemiplimab: ↑ risk of developing autoimmune conditions, including:
- Avelumab, durvalumab, and atezolizumab: same as above
- Ipilimumab: same as above
Contraindications to anti-TNF-α treatment (infliximab, adalimumab, etanercept)
- Chronic infections, particularly tuberculosis: Rule out latent tuberculosis before starting therapy (the activity of TNF-α plays a major role in formation and stabilization of granulomas against Mycobacterium tuberculosis).
- Multiple sclerosis
- Immunosuppressed individuals
- Systemic or localized infections
- Moderate to severe heart failure (NYHA class III/IV)
- For side effects of glucocorticoids see “ .”
We list the most important adverse effects. The selection is not exhaustive.