Immunomodulatory imide drug

Immunomodulatory imide drugs (IMiDs) are a class of immunomodulatory drugs[1] (drugs that adjust immune responses) containing an imide group. The IMiD class includes thalidomide and its analogues (lenalidomide, pomalidomide, and apremilast).[1]

"IMiD" redirects here. For IMID, see immune-mediated inflammatory diseases.
Immunomodulatory imide drug
Drug class
Thalidomide
Class identifiers
UseErythema nodosum leprosum, multiple myeloma, myelodysplastic syndrome, acute myeloid leukaemia and other immunologic conditions
ATC codeL04AX
Biological targetTNF, IL-6, VEGF, NF-kB, etc.
Clinical data
Drugs.comDrug Classes
In Wikidata

The name "IMiD" alludes to both "IMD" for "immunomodulatory drug" and the forms imide, imido-, imid-, and imid.

Generations

There are three generations of IMiDs, with each successive generation being better tolerated and more active against inflammatory and malignant conditions.[1]

Medical use

The primary use of IMiDs in medicine is in the treatment of cancers and autoimmune diseases (including one that is a response to the infection leprosy).[2] Indications for these agents that have received regulatory approval include:[3]

Off-label indications for which they seem promising treatments include:[4]

Adverse effects

The major toxicities of approved IMiDs are peripheral neuropathy, thrombocytopenia, anaemia and venous thromboembolism.[4] There may be an increased risk of secondary malignancies, especially acute myeloid leukaemia in those receiving IMiDs.[4]

Mechanism of action

Their mechanism of action is not entirely clear, but it is known that they inhibit the production of tumour necrosis factor, interleukin 6 and immunoglobulin G and VEGF (which leads to its anti-angiogenic effects), co-stimulates T cells and NK cells and increases interferon gamma and interleukin 2 production.[5][6][7] Their teratogenic effects appear to be mediated by binding to cereblon.[8] Apremilast, on the other hand, inhibits PDE4.[4]

References
  1. Knight, R (August 2005). "IMiDs: a novel class of immunomodulators". Seminars in Oncology. 32 (4 Suppl 5): S24–S30. doi:10.1053/j.seminoncol.2005.06.018. PMID 16085014.
  2. Pan, B; Lentzsch, S (October 2012). "The application and biology of immunomodulatory drugs (IMiDs) in cancer". Pharmacology & Therapeutics. 136 (1): 56–68. doi:10.1016/j.pharmthera.2012.07.004. PMID 22796518.
  3. Sedlarikova, L; Kubiczkova, L; Sevcikova, S; Hajek, R (October 2012). "Mechanism of immunomodulatory drugs in multiple myeloma". Leukemia Research. 36 (10): 1218–1224. doi:10.1016/j.leukres.2012.05.010. PMID 22727252.
  4. Vallet, S; Witzens-Harig, M; Jaeger, D; Podar, K (March 2012). "Update on immunomodulatory drugs (IMiDs) in hematologic and solid malignancies". Expert Opinion on Pharmacotherapy. 13 (4): 473–494. doi:10.1517/14656566.2012.656091. PMID 22324734.
  5. Quach, H; Ritchie, D; Stewart, AK; Neeson, P; Harrison, S; Smyth, MJ; Prince, HM (January 2010). "Mechanism of action of immunomodulatory drugs (IMiDS) in multiple myeloma". Leukemia. 24 (1): 22–32. doi:10.1038/leu.2009.236. PMC 3922408. PMID 19907437.
  6. Andhavarapu, S; Roy, V (February 2013). "Immunomodulatory drugs in multiple myeloma". Expert Review of Hematology. 6 (1): 69–82. doi:10.1586/ehm.12.62. PMID 23373782.
  7. Sedlarikova, L; Kubiczkova, L; Sevcikova, S; Hajek, R (October 2012). "Mechanism of immunomodulatory drugs in multiple myeloma". Leukemia Research. 36 (10): 1218–1224. doi:10.1016/j.leukres.2012.05.010. PMID 22727252.
  8. Chang, XB; Stewart, AK (2011). "What is the functional role of the thalidomide binding protein cereblon?". International Journal of Biochemistry and Molecular Biology. 2 (3): 287–94. PMC 3193296. PMID 22003441.
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