Table. Immunosuppressive potential of small molecule targeted therapies

Immunosuppressant category	Drug(s)	Licensed indication(s)	Overall immunosuppressive potential	Mechanism of action		Half-life (mean)	Duration of immunosuppression
Janus kinase (JAK) inhibitors	Baricitinib	Rheumatoid arthritis (RA), atopic dermatitis	Moderate	Inhibit JAK enzymes, which are intracellular enzymes involved in stimulating haematopoiesis and immune cell function		About 12–16 hours	Exact duration of potential immunosuppression is not well defined
	Tofacitinib	Ankylosing spondylitis, juvenile idiopathic arthritis (JIA), RA, psoriatic arthritis, ulcerative colitis	Moderate	Inhibit JAK enzymes, which are intracellular enzymes involved in stimulating haematopoiesis and immune cell function		About 3 hours (immediate release solution and tablet) About 6–8 hours (extended release)	Exact duration of potential immunosuppression is not well defined
	Ruxolitinib	Graft-versus-host disease (GVHD), myelofibrosis, polycythaemia vera	Moderate	In myelofibrosis and polycythaemia vera, JAK enzyme activity is dysregulated. Ruxolitinib modulates the affected JAK1/2 activity. In GVHD, JAK-STAT signalling is involved with the regulation of the development, proliferation and activation of immune cell types important to GVHD pathogenesis		About 3 hours	Exact duration of potential immunosuppression is not well defined
BCR-ABL tyrosine kinase inhibitors	Imatinib Dasatinib Ponatinib	Acute lymphoblastic leukemia, chronic myeloid leukemia, aggressive systemic mastocytosis	Moderate	Inhibit BCR-ABL tyrosine kinase and induces apoptosis in BCR-ABL positive cell lines in Philadelphia chromosome–positive leukemias		15–40 hours	Exact duration of potential immunosuppression is not well defined
Bruton tyrosine kinase (BTK) inhibitors	Ibrutinib Acalabrutinib	GVHD, lymphocytic leukemia, lymphoma	Moderate	Irreversibly inhibit BTK, an integral component of the B-cell receptor and cytokine receptor pathways, reducing B-cell proliferation and survival		1–6.5 hours	Exact duration of potential immunosuppression is not well defined
Antineoplastic kinase (ALK) inhibitors	Alectinib Ceritinib	ALK-positive non-small cell lung cancer	Mild	Inhibit proliferation of ALK-dependent cancer cells		About 41 hours	Exact duration of potential immunosuppression is not well defined
Cyclin-dependent kinase (CDK) inhibitors	Palbociclib Ribociclib	Breast cancer	Mild	Disrupt the cell cycle, specifically the G1 phase and supress tumour growth through multiple mechanisms.		About 30 hours	Exact duration of potential immunosuppression is not well defined
Sphingosine-1-phosphate receptor modulators	Fingolimod	Multiple sclerosis	Mild		Reduce lymphocytes in the central nervous system	6–9 days	Not generally immunosuppressive
Note: This is not an exhaustive list. Licensed indications were referenced from database of the Australian Therapeutic Goods Administration (TGA). Furthermore, the underlying disease for which the medication is prescribed, and concomitant immunosuppressant use, may alter this categorisation. For further information regarding the immunosuppressive potential of underlying conditions, please also consider Table. Immunosuppressive potential of certain medical conditions.

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