Table. Immunosuppressive potential of biological therapies

Immunosuppressant category	Drug(s)	Licensed indication(s)	Overall immunosuppressive potential	Mechanism of action	Half-life (mean)	Duration of immunosuppression
Anti T-lymphocyte therapies	Abatacept	Graft-versus-host disease (GVHD), juvenile idiopathic arthritis (JIA), rheumatoid arthritis (RA), psoriatic arthritis	Severe	Selective co-stimulation modulator that inhibits T-cell activation	8–25 days	Duration of T-cell suppression after therapy end is not well defined
Anti T-lymphocyte therapies	Basiliximab	Prevention of renal transplant acute rejection	Severe	Blocks the alpha-chain of IL-2 receptor complex. This receptor is expressed on activated T-lymphocytes and is a critical pathway for activating cell-mediated allograft rejection	7.2 ±3.2 days	Immune recovery after transplant is impaired for at least 12 months
Anti B-lymphocyte antibodies	Rituximab^a	Chronic lymphocytic leukemia, RA, non-Hodgkin lymphoma, granulomatosis with polyangiitis (Wegener’s) (GPA) and microscopic polyangiitis (MPA)	Severe	Directed against the B-cell surface CD20 antigen, activating complement-dependent B-cell cytotoxicity	21–32 days	B-cell recovery occurs 6–12 months after therapy ends, although there is significant variability between patients and diseases reported
	Ofatumumab	Multiple sclerosis	Severe	Binds CD20 resulting in complement-dependent cell lysis and antibody-dependent cell-mediated toxicity	About 17 days	Duration of B-cell suppression after therapy ends is not well defined
	Ocrelizumab	Multiple sclerosis	Severe	Selectively depletes CD20 expressing B-cells through antibody-dependent cell-mediated phagocytosis and cytotoxicity, as well as complement-mediated cytolysis	26 days	Duration of B-cell suppression after therapy ends is not well defined
	Obinutuzumab	Chronic lymphocytic leukaemia, follicular lymphoma	Severe	Binds CD20 and activates antibody-dependent cellular cytotoxicity and phagocytosis, resulting in cell death	25–35 days	Duration of B-cell suppression after therapy ends is not well defined
	Belimumab	Lupus nephritis, systemic lupus erythematosus (SLE)	Severe	Active against the B-cell survival molecule BLyS family, reducing the activity of B-cell mediated immunity and the autoimmune response	About 19 days	Duration of B-cell suppression after therapy ends is not well defined
Agents targeting other cellular markers	Alemtuzumab	B-cell chronic lymphocytic leukemia, multiple sclerosis	Severe	Directed against the CD52 receptor of B-lymphocytes, T-lymphocytes, NK cells and macrophages, resulting in profound lymphocyte depletion	6–21 days	T- and B-cells may be depleted for many months after therapy ends
	Blinatumomab	Acute lymphoblastic leukaemia	Severe	Activates T-cells by binding to the CD3 receptor and forming a complex with CD19 on the surface of B-cells, resulting in B-cell lysis and subsequent depletion of both T- and B-lymphocytes	2–3 hours	Duration of T- and B-cell suppression after therapy ends is not well defined
	Daratumumab	Multiple myeloma	Severe	Depletes CD38-positive myeloid-derived cells, alongside T- and B-lymphocytes	18 ±9 days	Duration of T- and B-cell suppression after therapy ends is not well defined
Tumor necrosis factor-α inhibitors^b	Infliximab	Ankylosing spondylitis, RA, psoriatic arthritis, psoriasis, Crohn’s disease, ulcerative colitis	Moderate	Binds to TNF-α, reducing cytokine-driven inflammatory processes	7–12 days	Data suggest that lymphocyte subsets and T-cell proliferative responses were not altered after completion of infliximab therapy in patients with Crohn’s disease
	Adalimumab	JIA, psoriatic arthritis, RA, ankylosing spondylitis, psoriatic arthritis, psoriasis, Crohn’s disease, ulcerative colitis, hidradenitis suppurativa, uveitis	Moderate	Inhibits both soluble and membrane-bound TNF-α, reducing the progression of structural damage in RA, psoriatic arthritis and inflammatory bowel disease. Reduces epidermal thickness and inflammatory cell infiltration in plaque psoriasis	About 2 weeks	Exact duration of potential immunosuppression is not well defined
	Etanercept	Ankylosing spondylitis, psoriasis, psoriatic arthritis, JIA, RA, non-radiographic axial spondyloarthritis	Moderate	Acts as a decoy soluble receptor to TNF-α and β	About 3–5 days (shorter than other TNF-α inhibitors)	Exact duration of potential immunosuppression is not well defined
	Certolizumab	Ankylosing spondylitis, non-radiographic axial spondyloarthritis, RA , psoriasis	Moderate	Inhibits both soluble and membrane-bound TNF-α, although it is structurally different to other TNF-α inhibitors and does not inhibit cell-mediated cytotoxicity	About 14 days (pegylation of certolizumab allows for delayed elimination and an extended half-life)	Exact duration of potential immunosuppression is not well defined
	Golimumab	Ankylosing spondylitis, psoriatic arthritis, RA, polyarticular JIA, inflammatory bowel disease	Moderate	Inhibits both soluble and membrane-bound TNF-α, reducing the secretion of other pro-inflammatory cytokines and fibroblast proliferation	12 days	Exact duration of potential immunosuppression is not well defined
Interleukin (IL) inhibitors	Anakinra	RA, cryopyrin-associated periodic syndromes (CAPS), JIA	Mild	IL-1 receptor antagonist that reduces inflammatory responses	4–6 hours	Not generally immunosuppressive
	Canakinumab	Cryopyrin-associated periodic syndrome, familial cold autoinflammatory syndrome	Mild	Inhibits IL-1β to reduce inflammation	23–26 days	Not generally immunosuppressive
	Tocilizumab	Cytokine release syndrome, giant cell arteritis, RA, JIA	Moderate	Inhibits IL-6, reducing cytokine and acute phase reactant production	16–19 days (the long half-life may extend the risk period)	Exact duration of potential immunosuppression is not well defined
	Sarilumab	RA	Moderate	Inhibits IL-6, reducing cytokine and acute phase reactant production	8–10 days (shorter than other IL-6 inhibitors)	Exact duration of potential immunosuppression is not well defined
	Tildrakizumab	Plaque psoriasis	Moderate	Inhibits the proinflammatory cytokines and chemokines that are associated with binding of naturally occurring IL-23	About 23 days	Exact duration of potential immunosuppression is not well defined
	Risankizumab	Crohn’s disease, psoriasis, psoriatic arthritis	Moderate	Binds to the p19 subunit of IL-23, preventing the release of proinflammatory cytokines and chemokines	About 21–28 days	Exact duration of potential immunosuppression is not well defined
	Secukinumab	Spondylarthritis, enthesitis-related arthritis, plaque psoriasis, psoriatic arthritis, hidradenitis suppurativa	Mild	Binds to IL-17A to prevent the release of proinflammatory cytokines and chemokines	22–31 days	Not generally immunosuppressive
	Ixekizumab	Spondylarthritis, plaque psoriasis, psoriatic arthritis	Mild	Selectively binds IL-17A to inhibit the release of proinflammatory cytokines and chemokines	13 days	Not generally immunosuppressive
	Ustekinumab	Crohn’s disease, plaque psoriasis, psoriatic arthritis, ulcerative colitis	Mild	Binds to and interferes with the proinflammatory cytokines, IL-12 and IL-23	14–80 days	Not generally immunosuppressive
	Guselkumab	Plaque psoriasis, psoriatic arthritis	Mild	Binds with IL-23, inhibiting release of proinflammatory cytokines and chemokines	15–18 days	Not generally immunosuppressive
Inhibitors targeting atopy	Dupilumab	Asthma, atopic dermatitis, prurigo nodularis, chronic Rhinosinusitis	Mild	Inhibits IL-4 and IL-13 to prevent the release of proinflammatory cytokines, chemokines, nitric oxide and IgE	11–20 days	Not generally immunosuppressive
	Mepolizumab	Asthma, eosinophilic granulomatosis, chronic rhinosinusitis	Mild	Inhibits IL-5 signalling reducing the production and survival of eosinophils	16–22 days	Not generally immunosuppressive
	Omalizumab	Asthma, chronic rhinosinusitis, chronic idiopathic urticaria	Mild	Inhibits IgE by binding to mast cells and basophils	24–26 days	Not generally immunosuppressive
Integrin inhibitors	Natalizumab	Multiple sclerosis	Mild	Binds to the α4 subunit of integrin, limiting adhesion and transmigration of leukocytes	26.8 days (median)	Not generally immunosuppressive
Integrin inhibitors	Vedolizumab	Ulcerative colitis, Crohn’s disease, pouchitis	Mild	Blocks the interaction of α4β7 integrin to inhibit the migration of memory T-cells in inflamed gastrointestinal tissue	26 days	Not generally immunosuppressive
Interferon-α (IFN) receptor inhibitors	Anifrolumab	SLE	Mild	Blocks type 1 IFN receptors, reducing inflammatory and immunological processes	12 days	Not generally immunosuppressive
RANK-ligand inhibitors	Denosumab	Osteoporosis	Mild	Suppresses bone resorption	26 days	Unlikely to be immunosuppressive after treatment ends
Calcitonin gene receptor protein (CGRP) inhibitors	Eptinezumab	Migraine	Mild	Antagonises CGRP function, which are associated with the development of migraine	27 days	Unlikely to be immunosuppressive after treatment ends
Immune checkpoint inhibitors	Atezolizumab	Urothelial carcinoma, hepatocellular carcinoma, non-small cell lung cancer, small cell lung cancer	Mild	Binds to programmed-death ligand-1 (PD-L1) to selectively prevent the interaction between PD-1 and CD80 receptors to restore anti-tumour T-cell function	27 days	Unlikely to be immunosuppressive after treatment ends
	Pembrolizumab	Carcinoma, cervical cancer, oesophageal cancer, lymphoma, melanoma, non-small cell lung cancer, head and neck squamous cell cancer, etc	Mild	Inhibits PD-1 activity to reduce the negative immune regulation caused by PD-1 receptor signalling to induce anti-tumour responses	22 days	Unlikely to be immunosuppressive after treatment ends
	Nivolumab	Colorectal cancer, melanoma, carcinoma oesophageal cancer, non-small cell lung cancer etc.	Mild	Selectively inhibits PD-1 activity, restoring tumour-specific T-cell response	25 days	Unlikely to be immunosuppressive after treatment ends
	Ipilimumab	Carcinoma, melanoma, non-small cell lung cancer etc.	Mild	Binds to cytotoxic T-lymphocyte protein 4 (CTLA-4), allowing for enhanced T-cell activation and proliferation	About 20 days	Unlikely to be immunosuppressive after treatment ends
Complement inhibitors^c	Eculizumab	Atypical haemolytic uraemic syndrome, refractory myasthenia gravis, neuromyelitis optica spectrum disorder, paroxysmal nocturnal haemoglobinuria	Mild	Blocks the formation of C5b, inhibiting formation of the membrane attack complex (MAC), resulting in increased risk of disease with encapsulated bacteria, particularly Neisseria spp	8-15 days	Unlikely to be immunosuppressive after treatment ends
	Ravulizumab	Atypical haemolytic uraemic syndrome, refractory myasthenia gravis, paroxysmal nocturnal haemoglobinuria	Mild	Binds to C5, inhibiting formation of terminal MAC	7–8 weeks	Unlikely to be immunosuppressive after treatment ends
	Pegcetacoplan	Paroxysmal nocturnal haemoglobinuria	Mild	Binds to C3 to regulate downstream effectors of complement activation, controlling intravascular and extravascular haemolysis	8 days (median)	Unlikely to be immunosuppressive after treatment ends
Footnotes: ^a For perinatal exposure risks, see infants subsection ^b The immunosuppressive potential varies across this class, with etanercept the least immunosuppressive and infliximab the most; however, direct attributable immunosuppressive risks are not well studied, as TNF-inhibitors are often used in conjunction with other immunosuppressive agents (such as corticosteroids). For prenatal exposure risks, see infants section. ^c This class of agents has a low overall immunosuppressive capacity, yet result in a moderately increased risk of infection with encapsulated bacteria, particularly N. meningitidis. 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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