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 |
| 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 | Rituximaba | 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 inhibitorsb | 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 |
| 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 inhibitorsc | 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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