Table. Immunosuppressive potential of conventional (non-biological) immunosuppressive therapies
| Immunosuppressant category | Drug(s) | Licensed indication(s) | Overall immunosuppressive potential | Mechanism of action | Half-life (mean) | Duration of immunosuppression |
|---|---|---|---|---|---|---|
| General | Hydroxychloroquine | Systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), malaria | Mild | Suppresses toll-like receptors to trigger important immunomodulatory effects, which impairs complement-dependent antigen-antibody reactions | About 40 days | Not typically considered as an immunosuppressant, but may lower lymphocyte count. Exact duration of immune recovery after drug discontinuation is not well defined |
| Sulfasalazine Mesalazine Osalazine | RA, ulcerative colitis, Crohn’s disease | Mild | Immunomodulatory agents that block the production of COX-derived products of arachidonic acid metabolism | Sulfasalazine: about 10 hours Mesalazine: about 25 hours Olsalazine: about 55 minutes Olsalazine-S: 7 days due to slow dissociation from the protein binding site | Not typically considered as an immunosuppressant, but may lower lymphocyte count. Exact duration of immune recovery after drug discontinuation is not well defined | |
| Leflunomide | RA, psoriatic arthritis | Moderate | Inhibits pyrimidine synthesis, resulting in antiproliferative and anti-inflammatory effects | 18–19 days; the active metabolite has a prolonged half-life of 1–4 weeks | Exact duration of potential immunosuppression is not well defined | |
| Teriflunomide | Multiple sclerosis | Moderate | Inhibits pyrimidine synthesis, which reduces deactivated lymphocytes in the central nervous system | 18–19 days | Exact duration of potential immunosuppression is not well defined | |
| Mercaptopurine | Acute lymphoblastic leukaemia | Moderate | Inhibits DNA and RNA synthesis | 1–5.4 hours | Exact duration of potential immunosuppression is not well defined | |
| Azathioprine ≤3 mg/kg/day | Rheumatic disorders | Mild | Inhibits purine and protein synthesis, which reduces circulating lymphocytes and immunoglobulin production | About 2 hours | Exact duration of potential immunosuppression is not well defined | |
| Azathioprine >3 mg/kg/day | Rheumatic disorders | Moderate | ||||
| Azathioprine | Prevention of rejection in kidney transplant | Severe | Inhibits purine and protein synthesis, which reduces circulating lymphocytes and immunoglobulin production | About 2 hours | Immune recovery after transplant is impaired for at least 12 months | |
| Methotrexate ≤25 mg/week | RA, psoriasis arthritis | Mild | Folate antimetabolite that binds to dihydrofolate reductase, interfering with DNA synthesis, repair and cellular replication | 1–15 hours | Lymphocyte recovery occurs 1–3 months after discontinuation. In RA, temporary discontinuation for 4 weeks improves some vaccine responses (eg for influenza) | |
| Methotrexate >25 mg/week | RA, psoriasis arthritis | Moderate | ||||
| Methotrexate ≤25 mg/week | Oncology indications | Moderate | Folate antimetabolite that binds to dihydrofolate reductase, interfering with DNA synthesis, repair and cellular replication | 1–15 hours | Exact duration of lymphocyte recovery is not defined in oncological populations | |
| Methotrexate >25 mg/week | Oncology indications | Severe | ||||
| Mycophenolate | Prevention of rejection after organ transplant | Severe | Blocks DNA synthesis and exhibits a cytostatic effect on T- and B-lymphocytes | 15–23 hours | Immune recovery after transplant is impaired for at least 12 months | |
| Cyclophosphamide (about 3 mg/kg/day) | Nephrotic syndrome | Moderate | Impairs DNA replication and transcription, resulting in altered cellular function and T- and B-lymphocyte depletion | 3–12 hours | Exact duration of immune recovery is not well defined | |
| Cyclophosphamide (40–50 mg/kg/day) | Oncology indications | Severe | ||||
| Calcineurin inhibitors | Ciclosporin (0.25–5 mg/kg/day) | Psoriasis, RA | Mild | Inhibits the synthesis of interleukins (IL-2), which are essential for the self-activation of T-lymphocytes and their differentiation | 6–20 hours | Exact duration of immune recovery is not defined in patients receiving this medication for rheumatic indications. |
| Ciclosporin (about 5 mg/day or 6 mg/kg/day for children) | Nephrotic syndrome | Moderate | 6–20 hours | |||
| Ciclosporin (8–12 mg/kg/day for children) | Prevention of rejection after organ transplant | Severe | 6–20 hours | Immune recovery after transplant is impaired for at least 12 months | ||
| Tacrolimus | Prevention of rejection after organ transplant | Severe | Inhibits T-cell activation | 10–46 hours | Immune recovery after transplant is impaired for at least 12 months | |
| Mammalian target of rapamycin (mTOR) inhibitors | Sirolimus (1–2 mg/day) | Lymphangioleiomyomatosis | Moderate | Inhibits the regulatory kinase mTOR, which suppresses cytokine mediated T-cell proliferation | 13–62 hours | Exact duration of potential immunosuppression is not well defined |
| Sirolimus (2–5 mg/day) | Prevention of organ rejection after kidney transplant | Severe | Inhibits the regulatory kinase mTOR, which suppresses cytokine mediated T-cell proliferation | 13–62 hours | Immune recovery after transplant is impaired for at least 12 months | |
| Everolimus (about 10 mg/day) | Oncology indications (eg breast cancer, renal cell carcinoma, neuroendocrine tumours) | Moderate | Reduces protein synthesis and induces cell growth arrest and apoptosis | About 30 hours | Exact duration of immunosuppression is not well defined in oncological populations | |
| Everolimus | Prevention of rejection after organ transplant | Severe | Reduces protein synthesis and induces cell growth arrest and apoptosis | About 30 hours | Immune recovery after transplant is impaired for at least 12 months | |
| 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. | ||||||
References
- Anolik JH, Friedberg JW, Zheng B, et al. B-cell reconstitution after rituximab treatment of lymphoma recapitulates B-cell ontogeny. Clinical Immunology 2007 Feb;122(2):139-45.
- Borba HH, Wiens A, de Souza TT, Correr CJ, Pontarolo R. Efficacy and safety of biologic therapies for systemic lupus erythematosus treatment: systematic review and meta-analysis. BioDrugs 2014;28:211-28.
- Colucci M, Carsetti R, Cascioli S, et al. B-cell reconstitution after rituximab treatment in idiopathic nephrotic syndrome. Journal of the American Society of Nephrology 2016 Jun;27(6):1811-22.
- Cornillie F, Shealy D, D'Haens G, et al. Infliximab induces potent anti-inflammatory and local immunomodulatory activity but no systemic immune suppression in patients with Crohn's disease. Alimentary Pharmacology & Therapeutics 2001 Apr;15(4):463-73.
- Davis JS, Ferreira D, Paige E, Gedye C, Boyle M. Infectious complications of biological and small molecule targeted immunomodulatory therapies. Clinical Microbiology Reviews 2020;33:10.
- Dunleavy K, Hakim F, Kim HK, et al. B-cell recovery following rituximab-based therapy is associated with perturbations in stromal derived factor-1 and granulocyte homeostasis. Blood 2005 Aug 1;106(3):795-802.
- Drgona L, Gudiol C, Lanini S, Salzberger B, Ippolito G, Mikulska M. ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (agents targeting lymphoid or myeloid cells surface antigens [II]: CD22, CD30, CD33, CD38, CD40, SLAMF-7 and CCR4). Clinical Microbiology and Infection 2018;24:S83-S94.
- Hsieh YC, Kirschner K, Copland M. Improving outcomes in chronic myeloid leukemia through harnessing the immunological landscape. Leukemia 2021;35:1229–1242.
- Issa NC, Fishman JA, Snydman DR. Infectious complications of antilymphocyte therapies in solid organ transplantation. Clinical Infectious Diseases 2009;48:772-86.
- Khraishi M, Russell A, Olszynski WP. Safety profile of abatacept in rheumatoid arthritis: a review. Clinical Therapeutics 2010;32:1855-70.
- Martinez-Cabriales SA, Kirchhof MG, Constantinescu CM, et al. Recommendations for vaccination in children with atopic dermatitis treated with dupilumab: a consensus meeting, 2020. American Journal of Clinical Dermatology 2021; 22:443-55.
- McConachie SM, Wilhelm SM, Bhargava A, Kale-Pradhan PB. Biologic-induced infections in inflammatory bowel disease: the TNF-alpha antagonists. Annals of Pharmacotherapy 2018;52:571-9.
- Palma M, Mulder TA, Österborg A. BTK inhibitors in chronic lymphocytic leukemia: biological activity and immune effects. Frontiers in Immunology 2021; Jul 1(12):686768.
- Rodziewicz M, Dyball S, Lunt M, et al. Early infection risk in patients with systemic lupus erythematosus treated with rituximab or belimumab from the British Isles Lupus Assessment Group Biologics Register (BILAG-BR): a prospective longitudinal study. The Lancet Rheumatology 2023;5(5):e284-92.
- Sarantopoulos S, Stevenson KE, Kim HT, et al. Recovery of B-cell homeostasis after rituximab in chronic graft-versus-host disease. Blood 2011;117(7):2275–83.
- Sepriano A, Kerschbaumer A, Smolen JS, et al. Safety of synthetic and biological DMARDs: a systematic literature review informing the 2019 update of the EULAR recommendations for the management of rheumatoid arthritis. Annals of the Rheumatic Diseases 2020;79:760-70.
- Tanaka Y, McInnes IB, Taylor PC, et al. Characterization and changes of lymphocyte subsets in baricitinib-treated patients with rheumatoid arthritis: an integrated analysis. Arthritis & Rheumatology 2018 Dec;70(12):1923-32.
- Thueringer JT, Doll NK, Gertner E. Anakinra for the treatment of acute severe gout in critically ill patients. Seminars in Arthritis and Rheumatism 2015;45:81-5.
- Uettwiller F, Rigal E, Hoarau C. Infections associated with monoclonal antibody and fusion protein therapy in humans. MAbs 2011;3:461-6.
- van Arkel C, Boeree M, Netea MG, van Crevel R, van Laarhoven A. Interleukin-1 receptor antagonist anakinra as treatment for paradoxical responses in HIV-negative tuberculosis patients: a case series. 2022 Sep 9;3(9):603-11.
- van Dartel SA, Fransen J, Kievit W, et al. Difference in the risk of serious infections in patients with rheumatoid arthritis treated with adalimumab, infliximab and etanercept: results from the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry. Annals of the Rheumatic Diseases 2013;72:895-900.
- van Vollenhoven R, Lee EB, Strengholt S, et al. Evaluation of the short-, mid-, and long-term effects of tofacitinib on lymphocytes in patients with rheumatoid arthritis. Arthritis & Rheumatology 2019 May;71(5):685-95.
- Vigna-Pérez M, Abud-Mendoza C, Portillo-Salazar H, et al. Immune effects of therapy with adalimumab in patients with rheumatoid arthritis. Clinical and Experimental Immunology 2005 Aug;141(2):372-80.
- Worch J, Makarova O, Burkhardt B. Immunreconstitution and infectious complications after rituximab treatment in children and adolescents: what do we know and what can we learn from adults? Cancers 2015;7:305-28.
Page history
Last updated
Last reviewed