Biological response modifiers (BRMs) are substances that modify immune responses. They can be endogenous (produced naturally within the body) or exogenous (as pharmaceutical drugs), and they can either enhance an immune response or suppress it. Some of these substances arouse the body's response to an infection, and others can keep the response from becoming excessive. Thus they serve as immunomodulators in immunotherapy (therapy that makes use of immune responses), which can be helpful in treating cancer (where targeted therapy often relies on the immune system being used to attack cancer cells) and in treating autoimmune diseases (in which the immune system attacks the self), such as some kinds of arthritis and dermatitis. Most BRMs are biopharmaceuticals (biologics), including monoclonal antibodies, interleukin 2, interferons, and various types of colony-stimulating factors (e.g., CSF, GM-CSF, G-CSF).[1] "Immunotherapy makes use of BRMs to enhance the activity of the immune system to increase the body's natural defense mechanisms against cancer",[2] whereas BRMs for rheumatoid arthritis aim to reduce inflammation.
Some conditions which biologics are used to treat are rheumatic disorders[3] such as psoriatic arthritis,[4] ankylosing spondylitis and non-radiographic axial spondyloarthritis,[5] and inflammatory bowel disease.[6]
Medical uses
editBiologics provide immunotherapy[4] and can function as disease-modifying antirheumatic drugs.[3]
Biologics can generally be grouped by their "class", that is, their specific mechanism of action and affected targets. Some classes are TNF inhibitors, anti-IL-17A antibodies, and IL-23 antibodies.[7]
For people with moderate to severe psoriatic arthritis, biologics can provide some relief of the symptoms,[4] and even slow down or halt the progression of the disease. Classes of biologics typically used for psoriatic arthritis include TNF inhibitors, anti-IL17-A antibodies, IL-23 antibodies, and those that act on both IL-12 and IL-23.[7]
Biologics can treat inflammatory bowel disease. Classes of biologics typically used for inflammatory bowel disease include TNF inhibitors, and anti-CD28 antibodies.[6]
Contraindications
editBiologics are generally used after considering other less invasive treatments.[4] Before using biologics to treat psoriasis, treatment with topical moisturizers or steroids, or light therapy may provide relief. Other drugs which may provide relief include acitretin, ciclosporin, and methotrexate, but since these drugs have their own major side effects, doctors and patients should discuss whether to try one of these or a biologic first.[4]
Most biologics are injections so are not appropriate for use by someone with intense fear of needles.[4] A person with any infection should not use biologics.[4]
Other contraindications for biologics include cancer, certain neurologic disorders, being pregnant or breastfeeding, history of heart failure, or history of tuberculosis.[4]
Adverse effects
editCommon adverse effects of biologic administration are injection site reactions including redness, pain, and itching.[8] Other adverse effects include headache, skin reactions, respiratory tract infection, and urinary tract infection.[4][9] Adverse effects may be class-dependent, and so switching to a biologic of another class may ameliorate those effects.[7]
Potential serious adverse effects include allergic reactions, liver damage, cancer, and serious infections including tuberculosis, pneumonia, staph infection, and fungal infection.[4][9]
Patients with systemic lupus erythematosus (SLE) who are treated with the standard of care, including biologic response modifiers, experience a higher risk of mortality and opportunistic infection compared to the general population.[10]
Examples
editBiopharmaceuticals
editBiologics for immunosuppression include adalimumab, certolizumab, etanercept, golimumab, infliximab, ixekizumab, belimumab, and ustekinumab.[4]
| Drug | Mechanism of action | Indications | Toxicity |
|---|---|---|---|
| Abciximab | A monoclonal antibody that binds to the glycoprotein receptor IIb/IIIa on activated platelets, preventing aggregation | Acute coronary syndromes, percutaneous transluminal coronary angioplasty | Bleeding, thrombocytopenia |
| Anakinra (Kineret) | A recombinant version of the Interleukin 1 receptor antagonist. | Rheumatoid arthritis | Allergic response, neutropenia |
| Etanercept (Enbrel) | Recombinant form of human TNF receptor that binds TNF | Rheumatoid arthritis, psoriasis, ankylosing spondylitis | Serious infections; sepsis; reactivation of latent tuberculosis and hepatitis B infections[11][12] |
| Infliximab (Remicade) | A monoclonal antibody to TNF, proinflammatory cytokine | Crohn's disease, rheumatoid arthritis, ankylosing spondylitis | Respiratory infection, fever, hypotension. Predisposes to infections (reactivation of latent TB) |
| Rituximab (Rituxan) | A monoclonal antibody to CD20 surface immunoglobulin | Lymphoma and a variety of autoimmune diseases, although it may be ineffective in treating IgA-mediated diseases.[13] | Cardiac arrest, cytokine release syndrome, tumor lysis syndrome and acute kidney injury, infections,[14] hepatitis B reactivation, immune toxicity, pulmonary toxicity,[15] bowel obstruction and perforation[16][17][18] |
| Trastuzumab (Herceptin) | A monoclonal antibody against HER2/neu (erb-B2). Helps kill breast cancer cells that overexpress HER-2, possibly through antibody-dependent cytotoxicity | Metastatic breast cancer | Cardiotoxicity including congestive heart failure[19] |
Natural BRMs
editExtracts from some medicinal mushrooms are natural biological response modifiers.[20]
Manufacturing
editGenetically engineered cell cultures in pharmaceutical labs produce the biologics.[21]
History
editBiologics are the second generation of biopharmaceutical products.[21] The first generation were the biopharmaceutical products which could be extracted from organisms without biotechnology from the Information Age,[21] such as blood for transfusion, early insulin extracted from animals, and vaccines from eggs.[21]
When biologic drugs became available they led to significant changes in the management of various autoimmune diseases.[22]
Society and culture
editTerm
editThe term "biologic therapy" is nonspecific,[23] and can refer to any biopharmaceutical medication.[24] However, many sources use the term to refer to immunotherapy treatments.[4][3][9]
The explanation for this is that while "biologic" or "biopharmaceutical" refers to the chemical composition of medications which might be used to treat a range of medical conditions, when the term "biologic" became popular, many biologic medications available provided immunosuppression.[25]
Legal status
editBiosimilar is a term used to describe a biopharmaceutical product which seems so close in composition and effect to another that they are functionally identical, analogous to generic drugs. In this context, some publications describe "biologics" as "biosimilars".[26]
Economics
editBiologic drugs are expensive.[4] In the United States treatment with biologic drugs typically costs US$2,000–6,000 per month,[4] compared to US$12–600 per month for conventional (small-molecule) DMARDs.[27]
References
edit- ^ "Definition of Biological response modifiers". medterms.com. MedicineNet.com. Archived from the original on 2012-08-04.
- ^ "Biological Response Modifiers (BRM)".
- ^ a b c Singh, JA; Christensen, R; Wells, GA; Suarez-Almazor, ME; Buchbinder, R; Lopez-Olivo, MA; Tanjong Ghogomu, E; Tugwell, P (7 October 2009). Singh, Jasvinder A. (ed.). "Biologics for rheumatoid arthritis: an overview of Cochrane reviews". The Cochrane Database of Systematic Reviews (4): CD007848. doi:10.1002/14651858.CD007848.pub2. PMC 10636593. PMID 19821440.
- ^ a b c d e f g h i j k l m n "Biologic Medications for Psoriasis". Consumer Reports. August 2014. Retrieved 17 July 2017.
- ^ Ward, MM; Deodhar, A; Gensler, LS; Dubreuil, M; Yu, D; Khan, MA; Haroon, N; Borenstein, D; Wang, R; Biehl, A; Fang, MA; Louie, G; Majithia, V; Ng, B; Bigham, R; Pianin, M; Shah, AA; Sullivan, N; Turgunbaev, M; Oristaglio, J; Turner, A; Maksymowych, WP; Caplan, L (October 2019). "2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis". Arthritis Care & Research. 71 (10): 1285–1299. doi:10.1002/acr.24025. PMC 6764857. PMID 31436026.
- ^ a b D'Haens, G. (1 May 2007). "Risks and benefits of biologic therapy for inflammatory bowel diseases". Gut. 56 (5): 725–732. doi:10.1136/gut.2006.103564. PMC 1942157. PMID 17440187.
- ^ a b c Tsai, YC; Tsai, TF (May 2020). "Switching biologics in psoriasis - practical guidance and evidence to support". Expert Review of Clinical Pharmacology. 13 (5): 493–503. doi:10.1080/17512433.2020.1767590. PMID 32394765. S2CID 218599646.
- ^ Kim, PJ; Lansang, RP; Vender, R (July 2023). "A Systematic Review and Meta-Analysis of Injection Site Reactions in Randomized-Controlled Trials of Biologic Injections". Journal of Cutaneous Medicine and Surgery. 27 (4): 358–367. doi:10.1177/12034754231188444. PMC 10486173. PMID 37533141.
- ^ a b c Singh, JA; Wells, GA; Christensen, R; Tanjong Ghogomu, E; Maxwell, L; Macdonald, JK; Filippini, G; Skoetz, N; Francis, D; Lopes, LC; Guyatt, GH; Schmitt, J; La Mantia, L; Weberschock, T; Roos, JF; Siebert, H; Hershan, S; Lunn, MP; Tugwell, P; Buchbinder, R (16 February 2011). "Adverse effects of biologics: a network meta-analysis and Cochrane overview". The Cochrane Database of Systematic Reviews. 2016 (2): CD008794. doi:10.1002/14651858.CD008794.pub2. PMC 7173749. PMID 21328309.
- ^ Shamliyan, Tatyana A.; Dospinescu, Paula (July 2017). "Additional Improvements in Clinical Response From Adjuvant Biologic Response Modifiers in Adults With Moderate to Severe Systemic Lupus Erythematosus Despite Immunosuppressive Agents: A Systematic Review and Meta-analysis". Clinical Therapeutics. 39 (7): 1479–1506.e45. doi:10.1016/j.clinthera.2017.05.359. ISSN 1879-114X. PMID 28673504.
- ^ "Enbrel- etanercept solution Enbrel- etanercept kit". DailyMed. Retrieved 17 April 2021.
- ^ Safety Update on TNF- α Antagonists: Infliximab and Etanercept (PDF). U.S. Food and Drug Administration (FDA). pp. 13–14. Archived from the original (PDF) on 24 September 2015. Retrieved 20 December 2013.
- ^ He Y, Shimoda M, Ono Y, Villalobos IB, Mitra A, Konia T, Grando SA, Zone JJ, Maverakis E (2015). "Persistence of Autoreactive IgA-Secreting B Cells Despite Multiple Immunosuppressive Medications Including Rituximab". JAMA Dermatol. 151 (6): 646–50. doi:10.1001/jamadermatol.2015.59. PMID 25901938.
- ^ Kyriakidis I, Mantadakis E, Stiakaki E, Groll AH, Tragiannidis A (October 2022). "Infectious Complications of Targeted Therapies in Children with Leukemias and Lymphomas". Cancers. 14 (20): 5022. doi:10.3390/cancers14205022. PMC 9599435. PMID 36291806.
- ^ Burton C, Kaczmarski R, Jan-Mohamed R (June 2003). "Interstitial pneumonitis related to rituximab therapy". The New England Journal of Medicine. 348 (26): 2690–1, discussion 2690–1. doi:10.1056/NEJM200306263482619. PMID 12826649.
- ^ "Reports of Bowel Obstruction and Perforation with RITUXAN (rituximab)" (PDF). Roche Canada. 10 November 2006. Archived from the original (PDF) on 27 March 2014.
- ^ "Rituxan- rituximab injection, solution". DailyMed. 6 November 2019. Retrieved 2 February 2020.
- ^ "Rituximab". The American Society of Health-System Pharmacists. Archived from the original on 27 March 2016. Retrieved 8 December 2016.
- ^ Seidman A, Hudis C, Pierri MK, Shak S, Paton V, Ashby M, Murphy M, Stewart SJ, Keefe D (March 2002). "Cardiac dysfunction in the trastuzumab clinical trials experience". Journal of Clinical Oncology. 20 (5): 1215–1221. doi:10.1200/JCO.20.5.1215. PMID 11870163.
- ^ Tzianabos AO (2000). "Polysaccharide immunomodulators as therapeutic agents: structural aspects and biologic function". Clin Microbiol Rev. 13 (4): 523–33. doi:10.1128/CMR.13.4.523-533.2000. PMC 88946. PMID 11023954.
- ^ a b c d Zimney, Ed (2 December 2008). "Understanding biologics: How they differ from drugs and why they cost more - Dr. Z's Medical Report". Everyday Health. Archived from the original on 13 August 2017. Retrieved 17 July 2017.
- ^ Drosos, AA; Pelechas, E; Kaltsonoudis, E; Markatseli, TE; Voulgari, PV (June 2021). "Biologic Therapies and Autoimmune Phenomena". Mediterranean Journal of Rheumatology. 32 (2): 96–103. doi:10.31138/mjr.32.2.96. PMC 8369271. PMID 34447904.
- ^ "What biological therapies are". www.cancerresearchuk.org. Cancer Research UK. 25 Nov 2014.
- ^ Center for Biologics Evaluation and Research (5 August 2015). "What Are "Biologics" Questions and Answers". www.fda.gov. Retrieved 17 July 2017.
- ^ "Biopharmaceutical". ScienceDaily. Retrieved 2018-12-07.
- ^ Food and Drug Administration (27 August 2015). "Information for Consumers (Biosimilars)". www.fda.gov.
- ^ Table 4, Cost Comparison Table for the Treatment of Plaque Psoriasis. Canadian Agency for Drugs and Technologies in Health. June 2019. Retrieved 16 October 2023.
- Deepak A. Rao; Le, Tao; Bhushan, Vikas. First Aid for the USMLE Step 1 2008 (First Aid for the Usmle Step 1). McGraw-Hill Medical. ISBN 0-07-149868-0.