Biological response modifier

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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.

Contents

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

Biologics 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

Biologics 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

Common 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

Biopharmaceuticals

Biologics 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 angioplastyBleeding, 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 cytotoxicityMetastatic breast cancer Cardiotoxicity including congestive heart failure [19]

Natural BRMs

Extracts from some medicinal mushrooms are natural biological response modifiers. [20]

Manufacturing

Genetically engineered cell cultures in pharmaceutical labs produce the biologics. [21]

History

Biologics 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

Term

The 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]

Biosimilar 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

Biologic 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]

Related Research Articles

<span class="mw-page-title-main">Psoriasis</span> Skin disease

Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by patches of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small localized patches to complete body coverage. Injury to the skin can trigger psoriatic skin changes at that spot, which is known as the Koebner phenomenon.

Rheumatology is a branch of medicine devoted to the diagnosis and management of disorders whose common feature is inflammation in the bones, muscles, joints, and internal organs. Rheumatology covers more than 100 different complex diseases, collectively known as rheumatic diseases, which includes many forms of arthritis as well as lupus and Sjögren's syndrome. Doctors who have undergone formal training in rheumatology are called rheumatologists.

Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies, while immunotherapies that reduce or suppress are classified as suppression immunotherapies. Immunotherapy is under preliminary research for its potential to treat various forms of cancer.

<span class="mw-page-title-main">Immunosuppressive drug</span> Drug that inhibits activity of immune system

Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent the activity of the immune system.

<span class="mw-page-title-main">Infliximab</span> Biopharmaceutical drug for autommune disorders

Infliximab, a chimeric monoclonal antibody, sold under the brand name Remicade among others, is a medication used to treat a number of autoimmune diseases. This includes Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, and Behçet's disease. It is given by slow injection into a vein, typically at six- to eight-week intervals.

<span class="mw-page-title-main">Ankylosing spondylitis</span> Type of arthritis of the spine

Ankylosing spondylitis (AS) is a type of arthritis characterized by long-term inflammation of the joints of the spine, typically where the spine joins the pelvis. With AS, eye and bowel problems, and back pain may occur. Joint mobility in the affected areas sometimes worsens over time. Ankylosing spondylitis is believed to involve a combination of genetic and environmental factors. More than 8% of people affected in the UK have a specific human leukocyte antigen known as the HLA-B27 antigen. The underlying mechanism is believed to be autoimmune or autoinflammatory. Diagnosis is based on symptoms with support from medical imaging and blood tests. AS is a type of seronegative spondyloarthropathy, meaning that tests show no presence of rheumatoid factor (RF) antibodies.

<span class="mw-page-title-main">Psoriatic arthritis</span> Long-term inflammatory arthritis

Psoriatic arthritis (PsA) is a long-term inflammatory arthritis that occurs in people affected by the autoimmune disease psoriasis. The classic feature of psoriatic arthritis is swelling of entire fingers and toes with a sausage-like appearance. This often happens in association with changes to the nails such as small depressions in the nail (pitting), thickening of the nails, and detachment of the nail from the nailbed. Skin changes consistent with psoriasis frequently occur before the onset of psoriatic arthritis but psoriatic arthritis can precede the rash in 15% of affected individuals. It is classified as a type of seronegative spondyloarthropathy.

Etanercept, sold under the brand name Enbrel among others, is a biologic medical product that is used to treat autoimmune diseases by interfering with tumor necrosis factor (TNF), a soluble inflammatory cytokine, by acting as a TNF inhibitor. It has US Food and Drug Administration (FDA) approval to treat rheumatoid arthritis, juvenile idiopathic arthritis and psoriatic arthritis, plaque psoriasis and ankylosing spondylitis. Tumor necrosis factor alpha (TNFα) is the "master regulator" of the inflammatory (immune) response in many organ systems. Autoimmune diseases are caused by an overactive immune response. Etanercept has the potential to treat these diseases by inhibiting TNF-alpha.

<span class="mw-page-title-main">Rituximab</span> Biopharmaceutical drug

Rituximab, sold under the brand name Rituxan among others, is a monoclonal antibody medication used to treat certain autoimmune diseases and types of cancer. It is used for non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis, idiopathic thrombocytopenic purpura, pemphigus vulgaris, myasthenia gravis and Epstein–Barr virus-positive mucocutaneous ulcers. It is given by slow intravenous infusion. Biosimilars of Rituxan include Blitzima, Riabni, Ritemvia, Rituenza, Rixathon, Ruxience, and Truxima.

<span class="mw-page-title-main">Cancer immunotherapy</span> Artificial stimulation of the immune system to treat cancer

Cancer immunotherapy (immuno-oncotherapy) is the stimulation of the immune system to treat cancer, improving the immune system's natural ability to fight the disease. It is an application of the fundamental research of cancer immunology and a growing subspecialty of oncology.

Adalimumab, sold under the brand name Humira and others, is a disease-modifying antirheumatic drug and monoclonal antibody used to treat rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, plaque psoriasis, hidradenitis suppurativa, and uveitis. It is administered by subcutaneous injection. It works by inactivating tumor necrosis factor-alpha (TNFα).

A biopharmaceutical, also known as a biological medical product, or biologic, is any pharmaceutical drug product manufactured in, extracted from, or semisynthesized from biological sources. Different from totally synthesized pharmaceuticals, they include vaccines, whole blood, blood components, allergenics, somatic cells, gene therapies, tissues, recombinant therapeutic protein, and living medicines used in cell therapy. Biologics can be composed of sugars, proteins, nucleic acids, or complex combinations of these substances, or may be living cells or tissues. They are isolated from living sources—human, animal, plant, fungal, or microbial. They can be used in both human and animal medicine.

A TNF inhibitor is a pharmaceutical drug that suppresses the physiologic response to tumor necrosis factor (TNF), which is part of the inflammatory response. TNF is involved in autoimmune and immune-mediated disorders such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, psoriasis, hidradenitis suppurativa and refractory asthma, so TNF inhibitors may be used in their treatment. The important side effects of TNF inhibitors include lymphomas, infections, congestive heart failure, demyelinating disease, a lupus-like syndrome, induction of auto-antibodies, injection site reactions, and systemic side effects.

<span class="mw-page-title-main">Certolizumab pegol</span> Pharmaceutical drug

Certolizumab pegol, sold under the brand name Cimzia, is a biopharmaceutical medication for the treatment of Crohn's disease, rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. It is a fragment of a monoclonal antibody specific to tumor necrosis factor alpha (TNF-α) and is manufactured by UCB.

<span class="mw-page-title-main">Biological therapy for inflammatory bowel disease</span>

Biological therapy, the use of medications called biopharmaceuticals or biologics that are tailored to specifically target an immune or genetic mediator of disease, plays a major role in the treatment of inflammatory bowel disease. Even for diseases of unknown cause, molecules that are involved in the disease process have been identified, and can be targeted for biological therapy. Many of these molecules, which are mainly cytokines, are directly involved in the immune system. Biological therapy has found a niche in the management of cancer, autoimmune diseases, and diseases of unknown cause that result in symptoms due to immune related mechanisms.

Ustekinumab, sold under the brand name Stelara among others, is a monoclonal antibody medication developed by Janssen Pharmaceuticals, for the treatment of Crohn's disease, ulcerative colitis, plaque psoriasis and psoriatic arthritis, targeting both IL-12 and IL-23.

<span class="mw-page-title-main">Enteropathic arthropathy</span> Medical condition

Enteropathic arthropathy commonly referred to as enteropathic arthritis, is a type of arthritis linked to Crohn's disease, ulcerative colitis, and chronic inflammatory bowel diseases.

<span class="mw-page-title-main">Secukinumab</span> Monoclonal antibody against IL-17

Secukinumab, sold under the brand name Cosentyx among others, is a human IgG1κ monoclonal antibody used for the treatment of psoriasis, ankylosing spondylitis, and psoriatic arthritis. It binds to the protein interleukin (IL)-17A and is marketed by Novartis.

<span class="mw-page-title-main">Antiarthritics</span> Drug class

An antiarthritic is any drug used to relieve or prevent arthritic symptoms, such as joint pain or joint stiffness. Depending on the antiarthritic drug class, it is used for managing pain, reducing inflammation or acting as an immunosuppressant. These drugs are typically given orally, topically or through administration by injection. The choice of antiarthritic medication is often determined by the nature of arthritis, the severity of symptoms as well as other factors, such as the tolerability of side effects.

Passive antibody therapy, also called serum therapy, is a subtype of passive immunotherapy that administers antibodies to target and kill pathogens or cancer cells. It is designed to draw support from foreign antibodies that are donated from a person, extracted from animals, or made in the laboratory to elicit an immune response instead of relying on the innate immune system to fight disease. It has a long history from the 18th century for treating infectious diseases and is now a common cancer treatment. The mechanism of actions include: antagonistic and agonistic reaction, complement-dependent cytotoxicity (CDC), and antibody-dependent cellular cytotoxicity (ADCC).

References

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  2. ↑ "Biological Response Modifiers (BRM)".
  3. 1 2 3 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.
  4. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 "Biologic Medications for Psoriasis". Consumer Reports . August 2014. Retrieved 17 July 2017.
  5. ↑ 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.
  6. 1 2 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.
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  10. ↑ 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.
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  27. ↑ 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.
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