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June 2024,Volume 46, No.2
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Internet
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What’s in the web for family physicians − a review on biologic treatmentSio-pan Chan 陳少斌，Wilbert WB Wong 王維斌，Alfred KY Tang 鄧權恩
Biologics have been utilised as targeted therapy in numerous malignancies for quite some time. With rapid advancement of biologic development, they have now become a cornerstone in the treatment of many autoimmune diseases. Biologic treatment may have a profound impact on the outcome of many chronic disorders, notable examples being Rheumatoid Arthritis, Psoriasis and Psoriatic arthritis, Inflammatory Bowel Disease (IBD), Systemic Lupus Erythematosus (SLE) and Multiple Sclerosis (MS), just to name a few. As primary care physicians, most of us are not familiar with biologics, let alone using them, maybe with the exception of Denosumab (Prolia), which is a monoclonal antibody targeted for treatment of osteoporosis. This article aims to conduct a review of biologic therapies, which have revolutionised the treatment of numerous common diseases. Unl ike convent ional medicines which a re mostly simple chemicals, biologics are made from living organisms or their components, such as proteins, antibodies, or nucleic acids. These complex molecules are produced using biotechnology techniques in living cells, such as bacteria, yeast, or mammalian cells. Their diverse modes of action include: 1. Monoclonal antibodies (mAbs) Monoclonal antibodies are laboratory-produced molecules engineered to serve as substitute antibodies that can restore, enhance, or mimic the immune system's attack on cancer cells. They are designed to bind to specific targets found on cancer cells or other cells that are associated with diseases. By binding to these targets, mAbs can directly block the growth of cancer cells, mark cancer cells so that they will be better seen and destroyed by the immune system, or deliver toxic substances directly to cancer cells. 2. Vaccines Vaccines work by stimulating the body's immune system to recognise and fight pathogens, such as bacteria or viruses. They do this by introducing a harmless piece or aspect of the pathogen (such as a protein or a dead or weakened form of the pathogen) into the body, which does not cause the disease but does provoke an immune response. This response includes the production of memory cells that will remember how to fight the pathogen in the future, providing immunity against the disease, e.g. mRNA vaccine for COVID-19. 3. Growth factors These are types of biologics that s t imulate cell growth, proliferation, healing, and cellular differentiation. For example, erythropoietin is a growth factor that stimulates the production of red blood cells, and it is used to treat anaemia, particularly in patients with chronic kidney disease. 4. Enzyme replacement therapies For patients with certain genetic disorders that result in the deficiency or malfunction of specific enzymes, enzyme replacement therapies can be used to provide the missing enzymes. For example, in the treatment of Gaucher's disease, patients receive regular infusions of a recombinant enzyme that they lack due to a genetic mutation. 5. Gene therapies Gene therapies involve altering the genetic material within a patient's cells to treat or prevent disease. This can be done by replacing a disease-causing gene with a healthy copy, inactivating a diseasecausing gene that is not functioning properly, or introducing a new or modified gene into the body to help treat a disease. 6. Cell therapy Cell therapy is a cutting-edge medical treatment that involves using living cells to help repair, regenerate, or replace damaged tissues in the body. One of the most promising forms of cell therapy is CAR-T cell therapy, which stands for chimeric antigen receptor T-cell therapy. This innovative approach involves genetically modifying a patient's own T-cells to recognise and attack cancer cells. By enhancing the immune system's ability to target and destroy cancer cells, CAR-T cell therapy has shown remarkable success in treating certain types of blood cancers, such as leukemia and lymphoma. This personalised form of treatment holds great potential for revolutionising cancer therapy and improving patient outcomes. However, biologics are not silver bullets for all, important drawbacks for biologics include altered immune responses of the recipients, important consequences include infection risks, allergic reaction, autoimmune disorders with increased risk of cardiovascular events such as strokes and heart attacks, blood disorder such as anaemia and cytopenia and some may develop neurological conditions such as MS or Guillain-Barre syndrome. In addition, biologic therapies seldom cure diseases, they are primarily used to alleviate symptoms for the duration of their administration. Over time, patients may develop a tolerance, necessitating the use of newer and more costly biologics. The cumulative cost of lifelong biologic treatment can be exorbitant for both individuals and governments alike. Furthermore, the complexity of biologic medications, the prevalence of off-label uses, the potential serious side effects, and the very high cost of treatments all contribute to potential mine-fields for medical litigation. This article explores some of the more prevalent biologic therapies currently available based on web resources, focusing on treatments for common conditions likely to be encountered in daily clinical practice. Hopefully it will provide some guidance on discussing such treatment options with patients. Rheumatoid arthritis (RA)
Rheumatoid arthritis Conventional treatment for rheumatoid arthritis often involves the use of NSAIDs and DMARDs such as methotrexate. While these medications can help manage symptoms and slow disease progression, they may not be effective for all patients and can have significant side effects. Biologics, on the other hand, target specific molecules involved in the inflammatory process, such as tumour necrosis factor (TNF) or interleukin-6 (IL-6), and have been shown to be more effective in controlling symptoms and preventing joint damage in some patients. Psoriasis
Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics
Conventional treatments for psoriasis include
topical corticosteroids, phototherapy, and systemic
medications such as methotrexate or cyclosporine. While
these treatments can help reduce inflammation and skin
lesions, they may not be effective for all patients and
can have long-term side effects. Biologics targeting
specific cytokines, such as TNF or interleukin-17 (IL-
17), have shown to be highly effective in treating
moderate to severe psoriasis, with a lower risk of
systemic side effects compared to conventional systemic
medications (Blauvelt et al., 2017).
Atopic eczema (Atopic dermatitis)
National Eczema Association – Biologics
Conventional treatments for eczema often involve
the use of emollients, topical corticosteroids, and
antihistamines to manage symptoms. While these
treatments can provide relief for some patients, they
may not address the underlying immune dysregulation.
Biologics targeting specific immune pathways, such
as interleukin-4 (IL-4) or interleukin-13 (IL-13), have
shown promising results in the treatment of moderate
to severe eczema, particularly in patients who do not
respond to conventional therapies (Simpson et al.,
2016).
Inflammatory bowel disease (IBD)
ACG Clinical Guideline: Management of Crohn'sse in Adults
Conventional treatments for inflammatory bowel
diseases (IBD) such as Crohn's disease and ulcerative
colitis include amino salicylates, corticosteroids, and
immunomodulators. While these medications can
help induce and maintain remission, they may not be
effective for all patients and can have significant side
effects. Biologics targeting specific cytokines, such as
TNF or integrins, have revolutionised the treatment of
IBD, offering better control of symptoms and improved
quality of life for many patients, particularly those with
moderate to severe disease (Feagan et al., 2017).
Asthma
Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention, 2020.
Conventional treatments for asthma include
inhaled corticosteroids, long-acting beta-agonists,
and leukotriene modifiers to control inflammation
and bronchoconstriction. While these medications are
effective for many patients, some individuals may have
refractory or severe asthma that is not well-controlled
with conventional therapies. Biologics targeting specific
immune pathways, such as interleukin-5 (IL-5) or
immunoglobulin E (IgE), have shown to be effective
in reducing exacerbations and improving lung function
in patients with severe asthma, particularly those with
eosinophilic or allergic phenotypes (Pavord et al.,
2012).
Cancer treatments
Biologic therapies have transformed cancer
treatment by targeting specific molecules involved in
the growth and spread of cancer cells. Monoclonal
antibodies, such as trastuzumab (Herceptin) for HER2-
positive breast cancer and rituximab (Rituxan) for
certain lymphomas, and immune checkpoint inhibitors,
such as pembrolizumab (Keytruda) and nivolumab
(Opdivo) for various cancers, are examples. Cancer
therapeutic is outside the scope of this article and will
not be discussed here.
Sio-pan Chan, MBBS (HK), DFM (HKCU), FHKFP, FHKAM (Family Medicine)
Correspondence to: Dr Sio-pan Chan, SureCare Medical Centre (CWB), Room 1116-7,
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