Biological Therapy

 

What is biological therapy?

Biological therapy is a drug treatment that targets the immune system. The drug can either suppress the immune system for patients with diseases that result from an over-active immune response or activate the immune system in patients with low immune protection.  Biologics are medications that can be derived from the genetic material of live cells (DNA), proteins, or sugars to treat chronic autoimmune diseases.

These medications are created using advanced technology, based on Recombinant DNA technology (1). The word “biologics” refers to many types of medications and includes commonly prescribed drugs like insulin. Biologic infusions are traditionally given in a hospital or healthcare facility, but new technologies can allow them to be given at home.

 

 

What are the different types of biologics?

 

Enzyme Modulator: These modulators mainly target proteases, which are enzymes that split proteins.

Receptor modulator: These modulators target inflammatory mediators such as cytokines and growth factors.

Monoclonal Antibodies: These are laboratory produced antibodies specifically designed to bind to the surface proteins that coat a tumor or abnormal cells and kills or disables them. They are commonly used to treat different types of autoimmune conditions and cancer.

Immunoglobulins: These antibody proteins are components of blood. Purified IgG contains a broad range of antibodies that target various types of infectious organisms, administered to patients with immunoglobulin deficiencies or reduced immunity.

 

 

What are they used to treat?

Biologic infusions can be used for many illnesses, and are generally used to treat chronic autoimmune diseases and tumors, both benign and malignant (i.e. cancer).

Autoimmune Diseases:

 

Rheumatoid Arthritis

• Psoriasis
• Psoriatic Arthritis
• Ankylosing Spondylitis
• Juvenile Idiopathic Arthritis (pJIA)
• Crohn’s Disease
• Ulcerative Colitis
• Multiple Sclerosis
• Lupus Erythematosus
• Inflammatory eye diseases

 

Tumors:

• Lymphoma: Hodgkin’s and Non-Hodgkin’s Lymphoma
• Leukemia including B-cell Acute Leukemia and CLL (Chronic Lymphocytic Leukemia)

 

How is biological therapy delivered?

Biological therapy can be delivered intravenously or subcutaneously. The frequency of these types of infusions differs; intravenous infusions of biologics are generally given every month or every other month, depending on the medication, whereas subcutaneous infusions require more frequent administration.

 

Intravenous Infusion of Biologics

Intravenous infusions are typically administered in a hospital or infusion center since the intravenous route and certain high risk medications present risks such as overdose or air embolus during the infusion that are best managed by a professional. However, home infusions for non-critical medications are also becoming more common as medical devices (‘Smart pumps’) become more reliable and mitigate the risks of receiving the infusion at home.

 

Infusions at home typically involve nurse visits at regularly scheduled time intervals to access the intravenous port, collect blood work, administer the medication, and monitor vital signs. Smart pumps such as the Sapphire ™ infusion pump and Avoset ™ infusion pump can administer both intravenous and subcutaneous infusions.

 

Sapphire™ infusion pump’s Multi-step mode offers the possibility to give an infusion in small, incrementing doses to detect any hypersensitivity earlier, and help tolerate the infusion itself. Sapphire™ infusion pump’s drug library can guide the clinician during programming and thereby reduce medication administration errors. With Sapphire™ Connect, Sapphire pumps can transmit treatment data to the cloud-based infusion management system through universal ‘plug and play’ cellular technology. Additionally, Avoset’s cloud-based infusion management system transforms home-infusion that enhances the user experience and reduces medication errors through the web-based programming tool.

 

Subcutaneous Injection of Biologics

Subcutaneous treatments such as Subcutaneous Immunoglobulin are biologic drugs for treating primary immunodeficiency (PI), which can be infused by a healthcare provider or through self-administration at home. They typically require more frequent doses compared to intravenous infusion as they are effective for a shorter period of time but have less adverse reactions compared to IVIG (8). These are injections of medicine into the “subcutaneous” tissue just below the skin — most commonly in the lower abdomen, upper arm, or thigh. Patients are known to find SCIg more convenient and enable greater independence (9).

These injections are simple enough to be administered by the patient themselves at home, much like diabetic patients who administer their own insulin. Continuous advances in medical device technology are improving patient ease of use and compliance and decreasing the drug administration burden on healthcare professionals.

 

Common biologics that are infused?

There are many biologic medications currently available for subcutaneous or intravenous infusion. The following are commonly prescribed biologics, although new biologics are introduced frequently to target specific diseases.

• IVIG – (multiple brands including Gammagard S/D, Octagam, Privigen, Gamunex, Bivigam)  – Intravenous immune globulin is an IV drug made of antibodies that are prepared from donated blood. It is used primarily to treat immunosuppression caused by diseases like leukemia, or to treat auto-immune conditions such as Immune thrombocytopenia, Chronic inflammatory demyelinating polyneuropathy (CIDP), Kawasaki disease, lupus and other conditions. The infusion takes 1 to 4 hours. To treat immune deficiency, multiple small doses are given, whereas to treat auto immune conditions, a few large doses are given. Sub-cutaneous immune globulin can also be given.
• RITUXAN® (rituximab) is a CD20-directed cytolytic antibody for the treatment of Non-Hodgkin’s Lymphoma, B-cell acute leukemia, Chronic Lymphocytic Leukemia, Rheumatoid Arthritis (RA), Granulomatosis with Polyangiitis (GPA) (Wegener’s Granulomatosis) and Microscopic Polyangiitis (MPA) and moderate to severe Pemphigus Vulgaris (PV).

• ORENCIA® (abatacept) – for moderate to severe rheumatoid arthritis, Polyarticular Juvenile Idiopathic Arthritis (pJIA) and Adult Psoriatic Arthritis (PsA)

• ACTEMRA® (tocilizumab)- recombinant humanized anti-interleukin-6 receptor (IL-6R) monoclonal antibody which has a main use in the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis (sJIA) and polyarticular juvenile idiopathic arthritis (pJIA).

For inflammatory bowel diseases (IBD) there are four classes of biological agents that are commonly used in practice:

 

• REMICADE® (infliximab) - used for rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, plaque psoriasis, and ulcerative colitis. Patients who are antibody positive are more likely to have an infusion reaction. This drug is dosed based on exact weight. Infusions last approximately 2 hours.
• ENTYVIO® (vedolizumab) used to treat ulcerative colitis and Crohn’s disease. Infusions last about 30 minutes.
• STELARA® (ustekinumab) used to treat IBD such as ulcerative colitis and Crohn’s disease, and moderate to severe plaque psoriasis and psoriatic arthritis. The initial dose is an IV infusion which lasts over at least 1 hour.  Each dose after the IV infusion is given as a subcutaneous injection either by self-administration or by a healthcare professional.
• TYSABRI® (natalizumab) — a monotherapy for multiple sclerosis and is indicated for Crohn’s disease for patients who are unable to tolerate, conventional CD therapies and inhibitors of TNF-α. This infusion lasts for 1 hour.

Patients are monitored for an hour after the infusion to check for side effects and adverse reactions.

 

What are the side effects?

As with any prescription medication, biological therapy has a risk of side effects. They vary from person-to-person and may range from mild to severe, the latter usually associated with anaphylaxis. The package insert describes the most common and most serious side effects. They typically include:

• Headache
• Fatigue
• Fever
• Chills
• Nausea
• Vomiting
• Skin rash
• Loss of appetite
• Swelling/inflammation at the access site
• Muscle aches
• Low blood pressure
• Infections
• Anaphylaxis
• Diarrhea

 

This list is not exhaustive and other severe side effects exist, varying per drug.

Other Risks:

Some biologics are derived directly from ‘live’ human cells and tissue and there is an exceedingly low risk of disease transmission, such as viral infection. There is no current report of any patient contracting HIV from biologics as the methods used to purify the drug are effective in killing bacteria, viruses and other infectious organisms.

Tolerance of Infusions

Biologics can vary from patient to patient in terms of tolerance. Infusing a dose at a high rate from the start of the infusion can affect tolerance.  Therefore, infusions are often given in small, incrementing doses (multi-step) to detect any hypersensitivity earlier but also to help tolerate the infusion itself.

As with any therapy, your health care provider will always assess the benefits of your treatment against the risks of side effects or serious adverse events.

Did you know?

97% of infliximab infused with Sapphire Infusion pumps are programmed with the multi-step profile

How do biologic infusions at home compare to infusions in treatment centers?

Most biologic infusions are given in hospitals and infusion centers under direct clinical supervision. However, infusions of intravenous biologic agents pose a significant logistical burden to patients in the form of days missed from work and transportation (3). To minimize the burden, home infusions (HIs) of biological agents are a solution to reduce the impact on daily life. Home infusions became more common during the COVID pandemic to reduce the risk of viral exposure. A study of IBD’s, (Chron’s Disease or Ulcerative Colitis) found that most transitions to the home environment were successful, with the main barrier being insurance companies (6). There is some evidence, albeit in small cohorts, that demonstrates that Home Infusions (HIs) of biological agents used to treat IBD are safe and cost-effective and can result in high patient satisfaction (4,5).

In a retrospective cohort study of 11,892 patients receiving infusions in a hospital/infusion center setting, it was found that the most common reasons for interest in HIs were that it may save time and be less disruptive to a normal schedule (39%), ease and comfort of being at home (36%), and transportation issues (11%). Younger patients were particularly interested in receiving infusions at home.  In the same study, 1,573 patients already receiving infusions at home, 59% reported that it saved time and was less disruptive to their schedule. Of these patients, 89% had previously received infusions in a treatment center or hospital (2).

Despite the benefits of home infusion, a more recent study of 69 patients indicates that HIs have an increase in adverse outcomes and therapy disruption compared to hospital infusions when treating IBD (7). Larger prospective studies are needed for clear practice guidelines.

 

Biological products represent the cutting-edge of biomedical research and, in time, may offer the most effective means to treat a variety of medical illnesses and conditions that presently have no other treatments available. As biological drug solutions advance, ensure you use cutting edge drug delivery solutions. Eitan Medical products can deliver biologic therapies effectively; the Sapphire Infusion Pump and Avoset Infusion pump are both indicated for infusion of biological therapies and can provide preset programs that enable efficient use in infusion centers, hospitals and at home. Remote monitoring using the Eitan Insights™ platform together with Sapphire Connect™ can help provide visibility to near-real time infusion data. Remote access to infusion pump event log data through the Eitan Insights™ platform has the potential to reduce drug wastage, which is especially significant for costly biologic therapies.

 

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The information, including but not limited to, text, graphics, images and other material contained in this blog, are for informational purposes only. No material on this blog is intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of something you have read on this blog

 

References

 

1. Kinch, Michael S. (2015). An overview of FDA-approved biologics medicines. Drug Discovery Today, 20(4), 393–398. doi:10.1016/j.drudis.2014.09.003
2. Kochar et al (2021) Home Infusions for Inflammatory Bowel Disease Are Safe: US Experience and Patient PerspectivesCrohn's & Colitis 360, 2021, 3, 1–6 https://doi.org/10.1093/crocol/otab063 Advance access publication 1 September 2021
3. Buisson A, Seigne  AL, D′huart  MC, et  al. The extra burden of infliximab infusions in inflammatory bowel disease. Inflamm Bowel Dis. 2013;19(11):2464–2467
4. Condino AA, Fidanza S, Hoffenberg EJ. A home infliximab infusion progr J Pediatr Gastroenterol Nutr. 2005;40(1):67–69
5. Kuin S, Stolte SB, van den Brink GR, et al. Short Article: Remicade infusions at home: an alternative setting of infliximab therapy for patients with Crohn’s disease. Eur J Gastroenterol Hepatol. 2016;28(2):222–225
6. Farhoud, Adel MD1; Pasam, Ravi Teja MBBS, MPH1; Gadupudi, Salini1; Pellish, Randall MD1; Chaudrey, Khadija MD1. S0791 Transition to Home Biologic Infusions in Inflammatory Bowel Disease (IBD) Patients During the COVID-19 Pandemic. The American Journal of Gastroenterology: October 2020 - Volume 115 - Issue - p S405 doi: 10.14309/01.ajg.0000705212.90161.9d
7. Fenster, Marc; Ungaro, Ryan C.; Hirten, Robert; Gallinger, Zane; Cohen, Louis; Atreja, Ashish; Mehandru, Saurabh; Colombel, Jean-Frederic; Cohen, Benjamin L. (2019). Home vs Hospital Infusion of Biologic Agents for Patients With Inflammatory Bowel Diseases. Clinical Gastroenterology and Hepatology, S1542356519302940–. doi:10.1016/j.cgh.2019.03.030
8. Gaspar, J., Gerritsen, B., Jones, A. (1998). Immunoglobulin replacement treatment by rapid subcutaneous infusion.. Archives of Disease in Childhood, , 79(1), 48-51.
9. Overton, P. M., Shalet, N., Somers, F., & Allen, J. A. (2021). Patient preferences for subcutaneous versus intravenous administration of treatment for chronic immune system disorders: a systematic review. Patient preference and adherence, 811-834