Section II: Biologics

What Are Biologics?

A biologic drug is created from and in a living system using sugars, proteins, nucleic acids or cells from human, plant or animal sources. Biologics are generally complex large or small molecules that can be genetically engineered using recombinant DNA. The process is, in fact, the product in that each biologic drug is produced to target and quell specific immune responses in the body. Technically, anything made with living material is a biologic, such as blood and blood products, vaccines, diagnostic medications, and insulin (FDA, 2015). In fact, Humulin was the first FDA approved biologic therapy developed using recombinant DNA in 1982 (Humulin.com). This cutting edge target-specific technology allows biologics to be used to treat many diseases or conditions. Some biologics can treat several diseases while others are created specifically for one type of cancer or medical condition. For example, Adalimumab (Humira) is used to treat rheumatoid arthritis, Crohn’s disease, ankylosing spondylitis, etc., while Ranibizumab (Lucentis) was developed and approved to specifically treat the wet form of macular degeneration (FDA, 2015). By the time you read this article, the FDA will no doubt approve these drugs for the treatment of other conditions.


Biologic Facts

The first MAB was approved by the FDA in 1986. OKT3 was used as an induction therapy for transplant recipients. Many side effects occurred since it was made from rabbit serum. Trivia: OKT3 was nicknamed "Shake and Bake" due to the high incidence of side effects (Mosby, 2010). Despite their success, biologics did not gain much attention until the late 1990’s with the approval of Enbrel® for rheumatoid arthritis (Enbrel.com, 2016). The technology and commercial success of Enbrel® ignited an increase in demand for such drugs and fueled pharmaceutical companies to develop disease-specific drugs and immunotherapies. There are approximately 47 MAB drugs approved by the FDA as of 2014 and at least 4-5 new drugs are approved each year. There are hundreds in development and sales are expected to be more than $125 billion by 2020 (Ecker et al, 2015). TV commercials featuring these new drugs are prompting patients to request these therapies, thus increasing their popularity and use.

With so many of these drugs now being prescribed, it is sometimes difficult to tell what is a biologic versus a non-biologic medication. Here is a clue: It’s all in a name. Identifying immunosuppressant medications, including the biologics, often have tell-tale generic roots that defines what type of drug it is. For instance, you know that drugs beginning or ending with "-vir" are antiviral drugs. Most are noted in the generic name, but the older drugs may not have them or have them in their brand name. Some examples are listed in the table below. Obviously, no one expects you to be an expert and there are several exceptions to the rule, but being aware of the common stems can give you a quick heads up to a potentially immunosuppressed patient.

Stem Meaning Example

-imus

Immunosuppressant - Suppresses entire immune response to foreign invaders.

tacrolimus
sirolimus

-cept

Receptor molecules that reduce the strength of the body’s immune system.

belatacept
CellCept (brand name)

-mab

Monoclonal antibodies target and attach to specific cells such as antigens created by rejection or autoimmune disease activity in the leukocytes.

rituximab
adalimumab

From the NLM Drug Information Portal (10/2016)



Monoclonal Antibodies (MABs)

Monoclonal antibodies are man-made antibodies that are a clone of a unique parent cell (Mayo Clinic, 2016). MABs are used as a type of immunotherapy that singularly binds with certain cells that then stimulate the body to attack the targeted antigen. These MABs make up the majority of biologics being used to treat diseases like rheumatoid arthritis, irritable bowel syndrome and transplant rejection. One type of MAB, the anti-TNF-alpha, reduces inflammation in patients with auto-immune disorders such as RA. MABs and anti-TNF-alpha therapies have truly changed the management of many auto-immune diseases, transplant rejections, and other inflammatory conditions. However, they also carry the highest potential risk to patients including cancer, tuberculosis, and hepatitis (FDA, 2014).

The MABs have been developed to target dozens of specific diseases and conditions. The following list is just some of the disorders now treated or managed with FDA approved biologics. The list of drugs for these and other conditions that are approved and those in development is exhaustive and ever-increasing. The entire list can be found on the FDA website (FDA.gov).



Biologics for Cancer

Biologics can be created to induce the immune system to recognize and attack cancer cells. Gene therapy and immunotherapy have been used for years to treat cancer. Most nurses are already aware that immunosuppression is inherent in this population and usually placed in protective isolation. Therefore they will not be discussed in detail here. Some examples of biologic cancer therapies include:


Biologic MAB Therapy

Specific Risks

Biologics are generally well tolerated and safe to use. However, because these drugs, especially the anti-TNF-alpha monoclonal antibody therapies, inhibit the immune response, there is an increased risk for infections and certain cancers related to immunosuppression (Bongartz, et al., 2006). Upper respiratory infections are the most common side effect and many are easily treated. Tuberculosis is the most serious infectious complication arising from the use of biologic therapy (Meisel and Rizvi, 2011). For this reason, patients are screened for TB prior to starting a biologic and monitored while using the drugs. Bacterial, fungal and viral infections have also been reported. Aspergillosis for example, can be fatal in the immunocompromised patient (Bongartz, et. al., 2006).

Although uncommon, lymphoma is the most reported malignancy in those who are receiving anti-TNF-alpha monoclonal antibody therapy, not to mention other immunosuppressant therapies. This is not new information. As noted by a meta-analysis done by Bongartz et al. in 2006, several studies compared the anti-TNF-alpha drugs to placebo therapy. The total occurrence of malignancies in the anti-TNF-alpha patients were 29/3192 compared with 3/1428 placebo patients. Patients are usually instructed by the MD office or clinic to check for swollen lymph nodes and report them immediately. Because of these serious adverse reactions, some of the drugs have a FDA black box warning regarding tuberculosis, lymphoma, and other adverse effects. Below is a list of popular biologics with known black box warnings. Obviously, nurses should consult with the pharmacist to get the most current list of drugs, side effects, and black box warnings.

Black Box Warnings

Drug

Brand

Warning

Mycophenylate mofetil or mycophenolic acid

Cellcept
Myfortic

Teratogenic

Belatacept

Nulojix

Lymphoma

Infliximab

Remicade

Worsening CHF, histoplasmosis, listeriosis, pneumocystosis

Adalimumab

Humira

TB

Etanercept

Enbrel

TB, nervous system disorders, severe sepsis

Trastuzumab

Herceptin

Cardiomyopathy, pulmonary toxicity, infusion reactions

Palivizumab

Synagis

Anaphylaxis, liver, GI toxicity

From the US Food and Drug Administration (FDA)

Other serious, but less common risks noted in the Bongartz meta-analysis include CHF, cardiovascular events, progressive multifocal encephalopathy, and demyelinating diseases. As you can see from the table, most of these drugs have been around awhile. Unfortunately, it can take years to discover and report these adverse effects and longer still to announce black box warnings. The other downside to these drugs is potential drug tolerance over time, making the drug ineffective. This sounds scary, but these events are not common. Nurses can be forewarned and forearmed by becoming familiar with these biologics, especially the MAB/anti-TNF-alpha class drugs.



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