Approximately 34 monoclonal antibody drugs have been approved by the Food and Drug Administration. Many have been released within the past 5 to 7 years, so primary care clinicians may not be very familiar with them. This article outlines the key things NPs and PAs in primary care should know about this innovative class of medications.
Monoclonal antibodies work at the cellular level by binding to receptor sites. Many diseases derive from the inflammatory response. At the molecular level of the inflammatory response, interchanges occur among interleukins, tumor necrosis factor, interferons, white blood cells, neutrophils (T cells), lymphocytes (B cells) and eosinophils. It is in this cell intercommunication via the cytokines that monoclonal antibodies have their effect. Monoclonal antibodies block the release of cytokines by binding to various cellular receptor sites, shutting down the inflammatory pathway and halting disease progression.
The figure accompanying this article illustrates these events in a simplified fashion.1 Initially, an injury or infection occurs. If it is localized, neutrophils accumulate at the site. Clotting factors then become involved, allowing fibrin to be deposited. This process activates the natural killer T cells and the macrophages. The natural killer cells and macrophages (also T cells) release cytokines, which increase swelling. The cytokines then activate the B cell lymphocytes. The accumulation of the B cells then release antibody, which is cytotoxic to the invading microorganism. Once this step occurs, healing then follows.
If the injury or infection is systemic, the patient develops fever. White blood cells and stress hormones (hydrocortisone) are released. This calls in the acute-phase proteins. This complement system (a system of serum and cell surface proteins involved in functions related to inflammation and immunity) activates the release of cytokines through the classical pathway.
Cytokine release then increases swelling of the site or sites, which calls forth B cell lymphocytes. B cell accumulation releases antibody that is cytotoxic to the invading microorganism. After these events, healing can again occur.
Because each monoclonal antibody has a specific target site of cell surface attachment, multiple monoclonal antibodies will eventually be used in clinical practice. Due to their effects at the molecular level, they are considered immune modulators. One of the drawbacks to monoclonals is their cost. Many of these drugs cost hundreds or even thousands of dollars per infusion or injection.
Monoclonal antibodies are being used to treat a variety of diseases. These include Crohn disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosis, psoriasis, asthma, multiple sclerosis, certain cancers, gout, neovascular age-related macular degeneration and osteoporosis. They are sometimes prescribed for transplant recipients.
Monoclonals in Primary Care
In primary care settings, monoclonals are not first-line therapy. In general, patients who are treated with biologic agents have moderate to severe disease and have not responded to or have broken through their previous therapies. These therapies may consists of nonsteroidal anti-inflammatories, prednisone, fluticasone/salmeterol, first-line cancer chemotherapy agents, interferons or disease-modifying anti-rheumatic drugs.2,3
Typical monoclonal choices include anti-TNF agents, anti-cytokine receptor agents and anti IL-1 drugs.2,3 These agents have a long lasting effect on the immune system; some are still in the system after 6 months. They bind or kill B cells, de-activate T cells and bind cytokine receptor sites so as to inactivate cytokine activation of the immune system.2 Subsequently, these patients should be considered immunosuppressed. Many of these patients have neutropenia.4
When immunocompromised patients present in primary care settings, providers should first consider the condition of the immune system. An upper or lower respiratory illness should be treated with an antibiotic. In the case of influenza, an antiviral is necessary.
Patients who take monoclonal drugs must be followed by the prescribing specialist, who is familiar with the side effects and the likelihood of response. Patients should have been advised by the specialist about side effects and indications for office visits or emergency care. Typically, patients are also told to stop monoclonal antibody treatment if an upper respiratory infection develops. If a primary care provider diagnoses infection or receives a report of nausea and/or vomiting in a patient taking a monoclonal, he or she should advise the patient to stop the medication until the acute problem has resolved. The patient should contact the specialist to determine when to re-start the medication.
Monoclonal antibodies are typically delivered as weekly injections, biweekly injections or as an IV infusion every 6 to 8 weeks.
Some of the more commonly used monoclonals are listed in the table. The suffixes used in the compound names of monoclonal antibodies provide information about the drug's action:2
- "-cept" refers to fusion of a receptor to the Fc part of the human IgG molecule
- "-mab" indicates a monoclonal antibody, typically a mouse antibody
- "-ximab" indicates a chimeric monoclonal antibody (typically a combination of human and mouse)
- "-zumab" indicates a humanized monoclonal antibody.
Primary care providers should be aware of the most common side effects of these drugs. Of primary concern is the 30% chance that patients taking monoclonals will develop upper respiratory infections.4 Effects on the GI tract are fairly common, resulting in nausea, vomiting, abdominal pain and/or diarrhea.5 Keep these symptoms in mind when a patient who complains of GI symptoms does not have a fever or flu symptoms as well.
1. Douglas T. Lecture notes distributed in immunology class at the University of Texas School of Public Health, 2009.
2. Stone JH. Overview of biologic agents in the rheumatic diseases. UpToDate. http://www.uptodate.com/contents/overview-of-biologic-agents-in-the-rheumatic-diseases
3. Feldman SR. Treatment of psoriasis. UpToDate. http://www.uptodate.com/contents/treatment-of-psoriasis
4. Stone JH. Tumor necrosis factor-alpha inhibitors: Risk of bacterial, viral and fungal infections. UpToDate. http://www.uptodate.com/contents/tumor-necrosis-factor-alpha-inhibitors-risk-of-bacterial-viral-and-fungal-infections
Sharon Bahrych is a physician assistant who lives in Denver. She writes about her experiences in patient care at http://paviewonmedicine.blogspot.com.