1. Biologic Response–Modifying and Antirheumatic Drugs
Chapter 47
Biologic Response–Modifying and Antirheumatic Drugs
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2. Biologic Response–Modifying Drugs
Alter the body’s response to diseases such as cancer and autoimmune, inflammatory, and infectious diseases
Hematopoietic drugs
Immunomodulating drugs
Interferons
Monoclonal antibodies
interleukin receptor agonists and antagonists
Miscellaneous drugs
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3. Immunomodulating Drugs
Medications that therapeutically alter a patient’s immune response to malignant tumor cells
Drugs that modify the body’s own immune response so that it can destroy various viruses and cancerous cells
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4. Biologic Response Modifiers (BRMs)
Fourth part of cancer therapy, in addition to:
Surgery
Chemotherapy
Radiation
Also used for other diseases
Autoimmune
Inflammatory
Infectious
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BRMs: Subclasses
Hematopoietic drugs
Interferons (IFNs)
Monoclonal antibodies
Interleukin receptor agonists and antagonists
Disease-modifying antirheumatic drugs
Miscellaneous drugs
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6. BRMs: Mechanisms of Action
Enhancement or restoration of the host’s immune system defenses against the tumor
Direct toxic effect on the tumor cells, which causes them to lyse, or rupture
Adverse modification of the tumor’s biology, which makes it harder for the tumor cells to survive and reproduce
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The Immune System
Two components of the immune system work together to recognize and destroy foreign particles and cells in the blood or other body tissues
Humoral immunity
Mediated by B-cell functions (antibodies)
Cell-mediated immunity (CMI)
Mediated by T-cell functions
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8. The Immune System (cont’d)
Tumor antigens (chemical or tumor “markers”) label tumor cells as abnormal cells
Antibodies attack tumor cells
B-lymphocytes (B cells) from the humoral immune system
T-lymphocytes (T cells) from the cell-mediated immune system
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Humoral Immune System
B-lymphocytes (B cells)
Originate from bone marrow
When a foreign substance (antigen) is present, these turn into plasma cells, which in turn produce antibodies
Antibody-antigen complex
Memory cells
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10. Humoral Immune System (cont’d)
Antibodies also known as immunoglobulins (Ig)
Monoclonal antibodies
Five major types of naturally occurring immunoglobulins
IgA, IgD, IgE, IgG, IgM
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12. Cell-Mediated Immune System
T-lymphocytes (T cells)
Originate from bone marrow but mature in the thymus gland
Three types with different functions
Cytotoxic T cells
T-helper cells
T-suppressor cells
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13. Cell-Mediated Immune System (cont’d)
Cytotoxic T cells directly kill their targets by causing cell lysis or rupture
T-helper cells direct the actions of many other components of the immune system
T-suppressor cells serve to limit or control the immune response
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14. Cell-Mediated Immune System (cont’d)
A healthy immune system has about twice as many T-helper cells as T-suppressor cells at any one time
Overactive T-suppressor cells may be responsible for clinically significant cancer cases by permitting tumor growth beyond immune system control
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15. Cell-Mediated Immune System (cont’d)
Other cells of the cell-mediated immune system help to destroy cancer cells
Macrophages (derived from monocytes)
Natural killer (NK) cells
Polymorphonuclear (PMN) leukocytes (neutrophils)
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17. Therapeutic Effects of BRMs
Regulation or enhancement of the immune response
Cytotoxic or cytostatic activity against cancer cells
Inhibition of metastases, prevention of cell division, or inhibition of cell maturation
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18. Hematopoietic Drugs (HDs)
HDs promote the synthesis of various types of major blood components by promoting the growth, or differentiation, and function of their precursor cells in the bone marrow
Produced by rDNA technology
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19. Hematopoietic Drugs (cont’d)
HDs are used to:
Decrease the duration of chemotherapy-induced anemia, neutropenia, and thrombocytopenia
Enable higher doses of chemotherapy to be given
Other uses
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20. Hematopoietic Drugs (cont’d)
Erythropoietic drugs
epoetin alfa (Epogen, Procrit)
darbepoetin alfa (Aranesp)
Colony-stimulating factors (CSFs)
filgrastim (Neupogen)
pegfilgrastim (Neulasta)
sargramostin (Leukine)
Platelet-promoting drugs
oprelvekin (Neumega)
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21. Hematopoietic Drugs: Mechanism of Action
Decrease the duration of chemotherapy-induced anemia, neutropenia, and thrombocytopenia
Allow for higher dosages of chemotherapy
Decrease bone marrow recovery time after bone marrow transplantation or irradiation
Stimulate other cells in the immune system to destroy or inhibit the growth of cancer cells, as well as virus- or fungus-infected cells
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22. Hematopoietic Drugs (cont’d)
filgrastim (Neupogen)
Granulocyte colony-stimulating factor (G-CSF)
Stimulates precursor cells for the type of WBCs known as granulocytes
Administered before patient develops infection
pegfilgrastim (Neulasta)
Longer-acting form of filgrastim
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23. Hematopoietic Drugs (cont’d)
sargramostim (Leukine)
Granulocyte-macrophage colony-stimulating factor (GM-CSF)
Stimulates bone marrow precursor cells that make both granulocytes and phagocytic (cell-eating) cells; known as monocytes
Indicated for promoting bone marrow recovery after autologous (own marrow) or allogenic (donor marrow) bone marrow transplantation in patients with leukemia and lymphoma
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24. Hematopoietic Drugs (cont’d)
oprelvekin (Neumega)
Both a hematopoietic drug and one of the interleukins (IL-11)
Enhances synthesis of platelets
Indicated for the prevention of chemotherapy-induced severe thrombocytopenia and avoidance of the need for platelet transfusions
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25. Hematopoietic Drugs: Indications
Used in patients who have experienced destruction of bone marrow cells as a result of cytotoxic chemotherapy
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26. Hematopoietic Drugs: Indications (cont’d)
Decrease the duration of low neutrophil counts, thus reducing the incidence and duration of infections
Enhance the functioning of mature cells of the immune system, resulting in greater ability to kill cancer cells as well as viral- and fungal-infected cells
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27. Hematopoietic Drugs: Indications (cont’d)
Also enhance RBC and platelet counts in patients with bone marrow suppression resulting from chemotherapy
Allow for higher doses of chemotherapy, resulting in the destruction of a greater number of cancer cells
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28. Classroom Response Question
A patient’s chemotherapy has ended at 1800 on a Tuesday afternoon. When is it appropriate to start therapy with filgrastim?
1800 on Tuesday
0600 on Wednesday
1800 on Wednesday
1 week later, 1800 the next Tuesday
Correct answer: C
Rationale: Filgrastim and sargramostim have significant drug interactions when given with myelosuppressive antineoplastic drugs. Typically filgrastim and sargramostim are not given within 24 hours of administration of myelosuppressive antineoplastics.
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29. Hematopoietic Drugs: Adverse Effects
Usually mild
Most common include:
Fever
Muscle aches
Bone pain
Flushing
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Interferons (IFNs)
Proteins with three basic properties
Antiviral
Antitumor
Immunomodulating
Used to treat certain viral infections and cancer
Alpha, beta, and gamma interferons
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Interferons (cont’d)
Manufactured from Escherichia coli bacteria with rDNA technology
Also obtained from pooled human leukocytes that have been stimulated by synthetic and natural antigens
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Interferons (cont’d)
Recombinantly made IFNs are identical to the IFNs that are present within the human body and have the same properties
IFNs protect human cells from viruses and prevent cancer cells from dividing and replicating
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33. Interferons: Effects on Immune System
Restore the immune system’s function if it is impaired
Augment the immune system’s ability to function as the body’s defense
Inhibit the immune system from working
Helpful in autoimmune disorders
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34. Interferons: Indications
Viral infections
Genital warts, hepatitis
Cancer
Chronic myelogenous leukemia, follicular lymphoma, hairy-cell leukemia, Kaposi’s sarcoma, malignant melanoma
Autoimmune disorders
Multiple sclerosis
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35. Interferons: Adverse Effects
Flulike effects
Fever, chills, headache, myalgia
Dose-limiting adverse effect is fatigue
Other adverse effects
Anorexia
Dizziness
Nausea
Vomiting
Diarrhea
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Interferons (cont’d)
Interferon alfa products: “leukocyte interferons”—produced from human leukocytes
interferon alfa-2a
interferon alfa-2b
interferon alfa-n3
interferon alfacon-1
peginterferon alfa-2a
peginterferon alfa-2b
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Interferons (cont’d)
Interferon beta products
interferon beta-1a
interferon beta-1b
Interferon gamma products
interferon gamma-1b (Actimmune)
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38. Monoclonal Antibodies (MABs)
Treatment of cancer, rheumatoid arthritis, multiple sclerosis, and organ transplantation
Specifically target cancer cells and have minimal effect on healthy cells
Fewer adverse effects than traditional antineoplastic medications
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39. Monoclonal Antibodies (MABs) (cont’d)
Cancer treatment
alemtuzumab (Campath)
bevacizumab (Avastin)
cetuximab (Erbitux)
gemtuzumab ozogamicin (Mylotarg)
Other disease processes, including rheumatoid arthritis
adalimumab (Humira)
infliximab (Remicade)
natalizumab (Tysabri)
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40. Classroom Response Question
Which statement regarding use of monoclonal antibodies in the treatment of cancer does the nurse identify as being true? Monoclonal antibodies
are not as effective as other chemotherapy drugs.
have few adverse effects.
may cause flulike effects but do not cause the typical adverse effects associated with chemotherapy.
are only used in cases of last resort when other chemotherapy drugs have failed.
Correct answer: C
Rationale: Because these drugs only target cancer cells, they do not have the adverse effects that are typically associated with chemotherapy. However, they do cause acute symptoms that are similar to classic allergy or flulike symptoms. As a result, these symptoms are managed during therapy.
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Interleukins
Beneficial antitumor action
Interleukin receptor agonists
aldesleukin (IL-2)
oprelvekin (IL-11)*
denileukin diftitox
tocilizumab (IL-6)
anakinra
*Also classified as an HD
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42. Interleukins: Capillary Leak Syndrome
Severe toxicity of aldesleukin therapy
Capillaries lose ability to retain vital colloids in the blood; these substances are “leaked” into the surrounding tissues
Result: massive fluid retention
Respiratory distress
Heart failure MI
Dysrhythmias
Reversible after interleukin therapy is discontinued
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43. Interleukins (cont’d)
aldesleukin (Proleukin)
Treatment of metastatic renal cell carcinoma and metastatic melanoma
Off-label uses include HIV infection and AIDS, and non-Hodgkin’s lymphoma
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44. Interleukins (cont’d)
anakinra (Kineret)
IL-1 receptor antagonist
Used to control symptoms of rheumatoid arthritis
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Rheumatoid Arthritis
Autoimmune disorder causing inflammation and tissue damage in joints
Diagnosis primarily symptomatic
Treatment consists of NSAIDs and disease-modifying antirheumatic drugs
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Osteoarthritis
Another type of arthritis
Age-related degeneration of joint tissues
Pain and reduced function  
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47. Disease-Modifying Antirheumatic Drugs (DMARDs)
Modify the disease of rheumatoid arthritis
Exhibit antiinflammatory, antiarthritic, and immunomodulating effects
Inhibit the movement of various cells into an inflamed, damaged area, such as a joint
Slow onset of action of several weeks, versus minutes to hours for NSAIDs
Also referred to as slow-acting antirheumatic drugs (SAARDs)
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Nonbiologic DMARDs
methotrexate
leflunomide (Arava)
hydroxychloroquine
sulfasalazine
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Biologic DMARDs
adalimumab
anakinra
etanercept
infliximab
abatacept
rituximab
tocilizumab
Others
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50. Disease-Modifying Antirheumatic Drugs (DMARDs) (cont’d)
etanercept (Enbrel)
Used to treat rheumatoid arthritis (including juvenile RA) and psoriasis
Patients must be screened for latex allergy (some dosage forms may contain latex)
Onset of action: 1 to 2 weeks
Contraindicated in presence of active infections
Reactivation of hepatitis and TB have been reported
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51. Disease-Modifying Antirheumatic Drugs (DMARDs) (cont’d)
abatacept (Orencia)
Used to treat rheumatoid arthritis
Caution if history of recurrent infections or COPD
Patients must be up to date on immunizations before starting therapy
May increase risk of infections associated with live vaccines
May decrease response to vaccines
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Nursing Implications
Assess for allergies, specifically allergies to egg proteins, IgG, or neomycin
Assess for conditions that may be contraindications
Assess baseline blood counts; perform cardiac, renal, and liver studies
Assess for presence of infection
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53. Nursing Implications (cont’d)
Follow specific guidelines for preparation and administration of drugs
Monitor the patient’s response during therapy
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54. Nursing Implications (cont’d)
Teach patients to report signs of infection immediately
Sore throat
Diarrhea
Vomiting
Fever over 100.5° F (38.1° C) or higher
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55. Nursing Implications (cont’d)
Monitor for therapeutic responses
Decrease in growth of lesion or mass
Improved blood counts
Absence of infection, anemia, and hemorrhage
Monitor for adverse effects
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Case Study
A 40-year-old female patient is seen in the clinic. She has been newly diagnosed with rheumatoid arthritis. Which medication does the nurse anticipate being ordered for the patient?
methotrexate
adalimumab
infliximab
etanercept
Correct answer: A
Rationale: For the treatment of rheumatoid arthritis, the recommend therapy with nonbiologic DMARDs usually begins with methotrexate or leflunomide for most patients. Biologic DMARDs are generally reserved for those patients whose disease does not respond to methotrexate or leflunomide. The biologic DMARDs include etanercept, infliximab, adalimumab, abatacept, and rituximab.
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Case Study (cont’d)
Prior to administering methotrexate, it is most important for the nurse to assess the patient for
allergy to eggs.
congestive heart failure.
latent tuberculosis.
hypothyroidism.
Correct answer: C
Rationale: Prior to administering DMARDs, it is important for the nurse to assess the patient for contraindications to the use of DMARDs such as active bacterial infections, active herpes, active/latent tuberculosis, and acute or chronic hepatitis B or C.
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Case Study (cont’d)
The patient is scheduled for discharge. Which information does the nurse include when teaching the patient about methotrexate therapy?
You can expect to develop mouth sores that will improve with time when taking this medication.
Administer the methotrexate injection daily in the early morning.
Mix the methotrexate with sterile saline prior to administration.
Administer the methotrexate subcutaneously into the thigh, abdomen, or upper arm, rotating injection sites.
Correct answer: D
Rationale: Methotrexate should be administered subcutaneously into the thigh, abdomen, or upper arm, rotating injection sites. Methotrexate should not be administered with other solutions and without use of a filter. Methotrexate is taken weekly. The development of stomatitis should be reported to the prescriber immediately.
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Case Study (cont’d)
The patient improved within the first three months of treatment with methotrexate. Six months later, the patient experienced worsening of symptoms. The prescriber will most likely order which monoclonial antibody for the treatment of rheumatoid arthritis?
adalimumab (Humira)
trastuzumab (Herceptin)
rituximab (Rituxan)
cetuximab (Erbitux)
Correct answer: A
Rationale: Adalimumab (Humira) is indicated for the treatment of severe, progressive RA for which other RA therapies have failed. Trastuzumab (Herceptin) is indicated for the treatment of breast cancer. Rituximab (Rituxan) is used for the treatment of non-Hodgkin’s lymphoma, and cetuximab (Erbitux) is indicated for the treatment of metastatic colorectal cancer.
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