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Chapter 47
Biologic Response–Modifying and
Antirheumatic Drugs
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
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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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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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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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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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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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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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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12
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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13
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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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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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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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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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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Hematopoietic Drugs (cont’d)

Erythropoietic drugs



Colony-stimulating factors (CSFs)




epoetin alfa (Epogen, Procrit)
darbepoetin alfa (Aranesp)
filgrastim (Neupogen)
pegfilgrastim (Neulasta)
sargramostin (Leukine)
Platelet-promoting drugs

oprelvekin (Neumega)
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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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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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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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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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Hematopoietic Drugs:
Indications

Used in patients who have experienced
destruction of bone marrow cells as a result of
cytotoxic chemotherapy
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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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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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Classroom Response Question
A patient’s chemotherapy has ended at 1800 on a
Tuesday afternoon. When is it appropriate to start
therapy with filgrastim?
A. 1800 on Tuesday
B. 0600 on Wednesday
C. 1800 on Wednesday
D. 1 week later, 1800 the next Tuesday
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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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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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Interferons: Indications

Viral infections


Cancer


Genital warts, hepatitis
Chronic myelogenous leukemia, follicular lymphoma,
hairy-cell leukemia, Kaposi’s sarcoma, malignant
melanoma
Autoimmune disorders

Multiple sclerosis
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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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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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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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Classroom Response Question
Which statement regarding use of monoclonal antibodies in
the treatment of cancer does the nurse identify as being
true? Monoclonal antibodies
A. are not as effective as other chemotherapy drugs.
B. have few adverse effects.
C. may cause flulike effects but do not cause the typical
adverse effects associated with chemotherapy.
D. are only used in cases of last resort when other
chemotherapy drugs have failed.
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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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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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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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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 diseasemodifying 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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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
adalimumab
abatacept
rituximab
tocilizumab
Others
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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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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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Nursing Implications (cont’d)


Follow specific guidelines for preparation and
administration of drugs
Monitor the patient’s response during therapy
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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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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?
A. methotrexate
B. adalimumab
C. infliximab
D. etanercept
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Case Study (cont’d)
Prior to administering methotrexate, it is most
important for the nurse to assess the patient for
A. allergy to eggs.
B. congestive heart failure.
C. latent tuberculosis.
D. hypothyroidism.
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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?
A. You can expect to develop mouth sores that will
improve with time when taking this medication.
B. Administer the methotrexate injection daily in the early
morning.
C. Mix the methotrexate with sterile saline prior to
administration.
D. Administer the methotrexate subcutaneously into the
thigh, abdomen, or upper arm, rotating injection sites.
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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?
A. adalimumab (Humira)
B. trastuzumab (Herceptin)
C. rituximab (Rituxan)
D. cetuximab (Erbitux)
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