Chapter 47 Biologic Response–Modifying and Antirheumatic Drugs Copyright © 2014 by Mosby, an imprint of Elsevier Inc

Chapter 47

Biologic Response–Modifying and Antirheumatic Drugs

Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

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

Biologic Response–Modifying Drugs

Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 2

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

Immunomodulating Drugs


Fourth part of cancer therapy, in addition to: Surgery Chemotherapy Radiation

Also used for other diseases Autoimmune Inflammatory Infectious

Biologic Response Modifiers (BRMs)


Hematopoietic drugs Interferons (IFNs) Monoclonal antibodies Interleukin receptor agonists and antagonists Disease-modifying antirheumatic drugs Miscellaneous drugs

BRMs: Subclasses


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

BRMs: Mechanisms of Action


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

The Immune System


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

The Immune System (cont’d)


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

Humoral Immune System


Antibodies also known as immunoglobulins (Ig) Monoclonal antibodies Five major types of naturally occurring

immunoglobulins IgA, IgD, IgE, IgG, IgM

Humoral Immune System (cont’d)



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

Cell-Mediated Immune System


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

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



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)




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

Therapeutic Effects of BRMs


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

Hematopoietic Drugs (HDs)


HDs are used to: Decrease the duration of chemotherapy-induced

anemia, neutropenia, and thrombocytopenia Enable higher doses of chemotherapy to be given Other uses

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)



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

Hematopoietic Drugs: Mechanism of Action


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



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



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



Used in patients who have experienced destruction of bone marrow cells as a result of cytotoxic chemotherapy

Hematopoietic Drugs:Indications


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

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

Hematopoietic Drugs:Indications (cont’d)


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


Usually mild Most common include:

Fever Muscle aches Bone pain Flushing

Hematopoietic Drugs:Adverse Effects


Proteins with three basic properties Antiviral Antitumor Immunomodulating

Used to treat certain viral infections and cancer Alpha, beta, and gamma interferons

Interferons (IFNs)


Manufactured from Escherichia coli bacteria with rDNA technology

Also obtained from pooled human leukocytes that have been stimulated by synthetic and natural antigens

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



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


Viral infections Genital warts, hepatitis

Cancer Chronic myelogenous leukemia, follicular lymphoma,

hairy-cell leukemia, Kaposi’s sarcoma, malignant melanoma

Autoimmune disorders Multiple sclerosis

Interferons: Indications


Flulike effects Fever, chills, headache, myalgia

Dose-limiting adverse effect is fatigue Other adverse effects

Anorexia Dizziness Nausea Vomiting Diarrhea

Interferons: Adverse Effects


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



Interferon beta products interferon beta-1a interferon beta-1b

Interferon gamma products interferon gamma-1b (Actimmune)



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

Monoclonal Antibodies (MABs)


Cancer treatment alemtuzumab (Campath) bevacizumab (Avastin) cetuximab (Erbitux) gemtuzumab ozogamicin (Mylotarg)

Other disease processes, including rheumatoid arthritis adalimumab (Humira) infliximab (Remicade) natalizumab (Tysabri)

Monoclonal Antibodies (MABs) (cont’d)


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.


Beneficial antitumor action Interleukin receptor agonists

aldesleukin (IL-2) oprelvekin (IL-11)* denileukin diftitox tocilizumab (IL-6) anakinra

*Also classified as an HD

Interleukins


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

Interleukins: Capillary Leak Syndrome


aldesleukin (Proleukin) Treatment of metastatic renal cell carcinoma and

metastatic melanoma Off-label uses include HIV infection and AIDS, and

non-Hodgkin’s lymphoma

Interleukins (cont’d)


anakinra (Kineret) IL-1 receptor antagonist Used to control symptoms of rheumatoid arthritis

Interleukins (cont’d)


Autoimmune disorder causing inflammation and tissue damage in joints

Diagnosis primarily symptomatic Treatment consists of NSAIDs and disease-

modifying antirheumatic drugs

Rheumatoid Arthritis


Another type of arthritis Age-related degeneration of joint tissues Pain and reduced function

Osteoarthritis


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)

Disease-Modifying Antirheumatic Drugs (DMARDs)


methotrexate leflunomide (Arava) hydroxychloroquine sulfasalazine

Nonbiologic DMARDs


adalimumab anakinra etanercept infliximab adalimumab abatacept rituximab tocilizumab Others

Biologic DMARDs


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

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

Disease-Modifying Antirheumatic Drugs (DMARDs) (cont’d)


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

Nursing Implications


Follow specific guidelines for preparation and administration of drugs

Monitor the patient’s response during therapy

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



Monitor for therapeutic responses Decrease in growth of lesion or mass Improved blood counts Absence of infection, anemia, and hemorrhage

Monitor for adverse effects



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


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.

57Copyright © 2014 by Mosby, an imprint of Elsevier Inc.


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.



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)


Documents

Chapter 47 Biologic Response–Modifying and Antirheumatic Drugs Copyright © 2014 by Mosby, an imprint of Elsevier Inc