Chapter 47 Biologic ResponseModifying and Antirheumatic Drugs Copyright

Biologic Response–Modifying Drugs Alter the body’s response to diseases such as cancer and autoimmune, inflammatory, and infectious diseases Hematopoietic drugs Ø Immunomodulating drugs • Interferons (IFNs) • Monoclonal antibodies (MABs) • Interleukin (IL) receptor agonists and antagonists • Miscellaneous drugs Ø Copyright © 2017, Elsevier Inc. All rights reserved. 2

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 Copyright © 2017, Elsevier Inc. All rights reserved. 3

Immunomodulating Drugs (Cont. ) Fourth part of cancer therapy, in addition to: Surgery Ø Chemotherapy Ø Radiation Ø Also used for other diseases Autoimmune Ø Inflammatory Ø Infectious Ø Copyright © 2017, Elsevier Inc. All rights reserved. 4

Biologic Response–Modifying Drugs: Subclasses Hematopoietic drugs IFNs MABs IL receptor agonists and antagonists Disease-modifying antirheumatic drugs (DMARDs) Miscellaneous drugs Copyright © 2017, Elsevier Inc. All rights reserved. 5

Biologic Response–Modifying Drugs: 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 Copyright © 2017, Elsevier Inc. All rights reserved. 6

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 Ø Mediated by B-cell functions (antibodies) Cell-mediated immunity Ø Mediated by T-cell functions Copyright © 2017, Elsevier Inc. All rights reserved. 7

The Immune System (Cont. ) 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 Ø T-lymphocytes (T cells) from the cell-mediated immune system Ø Copyright © 2017, Elsevier Inc. All rights reserved. 8

Humoral Immune System B-lymphocytes (B cells) Originate from bone marrow Ø When a foreign substance (antigen) is present, these turn into plasma cells, which in turn produce antibodies. Ø Antibody–antigen complex Memory cells Copyright © 2017, Elsevier Inc. All rights reserved. 9

Humoral Immune System (Cont. ) Antibodies also known as immunoglobulins (Ig) MABs: antibodies that a single plasma cell makes that are all identical Five major types of naturally occurring immunoglobulins Ø A, D, E, G, and M Copyright © 2017, Elsevier Inc. All rights reserved. 10

Cells of the Humoral (Antibody. Mediated) Immune System Copyright © 2017, Elsevier Inc. All

Cell-Mediated Immune System T-lymphocytes (T cells) Ø Originate from bone marrow but mature in the thymus gland Three types with different functions Cytotoxic T cells Ø T-helper cells Ø T-suppressor cells Ø Copyright © 2017, Elsevier Inc. All rights reserved. 12

Cell-Mediated Immune System (Cont. ) 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. Copyright © 2017, Elsevier Inc. All rights reserved. 13

Cell-Mediated Immune System (Cont. ) 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. Copyright © 2017, Elsevier Inc. All rights reserved. 14

Cell-Mediated Immune System (Cont. ) Other cells of the cell-mediated immune system help to destroy cancer cells: Macrophages (derived from monocytes) Ø Natural killer (NK) cells Ø Polymorphonuclear leukocytes (neutrophils) Ø Copyright © 2017, Elsevier Inc. All rights reserved. 15

Cells of the Cellular Immune System Copyright © 2017, Elsevier Inc. All rights reserved.

Therapeutic Effects of Biologic Response–Modifying Drugs Enhancement of hematopoietic function Regulation or enhancement of the immune response, including cytotoxic or cytostatic activity against cancer cells Inhibition of metastases, prevention of cell division, or inhibition of cell maturation Copyright © 2017, Elsevier Inc. All rights reserved. 17

Hematopoietic Drugs Hematopoietic drugs (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 recombinant DNA technology Copyright © 2017, Elsevier Inc. All rights reserved. 18

Hematopoietic Drugs (Cont. ) HDs are used to: Decrease the duration of chemotherapy-induced anemia, neutropenia, and thrombocytopenia Ø Enable higher doses of chemotherapy to be given Ø Other uses Ø Copyright © 2017, Elsevier Inc. All rights reserved. 19

Hematopoietic Drugs (Cont. ) Erythropoietic drugs epoetin alfa Ø darbepoetin alfa Ø Colony-stimulating factors (CSFs) filgrastim Ø pegfilgrastim Ø sargramostin Ø Platelet-promoting drugs oprelvekin Ø romipliostim Ø Copyright © 2017, Elsevier Inc. All rights reserved. 20

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 Copyright © 2017, Elsevier Inc. All rights reserved. 21

Hematopoietic Drugs (Cont. ) Filgrastim (Neupogen) Granulocyte colony-stimulating factor (G-CSF) Ø Stimulates precursor cells for the type of white blood cells known as granulocytes (including basophils, eosinophils, and neutrophils) Ø Administered before patient develops infection Ø Copyright © 2017, Elsevier Inc. All rights reserved. 22

Hematopoietic Drugs (Cont. ) Pegfilgrastim (Neulasta) Ø Longer acting form of filgrastim Copyright ©

Hematopoietic Drugs (Cont. ) Sargramostim (Leukine) Granulocyte-macrophage colony-stimulating factor (GM-CSF) Ø Stimulates bone marrow precursor cells that make both granulocytes and phagocytic (cell-eating) cells; known as monocytes Ø Indicated for promoting bone marrow recovery after autologous (own marrow) or allogenic (donor marrow) bone marrow transplantation in patients with leukemia and lymphoma Ø Copyright © 2017, Elsevier Inc. All rights reserved. 24

Hematopoietic Drugs (Cont. ) Oprelvekin (Neumega) Both a hematopoietic drug and one of the ILs (IL-11) Ø Enhances synthesis of platelets Ø Indicated for the prevention of chemotherapy-induced severe thrombocytopenia and avoidance of the need for platelet transfusions Ø Stimulates the bone marrow cells, specifically megakaryocytes that eventually give rise to platelets Ø Copyright © 2017, Elsevier Inc. All rights reserved. 25

Hematopoietic Drugs (Cont. ) Romiplostim Ø CSF used to stimulate platelet production Copyright ©

Hematopoietic Drugs: Indications Used in patients who have experienced destruction of bone marrow cells

Hematopoietic Drugs: Indications (Cont. ) 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 Copyright © 2017, Elsevier Inc. All rights reserved. 28

Hematopoietic Drugs: Indications (Cont. ) Also enhance red blood cell 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 Copyright © 2017, Elsevier Inc. All rights reserved. 29

Audience Response System 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 Copyright © 2017, Elsevier Inc. All rights reserved. 30

Hematopoietic Drugs: Adverse Effects Usually mild Most common include: Fever Ø Muscle aches Ø

Interferons Proteins with three basic properties Antiviral Ø Antitumor Ø Immunomodulating Ø Used to treat certain viral infections and cancer Alpha, beta, and gamma IFNs Copyright © 2017, Elsevier Inc. All rights reserved. 32

Interferons (Cont. ) Recombinantly manufactured substances that are identical to the IFN cytokines that are naturally present in the human body IFNs Protect human cells from virus attack Ø Prevent cancer cells from dividing and replicating Ø Increase the activity of other cells in the immune system, such as macrophages, neutrophils, and NK cells Ø Copyright © 2017, Elsevier Inc. All rights reserved. 33

Interferons (Cont. ) 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. Copyright © 2017, Elsevier Inc. All rights reserved. 34

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. Ø Helpful in autoimmune disorders Copyright © 2017, Elsevier Inc. All rights reserved. 35

Interferons: Indications Viral infections Ø Cancer Ø Genital warts, hepatitis Chronic myelogenous leukemia, follicular lymphoma, hairy-cell leukemia, Kaposi’s sarcoma, malignant melanoma Autoimmune disorders Ø Multiple sclerosis (MS) Copyright © 2017, Elsevier Inc. All rights reserved. 36

Interferons: Adverse Effects Flulike effects Ø Fever, chills, headache, myalgia Dose-limiting adverse effect is fatigue Other adverse effects Anorexia Ø Dizziness Ø Nausea Ø Vomiting Ø Diarrhea Ø Copyright © 2017, Elsevier Inc. All rights reserved. 37

Interferons (Cont. ) IFN alfa products: “leukocyte IFNs”—produced from human leukocytes IFN alfa-2 a (Roferon-A) Ø IFN alfa-2 b (Intron-A) Ø IFN alfa-n 3 (Alferon-N) Ø IFN alfacon-1 (Infergen) Ø peginterferon alfa-2 a (Pegasys) Ø peginterferon alfa-2 b (PEG-Intron) Ø Copyright © 2017, Elsevier Inc. All rights reserved. 38

Interferons (Cont. ) IFN beta products IFN beta-1 a (Avonex, Rebif) Ø IFN beta-1

Monoclonal Antibodies Treatment of cancer, rheumatoid arthritis (RA), MS, and organ transplantation Specifically target cancer cells and have minimal effect on healthy cells Fewer adverse effects than traditional antineoplastic medications Copyright © 2017, Elsevier Inc. All rights reserved. 40

Monoclonal Antibodies (Cont. ) adalimumab+++ alemtuzumab basiliximab belimumab bevacixumab cetuximab certolizumab+++ golimumab+++ ibritumomab tiuxetan infliximab+++ natalizumab panitumamab rituximab trastuzumab Copyright © 2017, Elsevier Inc. All rights reserved. 41

Audience Response System Question Which statement regarding use of MABs in the treatment of cancer does the nurse identify as being true? A. MABs are not as effective as other chemotherapy drugs. B. MABs have few adverse effects. C. MABs may cause flulike effects but do not cause the typical adverse effects associated with chemotherapy. D. MABs are only used in cases of last resort when other chemotherapy drugs have failed. Copyright © 2017, Elsevier Inc. All rights reserved. 42

Interleukins Natural part of the immune system: classified as lymphokines Beneficial antitumor action IL receptor agonists aldesleukin (IL-2) Ø oprelvekin (IL-11)* Ø denileukin diftitox Ø tocilizumab (IL-6) Ø anakinra Ø *Also classified as an HD. Copyright © 2017, Elsevier Inc. All rights reserved. 43

Interleukins (Cont. ) Antitumor action: IL-2 is produced by activated T cells in response to macrophage-“processed” antigens and secreted IL-1. IL-2 derivative aldesleukin: stimulates or restores immune response Aldesleukin: binds to receptor sites on T cells, which stimulates the T cells to multiply Lymphokine-activated killer cells: recognize and destroy only cancer cells and ignore normal cells Copyright © 2017, Elsevier Inc. All rights reserved. 44

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 ● Ø Ø ● Respiratory distress Heart failure Myocardial infarction Dysrhythmias Reversible after IL therapy is discontinued Copyright © 2017, Elsevier Inc. All rights reserved. 45

Interleukins (Cont. ) Aldesleukin (Proleukin) Treatment of metastatic renal cell carcinoma and metastatic melanoma Ø Off-label uses include HIV infection and AIDS and non -Hodgkin’s lymphoma Ø Copyright © 2017, Elsevier Inc. All rights reserved. 46

Interleukins (Cont. ) Anakinra (Kineret) IL-1 receptor antagonist Ø Used to control symptoms of

Rheumatoid Arthritis Autoimmune disorder causing inflammation and tissue damage in joints Diagnosis primarily symptomatic Treatment consists of nonsteroidal antiinflammatory drugs (NSAIDs) and DMARDs Copyright © 2017, Elsevier Inc. All rights reserved. 48

Rheumatoid Arthritis (Cont. ) Copyright © 2017, Elsevier Inc. All rights reserved. 49

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

Disease-Modifying Antirheumatic Drugs Modify the disease of RA 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 Copyright © 2017, Elsevier Inc. All rights reserved. 51

Nonbiologic Disease-Modifying Antirheumatic Drugs methotrexate leflunomide hydroxychloroquine sulfasalazine Copyright © 2017, Elsevier Inc. All

Biologic Disease-Modifying Antirheumatic Drugs adalimumab tofacitinib anakinra certolizumab etanercept golimumab infliximab adalimumab abatacept rituximab tocilizumab Copyright © 2017, Elsevier Inc. All rights reserved. 53

Disease-Modifying Antirheumatic Drugs(Cont. ) Etanercept (Enbrel) Used to treat RA (including juvenile RA) and psoriasis Ø Patients must be screened for latex allergy (some dosage forms may contain latex) Ø Onset of action: 1 to 2 weeks Ø Contraindicated in presence of active infections • Reactivation of hepatitis and tuberculosis have been reported. Ø Copyright © 2017, Elsevier Inc. All rights reserved. 54

Disease-Modifying Antirheumatic Drugs (Cont. ) Abatacept (Orencia) Used to treat RA Ø Caution if the patient has a history of recurrent infections or chronic obstructive pulmonary disease Ø Patients must be up to date on immunizations before starting therapy Ø May increase risk of infections associated with live vaccines Ø May decrease response to vaccines Ø Copyright © 2017, Elsevier Inc. All rights reserved. 55

Nursing Implications Assess for allergies, specifically allergies to egg proteins, Ig. G, or neomycin. Assess for conditions that may be contraindications. Assess baseline blood counts; perform cardiac, renal, and liver studies. Assess for presence of infection. Copyright © 2017, Elsevier Inc. All rights reserved. 56

Nursing Implications (Cont. ) Follow specific guidelines for preparation and administration of drugs. Monitor the patient’s response during therapy. Copyright © 2017, Elsevier Inc. All rights reserved. 57

Nursing Implications (Cont. ) Teach patients to report signs of infection immediately: Sore throat Ø Diarrhea Ø Vomiting Ø Fever of 100. 5° F (38. 1° C) or higher Ø Copyright © 2017, Elsevier Inc. All rights reserved. 58

Nursing Implications (Cont. ) Monitor for therapeutic responses: Decrease in growth of lesion or mass Ø Improved blood counts Ø Absence of infection, anemia, and hemorrhage Ø Monitor for adverse effects. Copyright © 2017, Elsevier Inc. All rights reserved. 59

Case Study A 40 -year-old female patient is seen in the clinic. She has been newly diagnosed with RA. Which medication does the nurse anticipate being ordered for the patient? A. methotrexate B. adalimumab C. infliximab D. etanercept Copyright © 2017, Elsevier Inc. All rights reserved. 60

Case Study (Cont. ) Before administering methotrexate, it is most important for the nurse to assess the patient for: A. B. C. D. allergy to eggs. congestive heart failure. latent tuberculosis. hypothyroidism. Copyright © 2017, Elsevier Inc. All rights reserved. 61

Case Study (Cont. ) 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 before administration. D. Administer the methotrexate subcutaneously into the thigh, abdomen, or upper arm, rotating injection sites. Copyright © 2017, Elsevier Inc. All rights reserved. 62

Case Study (Cont. ) The patient improves within the first 3 months of treatment with methotrexate. Six months later, the patient experiences worsening of symptoms. The prescriber will most likely order which monoclonal antibody for the treatment of RA? A. B. C. D. adalimumab (Humira) trastuzumab (Herceptin) rituximab (Rituxan) cetuximab (Erbitux) Copyright © 2017, Elsevier Inc. All rights reserved. 63