Biologic Response–Modifying and Antirheumatic Drugs

1Winter 2013

Immunomodulators (IMs)

Include drugs from several classes◦ Immunosuppressants◦ Immunizing drugs

Biologic response modifiers (BRMs) Hematopoietic drugs Immunomodulating drugs

2Winter 2013

Immunomodulating DrugsImmunomodulating DrugsMedications 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

3Winter 2013

Biologic Response Modifiers Biologic Response Modifiers (BRMs)(BRMs)

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

Also used for other diseases◦Autoimmune◦ Inflammatory◦ Infectious

4Winter 2013

BRMs: SubclassesBRMs: Subclasses

Hematopoietic drugsInterferons (IFNs)Monoclonal antibodiesInterleukin receptor agonists and

antagonistsDisease-modifying antirheumatic

drugsMiscellaneous drugs

5Winter 2013

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

6Winter 2013

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 rDNA technology

7Winter 2013

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

8Winter 2013

Hematopoietic Drugs (cont’d)Erythropoietic drugs◦ epoetin Alpha (Epogen, Procrit)◦ darbepoetin Alpha (Aranesp)

Colony-stimulating factors (CSFs)◦ filgrastim (Neupogen)◦ pegfilgrastim (Neulasta)◦ sargramostin (Leukine)

Platelet-promoting drugs◦ oprelvekin (Neumega)

9Winter 2013

Hematopoietic Drugs (cont’d)

epoetin Alpha (Epogen, Procrit)◦Synthetic derivative of the hormone

erythropoietin◦Promotes the synthesis of RBCs by

stimulating RBC precursors

10Winter 2013

Hematopoietic Drugs (cont’d))

darbepoetin Alpha (Aranesp)◦Longer-acting form of epoetin Alpha◦Also used to stimulate RBC

production

11Winter 2013

Hematopoietic Drugs (cont’d)

filgrastim (Neupogen)◦Granulocyte colony-stimulating factor (G-

CSF)◦Stimulates precursor cells for the type of

WBCs known as granulocytespegfilgrastim (Neulasta)◦Longer-acting form of filgrastim

12Winter 2013

Hematopoietic Drugs (cont’d)

sargramostim (Leukine)◦Stimulates bone marrow precursor cells

that make both granulocytes and phagocytic (cell-eating) cells; known as monocytes

◦Granulocyte-macrophage colony-stimulating factor (GM-CSF)

13Winter 2013

Hematopoietic Drugs (cont’d)

oprelvekin (Neumega)◦Also classified as an interleukin (IL-11)◦Stimulates bone marrow cells

(megakaryocytes) that eventually become platelets

14Winter 2013

Hematopoietic Drugs:Indications

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

15Winter 2013

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

16Winter 2013

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

17Winter 2013

Hematopoietic Drugs:Adverse Effects

Usually mild◦Fever◦Muscle aches◦Bone pain◦Flushing◦Others

18Winter 2013

Hematopoietic Drugs: Epoetin

FDA warning◦Increased adverse effects when used

by patients with higher-than-normal hemoglobin Heart attack Heart failure Stroke Death

19Winter 2013

Hematopoietic Drugs:Interactions

Filgrastim and sargramostim should not be given within 24 hours of myelosuppressive antineoplastic therapy

These two types of drugs will directly antagonize each other

20Winter 2013

Interferons (IFNs)Proteins with three basic

properties◦Antiviral◦Antitumor◦Immunomodulating

Used to treat certain viral infections and cancer

21Winter 2013

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

22Winter 2013

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

23Winter 2013

Interferons: IndicationsViral infections◦Genital warts, hepatitis

Cancer◦Chronic myelogenous leukemia, follicular

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

Autoimmune disorders◦Multiple sclerosis, others

24Winter 2013

Interferons: Adverse EffectsFlulike effects◦ Fever, chills, headache, myalgia

Dose-limiting adverse effect is fatigue

Other adverse effects◦ Anorexia◦ Dizziness◦ Nausea◦ Vomiting◦ Diarrhea

25Winter 2013

Interferons (cont’d)

Three major classes of IFNs◦Alpha◦Beta◦Gamma

26Winter 2013

Interferons (cont’d)

Interferon alpha products: “leukocyte interferons”—produced from human leukocytes

◦ Interferon Alpha-2a, Interferon Alpha-2b◦ Interferon Alpha-n3, Interferon Alphacon-1◦Peginterferon Alpha-2a◦Peginterferon Alpha-2b

27Winter 2013

Interferons (cont’d)

Interferon beta products◦IFN beta-1a◦IFN beta-1b

Interferon gamma products◦Interferon gamma-1b

28Winter 2013

Monoclonal Antibodies (MABs)Used to target specific cancer cells

Minimal effect on healthy cells

Fewer adverse effects than traditional antineoplastic medications

Used to treat cancers and rheumatoid arthritis

29Winter 2013

30Winter 2013

Monoclonal Antibodies (MABs) (cont’d)Cancer treatment

◦ alemtuzumab (Campath)◦ bevacizumab (Avistatin)◦ cetuximab (Erbitux)◦ gemtuzumab ozogamicin (Mylotarg)

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

31Winter 2013

Monoclonal Antibodies (MABs) (cont’d)

Mechanisms of action and adverse effects vary with each drug

Used for specific types of cancer and in organ transplantation

Extremely specific drugs that target certain tumor cells and bypass normal cells

32Winter 2013

Interleukins and Related Drugs

Beneficial antitumor action

Interleukin receptor agonists◦ aldesleukin (IL-2, Proleukin)◦ oprelvekin (IL-11, Neumega)*◦ denileukin diftitox (Ontak)

IL-1 receptor antagonist◦ anakinra (Kineret)

*Also classified as an HD

33Winter 2013

Interleukins (cont’d)Aldesleukin acts indirectly to stimulate or restore

immune response

◦ Aids in causing T cells to multiply, including lymphokine-activated killer (LAK) cells

◦ LAK cells recognize and destroy only cancer cells, and ignore normal cells

◦ Used for metastatic renal cell carcinoma and malignant melanoma

◦ Under study for use in other types of cancer

34Winter 2013

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

35Winter 2013

Interleukins (cont’d)

denileukin diftitox

◦ IL-2 receptor antagonist (IL-2Ra)◦Binds to cell-surface IL-2 receptors on normal as

well as certain malignant cells◦Causes cell death

36Winter 2013

Interleukins (cont’d)anakinra (Kineret)

◦ IL-1 receptor antagonist ◦Used to control symptoms of rheumatoid

arthritis

37Winter 2013

Rheumatoid Arthritis

Autoimmune disorder causing inflammation and tissue damage in joints

Diagnosis primarily symptomatic

Treatment consists of NSAIDs and disease-modifying antirheumatic drugs

38Winter 2013

Antirheumatoid Arthritis DrugsAlso known as disease-modifying antirheumatic

drugs (DMARDs)

Slow onset of action—several weeks

May take 3 to 6 months to see full effects

Can have much more toxic adverse effects than NSAIDs

Antiinflammatory, antiarthritic, immunomodulating effects

39Winter 2013

Antirheumatoid Arthritis Drugs (cont’d)

Methotrexate

etanercept (Enbrel)

abatacept (Orencia)

leflunomide (Arava)

40Winter 2013

Antirheumatoid Arthritis Drugs (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

41Winter 2013

Antirheumatoid Arthritis Drugs (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 vaccines42Winter 2013

Nursing Implications (cont’d)

Teach patients to report signs of infection immediately◦Sore throat◦Diarrhea◦Vomiting◦ Fever over 100° F

43Winter 2013