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Special Alerts
Tumor Necrosis Factor (TNF) Blockers: Surveillance of Malignancies in Pediatric, Adolescent, and Young Adult Patients
November 2011
The U.S. Food and Drug Administration (FDA) is updating the public about an ongoing surveillance program of reported cases of malignancy in patients ≤30 years of age treated with TNF blockers, including adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab. The FDA is requiring enhanced safety surveillance by the manufacturers of TNF blockers to include:
- In-depth follow-up on all reported malignancy cases
- Expedited reporting of all malignancy cases to the FDA
- Yearly summary and assessment of malignancies and TNF blocker usage data
Collected data will be re-evaluated periodically by the FDA over the next 10 years. Healthcare professionals should continue to be alert for possible malignancies in patients being treated with TNF blockers and report positive findings to the FDA's MedWatch program (1-800-332-1088 or https://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm) or to the manufacturer.
For additional information, please refer to http://www.fda.gov/Drugs/DrugSafety/ucm278267.htm
Tumor Necrosis Factor-alpha (TNFα) Blockers: Risk of Infection from Legionella and Listeria
September 2011
The U.S. Food and Drug Administration (FDA) is notifying healthcare professionals of an update to the Boxed Warning for the entire class of tumor necrosis factor-alpha (TNFα) blockers including Remicade® (infliximab), Enbrel® (etanercept), Humira® (adalimumab), Cimzia® (certolizumab pegol), and Simponi® (golimumab). The Boxed Warning will include the risk of infection from two bacterial pathogens, Legionella and Listeria.
For additional information, please refer to http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm270977.htm
ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(et a NER sept)
Generic Available (U.S.)
No
Medication Guide
An FDA-approved patient medication guide, which is available with the product information and at http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088590.pdf, must be dispensed with this medication.
REMS Components
Enbrel®: Released from REMS requirement 8/10/11
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of moderately- to severely-active rheumatoid arthritis (RA); moderately- to severely-active polyarticular juvenile idiopathic arthritis (JIA); psoriatic arthritis; active ankylosing spondylitis (AS); moderate-to-severe chronic plaque psoriasis
Pregnancy Risk Factor
B
Pregnancy Considerations
Developmental toxicity studies performed in animals have revealed no evidence of harm to the fetus. There are no studies in pregnant women; this drug should be used during pregnancy only if clearly needed. A pregnancy registry has been established to monitor outcomes of women exposed to etanercept during pregnancy (877-311-8972).
Lactation
Excretion in breast milk unknown/not recommended
Breast-Feeding Considerations
It is not known whether etanercept is excreted in human milk. Because many drugs and immunoglobulins are excreted in human milk and the potential for serious adverse reactions exists, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Contraindications
Hypersensitivity to etanercept or any component of the formulation; patients with sepsis (mortality may be increased)
Warnings/Precautions
Boxed warnings:
• Infections: See “Concerns related to adverse effects” below.
• Malignancy: See “Concerns related to adverse effects” below
• Tuberculosis: See “Concerns related to adverse effects” below.
Concerns related to adverse effects:
• Anaphylaxis/hypersensitivity reactions: Allergic reactions may occur, if an anaphylactic reaction or other serious allergic reaction occurs, administration should be discontinued immediately and appropriate therapy initiated.
• Autoimmune disorder: Positive antinuclear antibody titers have been detected in patients (with negative baselines). Rare cases of autoimmune disorder, including lupus-like syndrome or autoimmune hepatitis, have been reported; monitor and discontinue if symptoms develop.
• Hepatitis B: Rare reactivation of hepatitis B (HBV) has occurred in chronic carriers of the virus, usually in patients receiving concomitant immunosuppressants; evaluate for HBV prior to initiation in all patients. Monitor during and for several months following discontinuation of treatment in HBV carriers; interrupt therapy if reactivation occurs and treat appropriately with antiviral therapy; if resumption of therapy is deemed necessary, exercise caution and monitor patient closely.
• Infections: [U.S. Boxed Warning]: Patients receiving etanercept are at increased risk for serious infections which may result in hospitalization and/or fatality; infections usually developed in patients receiving concomitant immunosuppressive agents (eg, methotrexate or corticosteroids) and may present as disseminated (rather than local) disease. Active tuberculosis (or reactivation of latent tuberculosis), invasive fungal (including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, and pneumocystosis) and bacterial, viral or other opportunistic infections (including legionellosis and listeriosis) have been reported in patients receiving TNF-blocking agents, including etanercept. Monitor closely for signs/symptoms of infection. Discontinue for serious infection or sepsis. Consider risks versus benefits prior to use in patients with a history of chronic or recurrent infection. Consider empiric antifungal therapy in patients who are at risk for invasive fungal infection and develop severe systemic illness. Caution should be exercised when considering use in the elderly or in patients with conditions that predispose them to infections (eg, diabetes) or residence/travel from areas of endemic mycoses (blastomycosis, coccidioidomycosis, histoplasmosis), or with latent or localized infections. Do not initiate etanercept therapy with clinically important active infection. Patients who develop a new infection while undergoing treatment should be monitored closely.
• Malignancy: [U.S. Boxed Warning]: Lymphoma and other malignancies have been reported in children and adolescent patients receiving TNF-blocking agents, including etanercept. Half of the malignancies reported in children were lymphomas (Hodgkin's and non-Hodgkin's) while other cases varied and included malignancies not typically observed in this population. The impact of etanercept on the development and course of malignancy is not fully defined. Compared to the general population, an increased risk of lymphoma has been noted in clinical trials; however, rheumatoid arthritis alone has been previously associated with an increased rate of lymphoma. Lymphomas and other malignancies were also observed (at rates higher than expected for the general population) in adult patients receiving etanercept. Hepatosplenic T-cell lymphoma (HSTCL), a rare T-cell lymphoma, has also been associated with TNF-blocking agents, primarily reported in adolescent and young adult males with Crohn's disease or ulcerative colitis.
• Tuberculosis: [U.S. Boxed Warning]: Tuberculosis (disseminated or extrapulmonary) has been reported in patients receiving etanercept; both reactivation of latent infection and new infections have been reported. Patients should be evaluated for tuberculosis risk factors and for latent tuberculosis infection with a tuberculin skin test prior to starting therapy. Treatment of latent tuberculosis should be initiated before etanercept therapy; consider antituberculosis treatment if adequate course of treatment cannot be confirmed in patients with a history of latent or active tuberculosis or with risk factors despite negative skin test. Some patients who tested negative prior to therapy have developed active infection; monitor for signs and symptoms of tuberculosis in all patients.
Disease-related concerns:
• Alcoholic hepatitis: Use with caution in patients with moderate to severe alcoholic hepatitis. Compared to placebo, the mortality rate in patients treated with etanercept was similar at one month but significantly higher after 6 months.
• Demyelinating CNS disease: Use with caution in patients with pre-existing or recent onset CNS demyelinating disorders; rare cases of new onset or exacerbation of CNS demyelinating disorders have occurred; may present with mental status changes and some may be associated with permanent disability. Optic neuritis, transverse myelitis, multiple sclerosis, and new onset or exacerbation of seizures have been reported.
• Heart failure: Use with caution in patients with heart failure or decreased left ventricular function; worsening and new-onset heart failure has been reported.
• Hematologic disorders: Use with caution in patients with a history of significant hematologic abnormalities; has been associated with pancytopenia and aplastic anemia (rare cases in postmarketing experience). Patients must be advised to seek medical attention if they develop signs and symptoms suggestive of blood dyscrasias; discontinue if significant hematologic abnormalities are confirmed.
• Wegener's granulomatosis: Use is not recommended in patients with Wegener's granulomatosis who are receiving immunosuppressive therapy due to higher incidence of noncutaneous solid malignancies.
Concurrent drug therapy issues:
• Anakinra: Due to a higher incidence of serious infections, concomitant use with anakinra is not recommended.
Special populations:
• Varicella virus exposure: Patients with a significant exposure to varicella virus should temporarily discontinue therapy; treatment with varicella zoster immune globulin should be considered.
Dosage form specific issues:
• Benzyl alcohol: Some dosage forms may contain benzyl alcohol which has been associated with “gasping syndrome” in neonates.
• Latex: Some dosage forms may contain dry natural rubber (latex).
Other warnings/precautions:
• Immunizations: Patients should be brought up to date with all immunizations before initiating therapy. Live vaccines should not be given concurrently; there is no data available concerning secondary transmission of live vaccines in patients receiving therapy.
Adverse Reactions
Percentages reported for adults except where specified.
>10%:
Central nervous system: Headache (17%; children 19%)
Dermatologic: Rash (3% to 13%)
Gastrointestinal: Abdominal pain (5%; children 19%), vomiting (3%; children 13%)
Local: Injection site reaction (14% to 43%; bleeding, bruising, erythema, itching, pain or swelling)
Respiratory: Respiratory tract infection (upper; 38% to 65%), rhinitis (12%)
Miscellaneous: Infection (50% to 81%; children 62%), positive ANA (11%), positive antidouble-stranded DNA antibodies (15% by RIA, 3% by Crithidia luciliae assay)
≥3% to 10%:
Central nervous system: Dizziness (7%)
Dermatologic: Pruritus (2% to 5%)
Gastrointestinal: Nausea (children 9%), dyspepsia (4%), diarrhea (3%)
Neuromuscular & skeletal: Weakness (5%)
Respiratory: Pharyngitis (7%), cough (6%), respiratory disorder (5%), sinusitis (3%)
<3%, postmarketing, and/or case reports: Abscess, adenopathy, allergic reactions, anemia, angioedema, anorexia, aplastic anemia, appendicitis, aseptic meningitis, bursitis, cerebral ischemia, chest pain, cholecystitis, coagulopathy, demyelinating CNS disorders (suggestive of multiple sclerosis, transverse myelitis, or optic neuritis), cutaneous ulcer, deep vein thrombosis, depression, dyspnea, erythema multiforme, esophagitis, fatigue, fever, flushing, flu-like syndrome, gastroenteritis, gastrointestinal hemorrhage, gastritis, heart failure, hepatitis (autoimmune), hydrocephalus (with normal pressure), hyper-/hypotension, hypersensitivity, infections (bacterial, fungal, protozoal, viral), inflammatory bowel disease, interstitial lung disease, intestinal perforation, joint pain, leukemias, leukopenia, lupus erythematous (cutaneous), lupus-like syndrome, lymphadenopathy, lymphomas, malignancies, membranous glomerulopathy, MI, mouth ulcer, multiple sclerosis, myocardial ischemia, neutropenia, ocular inflammation, optic neuritis, pancytopenia, pancreatitis, paresthesia, polymyositis, psoriasis (including new onset, palmoplantar, pustular, or exacerbation), pulmonary disease, pulmonary embolism, pyrexia, renal calculus, sarcoidosis, seizure, stroke, Stevens-Johnson syndrome, subcutaneous nodules, taste disturbances, thrombocytopenia, thrombophlebitis, toxic epidermal necrolysis, transaminases increased, tuberculosis, tuberculous arthritis, urinary tract infection, urticaria, varicella infection, vasculitis (cutaneous), weight gain, xerophthalmia, xerostomia
Metabolism/Transport Effects
None known.
Drug Interactions
Abatacept: Anti-TNF Agents may enhance the adverse/toxic effect of Abatacept. An increased risk of serious infection during concomitant use has been reported. Risk X: Avoid combination
Anakinra: Anti-TNF Agents may enhance the adverse/toxic effect of Anakinra. An increased risk of serious infection during concomitant use has been reported. Risk X: Avoid combination
BCG: Immunosuppressants may diminish the therapeutic effect of BCG. Risk X: Avoid combination
Belimumab: Etanercept may enhance the adverse/toxic effect of Belimumab. Risk X: Avoid combination
Canakinumab: Anti-TNF Agents may enhance the adverse/toxic effect of Canakinumab. Specifically, the risk for serious infections and/or neutropenia may be increased. Risk X: Avoid combination
Certolizumab Pegol: Anti-TNF Agents may enhance the immunosuppressive effect of Certolizumab Pegol. Risk X: Avoid combination
Coccidioidin Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioidin Skin Test. Risk C: Monitor therapy
Cyclophosphamide: Etanercept may enhance the adverse/toxic effect of Cyclophosphamide. An increased risk of solid cancer development may be present. Risk X: Avoid combination
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Risk C: Monitor therapy
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination
Rilonacept: Anti-TNF Agents may enhance the adverse/toxic effect of Rilonacept. Risk X: Avoid combination
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Risk D: Consider therapy modification
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Risk C: Monitor therapy
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Risk X: Avoid combination
Ethanol/Nutrition/Herb Interactions
Herb/Nutraceutical: Echinacea may decrease the therapeutic effects of etanercept (avoid concurrent use).
Storage
Prefilled syringes, autoinjectors: Store prefilled syringes and autoinjectors 2°C to 8°C (36°F to 46°F); do not freeze. Protect from light; do not shake. The following stability information has also been reported: May be stored at room temperature for up to 4 days (Cohen, 2007).
Powder for reconstitution: Must be refrigerated at 2°C to 8°C (36°F to 46°F); do not freeze. The following stability information has also been reported: May be stored at room temperature for up to 7 days (Cohen, 2007).
Reconstitution
Reconstitute lyophilized powder aseptically with 1 mL sterile bacteriostatic water for injection, USP (supplied); swirl gently, do not shake. Do not filter reconstituted solution during preparation or administration.
Mechanism of Action
Etanercept is a recombinant DNA-derived protein composed of tumor necrosis factor receptor (TNFR) linked to the Fc portion of human IgG1. Etanercept binds tumor necrosis factor (TNF) and blocks its interaction with cell surface receptors. TNF plays an important role in the inflammatory processes and the resulting joint pathology of rheumatoid arthritis (RA), polyarticular-course juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS), and plaque psoriasis.
Pharmacodynamics/Kinetics
Onset of action: ~2-3 weeks; RA: 1-2 weeks
Half-life elimination: RA: SubQ: 72-132 hours
Time to peak: RA: SubQ: 35-103 hours
Dosage
SubQ:
Children 2-17 years: Juvenile idiopathic arthritis:
Once-weekly dosing: 0.8 mg/kg (maximum: 50 mg/dose) once weekly
Twice-weekly dosing: 0.4 mg/kg (maximum: 25 mg/dose) twice weekly (individual doses should be separated by 72-96 hours)
Adults:
Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis:
Once-weekly dosing: 50 mg once weekly
Twice weekly dosing: 25 mg given twice weekly (individual doses should be separated by 72-96 hours)
Plaque psoriasis:
Initial: 50 mg twice weekly, 72-96 hours apart; maintain initial dose for 3 months (starting doses of 25 or 50 mg once weekly have also been used successfully)
Maintenance dose: 50 mg once weekly
Elderly: Refer to adult dosing. Although greater sensitivity of some elderly patients cannot be ruled out, no overall differences in safety or effectiveness were observed.
Administration: Other
Administer subcutaneously. Rotate injection sites. New injections should be given at least one inch from an old site and never into areas where the skin is tender, bruised, red, or hard. Note: If the physician determines that it is appropriate, patients may self-inject after proper training in injection technique.
Powder for reconstitution: Follow package instructions carefully for reconstitution. The maximum amount injected at any single site should not exceed 25 mg.
Solution for injection: May be allowed to reach room temperature prior to injection.
Monitoring Parameters
Monitor improvement of symptoms and physical function assessments. Latent TB screening prior to initiating and during therapy; signs/symptoms of infection (prior to, during, and following therapy); CBC with differential; signs/symptoms/worsening of heart failure; HBV screening prior to initiating (all patients), HBV carriers (during and for several months following therapy); signs and symptoms of hypersensitivity reaction; symptoms of lupus-like syndrome; signs/symptoms of malignancy (eg, splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, weight loss).
Patient Education
If self-injecting, follow instructions for injection and disposal of needles exactly. If redness, swelling, or irritation appears at the injection site, contact prescriber. You may experience headache or dizziness. If stomach pain or cramping; unusual bleeding or bruising; difficulty breathing; persistent fever; paleness; or blood in vomitus, stool, or urine occurs, stop medication and contact prescriber immediately. Also immediately report skin rash, unusual muscle or bone weakness, or signs of respiratory flu or other infection (eg, chills, fever, sore throat, easy bruising or bleeding, mouth sores, unhealed sores). Report signs of malignancy (eg, splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, weight loss).
Geriatric Considerations
Clinical trials including those ≥65 years of age with rheumatoid arthritis have not demonstrated any differences in safety and efficacy between elderly and younger adults to date. Since elderly have a higher incidence of infections in general, caution should be used, with close monitoring and patient education.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Dizziness is common; may cause depression
Mental Health: Effects on Psychiatric Treatment
None reported
Nursing: Physical Assessment/Monitoring
Monitor for signs and symptoms of infection, especially respiratory infections. Perform tuberculin skin test prior to initiating therapy; monitor for signs of tuberculosis throughout therapy. Monitor for signs/symptoms of malignancy (eg, splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, weight loss). Assess for liver dysfunction. Monitor effectiveness of therapy (eg, pain, range of motion, mobility, ADL function, inflammation). If self-administered, teach patient appropriate injection technique and needle disposal.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution:
Enbrel®: 25 mg [contains benzyl alcohol (in diluent), sucrose 10 mg]
Injection, solution [preservative free]:
Enbrel®: 50 mg/mL (0.51 mL, 0.98 mL) [contains natural rubber/natural latex in packaging, sucrose 1%; prefilled syringe]
Enbrel® SureClick®: 50 mg/mL (0.98 mL) [contains natural rubber/natural latex in packaging, sucrose 1%; autoinjector]
Pricing: U.S. (www.drugstore.com)
Kit (Enbrel)
25 mg (4): $978.99
Solution (Enbrel)
25 mg/0.5 mL (0.51): $255.99
50 mg/mL (3.92): $1891.99
Solution (Enbrel SureClick)
50 mg/mL (3.92): $1910.02
References
Breedveld F, “New Tumor Necrosis Factor-Alpha Biologic Therapies for Rheumatoid Arthritis,” Eur Cytokine Netw, 1998, 9(3):233-8.
Cohen V, Jellinek SP, Teperikidis L, et al, “Room-Temperature Storage of Medications Labeled for Refrigeration,” Am J Health-Syst Pharm, 2007, 64(16):1711-15.
Data on file, Immunex Corporation.
Feldmann M, Brennan FM, and Maini RN, “Role of Cytokines in Rheumatoid Arthritis,” Annu Rev Immunol, 1996, 14:397-440.
Felson DT, Anderson JJ, Boers M, et al, “American College of Rheumatology. Preliminary Definition of Improvement in Rheumatoid Arthritis,” Arthritis Rheum, 1995, 38(6):727-35.
Fisher CJ Jr, Agosti JM, Opal SM, et al, “Treatment of Septic Shock With the Tumor Necrosis Factor Receptor:Fc Fusion Protein. The Soluble TNF Receptor Sepsis Study Group,” N Engl J Med, 1996, 334(26):1697-702.
Giannini EH, Ruperto N, Ravelli A, et al, “Preliminary Definition of Improvement in Juvenile Arthritis,” Arthritis Rheum, 1997, 40(7):1202-9.
Lovell DJ, Giannini EH, Reiff A, et al, “Etanercept in Children With Polyarticular Juvenile Rheumatoid Arthritis: Pediatric Rheumatology Collaborative Study Group,” N Engl J Med, 2000, 342(11):763-9.
Lovell DJ, Giannini EH, Reiff A, et al, “Long-Term Efficacy and Safety of Etanercept in Children With Polyarticular-Course Juvenile Rheumatoid Arthritis: Interim Results From an Ongoing Multicenter, Open-Label, Extended-Treatment Trial,” Arthritis Rheum, 2003, 48(1):218-26.
Mease PJ, Goffe BS, Metz J, et al, “Etanercept in the Treatment of Psoriatic Arthritis and Psoriasis: A Randomised Trial,” Lancet, 2000, 356(9227):385-90.
Moreland LW, Baumgartner SW, Schiff MH, et al, “Treatment of Rheumatoid Arthritis With a Recombinant Human Tumor Necrosis Factor Receptor (p75)-Fc Fusion Protein,” N Engl J Med, 1997, 337(3):141-7.
“New Drugs for Rheumatoid Arthritis,” Med Lett Drugs Ther, 1998, 40(1040):110-2.
Parakkal D, Sifuentes H, Semer R, et al, “Hepatosplenic T-Cell Lymphoma in Patients Receiving TNF-α Inhibitor Therapy: Expanding the Groups at Risk,” Eur J Gastroenterol Hepatol, 2011, 23(12):1150-6.
Ramey DR, Fries JF, and Singh G, “The Health Assessment Questionnaire 1995 - Status and Review,” Spilker B, ed, Quality of Life and Pharmacoeconomics in Clinical Trials, 2nd ed, Philadelphia, PA: Lippincott-Raven, 1996.
Saxne T, Palladino MA Jr, Heinegard D, et al, “Detection of Tumor Necrosis Factor Alpha but Not Tumor Necrosis Factor Beta in Rheumatoid Arthritis Synovial Fluid and Serum,” Arthritis Rheum, 1988, 31(8):1041-5.
Smith CA, Farrah T, and Goodwin RG, “The TNF Receptor Superfamily of Cellular and Viral Proteins: Activation, Costimulation, and Death,” Cell, 1994, 76(6):959-62.
van Oosten BW, Barkhof F, Truyen L, et al, “Increased MRI Activity and Immune Activation in Two Multiple Sclerosis Patients Treated With the Monoclonal Anti-tumor Necrosis Factor Antibody cA2,” Neurology, 1996, 47(6):1531-4.
Weinblatt ME, Kremer JM, Bankhurst AD, et al, “A Trial of Etanercept, A Recombinant Tumor Necrosis Factor Receptor:Fc Fusion Protein, in Patients With Rheumatoid Arthritis Receiving Methotrexate,” N Engl J Med, 1999, 340(4):253-9.
Wooley PH, Dutcher J, Widmer MB, et al, “Influence of a Recombinant Human Soluble Tumor Necrosis Factor Receptor FC Fusion Protein on Type II Collagen-Induced Arthritis in Mice,” J Immunol, 1993, 151(11):6602-7.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
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