-
ENBREL is indicated for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in patients with moderately to severely active rheumatoid arthritis. ENBREL can be initiated in combination with methotrexate (MTX) or used alone.
-
ENBREL is indicated for the treatment of patients 4 years or older with chronic moderate to severe plaque psoriasis (PsO) who are candidates for systemic therapy or phototherapy.
-
ENBREL is indicated for reducing signs and symptoms, inhibiting the progression of structural damage of active arthritis, and improving physical function in patients with psoriatic arthritis (PsA). ENBREL can be used with or without MTX.
-
ENBREL is indicated for reducing signs and symptoms in patients with active ankylosing spondylitis.
-
ENBREL is indicated for reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients ages 2 and older.
For patients 4-17 years old with chronic moderate to severe plaque psoriasis (PsO)
For patients 4-17 years old with chronic moderate to severe plaque psoriasis (PsO)
Take the next step
with ENBREL
with ENBREL
The FIRST and ONLY FDA-approved biologic therapy for chronic moderate to severe plaque PsO patients 4 years or older who are candidates for systemic therapy or phototherapy.1,2
The incidence of pediatric PsO is increasing
- Psoriasis affects 2%–4% of the US population, with ~1/3 of adult cases beginning during childhood3,4
- Earlier onset, before 20 years of age, is associated with significant disease5
- The exact percentage of the pediatric population impacted by PsO is not well defined, but there are approximately 20,000 new cases reported in children under 10 years old in the US annually6-8
- A 2009 retrospective study revealed that the incidence of pediatric PsO more than doubled from the early 1970s to the late 1990s9*
- Psoriasis has a strong hereditary component—up to 1 out of 2 pediatric patients may have a first-degree relative who also has PsO5
* Incidence increased from 29.6 per 100,000 patient-years in 1970-1974 to 62.7 per 100,000 patient-years in 1995-1999 (n=357 total pediatric psoriasis subjects between Jan 1, 1970, and Dec 31, 1999; P<0.001 for the trend).
Psoriasis is often misdiagnosed by non-dermatologists
- Pediatric PsO can be mistaken for atopic dermatitis—an observational study showed that 9.4% of pediatric patients with psoriasis were correctly diagnosed with PsO by non-dermatologists10
Visual similarities between pediatric PsO and atopic dermatitis
Some pediatric patients have difficulty accessing specialized care
- There are only 278 board-certified pediatric dermatologists, and they are unevenly distributed across the US13†
- Average wait to see a pediatric dermatologist is 7.7 weeks (53.9 days)14‡
† Eleven states do not have any board-certified pediatric dermatologists.
‡ According to a May 2012 Children's Hospital Association survey of 69 hospitals.
Consensus guidelines are lacking for pediatric PsO
- No treatment guidelines specifically exist for pediatric PsO—physicians must rely upon their own judgment to determine PsO severity and decide appropriate treatment.15
In the past 30 years, no systemic treatments have been approved for pediatric plaque PsO, including moderate to severe plaque PsO, in the US16
The ENBREL Pediatric Pivotal Study
- A 48-week, randomized, double-blind, placebo-controlled US and Canadian study (parent study) in 211 patients with moderate to severe plaque PsO between 4 and 17 years of age1,11
- The 48-week parent study was followed up by a long-term 264-week (5-year; n=182) open-label extension16
- Patients received dosing of 0.8 mg/kg up to a maximum dose of 50 mg QW. No loading dose or dose adjustments were made except for those based on weight1
- 42% of all patients (n=89/211) had a baseline weight of >62.5 kg (>138 lb)17
- Of the 89 patients, 47 received the maximum dose of ENBREL 50 mg QW and 42 received placebo QW during the 12-week, randomized, double-blind treatment phase17
* PASI=Psoriasis Area and Severity Index.
† BSA=Body Surface Area.
‡ 25% were Black or African American, Hispanic or Latino, Asian, Native Hawaiian or Other Pacific Islander, or Other
The Pediatric Pivotal Study evaluated the safety and efficacy of ENBREL
§§ At Week 312, n=69.
Open-label extension
- Long-term safety profile for up to 264 additional weeks was assessed in an open-label extension study; no new safety signals were identified1
- Primary endpoints: Subject incidence of adverse events, including infectious episodes, serious adverse events, and serious infectious episodes20
- Secondary endpoints: PASI 50/75/90 and sPGA of “clear” or “almost clear”20
§ If PASI score worsened >50% at or after Week 4, patients could receive open-label ENBREL
** Patients who did not reach PASI 50 at Week 24 or PASI 75 at Week 36 could discontinue or add low to moderate topical corticosteroids.
†† Patients who lost PASI 75 resumed open-label ENBREL treatment.
‡‡ Patients were allowed to discontinue treatment from Week 96 if they achieved an sPGA of clear/almost clear.
*** ITT NRI analysis.
ENBREL provides demonstrated efficacy1
~7 out of 10 pediatric patients achieved PASI 75 at 36 weeks with ENBREL19
* Open-label period or incomplete-responder arm; patients could enter the incomplete-responder arm at Week 24 or Week 36.
† ITT=intent to treat. NRI=nonresponder imputation.
PASI 50: 75% of patients taking ENBREL achieved PASI 50 at 12 weeks19‡
- 87% of patients taking ENBREL achieved PASI 50 at 36 weeks19‡
- 68% of patients taking ENBREL achieved PASI 75 at 36 weeks19‡
- 41% of patients taking ENBREL achieved PASI 90 at 36 weeks19‡
- 86%, 65%, and 38% of patients who switched from placebo to ENBREL achieved PASI 50, PASI 75, and PASI 90, respectively, at 36 weeks (Weeks 0–12: n=105; Weeks 16–36: n=103)19‡
‡ ITT NRI analysis.
Approximately half of pediatric ENBREL patients were "clear" or "almost clear" at 12 through 36 weeks18,21
§ ENBREL: n=106 through Week 12 and n=105 through Week 36. Placebo/ENBREL: n=105 through Week 12 and n=103 through Week 36.
** ITT NRI analysis.
- To evaluate maintenance of response, subjects who achieved PASI 75 response at Week 36 were re-randomized to either ENBREL or placebo during a 12-week randomized withdrawal period1
- The maintenance of PASI 75 response was evaluated at Week 481
- 65% of patients maintained PASI 75 response with ENBREL vs 49% with placebo at Week 481
In the combined parent study and open-label extension
In the combined parent study and open-label extension
Efficacy results through 312 weeks22
* Patients were treated and evaluated for 5 years or until they turned 18, whichever came last. Seven patients discontinued due to disease progression (3.8%).
Consider open-label (OLE) study limitations when interpreting the above results. The OLE study is not blinded, not controlled, and includes inherent self-selection bias. A total of 6 patients (3.3%) had adverse events that led to discontinuation of ENBREL and 5 patients (2.7%) had adverse events that led to discontinuation of the study.20
PASI 50: 88% of patients taking ENBREL achieved PASI 50 at Week 312.22†
PASI 75: 64% of patients taking ENBREL achieved PASI 75 at Week 312.22†
PASI 90: 29% of patients taking ENBREL achieved PASI 90 at Week 312.22†
† ITT as observed.
ENBREL provides results over time
- 38% of patients taking ENBREL maintained an sPGA of clear or almost clear at Week 31223‡
Consider open-label extension (OLE) study limitations when interpreting the above results. The OLE study is not blinded, not controlled, and includes inherent self-selection bias. A total of 6 patients (3.3%) had adverse events that led to discontinuation of ENBREL and 5 patients (2.7%) had adverse events that led to discontinuation of the study.20
~4 out of 10 patients treated with ENBREL consistently experienced clear or almost clear skin through 312 weeks23‡
‡ As observed.
In a post hoc analysis of the ENBREL Pediatric Pivotal Study
In a post hoc analysis of the ENBREL Pediatric Pivotal Study
ENBREL improved PASI regardless of BMI*-for-age percentiles
- Post hoc analysis is exploratory and no statistical conclusions can be drawn
*BMI=Body Mass Index.
† Healthy weight=BMI 5th-84th percentile, overweight=BMI 85th-94th percentile, and obese=BMI ≥95th percentile.25
For pediatric patients with chronic moderate to severe plaque PsO
For pediatric patients with chronic moderate to severe plaque PsO
Types of adverse events and reactions reported in pediatric patients1
Adverse events observed in the 12-week double-blind period
- No serious adverse event was reported during the 12-week double-blind period19†
- 1 subject withdrew from the study during the 12-week double-blind period due to an adverse event19
Adverse reaction profile was generally similar to adult PsO‡
- In a 48-week clinical study in 211 children aged 4 to 17 years with pediatric plaque PsO, the adverse reactions reported were similar to those seen in previous studies in adults with PsO1
- In controlled trials, 7% of pediatric patients treated with ENBREL developed injection site reactions during the first 3 months of treatment1
IMPORTANT SAFETY CONSIDERATIONS
In general, the adverse reactions in pediatric patients were similar in frequency and type as those seen in adult patients. The types of infections reported in pediatric patients were generally mild and consistent with those commonly seen in the general pediatric population.
Long-term safety was consistent through 6 years of combined parent and open-label extension studies16
- Long-term safety profile for up to 264 additional weeks was assessed in an open-label extension study and no new safety signals were identified1
- No cases of malignancy, lymphoma, or opportunistic infection were reported among patients treated with ENBREL in the study16,20†
- 2 cases of serious infection among 181 pediatric patients treated with ENBREL16,20†
- Cellulitis (treatment related)
- Infectious mononucleosis
- Other serious adverse events included the following: abortion induced, anxiety, intestinal obstruction, osteonecrosis, and thyroid cyst16
IMPORTANT SAFETY CONSIDERATIONS
- Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, including ENBREL1
- Lymphoma: In clinical trials of all TNF inhibitors, more cases of lymphoma were seen compared to control patients. The risk of lymphoma may be up to several-fold higher in RA patients; the role of TNF inhibitors in the development of malignancies is unknown1,27,28
- NMSC: Nonmelanoma skin cancer has been reported in patients treated with TNF antagonists including ENBREL. Among adult psoriasis patients treated with ENBREL (n=1,245) in controlled clinical trials, the observed rate of NMSC was 0.04 events/pt-yr vs 0.01 events/pt-yr among control-treated patients (n=720)1
- Serious Infection: Infections, including serious infections, some fatal, have been observed in patients treated with ENBREL. Discontinue ENBREL if a patient develops a serious infection or sepsis. Patients are at increased risk for developing serious infections when taking ENBREL that may lead to hospitalization or death. Most patients who developed these serious infections were taking concomitant immunosuppressants1
- Tuberculosis: Cases of reactivation of TB or new TB infections have been observed in patients receiving ENBREL. Patients should be evaluated for TB risk factors and be tested for latent TB infection prior to initiating ENBREL and during treatment1
* An adverse event is any untoward medical event associated with the use of a drug, whether or not it is considered drug related.
† A serious adverse event is one that suggests a significant hazard or side effect, including but not limited to any event that is fatal, life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, is a persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.
‡ An adverse reaction is an adverse event for which there is some basis to believe there is a causal relationship between the drug and the occurrence of the adverse event.
Prescription Enbrel® (etanercept) is administered by injection.
IMPORTANT SAFETY INFORMATION AND INDICATIONS
SERIOUS INFECTIONS
Patients treated with ENBREL are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids or were predisposed to infection because of their underlying disease. ENBREL should not be initiated in the presence of sepsis, active infections, or allergy to ENBREL or its components. ENBREL should be discontinued if a patient develops a serious infection or sepsis. Reported infections include: 1) Active tuberculosis (TB), including reactivation of latent TB. Patients with TB have frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent TB before ENBREL use and periodically during therapy. Treatment for latent infection should be initiated prior to ENBREL use, 2) Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Empiric antifungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness, and 3) Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella and Listeria.
The risks and benefits of treatment with ENBREL should be carefully considered prior to initiating therapy in patients 1) with chronic or recurrent infection, 2) who have been exposed to TB, 3) who have resided or traveled in areas of endemic TB or endemic mycoses, or 4) with underlying conditions that may predispose them to infections such as advanced or poorly controlled diabetes. Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with ENBREL, including the possible development of TB in patients who tested negative for latent TB prior to initiating therapy.
MALIGNANCIES
Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with tumor necrosis factor (TNF) blockers, including ENBREL.
In adult clinical trials of all TNF blockers, more cases of lymphoma were seen compared to control patients. The risk of lymphoma may be up to several-fold higher in RA patients. The role of TNF blocker therapy in the development of malignancies is unknown.
Cases of acute and chronic leukemia have been reported in association with postmarketing TNF blocker use in RA and other indications. The risk of leukemia may be higher in patients with RA (approximately 2-fold) than the general population.
Melanoma and non-melanoma skin cancer (NMSC) have been reported in patients treated with TNF blockers, including ENBREL. Periodic skin examinations should be considered for all patients at increased risk for skin cancer.
Pediatric Patients
In patients who initiated therapy at ≤18 years of age, approximately half of the reported malignancies were lymphomas (Hodgkin’s and non-Hodgkin’s lymphoma). Other cases included rare malignancies usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. Most of the patients were receiving concomitant immunosuppressants.
NEUROLOGIC REACTIONS
Treatment with TNF-blocking agents, including ENBREL, has been associated with rare (<0.1%) cases of new onset or exacerbation of central nervous system demyelinating disorders, some presenting with mental status changes and some associated with permanent disability, and with peripheral nervous system demyelinating disorders. Cases of transverse myelitis, optic neuritis, multiple sclerosis, Guillain-Barré syndromes, other peripheral demyelinating neuropathies, and new onset or exacerbation of seizure disorders have been reported in postmarketing experience with ENBREL therapy. Prescribers should exercise caution in considering the use of ENBREL in patients with preexisting or recent-onset central or peripheral nervous system demyelinating disorders.
CONGESTIVE HEART FAILURE
Cases of worsening congestive heart failure (CHF) and, rarely, new-onset cases have been reported in patients taking ENBREL. Caution should be used when using ENBREL in patients with CHF. These patients should be carefully monitored.
HEMATOLOGIC REACTIONS
Rare cases of pancytopenia, including aplastic anemia, some fatal, have been reported. The causal relationship to ENBREL therapy remains unclear. Exercise caution when considering ENBREL in patients who have a previous history of significant hematologic abnormalities. Advise patients to seek immediate medical attention if they develop signs or symptoms of blood dyscrasias or infection. Consider discontinuing ENBREL if significant hematologic abnormalities are confirmed.
HEPATITIS B REACTIVATION
Reactivation of hepatitis B has been reported in patients who were previously infected with hepatitis B virus (HBV) and received concomitant TNF-blocking agents, including ENBREL. Most reports occurred in patients also taking immunosuppressive agents, which may contribute to hepatitis B reactivation. Exercise caution when considering ENBREL in these patients.
ALLERGIC REACTIONS
Allergic reactions associated with administration of ENBREL during clinical trials have been reported in <2% of patients. If an anaphylactic reaction or other serious allergic reaction occurs, administration of ENBREL should be discontinued immediately and appropriate therapy initiated.
IMMUNIZATIONS
Live vaccines should not be administered to patients on ENBREL. Pediatric patients, if possible, should be brought up to date with all immunizations prior to initiating ENBREL. In patients with exposure to varicella virus, temporarily discontinue ENBREL and consider prophylactic treatment with Varicella Zoster Immune Globulin.
AUTOIMMUNITY
Autoantibodies may develop with ENBREL, and rarely lupus-like syndrome or autoimmune hepatitis may occur. These may resolve upon withdrawal of ENBREL. Stop ENBREL if lupus-like syndrome or autoimmune hepatitis develops.
WEGENER’S GRANULOMATOSIS PATIENTS
The use of ENBREL in patients with Wegener’s granulomatosis receiving immunosuppressive agents (eg, cyclophosphamide) is not recommended.
MODERATE TO SEVERE ALCOHOLIC HEPATITIS
Based on a study of patients treated for alcoholic hepatitis, exercise caution when using ENBREL in patients with moderate to severe alcoholic hepatitis.
ADVERSE REACTIONS
The most commonly reported adverse reactions in RA clinical trials were injection site reaction and infection. In clinical trials of all other adult indications, adverse reactions were similar to those reported in RA clinical trials.
In general, the adverse reactions in pediatric patients were similar in frequency and type as those seen in adult patients. The types of infections reported in pediatric patients were generally mild and consistent with those commonly seen in the general pediatric population.
DRUG INTERACTIONS
The use of ENBREL in patients receiving concurrent cyclophosphamide therapy is not recommended. The risk of serious infection may increase with concomitant use of abatacept therapy. Concurrent therapy with ENBREL and anakinra is not recommended. Hypoglycemia has been reported following initiation of ENBREL therapy in patients receiving medication for diabetes, necessitating a reduction in anti-diabetic medication in some of these patients.
Please see Prescribing Information and Medication Guide.
INDICATIONS
ENBREL is indicated for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in patients with moderately to severely active rheumatoid arthritis. ENBREL can be initiated in combination with methotrexate (MTX) or used alone.
ENBREL is indicated for reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients ages 2 and older.
ENBREL is indicated for reducing signs and symptoms, inhibiting the progression of structural damage of active arthritis, and improving physical function in patients with psoriatic arthritis (PsA). ENBREL can be used with or without MTX.
ENBREL is indicated for reducing signs and symptoms in patients with active ankylosing spondylitis.
ENBREL is indicated for the treatment of patients 4 years or older with chronic moderate to severe plaque psoriasis (PsO) who are candidates for systemic therapy or phototherapy.
References:
- Enbrel® (etanercept) Prescribing Information, lmmunex Corporation, Thousand Oaks, Calif.
- Data on file, Amgen; Pediatric PsO Approval Letter: November 4, 2016.
- Rachakonda TD, Schupp CW, Armstrong AW. Psoriasis prevalence among adults in the United States. J Am Acad Dermatol. 2014;70:512-516.
- Thomas J, Parimalam K. Treating pediatric plaque psoriasis: challenges and solutions. Pediatric Health Med Ther. 2016;7:25-38.
- Burden-Teh E, Thomas KS, Ratib S, Grindlay D, Adaji E, Murphy R. The epidemiology of childhood psoriasis: a scoping review. Br J Dermatol. 2016;174:1242-1257.
- National Psoriasis Foundation. About psoriasis. https://www.psoriasis.org/about-psoriasis#children. Accessed September 5, 2017.
- Augustin M, Glaeske G, Radtke MA, Christophers E, Reich K, Schäfer I. Epidemiology and comorbidity of psoriasis in children. Br J Dermatol.2010;162:633-636.
- Wu JJ, Black MH, Smith N, Porter AH, Jacobsen SJ, Koebnick C. Low prevalence of psoriasis among children and adolescents in a large multiethnic cohort in southern California. J Am Acad Dermatol. 2011;65:957-964.
- Tollefson MM, Crowson CS, McEvoy MT, Kremers HM. Incidence of psoriasis in children: a population-based study. J Am Acad Dermatol. 2010;62:979-987.
- Kapila S, Hong E, Fischer G. A comparative study of childhood psoriasis and atopic dermatitis and greater understanding of the overlapping condition, psoriasis-dermatitis. Australas J Dermatol. 2012;53:98-105.
- Paller AS, Siegfried EC, Langley RG, et al. Etanercept treatment for children and adolescents with plaque psoriasis. N Engl J Med. 2008;358:241-251.
- Science Source Images Website. Atopic Dermatitis Behind the Knees. https://sciencesource.com/archive/Atopic-dermatitis-behind-the-knees-SS2560282.html.
- American Board of Medical Specialties. 2014-2015 AMBS board certification report. 2015.http://www.abms.org/media/
84770/2013_2014_abmscertreport.pdf. Accessed November 1, 2017. - Children’s Hospital Association. Pediatric specialist physician shortages affect access to care. 2012. https://www.childrenshospitals.org/issues-and-advocacy/graduate-medical-education/fact-sheets/2012/pediatricspecialist-physician-shortages-affect-access-to-care. Accessed November 1, 2017.
- Bronckers IM, Paller AS, van Geel MJ, van de Kerkhof PCM, Seyger MMB. Psoriasis in children and adolescents: diagnosis, management and comorbidities. Pediatr Drugs. 2015;17:373-384.
- Paller AS, Siegfried EC, Pariser DM, et al. Long-term safety and efficacy of etanercept in children and adolescents with plaque psoriasis. J Am Acad Dermatol.2016;74:280-287.
- Data on file, Amgen; Number of subjects with baseline weight over certain threshold: September 20, 2016.
- Data on file, Amgen; CSR 20030211 Pediatric PsO double-blind: September 18, 2006.
- Data on file, Amgen; CSR 20030211 Pediatric PsO final: July 16, 2007.
- Data on file, Amgen; CSR 20050111 Pediatric PsO OLE: June 1, 2012.
- Data on file, Amgen; CSR 20030211 Pediatric PsO sPGA week 2 to 48: April 21, 2017.
- Data on file, Amgen; CSR 20050111 Pediatric PsO OLE PASI 50, 75, 90 baseline to week 264: April 21, 2017.
- Data on file, Amgen; CSR 20050111 Pediatric PsO OLE sPGA baseline to week 264: April 21, 2017.
- Data on file, Amgen; CSR 20030211 Pediatric PsO PASI 75 and weight: April 21, 2017.
- Barlow SE; Expert Committee. Expert committee recommendations regarding the prevention, assessment, and treatment of child and adolescent overweight and obesity: summary report. Pediatrics. 2007;120:S164-S192.
- Data on file, Amgen; CSR 20050111 Serious adverse events: November 2, 2016.
- US Food and Drug Administration website. Humira label and approval history. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm
?fuseaction=Search.Label_ApprovalHistory#apphist. Accessed September 5, 2017. - US Food and Drug Administration website. Remicade label and approval history. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm
?fuseaction=Search.Label_ApprovalHistory#apphist. Accessed September 5, 2017.
IMPORTANT SAFETY INFORMATION AND INDICATIONS: SERIOUS INFECTIONS
Patients treated with ENBREL are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids or were predisposed to infection because of their underlying disease. ENBREL should not be initiated in the presence of sepsis, active infections, or allergy to ENBREL or its components. ENBREL should be discontinued if a patient develops a serious infection or sepsis. Reported infections include: 1) Active tuberculosis (TB), including reactivation of latent TB. Patients with TB have frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent TB before ENBREL use and periodically during therapy. Treatment for latent infection should be initiated prior to ENBREL use, 2) Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Empiric antifungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness, and 3) Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella and Listeria.
The risks and benefits of treatment with ENBREL should be carefully considered prior to initiating therapy in patients 1) with chronic or recurrent infection, 2) who have been exposed to TB, 3) who have resided or traveled in areas of endemic TB or endemic mycoses, or 4) with underlying conditions that may predispose them to infections such as advanced or poorly controlled diabetes. Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with ENBREL, including the possible development of TB in patients who tested negative for latent TB prior to initiating therapy.
MALIGNANCIES
Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with tumor necrosis factor (TNF) blockers, including ENBREL.
In adult clinical trials of all TNF blockers, more cases of lymphoma were seen compared to control patients. The risk of lymphoma may be up to several-fold higher in RA patients. The role of TNF blocker therapy in the development of malignancies is unknown.
Cases of acute and chronic leukemia have been reported in association with postmarketing TNF blocker use in RA and other indications. The risk of leukemia may be higher in patients with RA (approximately 2-fold) than the general population.
Melanoma and non-melanoma skin cancer (NMSC) have been reported in patients treated with TNF blockers, including ENBREL. Periodic skin examinations should be considered for all patients at increased risk for skin cancer.
Pediatric Patients
In patients who initiated therapy at ≤18 years of age, approximately half of the reported malignancies were lymphomas (Hodgkin’s and non-Hodgkin’s lymphoma). Other cases included rare malignancies usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. Most of the patients were receiving concomitant immunosuppressants.
NEUROLOGIC REACTIONS
Treatment with TNF-blocking agents, including ENBREL, has been associated with rare (<0.1%) cases of new onset or exacerbation of central nervous system demyelinating disorders, some presenting with mental status changes and some associated with permanent disability, and with peripheral nervous system demyelinating disorders. Cases of transverse myelitis, optic neuritis, multiple sclerosis, Guillain-Barré syndromes, other peripheral demyelinating neuropathies, and new onset or exacerbation of seizure disorders have been reported in postmarketing experience with ENBREL therapy. Prescribers should exercise caution in considering the use of ENBREL in patients with preexisting or recent-onset central or peripheral nervous system demyelinating disorders.
CONGESTIVE HEART FAILURE
Cases of worsening congestive heart failure (CHF) and, rarely, new-onset cases have been reported in patients taking ENBREL. Caution should be used when using ENBREL in patients with CHF. These patients should be carefully monitored.
HEMATOLOGIC REACTIONS
Rare cases of pancytopenia, including aplastic anemia, some fatal, have been reported. The causal relationship to ENBREL therapy remains unclear. Exercise caution when considering ENBREL in patients who have a previous history of significant hematologic abnormalities. Advise patients to seek immediate medical attention if they develop signs or symptoms of blood dyscrasias or infection. Consider discontinuing ENBREL if significant hematologic abnormalities are confirmed.
HEPATITIS B REACTIVATION
Reactivation of hepatitis B has been reported in patients who were previously infected with hepatitis B virus (HBV) and received concomitant TNF-blocking agents, including ENBREL. Most reports occurred in patients also taking immunosuppressive agents, which may contribute to hepatitis B reactivation. Exercise caution when considering ENBREL in these patients.
ALLERGIC REACTIONS
Allergic reactions associated with administration of ENBREL during clinical trials have been reported in <2% of patients. If an anaphylactic reaction or other serious allergic reaction occurs, administration of ENBREL should be discontinued immediately and appropriate therapy initiated.
IMMUNIZATIONS
Live vaccines should not be administered to patients on ENBREL. Pediatric patients, if possible, should be brought up to date with all immunizations prior to initiating ENBREL. In patients with exposure to varicella virus, temporarily discontinue ENBREL and consider prophylactic treatment with Varicella Zoster Immune Globulin.
AUTOIMMUNITY
Autoantibodies may develop with ENBREL, and rarely lupus-like syndrome or autoimmune hepatitis may occur. These may resolve upon withdrawal of ENBREL. Stop ENBREL if lupus-like syndrome or autoimmune hepatitis develops.
WEGENER’S GRANULOMATOSIS PATIENTS
The use of ENBREL in patients with Wegener’s granulomatosis receiving immunosuppressive agents (eg, cyclophosphamide) is not recommended.
MODERATE TO SEVERE ALCOHOLIC HEPATITIS
Based on a study of patients treated for alcoholic hepatitis, exercise caution when using ENBREL in patients with moderate to severe alcoholic hepatitis.
ADVERSE REACTIONS
The most commonly reported adverse reactions in RA clinical trials were injection site reaction and infection. In clinical trials of all other adult indications, adverse reactions were similar to those reported in RA clinical trials.
In general, the adverse reactions in pediatric patients were similar in frequency and type as those seen in adult patients. The types of infections reported in pediatric patients were generally mild and consistent with those commonly seen in the general pediatric population.
DRUG INTERACTIONS
The use of ENBREL in patients receiving concurrent cyclophosphamide therapy is not recommended. The risk of serious infection may increase with concomitant use of abatacept therapy. Concurrent therapy with ENBREL and anakinra is not recommended. Hypoglycemia has been reported following initiation of ENBREL therapy in patients receiving medication for diabetes, necessitating a reduction in anti-diabetic medication in some of these patients.
Please see Prescribing Information and Medication Guide.
INDICATIONS
ENBREL is indicated for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in patients with moderately to severely active rheumatoid arthritis. ENBREL can be initiated in combination with methotrexate (MTX) or used alone.
ENBREL is indicated for reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients ages 2 and older.
ENBREL is indicated for reducing signs and symptoms, inhibiting the progression of structural damage of active arthritis, and improving physical function in patients with psoriatic arthritis (PsA). ENBREL can be used with or without MTX.
ENBREL is indicated for reducing signs and symptoms in patients with active ankylosing spondylitis.
ENBREL is indicated for the treatment of patients 4 years or older with chronic moderate to severe plaque psoriasis (PsO) who are candidates for systemic therapy or phototherapy.
Prescription Enbrel® (etanercept) is administered by injection.
IMPORTANT SAFETY INFORMATION AND INDICATIONS
SERIOUS INFECTIONS
Patients treated with ENBREL are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids or were predisposed to infection because of their underlying disease. ENBREL should not be initiated in the presence of sepsis, active infections, or allergy to ENBREL or its components. ENBREL should be discontinued if a patient develops a serious infection or sepsis. Reported infections include: 1) Active tuberculosis (TB), including reactivation of latent TB. Patients with TB have frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent TB before ENBREL use and periodically during therapy. Treatment for latent infection should be initiated prior to ENBREL use, 2) Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Empiric antifungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness, and 3) Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella and Listeria.
The risks and benefits of treatment with ENBREL should be carefully considered prior to initiating therapy in patients 1) with chronic or recurrent infection, 2) who have been exposed to TB, 3) who have resided or traveled in areas of endemic TB or endemic mycoses, or 4) with underlying conditions that may predispose them to infections such as advanced or poorly controlled diabetes. Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with ENBREL, including the possible development of TB in patients who tested negative for latent TB prior to initiating therapy.
MALIGNANCIES
Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with tumor necrosis factor (TNF) blockers, including ENBREL.
In adult clinical trials of all TNF blockers, more cases of lymphoma were seen compared to control patients. The risk of lymphoma may be up to several-fold higher in RA patients. The role of TNF blocker therapy in the development of malignancies is unknown.
Cases of acute and chronic leukemia have been reported in association with postmarketing TNF blocker use in RA and other indications. The risk of leukemia may be higher in patients with RA (approximately 2-fold) than the general population.
Melanoma and non-melanoma skin cancer (NMSC) have been reported in patients treated with TNF blockers, including ENBREL. Periodic skin examinations should be considered for all patients at increased risk for skin cancer.
Pediatric Patients
In patients who initiated therapy at ≤18 years of age, approximately half of the reported malignancies were lymphomas (Hodgkin’s and non-Hodgkin’s lymphoma). Other cases included rare malignancies usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. Most of the patients were receiving concomitant immunosuppressants.
NEUROLOGIC REACTIONS
Treatment with TNF-blocking agents, including ENBREL, has been associated with rare (<0.1%) cases of new onset or exacerbation of central nervous system demyelinating disorders, some presenting with mental status changes and some associated with permanent disability, and with peripheral nervous system demyelinating disorders. Cases of transverse myelitis, optic neuritis, multiple sclerosis, Guillain-Barré syndromes, other peripheral demyelinating neuropathies, and new onset or exacerbation of seizure disorders have been reported in postmarketing experience with ENBREL therapy. Prescribers should exercise caution in considering the use of ENBREL in patients with preexisting or recent-onset central or peripheral nervous system demyelinating disorders.
CONGESTIVE HEART FAILURE
Cases of worsening congestive heart failure (CHF) and, rarely, new-onset cases have been reported in patients taking ENBREL. Caution should be used when using ENBREL in patients with CHF. These patients should be carefully monitored.
HEMATOLOGIC REACTIONS
Rare cases of pancytopenia, including aplastic anemia, some fatal, have been reported. The causal relationship to ENBREL therapy remains unclear. Exercise caution when considering ENBREL in patients who have a previous history of significant hematologic abnormalities. Advise patients to seek immediate medical attention if they develop signs or symptoms of blood dyscrasias or infection. Consider discontinuing ENBREL if significant hematologic abnormalities are confirmed.
HEPATITIS B REACTIVATION
Reactivation of hepatitis B has been reported in patients who were previously infected with hepatitis B virus (HBV) and received concomitant TNF-blocking agents, including ENBREL. Most reports occurred in patients also taking immunosuppressive agents, which may contribute to hepatitis B reactivation. Exercise caution when considering ENBREL in these patients.
ALLERGIC REACTIONS
Allergic reactions associated with administration of ENBREL during clinical trials have been reported in <2% of patients. If an anaphylactic reaction or other serious allergic reaction occurs, administration of ENBREL should be discontinued immediately and appropriate therapy initiated.
IMMUNIZATIONS
Live vaccines should not be administered to patients on ENBREL. Pediatric patients, if possible, should be brought up to date with all immunizations prior to initiating ENBREL. In patients with exposure to varicella virus, temporarily discontinue ENBREL and consider prophylactic treatment with Varicella Zoster Immune Globulin.
AUTOIMMUNITY
Autoantibodies may develop with ENBREL, and rarely lupus-like syndrome or autoimmune hepatitis may occur. These may resolve upon withdrawal of ENBREL. Stop ENBREL if lupus-like syndrome or autoimmune hepatitis develops.
WEGENER’S GRANULOMATOSIS PATIENTS
The use of ENBREL in patients with Wegener’s granulomatosis receiving immunosuppressive agents (eg, cyclophosphamide) is not recommended.
MODERATE TO SEVERE ALCOHOLIC HEPATITIS
Based on a study of patients treated for alcoholic hepatitis, exercise caution when using ENBREL in patients with moderate to severe alcoholic hepatitis.
ADVERSE REACTIONS
The most commonly reported adverse reactions in RA clinical trials were injection site reaction and infection. In clinical trials of all other adult indications, adverse reactions were similar to those reported in RA clinical trials.
In general, the adverse reactions in pediatric patients were similar in frequency and type as those seen in adult patients. The types of infections reported in pediatric patients were generally mild and consistent with those commonly seen in the general pediatric population.
DRUG INTERACTIONS
The use of ENBREL in patients receiving concurrent cyclophosphamide therapy is not recommended. The risk of serious infection may increase with concomitant use of abatacept therapy. Concurrent therapy with ENBREL and anakinra is not recommended. Hypoglycemia has been reported following initiation of ENBREL therapy in patients receiving medication for diabetes, necessitating a reduction in anti-diabetic medication in some of these patients.
Please see Prescribing Information and Medication Guide.
INDICATIONS
ENBREL is indicated for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in patients with moderately to severely active rheumatoid arthritis. ENBREL can be initiated in combination with methotrexate (MTX) or used alone.
ENBREL is indicated for reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients ages 2 and older.
ENBREL is indicated for reducing signs and symptoms, inhibiting the progression of structural damage of active arthritis, and improving physical function in patients with psoriatic arthritis (PsA). ENBREL can be used with or without MTX.
ENBREL is indicated for reducing signs and symptoms in patients with active ankylosing spondylitis.
ENBREL is indicated for the treatment of patients 4 years or older with chronic moderate to severe plaque psoriasis (PsO) who are candidates for systemic therapy or phototherapy.