Enbrel therapeutic indications

Indication

Enbrel in combination with MTX is indicated for the treatment of moderate to severe active RA in adults when the response to DMARDs, including MTX (unless contraindicated), has been inadequate.1

Enbrel can be given as monotherapy in case of intolerance to MTX or when continued treatment with MTX is inappropriate.1

Enbrel is also indicated in the treatment of severe, active and progressive RA in adults not previously treated with MTX.1

Enbrel, alone or in combination with MTX, has been shown to reduce the rate of progression of joint damage as measured by X-ray and to improve physical function.1

Contraindications

Hypersensitivity to the active substance or to any of the excipients1
Sepsis or risk of sepsis1
Treatment with Enbrel should not be initiated in patients with active infections, including chronic or localised infections1
 

RA dosing

Enbrel treatment should be initiated and supervised by specialist physicians experienced in the diagnosis and treatment of RA. Patients treated with Enbrel should be given the Patient Alert Card.1

25 mg Enbrel administered twice weekly is the recommended dose. Alternatively, 50 mg administered once weekly has been shown to be safe and effective.1

Clinical efficacy

Enbrel is efficacious both in combination with MTX and in monotherapy. Enbrel inhibits radiographic progression alone and in combination with MTX in moderate to severe RA.2,3

Enbrel monotherapy in RA patients

The TEMPO trial was a double-blind, randomised control trial in 686 patients with active, adult-onset RA. Subjects were randomised to receive Enbrel alone (25 mg Enbrel twice weekly + placebo); MTX alone (7.5 mg orally every week up to 20 mg within 8 weeks if the patient had any painful or swollen joints + placebo) or combination therapy (25 mg subcutaneous Enbrel injections twice a week + oral MTX capsules once a week). The primary efficacy endpoint was the numeric index of the ACR response area under the curve over the first 24 weeks. The primary radiographic endpoint was the change from baseline to Week 52 in total joint damage, assessed with the modified Sharp score and intention-to-treat analysis.3

Adapted from Van Riel PL et al. 2006.

Summary of the safety profile

The most commonly reported adverse reactions are injection site reactions (such as pain, swelling, itching, reddening and bleeding at the puncture site), infections (such as upper respiratory infections, bronchitis, bladder infections and skin infections), allergic reactions, development of autoantibodies, itching, and fever.1

Serious adverse reactions have also been reported for Enbrel. TNF-antagonists, such as Enbrel, affect the immune system and their use may affect the body's defenses against infection and cancer. Serious infections affect fewer than 1 in 100 patients treated with Enbrel. Reports have included fatal and life-threatening infections and sepsis. Various malignancies have also been reported with use of Enbrel, including cancers of the breast, lung, skin and lymph glands (lymphoma).1

Serious haematological, neurological and autoimmune reactions have also been reported. These include rare reports of pancytopenia and very rare reports of aplastic anaemia. Central and peripheral demyelinating events have been seen rarely and very rarely, respectively, with Enbrel use. There have been rare reports of lupus, lupus-related conditions, and vasculitis.1

Learn more about Enbrel dosing and methods of administration.

Before prescribing Enbrel refer to the full Summary of Product Characteristics.

ACR: American College of Rheumatology; DAS: disease activity score; DMARD: disease modifying anti-rheumatic drug; MTX: Methotrexate; RA: rheumatoid arthritis; TEMPO: Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes.

1.Enbrel (etanercept) SmPC. 50 mg solution for injection in pre-filled pen. Available at http://www.medicines.org.uk/emc [Accessed October 2017].
2.Emery P, et al. Lancet. 2008; 372(9636):375–382.
3.Klareskog L, et al. Lancet. 2004; 363:675–681.
4.Van Riel PL, et al. BMJ. 2006; 65: 1478–1483.

 

PP-ENB-GBR-0673 | November 2017

Indication

Enbrel is indicated for the treatment of polyarthritis (rheumatoid factor positive or negative) and extended oligoarthritis in children and adolescents from the age of 2 years who have had an inadequate response to, or who have proved intolerant of, MTX.1

Treatment of PsA in adolescents from the age of 12 years who have had an inadequate response to, or who have proved intolerant of, MTX.1

Treatment of enthesitis-related arthritis in adolescents from the age of 12 years who have had an inadequate response to, or who have proved intolerant of, conventional therapy.1

Enbrel has not been studied in children aged less than 2 years.1

Contraindications

Hypersensitivity to the active substance or to any of the excipients1
Sepsis or risk of sepsis1
Treatment with Enbrel should not be initiated in patients with active infections, including chronic or localised infections1

 

JIA dosing

The recommended dose of Enbrel is 0.4 mg/kg (up to a maximum of 25 mg per dose) given twice weekly as a subcutaneous injection with an interval of 3–4 days between doses or 0.8 mg/kg (up to a maximum of 50 mg per dose) given once weekly.1

Discontinuation of treatment should be considered in patients who show no response after 4 months.1

No formal clinical trials have been conducted in children aged 2–3 years. There is generally no applicable use of Enbrel in children aged below 2 years in the indication JIA.1

Clinical efficacy

The safety and efficacy of Enbrel were assessed in a two-part study in 69 children aged 4–17 years with polyarticular-course JIA who had a variety of JIA onset types (polyarthritis, pauciarthritis, systemic onset). Patients remained on a stable dose of a single nonsteroidal anti-inflammatory drug and/or prednisone (< 0.2 mg/kg/day or 10 mg maximum). In part 1, all patients received 0.4 mg/kg (maximum 25 mg per dose) Enbrel subcutaneously twice weekly. In part 2, patients with a clinical response at day 90 were randomised to remain on Enbrel or receive placebo for four months and assessed for disease flare. Responses were measured using the ACR Pedi 30, defined as ≥ 30% improvement in at least three of six and ≥ 30% worsening in no more than one of six JRA core set criteria.2

In part 1 of the study, 51 of 69 (74%) patients demonstrated a clinical response and entered part 2. In part 2, 6 of 25 (24%) patients remaining on Enbrel experienced a disease flare compared to 20 of 26 (77%) patients receiving placebo (p=0.007). From the start of part 2, the median time to flare was ≥ 116 days for patients who received Enbrel and 28 days for patients who received.2 

Of patients who demonstrated a clinical response at 90 days and entered part 2 of the study, some of the patients remaining on Enbrel continued to improve from month 3 through month 7, while those who received placebo did not improve.2

See the RA tab for more information about Enbrel efficacy in adult RA patients.

Summary of the safety profile in patients with JIA

In general, the adverse events in paediatric patients with JIA were similar in frequency and type to those seen in adult patients (see the RA page for undesirable effects in adults). Differences from adults and other special considerations are covered below.1

The types of infections seen in clinical trials in JIA patients aged 2–18 years were generally mild to moderate and consistent with those commonly seen in outpatient paediatric populations. Severe adverse events reported included varicella with signs and symptoms of aseptic meningitis, which resolved without sequelae, appendicitis, gastroenteritis, depression/personality disorder, cutaneous ulcer, oesophagitis/gastritis, group A streptococcal septic shock, type I diabetes mellitus, and soft tissue and post-operative wound infection.1

Several adverse events were reported more commonly in JIA patients receiving 3 months of Enbrel treatment compared to adult RA patients. These included headache, nausea, abdominal pain, and vomiting.1

There were 4 reports of macrophage activation syndrome in JIA clinical trials.1

There have been reports of inflammatory bowel disease and uveitis in JIA patients being treated with Enbrel from post-marketing sources, including a very small number of cases indicating a positive rechallenge.1

Before prescribing Enbrel refer to the full Summary of Product Characteristics.

Learn more about Enbrel dosing and methods of administration.

ACR Pedi: American College of Rheumatology Paediatric; JIA: juvenile idiopathic arthritis; JRA: juvenile rheumatoid arthritis; MTX: methotrexate; PsA: psoriatic arthritis; RA: rheumatoid arthritis.

1.Enbrel (etanercept) SmPC. Enbrel 10 mg powder and solvent for solution for injection for paediatric use. Available at http://www.medicines.org.uk/emc [Accessed October 2017].
2.Lovell DJ, et al. NEJM. 2000; 342:763–769.

 

PP-ENB-GBR-0675 | November 2017

Indication

Enbrel is indicated for the treatment of active and progressive PsA in adults when the response to previous DMARD therapy has been inadequate. Enbrel has been shown to improve physical function in patients with PsA, and to reduce the rate of progression of peripheral joint damage as measured by X-ray in patients with polyarticular symmetrical subtypes of the disease.1  

Contraindications

Hypersensitivity to the active substance or to any of the excipients1
Sepsis or risk of sepsis1
Treatment with Enbrel should not be initiated in patients with active infections, including chronic or localised infections1

 

PsA dosing

The recommended dose of Enbrel in adults is 25 mg administered twice weekly, or 50 mg administered once weekly.1

Data suggest that a clinical response is usually achieved within 12 weeks of treatment. Continued therapy should be carefully reconsidered in a patient not responding within this time period.1

Clinical efficacy

The efficacy of Enbrel was assessed in a randomised, double-blind, placebo-controlled study in 205 patients aged 18–70 years with active PsA. Patients also had plaque psoriasis with a qualifying target lesion ≥ 2 cm in diameter. Patients had previously been treated with NSAIDs (86%), DMARDs (80%), and corticosteroids (24%). Patients currently on MTX therapy (stable for ≥ 2 months) could continue at a stable dose of ≤ 25 mg/week MTX. Doses of 25 mg of Enbrel or placebo were administered SC twice a week for 6 months.2

Clinical responses were expressed as percentages of patients achieving the ACR 20, 50, and 70 response and improvement in PsARC.2

 Percentage of patients achieving ACR 20, 50, and 70 and improvement in PsARC2

[[{"fid":"8901","view_mode":"default","attributes":{"height":"960","width":"1471","style":"width: 727px;","class":"panopoly-image-original media-element file-default"},"type":"media"}]]

Among patients with PsA who received Enbrel, the clinical responses were apparent at the time of the first visit (4 weeks) and were maintained through 6 months of therapy. Enbrel was significantly better than placebo in all measures of disease activity (p < 0.001), and responses were similar with and without concomitant MTX therapy. Quality of life in PsA patients was assessed at every timepoint using the disability index of the HAQ. The disability index score was significantly improved at all timepoints in PsA patients treated with Enbrel, relative to placebo (p < 0.001).2

The percentage of patients without disease progression (TSS change ≤ 0.5) at 12 months was higher in the Enbrel group compared with the placebo group (73% vs. 47%, respectively, p ≤ 0.001). The effect of Enbrel on radiographic progression was maintained in patients who continued on treatment during the second year. The slowing of peripheral joint damage was observed in patients with polyarticular symmetrical joint involvement.2

Enbrel treatment resulted in improvement in physical function during the double-blind period, and this benefit was maintained during the longer-term exposure of up to 2 years.2

For more information on the efficacy of Enbrel in nr-AxSpA click here to watch Professor Maxime Dougados give an overview of EMBARK poster data.

Summary of the safety profile

The most commonly reported adverse reactions are injection site reactions (such as pain, swelling, itching, reddening and bleeding at the puncture site), infections (such as upper respiratory infections, bronchitis, bladder infections and skin infections), allergic reactions, development of autoantibodies, itching, and fever.1

Serious adverse reactions have also been reported for Enbrel. TNF-antagonists, such as Enbrel, affect the immune system and their use may affect the body's defenses against infection and cancer. Serious infections affect fewer than 1 in 100 patients treated with Enbrel. Reports have included fatal and life-threatening infections and sepsis. Various malignancies have also been reported with use of Enbrel, including cancers of the breast, lung, skin and lymph glands (lymphoma).1

Serious haematological, neurological and autoimmune reactions have also been reported. These include rare reports of pancytopenia and very rare reports of aplastic anaemia. Central and peripheral demyelinating events have been seen rarely and very rarely, respectively, with Enbrel use. There have been rare reports of lupus, lupus-related conditions, and vasculitis.1

Before prescribing Enbrel refer to the full Summary of Product Characteristics.

Learn more about Enbrel dosing and methods of administration.

ACR: American College of Rheumatology; DMARD: disease-modifying antirheumatic drug; HAQ: Health Assessment Questionnaire; JIA: juvenile idiopathic arthritis; MTX: methotrexate; nr-AxSpA: non-radiographic axial spondyloarthritis; NSAID: non-steroidal anti-inflammatory drug; PsA: psoriatic arthritis; PsARC: psoriatic arthritis response criteria; SC: subcutaneous; TNF: tumour necrosis factor; TSS: total sharp score.

1.Enbrel (etanercept) SmPC. 50 mg solution for injection in pre-filled pen. Available at http://www.medicines.org.uk/emc [Accessed October 2017].
2.Mease PJ, et al. Arthritis Rheum. 2004; 50:2264–2272.

 

PP-ENB-GBR-0676 | November 2017

Indication

Enbrel is indicated for the treatment of adults with severe active AS who have had an inadequate response to conventional therapy.1

Contraindications

Hypersensitivity to the active substance or to any of the excipients1
Sepsis or risk of sepsis1
Treatment with Enbrel should not be initiated in patients with active infections, including chronic or localised infections1

 

AS dosing

The recommended dose of Enbrel is 25 mg administered twice weekly, or 50 mg administered once weekly.1

Data suggest that a clinical response is usually achieved within 12 weeks of treatment. Continued therapy should be carefully reconsidered in a patient not responding within this time period.1

Clinical efficacy

The efficacy of Enbrel in AS was assessed in a randomised, double-blind study comparing twice-weekly administration of 25 mg Enbrel with placebo. The study enrolled 277 patients between 18–70 years of age with active AS, defined as VAS scores of ≥ 30 for average duration and intensity of morning stiffness plus VAS scores of ≥ 30 for at least 2 of the following 3 parameters: patient global assessment; average of VAS values for nocturnal back pain and total back pain; average of 10 questions on the BASFI. Patients receiving DMARDs, NSAIDs, or corticosteroids could continue them on stable doses. Doses of 25 mg of Enbrel or placebo were administered SC twice a week for 6 months in 138 patients.1

The primary measure of efficacy (ASAS 20) was a ≥ 20% improvement in at least 3 of the 4 ASAS domains (patient global assessments, back pain, BASFI, and inflammation) and absence of deterioration in the remaining domain. ASAS 50 and 70 responses used the same criteria with a 50% improvement or a 70% improvement, respectively.1

Compared to placebo, treatment with Enbrel resulted in significant improvements in the ASAS 20, ASAS 50 and ASAS 70 as early as 2 weeks after the initiation of therapy.1

Percentage of patients with improvements in ASAS 20, 50 and 701

[[{"fid":"8906","view_mode":"default","attributes":{"height":"969","width":"1503","style":"width: 886px;","class":"panopoly-image-original media-element file-default"},"type":"media"}]]

Among patients with AS who received Enbrel, the clinical responses were apparent at the time of the first visit (2 weeks) and were maintained through 6 months of therapy. Responses were similar in patients who were or were not receiving concomitant therapies at baseline.1

For more information on the efficacy of Enbrel in nr-AxSpA click here to watch Professor Maxime Dougados  give an overview of EMBARK poster data.

Summary of the safety profile

The most commonly reported adverse reactions are injection site reactions (such as pain, swelling, itching, reddening and bleeding at the puncture site), infections (such as upper respiratory infections, bronchitis, bladder infections and skin infections), allergic reactions, development of autoantibodies, itching, and fever.1

Serious adverse reactions have also been reported for Enbrel. TNF-antagonists, such as Enbrel, affect the immune system and their use may affect the body's defenses against infection and cancer. Serious infections affect fewer than 1 in 100 patients treated with Enbrel. Reports have included fatal and life-threatening infections and sepsis. Various malignancies have also been reported with use of Enbrel, including cancers of the breast, lung, skin and lymph glands (lymphoma).1

Learn more about Enbrel dosing and methods of administration.

Before prescribing Enbrel refer to the full Summary of Product Characteristics.

AS: ankylosing spondylitis; ASAS: Assessment in Ankylosing Spondylitis; BASFI: Bath Ankylosing Spondylitis Functional Index; DMARD: disease-modifying anti-rheumatic drug; nr-AxSpA: non-radiographic axial spondyloarthritis; NSAID: non-steroidal anti-inflammatory drug; SC: subcutaneous; TNF: tumour necrosis factor; VAS: visual analogue scale.

1. Enbrel (etanercept) SmPC. 50 mg solution for injection in pre-filled pen. Available at http://www.medicines.org.uk/emc [Accessed October 2017].

PP-ENB-GBR-0674 | November 2017

Indication

Enbrel is indicated for the treatment of adults with moderate to severe PsO who failed to respond to, or who have a contraindication to, or are intolerant to other systemic therapy including ciclosporin, MTX or PUVA.1

Enbrel is also indicated for the treatment of chronic severe PsO in children and adolescents from the age of 6 years who are inadequately controlled by, or are intolerant to, other systemic therapies or phototherapies.2

Contraindications

Hypersensitivity to the active substance or to any of the excipients1
Sepsis or risk of sepsis1
Treatment with Enbrel should not be initiated in patients with active infections, including chronic or localised infections1

 

PsO dosing

Adults

The recommended dose of Enbrel is 25 mg administered twice weekly or 50 mg administered once weekly. Alternatively, 50 mg given twice weekly may be used for up to 12 weeks followed, if necessary, by a dose of 25 mg twice weekly or 50 mg once weekly.1

Treatment with Enbrel should continue until remission is achieved, for up to 24 weeks. Continuous therapy beyond 24 weeks may be appropriate for some adult patients. Treatment should be discontinued in patients who show no response after 12 weeks.1

 If re-treatment with Enbrel is indicated, the same guidance on treatment duration should be followed. The dose should be 25 mg twice weekly or 50 mg once weekly.1

Children (age 6 years and above)

The recommended dose of Enbrel is 0.8 mg/kg (up to a maximum of 50 mg per dose) once weekly for up to 24 weeks. Treatment should be discontinued in patients who show no response after 12 weeks.2

If re-treatment with Enbrel is indicated, the above guidance on treatment duration should be followed. The dose should be 0.8 mg/kg (up to a maximum of 50 mg per dose) once weekly.2

There is generally no applicable use of Enbrel in children aged below 6 years in the indication PsO.2

Clinical efficacy

Clinical efficacy in adult patients

The efficacy of Enbrel in PsO was assessed in a randomised, double-blind, placebo-controlled study. The primary efficacy endpoint was the proportion of patients in each treatment group who achieved the PASI 75 (i.e., at least a 75% improvement in the PASI score from baseline) at 12 weeks.3

Patients ≥ 18 years old with active, but clinically stable, PsO involving ≥ 10% of the body surface area (n=112) were randomised to receive a dose of 25 mg of Enbrel (n=57) or placebo (n=55) twice a week for 24 weeks.3

 The Enbrel-treated group had a significantly higher proportion of patients with a PASI 75 response at week 12 (30%) compared to the placebo-treated group (2%) (p<0.0001). At 24 weeks, 56% of patients in the Enbrel-treated group had achieved the PASI 75 compared to 5% of placebo-treated patients.3  

Among patients with PsO who received Enbrel, significant responses relative to placebo were apparent at the time of the first visit (2 weeks) and were maintained through 24 weeks of therapy. In long-term (up to 34 months) open-label studies where Enbrel was given without interruption, clinical responses were sustained and safety was comparable to shorter-term studies.3

Clinical efficacy in paediatric patients

The efficacy of Enbrel in paediatric PsO was assessed in a randomised, double-blind, placebo-controlled study in 211 paediatric patients aged 4–17 years with moderate to severe PsO. Eligible patients had a history of receiving phototherapy or systemic therapy, or were inadequately controlled on topical therapy.4

Patients received Enbrel 0.8 mg/kg (up to 50 mg) or placebo once weekly for 12 weeks. At week 12, more patients randomised to Enbrel had positive efficacy responses (e.g., PASI 75) than those randomised to placebo.4

 Paediatric PsO outcomes at 12 weeks4

[[{"fid":"8911","view_mode":"default","attributes":{"height":"182","width":"1495","style":"width: 1007px;","class":"panopoly-image-original media-element file-default"},"type":"media"}]]

Adapted from Paller AS, et al. 2008.

*p < 0.0001 vs. with placebo.

After the 12-week double-blind treatment period, all patients received Enbrel 0.8 mg/kg (up to 50 mg) once weekly for additional 24 weeks. Responses observed during the open-label period were similar to those observed in the double-blind period.

During a randomised withdrawal period, significantly more patients re-randomised to placebo experienced disease relapse (loss of PASI 75 response) compared with patients re-randomised to Enbrel. With continued therapy, responses were maintained up to 48 weeks.4

Summary of the safety profile

The most commonly reported adverse reactions are injection site reactions (such as pain, swelling, itching, reddening and bleeding at the puncture site), infections (such as upper respiratory infections, bronchitis, bladder infections and skin infections), allergic reactions, development of autoantibodies, itching, and fever.1

Serious adverse reactions have also been reported for Enbrel. TNF-antagonists, such as Enbrel, affect the immune system and their use may affect the body's defenses against infection and cancer. Serious infections affect fewer than 1 in 100 patients treated with Enbrel. Reports have included fatal and life-threatening infections and sepsis. Various malignancies have also been reported with use of Enbrel, including cancers of the breast, lung, skin and lymph glands (lymphoma).1

Serious haematological, neurological and autoimmune reactions have also been reported. These include rare reports of pancytopenia and very rare reports of aplastic anaemia. Central and peripheral demyelinating events have been seen rarely and very rarely, respectively, with Enbrel use. There have been rare reports of lupus, lupus-related conditions, and vasculitis.1

Learn more about Enbrel dosing and methods of administration.

Before prescribing Enbrel refer to the full Summary of Product Characteristics.

MTX: methotrexate; PASI: psoriasis area and severity index; PsO: plaque psoriasis; PUVA: psoralen and ultraviolet-A light; sPGA: static Physician Global Assessment; TNF: tumour necrosis factor.

1.Enbrel (etanercept) SmPC. 50 mg solution for injection in pre-filled pen. Available at http://www.medicines.org.uk/emc [Accessed October 2017].
2.Enbrel (etanercept) SmPC. Enbrel 10 mg powder and solvent for solution for injection for paediatric use. Available at http://www.medicines.org.uk/emc [Accessed October 2017].
3.Gottlieb AB, et al. Arch Dermatol. 2003; 139:1627–1632.
4.Paller AS, et al. NEJM. 2008; 358:241–251.

 

PP-ENB-GBR-0677 | November 2017