When a pharmaceutical company changes an SPC or PIL, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.
Section 4.8 has been updated to add systemic vasculitis as a rare side-effect.
Section 3: Pharmaceutical form expanded
Section 4.2: Updated with “Enbrel is administered by subcutaneous injection”
Section 4.4: Updated with “The safety and efficacy of Enbrel in patients with chronic infections have not been evaluated.” In the infections information
Section 4.4: Updated with “Enbrel should be used with caution in patients with a history of hepatitis C.” in the Hepatitis C information
Section 4.4: Updated with “The use of Enbrel in combination with other systemic therapies or phototherapy for the treatment of psoriasis has not been studied.” in the Combination Therapy information
Section 4.5: Updated with “Physicians should use caution when considering combination therapy with sulfasalazine.” in the Concurrent treatment with sulfasalazine information
Section 4.8: addition of “† Please see sub-section ‘Undesirable effects in paediatric patients with polyarticular juvenile idiopathic arthritis’ above.” In General disorders and administration site conditions information Section 4.8: Update to information in Concurrent treatment with anakinra information. Section 5.1: Update to description of Pharmacotherapeutic group Section 5.2: Expansion of abbreviation - Enzyme-Linked Immunosorbent Assay (ELISA) Section 6.1: Addition of E number for Mannitol Section 6.3: Addition of information on in use shelf life Section 6.6: Addition of “Any unused product or waste material should be disposed of in accordance with local requirements.” Section 9: Update to date of last renewal
Section 4.8: Update to information in Concurrent treatment with anakinra information.
Section 5.1: Update to description of Pharmacotherapeutic group
Section 5.2: Expansion of abbreviation - Enzyme-Linked Immunosorbent Assay (ELISA)
Section 6.1: Addition of E number for Mannitol
Section 6.3: Addition of information on in use shelf life
Section 6.6: Addition of “Any unused product or waste material should be disposed of in accordance with local requirements.”
Section 9: Update to date of last renewal
Section 4.2 – addition of Continuous therapy beyond 24 weeks may be appropriate for some patients. To Plaque Psoriasis section Section 4.8 – addition of details from 5th double blind clinical trial and update to other clinical trial information Section 5.1 – addition of “An analysis of clinical trial data did not reveal any baseline disease characteristics that would assist clinicians in selecting the most appropriate dosing option (intermittent or continuous). Consequently, the choice of intermittent or continuous therapy should be based upon physician judgment and individual patient needs.” Section 5.1 – addition of “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.” To Adults with plaque psoriasis section
Section 4.8 – addition of details from 5th double blind clinical trial and update to other clinical trial information
Section 5.1 – addition of “An analysis of clinical trial data did not reveal any baseline disease characteristics that would assist clinicians in selecting the most appropriate dosing option (intermittent or continuous). Consequently, the choice of intermittent or continuous therapy should be based upon physician judgment and individual patient needs.”
Section 5.1 – addition of “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.” To Adults with plaque psoriasis section
Section 4.1 - Addition of paediatric psoriasis indication, i.e. the following wording
“Treatment of chronic severe plaque psoriasis in children and adolescents from the age of 8 years who are inadequately controlled by, or are intolerant to, other systemic therapies or phototherapies”
Several changes relating to this and the studies conducted are contained throughout the SPC
Section 4.4 – update with information on opportunistic infections
Section 4.8
Addition of ‘not known (could not be accurately estimated through clinical studies).’ to headings of frequency.
Addition of ‘Not known: Macrophage activation syndrome*, anti-neutrophilic cytoplasmic antibody positive vasculitis’ to Immune system disorders.
Common: Pruritus
Uncommon: Angioedema, urticaria, rash, psoriasiform rash, psoriasis (including new onset and pustular, primarily palms & soles)
Rare: Cutaneous vasculitis (including leukocytoclastic vasculitis), Stevens-Johnson syndrome, erythema multiforme
Very rare: Toxic epidermal necrolysis
Addition of text - There were 4 reports of macrophage activation syndrome in juvenile idiopathic arthritis clinical trials.
Section 6.3
Section 4.2 – update to dosage for Plaque psoriasis
Section 4.8 – update to Clinical Trial data
Section 4.4 and Section 4.5
Addition in both sections for statement regarding interaction with abatacept
Addition of Interstitial lung disease as an undesirable effect
Section 5.1
Update to the ‘Antibodies to Enbrel’ section
Section 4.2
Addition of wording for a Patient Alert Card
Section 4.4
Addition of warnings to the SPC regarding the evaluation of patients for infections before, during and after Enbrel use, screening for TB, what action to take should TB infection be found, the risk of reactivation of hepatitis B virus, and the worsening of hepatitis C
Section 4.5
Update to the interations section of the EU Enbrel SPC to include a statement relating to an absence of interaction between etanercept and either digoxin or warfarin
Section 10
Updated website address for EMEA
Treatment of active and progressive psoriatic arthritis in adults when the response to previous disease-modifying antirheumatic drug therapy has been inadequate. Enbrel has been shown to improve physical function in patients with psoriatic arthritis, 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.
....
The efficacy of Enbrel was assessed in a randomised, double-blind, placebo-controlled study in 205 patients with psoriatic arthritis. Patients were between 18 and 70 years of age and had active psoriatic arthritis (³ 3 swollen joints and ³ 3 tender joints) in at least one of the following forms: (1) distal interphalangeal (DIP) involvement; (2) polyarticular arthritis (absence of rheumatoid nodules and presence of psoriasis); (3) arthritis mutilans; (4) asymmetric psoriatic arthritis; or (5) spondylitis-like ankylosis. Patients also had plaque psoriasis with a qualifying target lesion ³ 2 cm in diameter. Patients had previously been treated with NSAIDs (86%), DMARDs (80%), and corticosteroids (24%). Patients currently on methotrexate therapy (stable for ³ 2 months) could continue at a stable dose of £ 25 mg/week methotrexate. Doses of 25 mg Enbrel (based on dose-finding studies in patients with rheumatoid arthritis) or placebo were administered SC twice a week for 6 months. At the end of the double-blind study, patients could enter a long-term open-label extension study for a total duration of up to 2 years.
Clinical responsesThe results were expressed as percentages of patients achieving the ACR 20, 50, and 70 response and percentages with improvement in Psoriatic Arthritis Response Criteria (PsARC). Results are summarised in the Table below.
Among patients with psoriatic arthritis 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 methotrexate therapy. Quality of life in psoriatic arthritis patients was assessed at every timepoint using the disability index of the HAQ. The disability index score was significantly improved at all timepoints in psoriatic arthritis patients treated with Enbrel, relative to placebo (p < 0.001). There is insufficient evidence of the efficacy of Enbrel in patients with ankylosing spondylitis-like psoriatic arthropathy due to the small number of patients studied.
Mean (SE) Annualized Change From Baseline in Total Sharp Score
Placebo
Etanercept
Time
(n = 104)
(n = 101)
Month 12
1.00 (0.29)
‑0.03 (0.09)a
SE = standard error.
a. p = 0.0001.
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.
There is insufficient evidence of the efficacy of Enbrel in patients with ankylosing spondylitis‑like and arthritis mutilans psoriatic arthropathies due to the small number of patients studied.
In general, the adverse events in paediatric patients were similar in frequency and type to those seen in adult patients. Differences from adults and other special considerations are discussed in the following paragraphs.
The types of infections seen in clinical trials in juvenile idiopathic arthritis patients aged 2 to 18 years were generally mild to moderate and consistent with those commonly seen in outpatient paediatric populations. Severe adverse events reported in a trial in 69 juvenile idiopathic arthritis patients aged 4 to 17 years included varicella with signs and symptoms of aseptic meningitis, which resolved without sequelae (see also section 4.4), 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.
In one study in children with juvenile idiopathic arthritis aged 4 to 17 years, Forty-three43 of 69 (62%) children with juvenile idiopathic arthritis experienced an infection while receiving Enbrel during 3 months of the study (part 1 open-label), and the frequency and severity of infections was similar in 58 patients completing 12 months of open-label extension therapy. The types of infections reported in juvenile idiopathic arthritis patients were generally mild and consistent with those commonly seen in outpatient paediatric populations. The types and proportion of adverse events in juvenile idiopathic arthritis patients were similar to those seen in trials of Enbrel in adult patients with rheumatoid arthritis, and the majority were mild. Several adverse events were reported more commonly in 69 juvenile idiopathic arthritis patients receiving 3 months of Enbrel compared to the 349 adult rheumatoid arthritis patients. These included headache (19% of patients, 1.7 events per patient year), nausea (9%, 1.0 event per patient year), abdominal pain (19%, 0.74 events per patient year), and vomiting (13%, 0.74 events per patient year).
"Following subcutaneous administration to lactacting rats, etanercept was excreted in the milk and detected in the serum of pups."