Adverse Effects of Etanercept

In this article, we will discuss the Adverse Effects of Etanercept (Enbrel®). So, let’s get started.

Adverse Reactions

Adverse Reactions in Adult Patients with Rheumatoid Arthritis. Psoriatic Arthritis, Ankylosing Spondylitis, or Plaque Psoriasis

The data described below reflect exposure to Etanercept (Enbrel®) in 2219 adult patients with RA followed for up to 80 months, in 182 patients with PSA for up to 24 months, in 138 patients with AS for up to 6 months, and in 1204 adult patients with PsO for up to 18 months.

In controlled trials, the proportion of Enbrel-treated patients who discontinued treatment due to adverse events was approximately 4% in the indications studied.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not predict the rates observed in clinical practice.

Infections

Infections, including viral, bacterial and fungal infections have been observed in adult and pediatric patients. Infections have been noted in all body systems and have been reported in patients receiving Etanercept (Enbrel®) alone or in
combination with other immunsuppressive agents.

In controlled portions of trials, the types and severity of infection were similar between Enbrel and the respective control group (placebo or MTX for RA and PsA patients) in RA, PA, AS, and PS patients. Infections consisted primarily or upper respiratory tract infection, sinusitis and influenza.

In controlled portions of trials in RAPSA AS and Pso, the rates of serious infection were similars in placebo (0.8% in placebo, 3.6% in MTX and 1.4% in Enbrel/Enbrel + MTX-treated groups). In clinical trials in rheumatologic indications, serious infections experienced by patients have included, but are not limited to, pneumonia, cellulitis, septic arthritis,
bronchitis, gastroenteritis, pyelonephritis, sepsis, abscess and osteomyelitis. In clinical trials in PsO, serious infections experienced by patients have included, but are not limited to, pneumonia, cellulitis, gastroenteritis, abscess and osteomyelitis. The rate of serious infections was not increased in open-label extension trials and was
similar to that observed in Etanercept (Enbrel® – and placebo-treated patients from controlled trials.

In 66 global clinical trials of 17.505 patients (21,015 patient-years of therapy), tuberculosis was observed in approximately 0.02% of patients. In 17,696 patients (27.169 patient-years of therapy) from 38 clinical trials and 4 cohort studies in the U.S. and Canada, tuberculosis was observed in approximately 0.006% of patients. These studies include reports of pulmonary and extrapulmonary tuberculosis.

Injection Site Reactions

In placebo-controlled trials in rheumatologic indications, approximately 37% of patients treated with Etanercept (Enbrel®) developed injection site reactions. In controlled trials in patients with PSO, 15% of patients treated with Etanercept (Enbrel®) developed injection site reactions during the first 3 months of treatment. All injection site reactions were described as mild to moderate (erythema, itching, pain, swelling, bleeding, bruising) and generally did not necessitate drug discontinuation. Injection site reactions generally occurred in the first month and subsequently decreased in frequency. The mean duration of injection site reactions was 3 to 5 days. Seven percent of patients experienced redness at a previous injection site when subsequent injections were given.

Immunogenicity

Patients with RA, PSA, AS or PSO were tested at multiple time points for antibodies to etanercept. Antibodies to the TNF receptor portion or other protein components of the Enbrel drug product were detected at least once in sera of approximately 6% of adult patients with RA, PSA, AS or PsO. These antibodies were all non-neutralizing. Results from JIA patients were similar to those seen in adult RA patients treated with Etanercept (Enbrel®).

In PsO studies that evaluated the exposure of etanercept for up to 120 weeks, the percentage of patients testing positive at the assessed time points of 24.48.72 and 96 weeks ranged from 3.6% -8,7% and were all non-neutralizing. The percentage of patients testing positive increased with an increase in the duration of study: however, the clinical significance of this finding is unknown. No apparent correlation of antibody development to clinical response or adverse events was observed. The immunogenicity data of Enbrel beyond 120 weeks of exposure are unknown.

The data reflect the percentage of patients whose test results were considered positive for antibodies to etanercept in an ELISA assay, and are highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of any antibody positivity in an assay is highly dependent on several factors, including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications and underlying disease. For these reasons, comparison of the incidence of antibodies to etanercept with the incidence of antibodies to other products may be misleading.

Autoantibodies

Patients with RA had serum samples tested for autoantibodies at multiple time points. In RA Studies I and II, the
percentage of patients evaluated for antinuclear antibodies (ANA) who developed new positive ANA (titer 21:40) was higher in patients treated with Enbrel (11%) than in placebo-treated patients (5%). The percentage of patients who developed new positive anti-double-stranded DNA antibodies was also higher by radioimmunoassay (15% of patients treated with Etanercept (Enbrel®) compared to 4% of placebo-treated patients) and by Chithidia luciliae assay (3% of patients treated with Etanercept (Enbrel®) compared to none of placebo-treated patients). The proportion of patients treated with Etanercept (Enbrel®) who developed anticardiolipin antibodies was similarly increased compared to placebo-treated patients. In RA Study III, no pattern of increased autoantibody development was seen in Enbrel patients compared to MTX patients.

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