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Kineret (Anakinra) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

The most serious adverse reactions were:

  • Serious Infections - see WARNINGS
  • Neutropenia, particularly when used in combination with TNF blocking agents

The most common adverse reaction with Kineret® is injection-site reactions. These reactions were the most common reason for withdrawing from studies.

Because clinical trials are conducted under widely varying and controlled conditions, adverse reaction rates observed in 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 a broader patient population in clinical practice.

The data described herein reflect exposure to Kineret® in 3025 patients, including 2124 exposed for at least 6 months and 884 exposed for at least one year. Studies 1 and 4 used the recommended dose of 100 mg per day. The patients studied were representative of the general population of patients with rheumatoid arthritis.

INJECTION-SITE REACTIONS

The most common and consistently reported treatment-related adverse event associated with Kineret® is injection-site reaction (ISR). The majority of ISRs were reported as mild. These typically lasted for 14 to 28 days and were characterized by 1 or more of the following: erythema, ecchymosis, inflammation, and pain. In studies 1 and 4, 71% of patients developed an ISR, which was typically reported within the first 4 weeks of therapy. The development of ISRs in patients who had not previously experienced ISRs was uncommon after the first month of therapy.

INFECTIONS

In studies 1 and 4 combined, the incidence of infection was 39% in the Kineret®-treated patients and 37% in placebo-treated patients during the first 6 months of blinded treatment. The incidence of serious infections in studies 1 and 4 was 2% in Kineret®-treated patients and 1% in patients receiving placebo over 6 months. The incidence of serious infection over 1 year was 3% in Kineret®-treated patients and 2% in patients receiving placebo. These infections consisted primarily of bacterial events such as cellulitis, pneumonia, and bone and joint infections, rather than unusual, opportunistic, fungal, or viral infections. Patients with asthma appeared to be at higher risk of developing serious infections; Kineret® 4% vs. placebo 0%. Most patients continued on study drug after the infection resolved.

In open-label extension studies, the overall rate of serious infections was stable over time and comparable to that observed in controlled trials. In clinical studies and postmarketing experience, rare cases of opportunistic infections have been observed and included fungal, mycobacterial and bacterial pathogens. Infections have been noted in all organ systems and have been reported in patients receiving Kineret® alone or in combination with immunosuppressive agents.

In patients who received both Kineret® and etanercept for up to 24 weeks, the incidence of serious infections was 7%. The most common infections consisted of bacterial pneumonia (4 cases) and cellulitis (4 cases). One patient with pulmonary fibrosis and pneumonia died due to respiratory failure.

MALIGNANCIES

Among 5300 RA patients treated with Kineret® in clinical trials for a mean of 15 months (approximately 6400 patient years of treatment), 8 lymphomas were observed for a rate of 0.12 cases/100 patient years. This is 3.6 fold higher than the rate of lymphomas expected in the general population, based on the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) database. 9 An increased rate of lymphoma, up to several fold, has been reported in the RA population, and may be further increased in patients with more severe disease activity. Thirty-seven malignancies other than lymphoma were observed. Of these, the most common were breast, respiratory system, and digestive system. There were 3 melanomas observed in study 4 and its long-term open-label extension, greater than the 1 expected case. The significance of this finding is not known. While patients with RA, particularly those with highly active disease, may be at a higher risk (up to several fold) for the development of lymphoma, the role of IL-1 blockers in the development of malignancy is not known.

HEMATOLOGIC EVENTS

In placebo-controlled studies with Kineret®, treatment was associated with small reductions in the mean values for total white blood count, platelets, and absolute neutrophil count (ANC), and a small increase in the mean eosinophil differential percentage.

In all placebo-controlled studies, 8% of patients receiving Kineret® had decreases in ANC of at least 1 WHO toxicity grade, compared with 2% of placebo patients. Nine Kineret®-treated patients (0.4%) developed neutropenia (ANC < 1 × 109/L). Two percent of patients treated concurrently with Kineret® and etanercept developed neutropenia (ANC < 1 × 109/L. While neutropenic, one patient developed cellulitis which recovered with antibiotic therapy.

IMMUNOGENICITY

In studies 1 and 4, from which data is available for up to 36 months, 49% of patients tested positively at one or more timepoints for anti-anakinra antibodies in a highly sensitive, anakinra-binding biosensor assay. Of the 1615 patients with available data at Week 12 or later, 30 (2%) were seropositive in a cell-based bioassay for antibodies capable of neutralizing the biologic effects of Kineret®. Of the 13 patients with available follow-up data, 5 patients remained positive for neutralizing antibodies at the end of the studies. No correlation between antibody development and adverse events was observed.

Antibody assay results are highly dependent on the sensitivity and specificity of the assays. Additionally, the observed incidence of antibody positivity in an assay may be influenced by several factors, including sample handling, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Kineret® with the incidence of antibodies to other products may be misleading.

OTHER ADVERSE EVENTS

Table 4 reflects adverse events in studies 1 and 4, that occurred with a frequency of >/= 5% in Kineret®-treated patients over a 6-month period.

Table 4. Percent of RA Patients Reporting Adverse Events (Studies 1 and 4)
Preferred term Placebo
  
(n = 733)
Kineret®
100 mg/day
(n = 1565)
Injection Site Reaction 29% 71%
Worsening of RA 29% 19%
URI 17% 14%
Headache 9% 12%
Nausea 7% 8%
Diarrhea 5% 7%
Sinusitis 7% 7%
Arthralgia 6% 6%
Flu Like Symptoms 6% 6%
Abdominal Pain 5% 5%



REPORTS OF SUSPECTED KINERET SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Kineret. The information is not vetted and should not be considered as verified clinical evidence.

Possible Kineret side effects / adverse reactions in 49 year old female

Reported by a health professional (non-physician/pharmacist) from Israel on 2011-10-11

Patient: 49 year old female

Reactions: Liver Injury, Hepatotoxicity, Hepatic Fibrosis, Hepatic Steatosis, Hepatosplenomegaly

Suspect drug(s):
Kineret



Possible Kineret side effects / adverse reactions in 4 year old male

Reported by a health professional (non-physician/pharmacist) from Spain on 2011-10-14

Patient: 4 year old male

Reactions: Alanine Aminotransferase Increased, Aspartate Aminotransferase Increased, Blood Lactate Dehydrogenase Increased

Suspect drug(s):
Kineret

Other drugs received by patient: Prednisone; Omeprazole; Calcium Carbonate; Vitamin D



Possible Kineret side effects / adverse reactions in 9 year old male

Reported by a health professional (non-physician/pharmacist) from Spain on 2011-10-14

Patient: 9 year old male

Reactions: Hepatomegaly, Aspartate Aminotransferase Increased, Alanine Aminotransferase Increased, Blood Lactate Dehydrogenase Increased

Suspect drug(s):
Kineret
    Dosage: 100 mg (100 mg, 1 in 1 d) subcutaneous
    Indication: Juvenile Arthritis
    Start date: 2011-07-01

Kineret
    Dosage: 100 mg (100 mg, 1 in 1 d) subcutaneous
    Indication: Histiocytosis Haematophagic
    Start date: 2011-07-01

Other drugs received by patient: Omeprazole; Prednisone; Vitamin D; Calcium Carbonate



See index of all Kineret side effect reports >>

Drug label data at the top of this Page last updated: 2006-06-14

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