Kineret (anakinra) - 3 indications

Scroll down for more information on each indication:

• for the treatment of Rheumatoid Arthritis; approved November 2001
• for the treatment of Cryopyrin-Associated Periodic Syndromes; approved January 2013
• for the treatment of deficiency of IL-1 receptor antagonist; approved December 2020

General Information

Kineret (anakinra) is an intravenous recombinant, nonglycosylated form of human interleukin-1 receptor antagonist (IL-1Ra). It blocks the biologic activity of IL-1 alpha and beta by competitively inhibiting IL-1 binding to the interleukin-1 type I receptor (IL-1RI), which is expressed in a wide variety of tissues and organs. IL-1 production is induced in response to inflammatory stimuli and mediates various physiologic responses including inflammatory and immunological responses.

Kineret is specifically indicated for:

• Reducing the signs and symptoms and slow the damage of moderate to severe active rheumatoid arthritis (RA) in people aged 18 years and older when 1 or more other drugs for RA have not worked;
• Neonatal-Onset Multisystem Inflammatory Disease, a severe form of Cryopyrin-Associated Periodic Syndromes (CAPS);
• the treatment of deficiency of IL-1 receptor antagonist (DIRA), an ultra-rare, autoinflammatory disease caused by a genetic mutation in the IL1RN gene

Kineret is supplied as a solution for subcutaneous injection. Scroll down for the recommended dosing/administration for each condition.

Mechanism of Action

Kineret (anakinra) is an intravenous recombinant, nonglycosylated form of human interleukin-1 receptor antagonist (IL-1Ra). It blocks the biologic activity of IL-1 alpha and beta by competitively inhibiting IL-1 binding to the interleukin-1 type I receptor (IL-1RI), which is expressed in a wide variety of tissues and organs. IL-1 production is induced in response to inflammatory stimuli and mediates various physiologic responses including inflammatory and immunological responses. Spontaneous mutations in the CIAS1/NLRP3 gene have been identified in a majority of patients with cryopyrin-associated periodic syndromes such as NOMID. CIAS1/NLRP3 encodes for cryopyrin, a component of the inflammasome. The activated inflammasome results in proteolytic maturation and secretion of IL-1ß, which has an important role in the systemic inflammation and manifestations of NOMID.

Side Effects

Adverse events associated with the use of Kineret for rheumatoid arthritis may include, but are not limited to, the following:

• Injection site reaction
• Infection
• Headache
• Nausea

Adverse events associated with the use of Kineret for NOMID may include, but are not limited to, the following:

• injection site reaction
• headache
• vomiting
• arthralgia
• pyrexia
• nasopharyngitis

Adverse events associated with the use of Kineret for DIRA may include, but are not limited to, the following:

• upper respiratory tract infections
• rash
• pyrexia
• influenza-like illness
• gastroenteritis

Indication 1 - for the treatment of Rheumatoid Arthritis

approved November 2001

Dosing/Administration

The recommended dose is 100 mg/day administered daily by subcutaneous injection. Higher doses did not result in a higher response. The dose should be administered at approximately the same time every day.

Clinical Trial Results

The safety and efficacy of Kineret  was tested in approximately 3,000 subjects across four placebo-controlled trials, which evaluated Kineret in combination with other DMARDs or as a monotherapy. The drug was shown, both alone and in combination with other therapies, to improve the signs and symptoms of RA. Many clinical responses, including a decrease in inflammation and pain, were seen in the fourth treatment week and most were seen by week 12.

Indication 2 - for the treatment of Cryopyrin-Associated Periodic Syndromes

approved January 2013

Dosing/Administration

The recommended starting dose is 1-2 mg/kg for Neonatal-Onset Multisystem Inflammatory Disease patients. The dose can be individually adjusted to a maximum of 8 mg/kg daily to control active inflammation. Adjust doses in 0.5 to 1 mg/kg increments. Once daily administration is generally recommended, but the dose may be split into twice daily administrations. Each syringe is intended for a single use. A new syringe must be used for each dose. Any unused portion after each dose should be discarded.

Clinical Trial Results

The FDA approval of Kineret was based on a long-term, open-label and uncontrolled study. This study included 43 NOMID patients 0.7 to 46 years of age who were given an initial Kineret dose of 1 to 2.4 mg/kg body weight. During the study, the dose was adjusted by 0.5 to 1 mg/kg increments to a protocol-specified maximum of 10 mg/kg daily, titrated to control signs and symptoms of disease. The maximum dose studied was 7.6 mg/kg/day. The average maintenance dose was 3 to 4 mg/kg daily. In general, the dose was given once daily, but for some subjects, the dose was split into twice daily administrations for better control of disease activity. The subjects were treated for up to 60 months. NOMID symptoms were assessed with a disease-specific Diary Symptom Sum Score (DSSS), which included the prominent disease symptoms fever, rash, joint pain, vomiting, and headache. Improvements occurred in all individual disease symptoms comprising the DSSS, as well as in the serum markers of inflammation. Results were consistent across all subgroups, including age, gender, presence of CIAS1 mutation, and disease phenotype. For 11 patients who went through a withdrawal phase, disease symptoms and serum markers of inflammation worsened after withdrawal and promptly responded to reinstitution of Kineret therapy. Upon withdrawal of treatment, the median time until disease flare criteria were met was 5 days.

Indication 3 - for the treatment of deficiency of IL-1 receptor antagonist

approved December 2020

Dosing/Administration

The recommended starting dose is 1-2 mg/kg daily for patients. The dose can be individually adjusted to a maximum of 8 mg/kg daily to control active inflammation. Adjust doses in 0.5 to 1 mg/kg increments. Each syringe is intended for a single use. A new syringe must be used for each dose. Any unused portion after each dose should be discarded.

Clinical Trial Results

The safety and efficacy of Kineret were evaluated in a long-term natural history study, including nine patients with DIRA (ages 1 month to 9 years at start of Kineret treatment) treated with Kineret for up to 10 years. All patients had genetically confirmed DIRA. The starting dose of Kineret was 1 to 2 mg/kg/day in the six patients for which the dose was reported (the remaining 3 patients’ starting dose was not reported). The dose was then individually adjusted to reach a stable efficacious dose to control active inflammation. The highest Kineret dose studied was 7.5 mg/kg/day. At the last visit during the first Kineret treatment period, the dose ranged from 2.2 and 6.1 mg/kg/day. Inflammatory remission was defined as achievement of all of the following criteria: CRP ≤ 5 mg/L, no pustulosis, no inflammatory bone disease and no concomitant glucocorticosteroids use. All nine patients achieved inflammatory remission while on Kineret treatment.