Efleura syringe in autoinjector 60 mg/ml 1 ml, 2 pcs.

Netakimab is a recombinant humanized monoclonal antibody that specifically binds interleukin-17A (IL-17A) found directly in tissues or in blood and other body fluids in therapeutic concentrations. IL-17A is a proinflammatory cytokine whose hyperproduction is predominantly due to the activation of Th17-lymphocytes. In the framework of the innate immunity IL-17A has a protective role.
In chronic immune inflammatory diseases pathological activation of Th17-lymphocytes and IL-17 hyperproduction stimulate T-cell response and increased production of other inflammatory mediators: IL-1, IL-6, tumor necrosis factor alpha (TNF-α), growth factors (G-CSF, GM-CSF) and various chemokines.

Netakimab has a high thermodynamic constant of specific binding to human IL-17A. According to preclinical studies, specific binding of netakimab in normal human tissues is limited to tissues of the lung, thymus, lymph node, tonsils, which is consistent with the data on the expression of IL-17 by cells of these tissues.

Administration of netakimab is not accompanied by statistically significant changes in the level of T-lymphocytes and has no effect on the level and the ratio of immunoglobulins of classes A, G and M.
Specific anti-inflammatory activity of netakimab was demonstrated in in vitro and in vivo tests. Netakimab dose-dependently inhibits IL-17 and TNFα-dependent production of interleukin-6 in cell culture at IC50 40 pM. In a model of collagen-induced arthritis in Javanese macaques (Macaca fascicularis), repeated (once a week for 4 weeks) subcutaneous injection of netakimab is accompanied by a decrease in the severity of inflammatory reaction in joints, which was confirmed by histological examination (articular cartilage remains intact, synovial membranes – without signs of lesions and inflammatory response, synoviocyte proliferation was not noted).

In psoriasis patients use of netakimab is accompanied with decrease of inflammation and hyperkeratosis in the skin, significant decrease of C-reactive protein and CRP level. In patients with active ankylosing spondylitis and psoriatic arthritis against the background of netakimab use there is a decrease of inflammation symptoms in the spine, entheses and joints, as well as a rapid decrease of C-reactive protein concentration, which is a marker of inflammation.

Indications

– Treatment of moderate to severe plaque psoriasis in adult patients when systemic therapy or phototherapy is indicated.

– Treatment of active ankylosing spondylitis in adult patients with insufficient response to standard therapy.

– Treatment of active psoriatic arthritis in monotherapy or in combination with methotrexate in case of insufficient response to standard therapy.

Active ingredient

Netakimab

Composition

1 ml of the solution contains:

Active ingredient:

Netakimab – 60 mg;

Excipients:

sodium acetate trihydrate – 1.74 mg,

trehalose dihydrate – 80 mg,

Poloxamer 188 – 0.5 mg,

glacial acetic acid – to pH 5.0,

water for injection – up to 1.0 ml.

How to take, the dosage

The use of Efleura^® should be under the supervision of physicians experienced in the treatment of diseases for which Efleura^® is indicated. After appropriate training it is possible for the patient to selfadminister the drug under the condition of dynamic monitoring by the attending physician. The drug Efleura^® may be used both in inpatient and outpatient settings.

Efleura^® is given at a dose of 120 mg in two subcutaneous injections of 1 ml of the drug at a concentration of 60 mg/ml.

The treatment of moderate to severe plaque psoriasis in adult patients when systemic therapy or phototherapy is indicated: The recommended dose of 120 mg as two subcutaneous injections of 1 ml (60 mg) of the drug each is given once weekly at weeks 0, 1 and 2, then once every 4 weeks.

Treatment of active ankylosing spondylitis with insufficient response to standard therapy: The recommended dose is 120 mg as two subcutaneous injections of 1 ml (60 mg) of the drug each. The drug is injected once a week at weeks 0, 1 and 2, then every 2 weeks thereafter.

The treatment of active psoriatic arthritis in monotherapy or in combination with methotrexate if there is an insufficient response to standard therapy: The recommended dose is 120 mg as two subcutaneous injections of 1 ml (60 mg) of the drug each. The drug is injected once a week at weeks 0, 1 and 2, then every 2 weeks until week 10 inclusive. From week 14 onward, the drug is administered at a dose of 120 mg in two subcutaneous injections of 1 ml (60 mg) each once every 4 weeks.

Interaction

No information on the presence of adverse drug interactions of the drug netakimab with other drugs has been received so far.

It is assumed that the drug netakimab may increase the immunosuppressive effect of glucocorticosteroids, methotrexate, sulfasalazine, leflunomide and other basic anti-inflammatory drugs.

Mixing the drug with other drugs, administration by infusion is strictly prohibited.

Special Instructions

The presence of potentially serious infections such as HIV, active hepatitis B and/or C, syphilis, tuberculosis are contraindications to the prescription of netakimab. The use of netakimab in this group of patients has not been studied. Given the immunosuppressive effect of netakimab, therapy with this drug may potentially lead to exacerbation of chronic infections and increased risk of primary infection. It is necessary to screen and evaluate the risk/benefit ratio of netakimab therapy in these patients.

In case of reactivation of hepatitis B therapy with netakimab should be discontinued and corresponding antiviral therapy should be prescribed.
Women of childbearing age and their sexual partners should use effective contraception during therapy.
When using netakimab potentially hypersensitivity reactions may develop.

In clinical trials of netakimab such adverse events have not been reported, but when using other IL17 inhibitors urticaria and anaphylactic reactions were noted in rare and very rare cases. In case of anaphylactic or other serious allergic reactions the use of Efleira® should be stopped immediately and an appropriate symptomatic therapy should be started.

Therapy with nethakimab in patients with current alcohol or drug addiction or mental diseases is associated with decreased compliance and, consequently, decreased effectiveness of therapy. Closer monitoring of patients with these conditions is necessary due to the lack of results of clinical trials in this category of patients and the possibility of increased risk of hepatotoxicity and other adverse effects.

Immunogenicity

In clinical trials of Efleira® in psoriasis therapy the formation of binding antibodies to netakimab was registered in less than 0.7% of cases. No neutralizing antibodies were detected. The obtained data demonstrate low immunogenicity of netakimab in therapy of patients with psoriasis.

Patients older than 65 years

Efficacy and safety of the drug in patients older than 65 years have not been studied. No significant age differences in distribution and excretion of the drug are expected.

Patients with impaired renal and hepatic function

Efficacy and safety of the drug in this category of patients have not been studied.

Patients under 18 years old, children

Study of efficacy and safety of the drug in children and persons under 18 years old was not conducted.

Vaccination

Immunization with live vaccines should not be performed during treatment with Efleira® because clinical safety assessment of this interaction has not been conducted within the framework of clinical trials. Immunization with live vaccines prior to treatment with Efleira®, as well as the interval between immunization and initiation of therapy should comply with current clinical guidelines. Immunization with inactivated vaccines during therapy with Netakimab should be performed with caution.

Contraindications

∙ Hypersensitivity to netakimab and any of the drug excipients.

∙ Clinically significant infectious diseases in the acute phase, including tuberculosis.

∙ Children and adolescents under 18 years.

∙ Pregnancy, breastfeeding.

Side effects

In clinical studies in patients with plaque psoriasis, Efleira® showed a favorable safety profile. No dose-limiting toxicity events were detected.

Most of the reported adverse events (AEs) associated with Efleira® were of mild to moderate severity as defined by STSAE v.4.03 and did not require discontinuation of therapy. There were no lethal outcomes connected with Efleira® therapy during the clinical trials.

The most frequent unintended reaction in the conducted clinical trials was neutropenia, the majority of cases were of mild or moderate degree of severity, had transient character and didn’t require additional therapy.

In this guideline adverse reactions are presented according to the MedDRA International Dictionary of Adverse Reactions. Below is a list of adverse reactions reported in patients who received netakimab within the framework of clinical trials and have a definite, probable or possible association with taking the drug. The frequency is given taking into account the following criteria: very frequently (≥1/10), frequently (≥1/100 to < 1/10), infrequently (≥1/1000 to < 1/100), rarely (≥1/10000 to < 1/1000), very rarely (≤10000).

Infectious and parasitic diseases: often – upper respiratory tract infections (including: infrequent – respiratory tract infections, follicular angina, sinusitis), infrequent – lower respiratory tract infections (including pneumonia), urinary tract infections, conjunctivitis, furunculosis.

Liver and biliary tract: frequently – hyperbilirubinemia.

Skin and subcutaneous tissue: infrequently – eczema, dermatitis.

Blood and lymphatic system: frequently – neutropenia, leukopenia, infrequently – lymphopenia, lymphocytosis, thrombocytopenia.

Nervous system: infrequent – dizziness.

Vascular: infrequent – increase of blood pressure.

General symptoms: infrequent – flu-like syndrome, abdominal pain.

Metabolism and nutrition: infrequent – hyperglycemia.

Laboratory tests: frequently – increased alanine aminotransferase (ALT), aspartate aminotransferase (AST) activity, infrequently – increased gamma-glutamyltransferase (GGT).

Overdose

There are no clinical data on overdose.

The maximum tolerated dose in humans has not been established. No phenomena of dose-limiting toxicity were registered in clinical trials: no pathological abnormalities were detected after subcutaneous administration of Netakimab at the maximum dose of 3 mg/kg (195 – 355 mg for adults with weight of 65 – 85 kg).

No specific antidote. Treatment is symptomatic.