Ixekizumab

Registered South African indications:

• Plaque psoriasis
• Psoriatic arthritis
• Radiographic and non-radiographic axial spondyloarthritis

Contraindications

South African manufacturer recommendations

• Hypersensitivity to the active ingredient or any of its excipients
• Clinically important active infections (e.g. active tuberculosis)
  (See additional prescribing points)
• Coadministration with live attenuated vaccines

International manufacturer recommendations

• Serious hypersensitivity to the active ingredient or any of its excipients
• Clinically important active infections (e.g. active tuberculosis)

Cautions

South African manufacturer recommendations

• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Elderly (≥75 years)
• Clinically important chronic infection
  - Human immunodeficiency virus (HIV) positive patients
• Latent tuberculosis infection
  (See additional prescribing points)
• Inflammatory bowel disease
  - Crohn's disease
  - Ulcerative colitis

International manufacturer recommendations

• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Elderly (≥75 years)
• Clinically important chronic infection
• History of recurrent infection
• Latent tuberculosis infection
  (See additional prescribing points)
• Inflammatory bowel disease
  - Crohn's disease 
  - Ulcerative colitis
• Coadministration with live vaccines
  (See additional prescribing points)

Forms avail. in SA and covered in this monograph: inj

This agent is intended for use under the guidance and supervision of a doctor experienced in the diagnosis and treatment of conditions for which it is indicated

Plaque psoriasis - moderate to severe
- For systemic therapy candidates

• SC: Initial: 160mg (two 80mg injections), at week 0; Followed by: 80mg, at weeks 2, 4, 6, 8, 10, and 12; Maintenance: 80mg, every 4 weeks

Active psoriatic arthritis (Additional agent may be required)
- In those who have responded inadequately to, or who are intolerant to one or more disease-modifying antirheumatic drug (DMARD) therapies

• SC: Initial: 160mg (two 80mg injections), at week 0; Maintenance: 80mg, every 4 weeks

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For psoriatic arthritis ixekizumab may be used alone or in combination with methotrexate

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For psoriatic arthritis patients with concomitant moderate to severe plaque psoriasis, the recommended dosing regimen is the same as for plaque psoriasis

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Active radiographic axial spondyloarthritis (Ankylosing spondylitis) 
- In those who have responded inadequately to conventional therapy
Active non-radiographic axial spondyloarthritis
- In those with objective signs of inflammation as indicated by elevated C-reactive protein (CRP) and/or magnetic resonance imaging (MRI) who have responded inadequately to nonsteroidal anti-inflammatory drugs (NSAIDs)

• SC: Initial: 160mg (two 80mg injections), at week 0; Maintenance: 80mg, every 4 weeks

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For all indications consideration should be given to discontinuing treatment in patients who have shown no response after 16 to 20 weeks of treatment. Some patients with initially partial response may subsequently improve with continued treatment beyond 20 weeks

Paed. forms avail. in SA and covered in this monograph: inj

Paed. dosages below include:

• South African manufacturer recommendations
• International manufacturer recommendations

South African manufacturer recommendations

This agent is intended for use under the guidance and supervision of a doctor experienced in the diagnosis and treatment of conditions for which it is indicated

Plaque psoriasis - moderate to severe
- For systemic therapy candidates

Younger than 6 years and <25kg

• Not established for use

Older than 6 years and >50kg

• SC: Initial: 160mg (two 80mg injections), at week 0; Maintenance: 80mg, every 4 weeks

Psoriatic arthritis

• Not established for use in children below 18 years

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For all indications consideration should be given to discontinuing treatment in patients who have shown no response after 16 to 20 weeks of treatment. Some patients with initially partial response may subsequently improve with continued treatment beyond 20 weeks

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International manufacturer recommendations

This agent is intended for use under the guidance and supervision of a doctor experienced in the diagnosis and treatment of conditions for which it is indicated

Plaque psoriasis - moderate to severe
- For systemic therapy candidates

Younger than 6 years and <25kg

• Not established for use

Between 6-17 years

• 25kg-<50kg: SC: Initial: 80mg, at week 0; Maintenance: 40mg, every 4 weeks
• >50kg: SC: Initial: 160mg (two 80mg injections), at week 0; Maintenance: 80mg, every 4 weeks

Psoriatic arthritis

• Not established for use in children below 18 years

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For all indications consideration should be given to discontinuing treatment in patients who have shown no response after 16 to 20 weeks of treatment. Some patients with initially partial response may subsequently improve with continued treatment beyond 20 weeks

Pregnancy 

• Caution; not recommended
• Safety of ixekizumab in pregnancy has not been established
• There is a limited amount of data from the use of ixekizumab in pregnant women
• Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonic/foetal development, parturition or post-natal development
• Ixekizumab should not be given to a pregnant woman
• Women of childbearing potential should use an effective method of contraception during treatment and for at least 10 weeks after treatment

Breastfeeding

South African manufacturer recommendations

• Caution; not recommended 
• Safety of ixekizumab in breastfeeding has not been established
• It is not known whether ixekizumab is excreted in human milk or absorbed systemically after ingestion. However, ixekizumab is excreted in the milk of cynomolgus monkeys
• Women receiving ixekizumab should not breastfeed their infants

International manufacturer recommendations

• Caution; not recommended 
• It is not known whether ixekizumab is excreted in human milk or absorbed systemically after ingestion. However, ixekizumab is excreted at low levels in the milk of cynomolgus monkeys
• A decision should be made whether to discontinue breastfeeding or to discontinue ixekizumab taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman

Fertility

South African manufacturer recommendations

• The effect of ixekizumab on human fertility has not been evaluated

International manufacturer recommendations

• The effect of ixekizumab on human fertility has not been evaluated
• Animal studies do not indicate direct or indirect harmful effects with respect to fertility

Renal Impairment

• Caution; no information available 

Hepatic Impairment 

• Caution; no information available 

Elderly

• ≥65 years: No dose adjustment recommended 
• ≥75 years: Caution; no dose adjustment recommended 
  There is limited information in subjects aged ≥75 years

Drugs in Sport

• Permitted - No warnings

Respiratory Disorders

• Upper respiratory tract infection
• Influenza
• Rhinitis
• Oropharyngeal pain

Gastrointestinal Disorders

• Oral candidiasis
• Nausea
• Inflammatory bowel disease
• Crohn's disease

Skin and Subcutaneous Tissue Disorders

• Cellulitis
• Urticaria
• Rash
• Eczema
• Injection site reactions
  - Erythema
  - Pain

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity reactions
  - Anaphylaxis
  - Angioedema
  - Urticaria
• Late serious hypersensitivity reactions (10-14 days following injection)
  - Widespread urticaria
  - Dyspnoea
  - High antibody titres
• Mucocutaneous herpes simplex
• Tinea infection
• Neutropenia
• Thrombocytopenia
• Anaphylaxis
• Immunogenicity
  - Anti-drug antibodies

Sensory Disorder

• Conjunctivitis

• Live vaccines

• Full blood count (FBC) with differential (baseline)
• Complete metabolic panel  (baseline)
• Screening prior to initiating therapy:
  - Tuberculosis (TB) (and during therapy)
  - Hepatitis B virus (HBV) (during and for several months following therapy)
  - Hepatitis C virus
  - HIV status (in high risk patients) 

Specific cases may require

• Chest X-ray if TB positive

Additional observations

• Signs and symptoms of:
  - Infection
  - Inflammatory bowel disease

Method of administration

• Ixekizumab is for subcutaneous administration. Injection sites may be alternated. If possible, areas of the skin that show psoriasis should be avoided as injection sites
• The solution must not be shaken
• After training in subcutaneous injection technique, a patient may self-inject ixekizumab. However, the physician should ensure appropriate follow-up of patients
• Doses less than 80mg which require dose preparation should only be administered by a healthcare professional
• In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded

Traceability

• In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded

Infections

• Ixekizumab should be used with caution in patients with clinically important chronic or active infection, including HIV-positive patients. If such an infection develops, monitor carefully and discontinue ixekizumab if the patient is not responding to standard therapy or the infection becomes serious. Do not resume ixekizumab until the infection resolves
• Patients should be instructed to seek medical advice if signs or symptoms suggestive of an infection occur
• If an infection develops, patients should be carefully monitored and ixekizumab discontinued if the patient is not responding to standard therapy or if the infection becomes serious
• Ixekizumab should not be resumed until the infection resolves
• Ixekizumab must not be given to patients with active tuberculosis (TB). Anti-TB therapy prior to initiation of ixekizumab in patients with latent TB should be considered

Inflammatory bowel disease (including Crohn's disease and ulcerative colitis)

• Cases of new or exacerbations of inflammatory bowel disease have been reported with ixekizumab
• Ixekizumab is not recommended in patients with inflammatory bowel disease
• If a patient develops signs and symptoms of inflammatory bowel disease or experiences an exacerbation of pre-existing inflammatory bowel disease, ixekizumab should be discontinued and appropriate medical management should be initiated

Immunisations

• Ixekizumab should not be used with live vaccines
• No data are available on the response to live vaccines; there are insufficient data on response to inactive vaccines

Ixekizumab is an IgG4 monoclonal antibody that binds with high affinity (<3pM) and specificity to interleukin 17A (both IL-17A and IL-17A/F). Elevated concentrations of IL-17A have been implicated in the pathogenesis of psoriasis by promoting keratinocyte proliferation and activation, as well as in the pathogenesis of psoriatic arthritis and axial spondyloarthritis by driving inflammation leading to erosive bone damage and pathological new bone formation. Neutralisation of IL-17A by ixekizumab inhibits these actions. 

Injection (per ml) 80mg

• Copellor (Eli Lilly) originator