Secukinumab

Registered South African indications:

• Plaque psoriasis - moderate to severe
  - In patients who are candidates for systemic therapy or phototherapy
• Active psoriatic arthritis
• Axial spondyloarthritis (axSpA) with or without radiographic damage
  Ankylosing spondylitis (AS)/ axSpA with radiographic damage
  - Active ankylosing spondylitis
  Non-radiographic axial spondyloarthritis (nr-axSpA)/ axSpA without radiographic damage 
  - Active non-radiographic axial spondyloarthritis with objective signs of inflammation as indicated by elevated C-reactive protein (CRP) and/or magnetic resonance imaging (MRI) evidence in adults who have responded inadequately to nonsteroidal anti-inflammatory drugs (NSAIDs)
• Juvenile idiopathic arthritis (JIA)
  - Active enthesitis-related arthritis (ERA)
  - Active juvenile psoriatic arthritis (JPsA)
• Hidradenitis suppurativa (HS) (acne inversa) - moderate to severe

Registered South African contraindications

• Hypersensitivity to the active substance or to any of the excipients
• Clinically important, active infection, e.g. active tuberculosis
• Live vaccines should not be given concurrently with secukinumab
• Pregnancy
• Breastfeeding

Contraindications registered in other jurisdictions

• Hypersensitivity to the active substance or to any of the excipients
• Clinically important, active infection, e.g. active tuberculosis

Recommendations below are applicable to South Africa and other jurisdictions

Caution in the following patient groups

• Pregnancy (Recommendations in other jurisdictions)
• Breastfeeding (Recommendations in other jurisdictions)
• Women of childbearing potential not using effective contraception
• Renal impairment
• Hepatic impairment

Traceability

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

Infections

• Secukinumab has the potential to increase the risk of infections
• Serious infections have been observed in patients receiving secukinumab in the post-marketing setting
• Caution should be exercised in patients with chronic infection or a history of recurrent infection
• Patients should seek medical advice if signs or symptoms suggestive of infection occur
• In the case of a serious infection, secukinumab should be withheld until resolution

Common infections

• In clinical studies, most infections were mild or moderate upper respiratory tract infections (e.g. nasopharyngitis) and did not require treatment discontinuation

Mucocutaneous candida infections

• Non-serious mucocutaneous candida infections were more frequently reported with secukinumab (300mg: 3.55 per 100 patient years) than with placebo (1.00 per 100 patient years) in psoriasis studies

Tuberculosis

• No increased susceptibility to tuberculosis was reported in clinical studies
• Secukinumab should not be used in patients with active tuberculosis
• Consider anti-tuberculosis therapy in patients with latent tuberculosis or past history of tuberculosis where adequate treatment cannot be confirmed
• Patients should be regularly monitored for signs and symptoms of active tuberculosis during and after treatment

Inflammatory bowel disease (IBD)

• Cases of new onset or exacerbation of Crohn’s disease and ulcerative colitis have been reported
• Caution is advised in patients with IBD
• Patients should be closely monitored

Hypersensitivity reactions

• Rare cases of anaphylactic reactions were observed in clinical studies
• Discontinue secukinumab immediately if an anaphylactic or serious allergic reaction occurs, and initiate appropriate therapy

Latex sensitivity - 1ml pre-filled-syringe/pen and 0.5ml pre-filled syringe 

• The removable needle caps of the pre-filled syringes/pens contain a derivative of natural rubber latex
• Latex-sensitive individuals may be at risk, although no natural rubber latex has been detected to date
• Use in latex-sensitive individuals has not been studied and there is therefore a potential risk of hypersensitivity reactions which cannot be completely ruled out

Vaccinations

• Live vaccines should not be given concurrently with secukinumab
• Concurrent administration of inactivated or non-live vaccines is permitted
• Secukinumab does not appear to suppress the humoral response to meningococcal or influenza vaccines
• Paediatric patients should receive all age-appropriate immunisations before starting therapy

Concomitant immunosuppressive therapy

• Safety and efficacy of combination with other immunosuppressants or phototherapy have not been evaluated in psoriasis studies (including in patients with psoriatic arthritis and ankylosing spondylitis)
• Secukinumab has been used with methotrexate, sulfasalazine, and/or corticosteroids in arthritis studies
• Caution is advised when considering use with other immunosuppressants

Effects on ability to drive and use machines

• Secukinumab has no or negligible influence on the ability to drive and use machines

Forms avail. in SA and covered in this monograph: pfp, poi, pfs

South African registered indications and dosages

Secukinumab is intended for use under the guidance and supervision of a physician experienced in the diagnosis and treatment of conditions for which secukinumab is indicated

Plaque psoriasis - moderate to severe
- In patients who are candidates for systemic therapy or phototherapy

• SC: Initial: 300mg, weekly; at weeks 0, 1, 2, 3 and 4; Maintenance: 300mg, 4 weekly; Patients may derive an additional benefit from receiving: 300mg, every 2 weeks

Active psoriatic arthritis
- Alone or in combination with methotrexate

• SC: Initial: 150mg, weekly; at weeks 0, 1, 2, 3 and 4; Maintenance: 150mg, 4 weekly (may be increased to 300mg based on clinical response)

- Patients with concomitant moderate to severe plaque psoriasis or who are anti-TNFα inadequate responders (IR)

• SC: Initial: 300mg, weekly, at weeks 0, 1, 2, 3 and 4; Maintenance: 300mg, 4 weekly

Axial spondyloarthritis (axSpA)
- Ankylosing spondylitis

• SC: Initial: 150mg, weekly; at weeks 0, 1, 2, 3 and 4; Maintenance: 150mg, 4 weekly (may be increased to 300mg based on clinical response)

- Non-radiographic axial spondyloarthritis (nr-axSpA)

• SC: Initial: 150mg, weekly; at weeks 0, 1, 2, 3 and 4; Maintenance: 150mg, 4 weekly

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For all of the above indications, available data suggest that a clinical response is usually achieved within 16 weeks of treatment. Consideration should be given to discontinuing treatment in patients who have shown no response by 16 weeks of treatment. Some patients with an initial partial response may subsequently improve with continued treatment beyond 16 weeks

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Hidradenitis suppurativa (HS) (acne inversa) - moderate to severe

• SC: Initial: 300mg, weekly, at weeks 0, 1, 2, 3 and 4; Maintenance: 300mg, every 2 weeks

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Each 300mg dose is given as one subcutaneous injection of 300mg or as two subcutaneous injections of 150mg depending on available strengths

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Method of administration
Secukinumab is to be administered by subcutaneous injection. If possible, areas of the skin that show psoriasis should be avoided as injection sites. The solution/the syringe/the pen must not be shaken. Patients and/or caregivers should be instructed to inject the full amount of secukinumab according to the instructions provided in the patient information leaflet. Comprehensive instructions for administration are given in the patient information leaflet. For patients receiving the 75mg dose, the 75mg/0.5mL pre-filled syringe should be used
The powder for solution for injection must be reconstituted before use. For instruction on reconstitution of the medicine before administration refer to the instruction for use in the product packaging

Forms avail. in SA and covered in this monograph: pfp, poi, pfs

South African registered indications and dosages

Secukinumab is intended for use under the guidance and supervision of a physician experienced in the diagnosis and treatment of conditions for which secukinumab is indicated

Paediatric plaque psoriasis - moderate to severe
- In patients who are candidates for systemic therapy or phototherapy

Younger than 6 years

• Not established for use

Older than 6 years and adolescents

• <25kg: SC: Initial: 75mg, weekly; at weeks 0, 1, 2, 3 and 4; Maintenance: 75mg, 4 weekly
• 25-<50kg: SC: Initial: 75mg, weekly; at weeks 0, 1, 2, 3 and 4; Maintenance: 75mg, 4 weekly (*may be increased to 150mg)
• ≥50kg: SC: Initial: 150mg, weekly; at weeks 0, 1, 2, 3 and 4; Maintenance: 150mg, 4 weekly (*may be increased to 300mg)

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*Some patients may derive additional benefit from the higher dose

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The 150mg solution for injection in pre-filled syringe or pen is not indicated for administration to paediatric patients with a weight <50kg

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For the above indication, available data suggests that a clinical response is usually achieved within 16 weeks of treatment. Consideration should be given to discontinuing treatment in patients who have shown no response by 16 weeks of treatment. Some patients with an initial partial response may subsequently improve with continued treatment beyond 16 weeks

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Juvenile idiopathic arthritis (JIA)
- Active enthesitis-related arthritis (ERA)
- Active juvenile psoriatic arthritis (JPsA)

Younger than 2 years

• Not established for use

Older than 2 years

• <50kg: SC: Initial: 75mg, weekly; at weeks 0, 1, 2, 3 and 4; Maintenance: 75mg, 4 weekly
• ≥50kg: SC: Initial: 150mg, weekly; at weeks 0, 1, 2, 3 and 4; Maintenance: 150mg, 4 weekly

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 Each 75mg dose is given as one subcutaneous injection of 75mg. Each 150mg dose is given as one subcutaneous injection of 150mg
Each 300mg dose is given as one subcutaneous injection of 300mg or as two subcutaneous injections of 150mg depending on available strengths

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Method of administration
Secukinumab is to be administered by subcutaneous injection. If possible, areas of the skin that show psoriasis should be avoided as injection sites. The solution/the syringe/the pen must not be shaken. Patients and/or caregivers should be instructed to inject the full amount of secukinumab according to the instructions provided in the patient information leaflet. Comprehensive instructions for administration are given in the patient information leaflet. For patients receiving the 75mg dose, the 75mg/0.5mL pre-filled syringe should be used
The powder for solution for injection must be reconstituted before use. For instruction on reconstitution of the medicine before administration refer to the instruction for use in the product packaging

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Safety and effectiveness in paediatric patients with the JIA categories of ERA and JPsA below the age of 2 years have not been established
The safety and efficacy in children with plaque psoriasis below the age of 6 years have not been established
The safety and efficacy in children below the age of 18 years in other indications have not yet been established. No data are available

Pregnancy

South African recommendations

• Contraindicated
• Secukinumab is contraindicated in pregnant women
• Women of childbearing potential should use an effective method of contraception during treatment and for at least 20 weeks after treatment

Recommendations in other jurisdictions

• Caution; not recommended
• There are no adequate data from the use of secukinumab in pregnant women
• Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. As a precautionary measure, it is preferable to avoid the use of secukinumab during pregnancy
• Women of childbearing potential should use an effective method of contraception during treatment and for at least 20 weeks after treatment

Breastfeeding

South African recommendations

• Contraindicated
• Because immunoglobulins are excreted in milk, secukinumab should not be administered to a woman who is breastfeeding

Recommendations in other jurisdictions

• Caution; not recommended
• It is not known whether secukinumab is excreted in human milk. Immunoglobulins are excreted in human milk and it is not known if secukinumab is absorbed systemically after ingestion. Because of the potential for adverse reactions in breastfeeding infants from secukinumab, a decision on whether to discontinue breastfeeding during treatment and up to 20 weeks after treatment or to discontinue therapy with secukinumab must be made taking into account the benefit of breastfeeding to the child and the benefit of secukinumab therapy to the woman

Fertility

Recommendations below are applicable to South Africa and other jurisdictions

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

Recommendations below are applicable to South Africa and other jurisdictions

• Caution; no information available
  No pharmacokinetic data are available in patients with renal impairment. Secukinumab has not been studied in these patient populations. No dose recommendations can be made
  The renal elimination of intact secukinumab, an IgG monoclonal antibody, is expected to be low and of minor importance

Recommendations below are applicable to South Africa and other jurisdictions

• Caution; no information available
  No pharmacokinetic data are available in patients with hepatic impairment. Secukinumab has not been studied in these patient populations. No dose recommendations can be made
  lgGs are mainly eliminated via catabolism and hepatic impairment is not expected to influence clearance of secukinumab

Recommendations below are applicable to South Africa and other jurisdictions

• No dose adjustment recommended

Infections and Infestations

Very common

• Upper respiratory tract infections

Common

• Oral herpes
• Tinea pedis (South African recommendations)

Uncommon

• Oral candidiasis
• Otitis externa
• Lower respiratory tract infections
• Tinea pedis (Recommendations in other jurisdictions)

Not known

• Mucosal and cutaneous candidiasis (including oesophageal candidiasis)

Blood and Lymphatic System Disorders

Uncommon

• Neutropenia

Immune System Disorders

Rare

• Anaphylactic reactions

Nervous System Disorders

Common

• Headache

Eye Disorders

Uncommon

• Conjunctivitis

Respiratory, Thoracic and Mediastinal Disorders

Common

• Rhinorrhoea

Gastrointestinal Disorders

Common

• Diarrhoea
• Nausea

Uncommon

• Inflammatory bowel disease
  • Including Crohn’s disease and ulcerative colitis (Post marketing reports: Frequency determined based on placebo-controlled clinical studies (phase III) in plaque psoriasis patients)

Skin and Subcutaneous Tissue Disorders

Uncommon

• Urticaria
• Dyshidrotic eczema (Post marketing reports: Frequency determined based on placebo-controlled clinical studies (phase III) in plaque psoriasis patients) 

Rare

• Exfoliative dermatitis (Cases were reported in patients with psoriasis diagnosis) 
• Hypersensitivity vasculitis

Not known

• Pyoderma gangrenosum

General Disorders and Administration Site Conditions

Common

• Fatigue

• Live vaccines

• Full blood count with differential (baseline)
• Complete metabolic panel (baseline)
• Tuberculosis screening
• Hepatitis B virus screening
• Hepatic C virus screening

Specific cases may require

• Chest x-ray (if TB positive)
• HIV screening (in high-risk patients (baseline))

Additional observations

• Signs and symptoms of
  - Infection
  - Inflammatory bowel disease

Secukinumab is a fully human IgG1/κ monoclonal antibody that selectively binds to and neutralises the proinflammatory cytokine interleukin-17A (IL-17A). Secukinumab works by targeting IL-17A and inhibiting its interaction with the IL-17 receptor, which is expressed on various cell types including keratinocytes. As a result, secukinumab inhibits the release of proinflammatory cytokines, chemokines and mediators of tissue damage and reduces IL-17A-mediated contributions to autoimmune and inflammatory diseases. Clinically relevant levels secukinumab reach the skin and reduce local inflammatory markers. As a direct consequence treatment with secukinumab reduces erythema, induration and desquamation present in plaque psoriasis lesions.

IL-17A is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. IL-17A plays a key role in the pathogenesis of plaque psoriasis, psoriatic arthritis and axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis) and is up-regulated in lesional skin in contrast to non-lesional skin of plaque psoriasis patients, and a higher frequency of IL-17-producing cells are detected in the synovial fluid of patients with psoriatic arthritis. The frequency of IL-17-producing cells is also significantly higher in the subchondral bone marrow of facet joints from patients with axial spondyloarthritis. Inhibition of IL-17A was shown to be effective in the treatment of ankylosing spondylitis, thus establishing the key role of this cytokine in axial spondyloarthritis.

Injection (150mg per 1ml) prefilled syringe

• Cosentyx (Norvatis) originator

Injection (150mg per 1ml) prefilled pen

• Cosentyx (Norvatis) originator