Guselkumab

Registered South African indications:

• Plaque psoriasis (moderate-to-severe)

Contraindications

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

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed
• Psoriatic arthritis (high dose regimen)
• Pre-vaccination period: within 12 weeks of the last dose of guselkumab
• Post-vaccination period: within 2 weeks after vaccination 
• May impair the ability to drive and operate machinery

Forms avail in SA and covered in this monograph: inj, pfs

Plaque psoriasis
- In adults who are candidates for systemic therapy
Psoriatic arthritis (additional agent may be required)
- In patients who have had an inadequate response or who have been intolerant to a prior disease-modifying antirheumatic drug (DMARD)

• SC: Initial: 100mg at weeks 0 and 4; Maintenance: 100mg, every 8 weeks thereafter

Plaque psoriasis: Consideration should be given to discontinuing treatment if no response is shown after 16 weeks of treatment

Psoriatic arthritis: Consideration should be given to discontinuing treatment if no response is shown after 24 weeks of treatment

For patients at high risk for joint damage in psoriatic arthritis, dose may be increased to 100mg, every 4 weeks

When prescribing guselkumab in psoriatic arthritis 100mg, every 4 weeks, it is recommended to evaluate liver enzymes at baseline and thereafter according to routine patient management. If increases in ALT or AST are observed and drug-induced liver injury is suspected, guselkumab should be temporarily interrupted until this diagnosis is excluded

Prior to initiating treatment with guselkumab, patients should be evaluated for tuberculosis (TB) infection

Patients treated with guselkumab should be instructed to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a clinically important or serious infection or is not responding to standard therapy, the patient should be monitored closely and guselkumab should be discontinued until the infection resolves

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

Not established for use in children below 18 years

Pregnancy

• Caution
• There are no data from the use of guselkumab in pregnant women
• Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonic/foetal development, parturition or postnatal development
• As a precautionary measure, it is preferable to avoid the use of guselkumab in pregnancy
• Women of childbearing potential should use effective methods of contraception during treatment and for at least 12 weeks after treatment

Breastfeeding

• Caution 
• It is unknown whether guselkumab is excreted in human milk
• Human IgGs are known to be excreted in breast milk during the first few days after birth, and decrease to low concentrations soon afterwards; consequently, a risk to the breastfed infant during this period cannot be excluded
• A decision should be made whether to discontinue or abstain from initiating treatment with guselkumab, taking into account the benefit of breastfeeding to the child and the benefit of guselkumab therapy to the woman

Fertility

• The effect of guselkumab 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
  No specific study has been conducted to determine the effect of renal impairment on the pharmacokinetics of guselkumab; no dose recommendation can be made. Renal elimination of intact guselkumab, an IgG mAb is expected to be low and of minor importance

Hepatic Impairment

• Caution; no information available
  No specific study has been conducted to determine the effect of hepatic impairment on the pharmacokinetics of guselkumab; no dose recommendation can be made. Hepatic impairment is not expected to influence clearance of guselkumab as IgG mAbs are mainly eliminated via intracellular catabolism

Elderly

• No dose adjustment recommended
  There is limited information in subjects ≥65 years and very limited information in subjects ≥75 years

Drugs in Sport

• Permitted - No warnings 

Central Nervous System Disorders

• Headache

Gastrointestinal Disorders

• Gastroenteritis
• Diarrhoea

Hepatobiliary Disorders

• Increased transaminases

Musculoskeletal Disorders

• Arthralgia

Skin and Subcutaneous Tissue Disorders

• Urticaria
• Rash
• Injection site reactions

Immune, Blood and Lymphatic System Disorders

• Respiratory tract infections
• Herpes simplex infections
• Tinea infections
• Decreased neutrophil count
• Hypersensitivity
  - Urticaria
  - Dyspnoea
• Anaphylaxis

• Immunosuppressants (including biologics)
• Phototherapy

• Tuberculosis screening

Additional observations

• Signs and symptoms of infection, including tuberculosis

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

Guselkumab is a human IgG1λ monoclonal antibody (mAb) that binds selectively to the interleukin 23 (IL-23) protein with high specificity and affinity. IL-23, a regulatory cytokine, affects the differentiation, expansion, and survival of T cell subsets, (e.g., Th17 cells and Tc17 cells) and innate immune cell subsets, which represent sources of effector cytokines, including IL-17A, IL-17F and IL-22 that drive inflammatory disease. In humans, selective blockade of IL-23 was shown to normalize production of these cytokines. Levels of IL-23 are elevated in the skin of patients with plaque psoriasis. In in vitro models, guselkumab was shown to inhibit the bioactivity of IL-23 by blocking its interaction with cell surface IL-23 receptor, disrupting IL-23-mediated signaling, activation and cytokine cascades. Guselkumab exerts clinical effects in plaque psoriasis and psoriatic arthritis through blockade of the IL-23 cytokine pathway.

Injection (per ml) 100mg

• Tremfya (Janssen Pharmaceutica) originator