What is guselkumab?
Guselkumab is a biologic treatment indicated for moderate to severe psoriasis.
The U.S. Food and Drug Administration (FDA) has approved guselkumab (Janssen Biotech, PA, USA; TREMFYA™) for the treatment of adults living with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Guselkumab is the first and only approved biologic therapy that selectively blocks only IL-23, a cytokine that plays a key role in plaque psoriasis.
Applications seeking approval of guselkumab in the European Union, Japan and other countries are currently under review.
What is guselkumab used for?
- Guselkumab is used for the treatment of adult patients with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy (ultraviolet light treatment).
- It is not known if guselkumab is safe and effective in children under 18 years of age.
How does guselkumab work?
- Guselkumab is a human monoclonal IgG1λ antibody that selectively binds to the p19 subunit of interleukin 23 (IL-23) and inhibits its interaction with the IL-23 receptor.
- While IL-23 promotes the normal inflammatory and immune responses, the p19 and p40 subunits of IL-23 are found to be over-expressed in the condition of psoriasis and other autoimmune inflammatory skin diseases.
- Guselkumab selectively binds to the p19 subunit of IL-23 in dendritic cells and keratinocytes and blocks its interaction with IL-23 receptor, which further prevents the release of other pro-inflammatory cytokines and chemokines via stimulation of immune cells such as Th17 cells.
- Guselkumab thus blocks the abnormally-heightened signalling of inflammatory cascades that promote epidermal abnormalities including keratinocyte hyperproliferation and psoriatic plaque formation.
How is guselkumab given?
- Guselkumab is administered by subcutaneous injection.
- The recommended dose is 100 mg at Week 0, Week 4, and every 8 weeks thereafter.
- Guselkumab should not be injected into areas where the skin is tender, bruised, red, hard, thick, scaly, or affected by psoriasis.
- It is intended for use under the guidance and supervision of a physician.
- Guselkumab may be administered by a health care professional, or a patient may self-inject after proper training in subcutaneous injection technique.
- Guselkumab may increase the risk of infection.
- A missed dose should be injected as soon as it is remembered and the next dose taken at the appropriate scheduled time.
Pretreatment evaluation for tuberculosis and immunisation
- Treatment with guselkumab should not be started in patients with any clinically important active infection until the infection resolves or is adequately treated.
- Patients with a history of latent tuberculosis should be suitably treated prior to administration of guselkumab, because it can reactivate latent tuberculosis infection.
- Patients should not be immunised with live vaccines during treatment with guselkumab.
Use in specific populations
- No data are available for use of guselkumab in pregnant women indicating a drug-associated risk for major birth defects and miscarriage.
- No adverse developmental effects in offspring from 0–6 months of age were observed in cynomolgus monkeys treated with guselkumab up to 30 times the maximum recommended dose for humans.
- See DermNet NZ page on safety of medicines taken during pregnancy.
- There is no information on the presence of guselkumab in human milk or its effects on the breastfed infant.
- The risk benefit potential should be considered when prescribing guselkumab to the mother.
- See DermNet NZ page on lactation and the skin.
- The safety and effectiveness of guselkumab in paediatric patients < 18 years of age have not been evaluated.
- Clinical studies with guselkumab did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects.
Hepatic or renal impairment
- No trials have been conducted to assess the effect of hepatic or renal impairment on the pharmacokinetics of guselkumab.
Adverse effects of guselkumab
The most common adverse reactions (≥ 1% of patients) reported include:
- upper respiratory infections
- injection site reactions
- tinea infections
- herpes simplex infections.
Drug interactions with guselkumab
- No data are available on the ability of live or inactive vaccines to elicit an immune response in patients receiving treatment with guselkumab.
- Live vaccines should not be used concomitantly during guselkumab treatment.
- Population pharmacokinetic analyses have indicated that concomitant use of ibuprofen, acetylsalicylic acid, or acetaminophen/paracetamol does not affect the clearance of guselkumab.
- The effect of drugs metabolised via the hepatic cytochrome P450 enzymes such as warfarin and ciclosporin may be altered during concomitant administration with guselkumab.
- Dosage modification of these drugs should be considered.
- Results from an exploratory drug-drug interaction study in subjects with moderate-to-severe psoriasis have suggested a low potential for clinically relevant drug interactions for drugs metabolised by CYP3A4 (midazolam), CYP2C9 (warfarin), CYP2C19 (omeprazole) and CYP1A2 but the interaction potential cannot be ruled out for drugs metabolised by CYP2D6.
Contraindications to guzelkumab
Guzelkumab should not be used in patients that:
- have an infection that does not go away or that keeps coming back
- have tuberculosis (TB) or have been in close contact with someone with TB
- recently received or are scheduled to receive a vaccine
- plan to become pregnant
- breastfeeding or plan to breastfeed.
Guselkumab is promising for plaque psoriasis in phase 3 studies.
- Guselkumab has shown an acceptable safety profile and good efficacy in the treatment of moderate-to-severe plaque psoriasis.
- It is a first-in-class biologic therapy that selectively blocks only IL-23, a cytokine that plays a key role in plaque psoriasis.
- Guselkumab has demonstrated superior results in skin clearance compared with adalimumab in head-to-head analyses.
- Clinical trial findings have also demonstrated the effectiveness of guselkinuab in patients who had an inadequate response to treatment with ustekinumab.
- A Phase 3 study evaluating guselkumab in the treatment of active psoriatic arthritis is ongoing, and a Phase 3 program evaluating the efficacy of guselkumab compared with secukinumab in the treatment of moderate to severe plaque psoriasis is underway.
- Although further studies are needed to assess long-term safety and efficacy, based on the results to date, guselkumab appears to be a promising therapeutic option for moderate-to-severe plaque-type psoriasis.