Guselkumab

Introduction to Guselkumab

Guselkumab is a fully human IgG1λ monoclonal antibody that selectively binds to the p19 subunit of interleukin-23 (IL-23). Developed by Janssen Biotech, it was approved by the FDA in 2017 for the treatment of moderate-to-severe plaque psoriasis in adults. In 2020, it received additional approval for active psoriatic arthritis.

Mechanism of Action

Guselkumab specifically targets the p19 subunit of IL-23, a key cytokine involved in the pathogenesis of psoriasis and psoriatic arthritis. By inhibiting IL-23, guselkumab disrupts the IL-23/Th17 axis, which plays a crucial role in the inflammatory processes of these conditions. This targeted approach helps reduce inflammation, normalize skin cell production, and alleviate joint symptoms associated with psoriatic disease.

Indications

Guselkumab is FDA-approved for the following indications:

  • Treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy
  • Treatment of adult patients with active psoriatic arthritis

While its primary indications are for adult patients, research is ongoing to evaluate its potential use in pediatric populations with psoriasis and psoriatic arthritis.

Dosage and Administration

The recommended dosage for guselkumab is the same for both plaque psoriasis and psoriatic arthritis:

  • 100 mg administered by subcutaneous injection at Week 0, Week 4, and every 8 weeks thereafter

Guselkumab is administered via subcutaneous injection. It's important to rotate injection sites and avoid areas where the skin is tender, bruised, erythematous, or affected by psoriasis. Patients may self-inject after proper training and medical assessment of their suitability for self-administration.

Efficacy

Clinical trials have demonstrated the efficacy of guselkumab in its approved indications:

  • Plaque Psoriasis:
    • In the VOYAGE 1 and VOYAGE 2 trials, about 73% of patients achieved PASI 90 at week 16, compared to 3% on placebo
    • In the ECLIPSE trial, guselkumab showed superior long-term efficacy compared to secukinumab in maintaining PASI 90 response through week 48
  • Psoriatic Arthritis:
    • In the DISCOVER-1 and DISCOVER-2 trials, significantly more patients achieved ACR20 response at week 24 compared to placebo
    • Improvements were observed in joint symptoms, skin manifestations, physical function, and quality of life measures
    • Guselkumab also demonstrated efficacy in inhibiting radiographic progression of joint damage

Guselkumab has shown rapid onset of action and sustained efficacy in long-term extension studies, with many patients maintaining response through 5 years of treatment.

Safety Profile

Guselkumab has demonstrated a favorable safety profile across clinical trials:

  • Most common adverse reactions (≥1%) include upper respiratory infections, headache, injection site reactions, arthralgia, diarrhea, gastroenteritis, tinea infections, and herpes simplex infections
  • Low rates of serious infections, malignancies, and major adverse cardiovascular events were reported
  • The safety profile remained consistent in long-term extension studies up to 5 years

As with other biologic agents, patients should be evaluated for tuberculosis before initiating treatment and monitored for signs of infection during therapy. Live vaccines should be avoided during treatment with guselkumab. Patients with a history of or active inflammatory bowel disease should be monitored closely, as cases of new or exacerbated Crohn's disease and ulcerative colitis have been reported.

Pediatric Considerations

While guselkumab is not currently approved for use in pediatric patients, research is ongoing:

  • A Phase III trial (NCT03451851) is evaluating the efficacy and safety of guselkumab in adolescents aged 12-17 years with moderate-to-severe plaque psoriasis
  • Another study (NCT04344899) is investigating guselkumab in pediatric patients aged 6-18 years with psoriatic arthritis
  • Pediatricians should be aware of ongoing research and potential future applications in managing severe pediatric cases of psoriasis and psoriatic arthritis
  • The long-term safety profile in pediatric populations is yet to be established

When considering biologic therapies for pediatric patients, it's crucial to weigh the potential benefits against the risks and lack of long-term safety data in this population. The targeted nature of guselkumab may offer a favorable risk-benefit profile, but more research is needed to confirm its safety and efficacy in children.

In the meantime, for pediatric patients with severe psoriasis or psoriatic arthritis who have failed conventional therapies, guselkumab may be considered as an off-label option in consultation with pediatric dermatologists or rheumatologists. However, such use should be carefully monitored and documented.



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