Risankizumab

Introduction to Risankizumab

Risankizumab is a humanized IgG1 monoclonal antibody that selectively inhibits interleukin-23 (IL-23) by binding to its p19 subunit. Developed by Boehringer Ingelheim and AbbVie, it was approved by the FDA in 2019 for the treatment of moderate-to-severe plaque psoriasis in adults. It has since gained additional approvals for psoriatic arthritis and Crohn's disease.

Mechanism of Action

Risankizumab specifically targets the p19 subunit of IL-23, a key cytokine in the pathogenesis of several inflammatory conditions. By inhibiting IL-23, risankizumab disrupts the IL-23/Th17 axis, which plays a crucial role in the inflammatory processes of psoriasis, psoriatic arthritis, and Crohn's disease. This targeted approach helps reduce inflammation and the associated symptoms of these conditions.

Indications

Risankizumab is FDA-approved for the following indications:

  • Treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy
  • Treatment of active psoriatic arthritis in adults
  • Treatment of moderately to severely active Crohn's disease in adults

While its primary indications are for adult patients, research is ongoing to evaluate its potential use in pediatric populations with these conditions.

Dosage and Administration

The recommended dosage for risankizumab varies by indication:

  • For plaque psoriasis and psoriatic arthritis:
    • 150 mg administered by subcutaneous injection at Week 0, Week 4, and every 12 weeks thereafter
  • For Crohn's disease:
    • Induction: 600 mg administered by intravenous infusion over at least one hour at Week 0, Week 4, and Week 8
    • Maintenance: 360 mg administered by subcutaneous injection at Week 12 and every 8 weeks thereafter

Risankizumab is administered via subcutaneous injection for psoriasis and psoriatic arthritis, and both intravenously and subcutaneously for Crohn's disease. It's important to rotate injection sites and avoid areas where the skin is tender, bruised, erythematous, or affected by psoriasis.

Efficacy

Clinical trials have demonstrated the efficacy of risankizumab across its approved indications:

  • Plaque Psoriasis:
    • In the UltIMMa-1 and UltIMMa-2 trials, 75% of patients achieved PASI 90 at week 16, compared to 5% on placebo
    • Sustained efficacy was observed through 52 weeks of treatment
  • Psoriatic Arthritis:
    • In the KEEPsAKE 1 and 2 trials, significantly more patients achieved ACR20 response at week 24 compared to placebo
    • Improvements were observed in joint symptoms, skin manifestations, and quality of life measures
  • Crohn's Disease:
    • In the ADVANCE and MOTIVATE trials, risankizumab demonstrated significant improvements in clinical remission and endoscopic response compared to placebo
    • The FORTIFY trial showed maintained clinical remission through 52 weeks of treatment

Safety Profile

Risankizumab has demonstrated a favorable safety profile across clinical trials:

  • Most common adverse reactions (≥1%) include upper respiratory infections, headache, fatigue, injection site reactions, and tinea infections
  • In Crohn's disease trials, additional common adverse reactions included anemia, pyrexia, abdominal pain, and urinary tract infection
  • Low rates of serious infections, malignancies, and major adverse cardiovascular events were reported
  • No dose-dependent increase in adverse events was observed

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 risankizumab.

Pediatric Considerations

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

  • A Phase III trial (NCT03875482) is evaluating the safety and efficacy of risankizumab in pediatric patients aged 6-17 years with moderate-to-severe plaque psoriasis
  • Another study (NCT04645836) is investigating risankizumab in pediatric patients with Crohn's disease
  • Pediatricians should be aware of ongoing research and potential future applications in managing severe pediatric cases of psoriasis and Crohn's disease
  • 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 risankizumab may offer a favorable risk-benefit profile, but more research is needed to confirm its safety and efficacy in children.



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