Psoriasis Treatment with Guselkumab (specific anti Il-23 therapy)

A Phase 2 Trial of Guselkumab versus Adalimumab for Plaque Psoriasis.
Gordon KB, Duffin KC, Bissonnette R, Prinz JC, Wasfi Y, Li S, Shen YK, Szapary P, Randazzo B, Reich K.
N Engl J Med. 2015 Jul 9;373(2):136-44. doi: 10.1056/NEJMoa1501646.

–Psoriasis affects around 2% of the world population
-Treatment depends on the extent of psoriasis and how the patient might adhere to it.
-Treatment options include topical agents, oral medication, phototherapy and injections.
–Biologics are the component of this last category. They include Tumor Necrosis Factor (TNF) inhibitors, anti Il-17 and anti-Il-23 antibodies:

• TNF inhibitors include adalimumab (A) (Humira, Abbvie) which have been around for a decade
• Specific anti Il-23 antibodies include Guselkumab (G)(Janssen-Cilag): it is a fully human IgG1 lambda
  monoclonal antibody that inhibits interleukin-23 specific signaling

• In this US study published in the NEJM G is compared with A over a 52-week prospective study:

• Methods:
• 293 patients with plaque psoriasis were randomly assigned to 7 groups*:
  • G 5mg (week 0, 4 and then every 12 weeks)
  • G 15mg (every 8 weeks)
  • G 50mg (weeks 0, 4 and then every 12 weeks)
  • G 100mg every 8 weeks
  • G 200mg (weeks 0, 4 and then every 12 weeks)
  • A: 80mg at week 0, 40mg at week one and then every other week
  • placebo (at 16 weeks, they were put on 100mg gulselkumab)
• Evaluation of results:
  • Physician’s Global Assessment (PGA): score of 0 (clear of lesions) or 1 (minimal psoriasis)(PGA01) at week 16
  • PASI (Psoriasis Area and Severity Index), PASI 75% improvement (PASI75) and 90% (PASI90)

• Results at 16 weeks:
  -the proportion of PGA01 was always higher in the G group when compared with placebo (statistically significant) (5mg=34%, 15mg=61%, 50mg=79%, 100mg=86%, 200mg=83%)
  -the proportion of PGA01 was higher than A (49%) in the groups treated with G 50mg (71%), 100mg (77%) and 200mg (81%) (no difference was seen for 5 and 15mg)
  -Infections were slightly higher in the G treated groups (20%) than A (14%) but the placebo rate was already high at 14%

• Comments
  • The problem with biologics generally speaking is that they tend to become less effective with time (antibodies ?). Guselkumab (G) seems to offer hope in this regard. Indeed at 40 weeks evaluation:
    -The number of patients with a PGA01 with G 100mg remains around 80% (as at 16weeks), whereas for A it falls from 60% to 50%.
  • Also G works faster than A Indeed for a dose of 100mg of G, the proportion of PSA01 reaches 80% whereas the peak for A is reached at 24 weeks (with a PGA01 of around 75%)
  • As for PASI one can note that maximum PASI75 improvement is at 20weeks (for G100mg) and reaches almost 95% of treated patients whereas PASI75 is reached in around 70% of individuals (also at 20 weeks)
  • A has been around a decade (time of publication) and offers an excellent safety profile, but G appears to be more effective…time will reveal its safety profile.

 Reminder: Phase 2 studies contrarily to phase 1 studies enable a medication to gather efficacy data (phase 1 studies evaluate safety). This study is funded by by Jansen-Cliag Pharmaceuticals

*subcutaneous injections

Article selection: Prof Dr Jean-Hilaire Saurat – dermatologist. Geneva, Switzerland