Guselkumab has shown superior long-term efficacy when compared to secukinumab for the management of moderate to severe psoriasis.

A phase 3 randomised controlled trial of the two biologics involved more than 1,000 adult patients from nine countries including Australia.

Patients were treated for 44 weeks with either the IL-23p19 inhibitor or the IL-17A inhibitor and followed to 56 weeks.

The study found the primary outcome of a PASI 90 response at 48 weeks was achieved by 84% of patients treated with guselkumab compared to 70% of patients treated with secukinumab on an intention-to-treat basis.

This followed an early advantage with secukinumab during weeks 3-12 and similar proportions of patients in each treatment group achieving PASI 90 at weeks 16-20. Guselkumab offered an improved clinical response over secukinumab from week 20.

However there was no significant difference between a major secondary outcome of PASI 75 response at weeks 12 and 48.

Proportions of patients with adverse events, infections, and serious adverse events were similar between the two treatments. Only 2% of patients in each treatment group discontinued treatment due to adverse events.

The authors concluded that guselkumab was superior in the first head-to-head comparison of the two biologics. They said that despite the early advantage with secukinumab, a 48-week endpoint was more appropriate for a life-long chronic disorder.

“The results of the study show the higher potential for longer-term control of psoriasis with the IL-23p19 inhibitor, guselkumab, than with the IL-17A inhibitor, secukinumab.”

“With additional, longer-term comparative data including real-world evidence from registries and claims databases, updating treatment guidelines to emphasise the importance of longer-term endpoints when choosing biologics for the treatment of psoriasis could be considered.”

The study was funded by Janssen Research & Development.

An accompanying Comment in The Lancet said the plethora of biologics for psoriasis had transformed patient outcomes to the point that skin clearance was now a realistic goal.

Dr Satveer Mahil and Professor Catherine Smith of the dermatology department, King’s College London, said the clinical relevance of a treatment difference of 14·2 percentage points between guselkumab and secukinumab was however unclear

“It is vital to assess the effect of guselkumab’s reported superior efficacy on patients’ perceptions of their disease burden. Patient-reported outcome measures such as Dermatology Life Quality Index and EQ-5D were not evaluated in Reich and colleagues’ study, which limits interpretability of the results.”

However they said blockade of IL-23 might cause “a more durable, albeit slower, response” since it places brakes on the inflammatory cascade at a more upstream point.

“It will therefore be interesting to ascertain whether comparator trials of newer IL-17A and IL-23p19 inhibitors replicate the current data.”