IL-23 and IL-17 inhibitors versus other biologics for psoriasis

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This British study was undertaken to address gaps left by randomized controlled trials in comparing the effectiveness of IL-23p19 and IL-17 inhibitors, specifically Skyrizi (risankizumab) and Kyntheum / Siliq (brodalumab), against each other in a representative clinical population.

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Background:
Interleukin (IL)-23p19 and IL-17 inhibitors have demonstrated high efficacy for psoriasis in randomized controlled trials, though real-world data, particularly for risankizumab (IL-23p19 inhibitor) and brodalumab (IL-17 receptor (IL-17R) inhibitor), is limited.

Objectives:
To assess drug survival of IL-23p19 and IL-17 inhibitors compared to other biologics for psoriasis.

Methods:
We conducted a cohort study using data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) from November 2007 to June 2023. Multivariable flexible parametric models assessed drug survival, with discontinuation due to ineffectiveness and adverse effects reported separately. The primary outcome measure was the absolute difference in restricted mean survival time at 2 years, referred to as adjusted survival time, between all comparators.

Results:
Among 19,034 treatment courses (median follow-up: 2.3 years), treatments included adalimumab (tumour necrosis factor-alpha (TNF-a) inhibitor, n = 6,815), ustekinumab (IL-12/23p40 inhibitor, n = 5,639), secukinumab (IL-17A inhibitor, n = 3,051), ixekizumab (IL-17A inhibitor, n = 1,072), brodalumab (n = 367), guselkumab (IL-23p19 inhibitor, n = 1,258) and risankizumab (n = 832).
Guselkumab and risankizumab had the highest adjusted survival times (years [interquartile ranges]) for effectiveness (1.93 [1.91–1.95] and 1.93 [1.90–1.96], respectively). Risankizumab had the highest survival for safety (1.94 [1.92–1.96]) followed by guselkumab (1.92 [1.90–1.94]) and ustekinumab (1.92 [1.91–1.93]). Brodalumab showed lower adjusted survival time for effectiveness (1.75 [1.69–1.81]) than most biologics except secukinumab and adalimumab; and similar survival for safety (1.85 [1.81–1.90]) compared to IL-17A inhibitors and adalimumab. In patients with psoriatic arthritis, ustekinumab showed reduced drug survival. Prior biologic exposure was associated with a dose–response reduction in survival which was significantly larger for IL-17 inhibitors.

Conclusions:
Guselkumab and risankizumab have the most favourable drug survival for effectiveness, with comparable safety to ustekinumab, and more favourable than other BADBIR biologics. Longer drug survival may reduce treatment burden by minimizing treatment switches, clinic visits and disease flares, supporting IL-23p19 inhibitors as a practical long-term option for psoriasis.

Source: onlinelibrary.wiley.com

*Funding: British Association of Dermatologists Biologic Register Ltd. (BADBRL)