How do IL-17 and IL-23 inhibitors fare in the treatment of psoriasis in direct comparison?
A recent study published in the British Journal of Dermatology is only the second paper to provide a direct comparison of the efficacy and onset speed of treatment with IL-17 and IL-23 inhibitors in patients with moderate to severe plaque psoriasis. The authors monitored the early response to treatment (at week 12), and the efficacy and safety of ixekizumab and guselkumab.
Facts about biological treatment of psoriasis in a nutshell
- Psoriasis patients desire a rapid and effective onset of treatment.
- Ixekizumab is a highly affine humanized monoclonal antibody that selectively binds to interleukin 17A (IL-17A). It shows faster and more effective clearance of psoriasis skin manifestations than etanercept and ustekinumab, its effect persists long-term, and its safety profile is very good.
- Guselkumab is a human monoclonal antibody that binds to IL-23p19 with high affinity and specificity.
- Data from clinical trials and systematic reviews suggest that IL-17 inhibitors may improve the condition of psoriasis patients faster than IL-23 inhibitors.
Methodology and course of the study
In the randomized, double-blind clinical trial IXORA-R, which lasted 24 weeks, patients with moderate to severe plaque psoriasis (sPGA ≥ 3, PASI ≥ 12, involvement ≥ 10% of body surface) were included. The primary goal of the study was to achieve 100% improvement in psoriasis skin manifestations (PASI 100) at week 12.
The included patients (n = 1027) were randomized (1:1) to treatment with ixekizumab at the dosage according to SPC (160 mg at week 0 and then 80 mg every 2 weeks until week 12) or guselkumab (100 mg at weeks 0, 4, and 12; to maintain blinding, these patients received a placebo dose at weeks 0, 2, 6, 8, and 10). This study evaluated the results up to week 12.
Results
At week 12, a 100% improvement in the PASI score (PASI 100) was observed in 41% of patients treated with ixekizumab and 25% of patients treated with guselkumab (odds ratio [OR] 2.14; 95% confidence interval [CI] 1.63–2.81; p < 0.001).
For all major secondary parameters, ixekizumab also showed significantly better results than guselkumab (see table below).
Table. Comparison of observed parameters: ixekizumab vs. guselkumab.
|
Observed parameter |
ixekizumab |
guselkumab |
p value |
|---|---|---|---|
|
PASI 50, week 1 |
143 (28) |
47 (9) |
< 0.001 |
|
PASI 75, week 2 |
119 (23) |
26 (5) |
< 0.001 |
|
PASI 90, week 4 |
109 (21) |
40 (8) |
< 0.001 |
|
PASI 100, week 4 |
35 (7) |
7 (1) |
< 0.001 |
|
PASI 90, week 8 |
304 (58) |
182 (36) |
< 0.001 |
|
PASI 100, week 8 |
154 (30) |
69 (14) |
< 0.001 |
|
sPGA 0, week 12 |
218 (42) |
128 (25) |
< 0.001 |
The frequency of serious adverse events was the same in both groups (3%) and no new safety signals were observed.
Conclusion
The presented study directly compares the effects of acute treatment with IL-17 and IL-23 inhibitors. The results indicate that ixekizumab shows significantly faster improvement of manifestations and symptoms than guselkumab in patients with moderate to severe psoriasis.
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Source: Blauvelt A., Papp K., Gottlieb A. et al. A head‐to‐head comparison of ixekizumab versus guselkumab in patients with moderate‐to‐severe plaque psoriasis: 12‐week efficacy, safety, and speed of response from a randomized, double‐blinded trial. Br J Dermatol 2019 Dec 30, doi: 10.1111/bjd.18851 [Epub ahead of print].
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