Efficacy of anti‐IL‐23 and anti‐IL‐17 after adalimumab failure in psoriatic patients

Abstract

BackgroundMany national guidelines at the European level recommend first‐line therapy based on the anti‐TNF‐alpha adalimumab for treatment of psoriasis and psoriatic arthritis, mainly for economic reasons. Consequently, patients being treated with newer IL‐17 and IL‐23 inhibitors underwent previous unsuccessful first‐line adalimumab‐based therapy.ObjectivesEvaluate the efficacy and safety of IL‐17 and IL‐23 inhibitors after treatment with adalimumab compared to adalimumab‐naive psoriatic patients.MethodsWe retrospectively analysed 1053 psoriatic patients treated with anti‐IL17 and anti‐IL23 agents, which included 68 and 24 adalimumab‐experienced and 399 and 260 bio‐naive patients. Efficacy was assessed with mean PASI, PASI90, PASI100, and <3.ResultsConcerning the achieving of PASI100, PASI90 and PASI < 3 in patients treated with anti‐IL17 agents, no significant differences were observed between adalimumab‐experienced and bio‐naive patients. In patients treated with an anti‐IL‐23 agent, a faster response was observed in bio‐naive patients, with PASI < 3 significantly higher than ADA‐experienced patients at 16 weeks (77% vs. 58% p = 0.048). In a sub‐analysis that evaluated the performance of anti‐IL17 and anti‐IL23 agents in adalimumab‐experienced patients with a history of secondary failure, no significant differences were found. In multivariate analysis of PASI100, only anti‐IL‐17 therapy appeared to have a negative impact at 52 weeks (OR: 0.54 p = 0.04) independently of previous treatment. For PASI90, type of treatment and bio‐naïve status did not seem to have an impact at any time point.ConclusionsAnti‐IL 23 and anti‐IL 17 agents are not significantly different in terms of efficacy in bio‐naive patients or as second‐line therapy after failure with a biosimilar or originator adalimumab.

‘Efficacy of anti‐IL‐23 and anti‐IL‐17 after adalimumab failure in psoriatic patients’—response to Yu et al.

“…Dear Editor, We would like to answer the issues raised by Dr. Yu and Cheng-Chun Wei in their letter titled "Regarding Mastorino et al's 'Efficacy of anti-IL-23 and anti-IL-17 after adalimumab failure in psoriatic patients' 1 as authors of the discussed article. 2 About the first point of the letter, concerning the rapidity of action of IL-17 inhibitors compared to IL23 inhibitors and the supposedly higher drug survival of the latter, we agree with the authors regarding the lack of real-life studies on the subject. From our point of view, we have published some papers showing a not different survival among the same biologics class and possibly suggesting a higher survival of IL-23 inhibitors at indirect comparison.…”

“…Regarding the prevention of joint involvement, some studies seem to observe this possibility in patients treated with guselkumab. 2 On the other hand, risankizumab and tildrakizumab proved effective in the management of skin involvement in both patients with psoriasis and psoriatic arthritis without significant differences. 6 Concerning the need for data on ethnic groups other than Caucasian, we totally agree with the authors' position; however, this necessarily falls within the limits of a real-life study conducted in a university hospital in Northern Italy.…”

Drug survival and clinical effectiveness of secukinumab, ixekizumab, brodalumab, guselkumab, risankizumab, tildrakizumab for psoriasis treatment

“…The high efficacy of these new biologics drives higher expectations and goals in the treatment of moderate‐to‐severe psoriasis 8 . Improvement of Psoriasis Area Severity Index by 90% (PASI90) or achievement of absolute PASI ≤ 3 until 16 weeks of treatment, achievement of Dermatology Life Quality Index (DLQI) of 0/1 until the same endpoints, safety, major drug survival (DS), and reduction of inflammatory progression are the current aims in the treatment of psoriasis 9,10 . Several randomized controlled trials (RCTs) have revealed the superiority of anti‐IL‐17 molecules ixekizumab and secukinumab compared to anti‐TNF alpha 11 .…”

Development of a Deep Eutectic Solvent-Assisted Kaempferol Hydrogel: A Promising Therapeutic Approach for Psoriasis-like Skin Inflammation

“…Previous reports suggest that abnormal crosstalk between keratinocytes and immune cells, mediated by T cells, is an important threat in the etiopathogenesis of psoriasis. The IL-23/IL-17 axis is particularly recognized as a key contributor to the initiation and progression of psoriasis. , When stimulated by IL-23, T17 cell-produced cytokines trigger an inflammatory response in keratinocytes through the activation of the NF-κB signaling pathway. This is followed by an up-regulation of inflammatory products derived from keratinocytes, ultimately contributing to keratinocyte proliferation. , Apart from the immune factor, the antioxidant system acts as a defense mechanism against reactive oxygen species (ROS).…”

“…The IL-23/IL-17 axis is particularly recognized as a key contributor to the initiation and progression of psoriasis. 4,5 When stimulated by IL-23, T17 cell-produced cytokines trigger an inflammatory response in keratinocytes through the activation of the NF-κB signaling pathway. This is followed by an up-regulation of inflammatory products derived from keratinocytes, ultimately contributing to keratinocyte proliferation.…”