Are new variants of psoriasis therapy (IL‐17 inhibitors) safe?

Abstract

Psoriasis is a chronic, recurrent, inflammatory, and proliferative skin disease. Its etiology has not yet been fully assessed, but undoubtedly it is a multifaceted disease. The key role in its pathomechanism is played by genetic, immunologic, and environmental factors and stress. If traditional methods of psoriasis treatment (phototherapy, methotrexate, retinoids, cyclosporine A) fail, we reach for the following biopharmaceuticals – infliximab, etanercept, adalimumab, or ustekinumab. However, genetic engineering progress discovers new possibilities – the pending clinical trials involve IL‐17, IL‐23 antagonists, PDE4 and ‐3 and ‐1. Psoriasis etiopathogenesis mainly involves the IL‐17A, IL‐17F, and IL‐17A/F subtypes, which affect the keratinocytes. The biological therapy molecularly oriented with the antagonists of interleukin 17 is based mainly on the influence onto the cytokine in the manner that prevents it from binding with the receptor. Three biopharmaceuticals are currently under third phase studies: two fully humanized antibodies neutralizing IL‐17 – ixekizumab and secukinumab, and one human monoclonal antibody, brodalumab. The below work will be devoted to the analysis of possible undesirable symptoms, which were observed during the studies. We will try to review the latest literature concerning the most important clinical trials conducted in many centers.

Identifying key components and therapeutic targets of the immune system in hidradenitis suppurativa with an emphasis on neutrophils

“…61,62 Another IL-17 inhibitor under phase III studies for psoriasis that could potentially be used for HS includes ixekizumab. 63,64 A recent open-label cohort study of 10 patients treated with subcutaneous brodalumab (anti-17A, IL-17C and IL-17F) showed promising results. 65 Bimekizumab (a dual IL-17A and IL-17F inhibitor) is currently under phase II multicentre clinical trials for moderate-to-severe HS (NCT03248531).…”

“…Previous studies have demonstrated that HS is associated with a significantly increased risk of co‐occurring and new‐onset inflammatory bowel disease (IBD); 60 secukinumab has been associated with worsening symptoms compared with placebo in clinical trials of Crohn disease, and therefore the onset and/or worsening of IBD needs to be closely monitored in phase III trials 61,62 . Another IL‐17 inhibitor under phase III studies for psoriasis that could potentially be used for HS includes ixekizumab 63,64 . A recent open‐label cohort study of 10 patients treated with subcutaneous brodalumab (anti‐17A, IL‐17C and IL‐17F) showed promising results 65 .…”

“…Secukinumab (NCT03713632), Ixekizumab 63,64 Anti-IL-17 antibodies currently indicated for treatment of psoriasis, psoriatic arthritis and ankylosing spondylitis; phase III trials are currently under way testing secukinumab's safety and efficacy in treatment of HS Bimekizumab (NCT03248531)…”

Generalized hypertrichosis associated with the use of interleukin 17 blockers in 2 patients with psoriasis

“…8 The use of biological IL-17A inhibitors can result in the appearance of some side effects such as infection, nasopharyngitis, upper respiratory tract infections, inflammation on the nasal mucosa, headaches, and candida infections. 9 In recent years, hypertrichosis has been reported in anecdotal cases or series cases. 1,2,10 Rongioletti et al, 2 reported on a patient with erythrodermic psoriasis who was treated with secukinumab.…”

The Role of IL-17-Producing Cells in Cutaneous Fungal Infections

“…In the skin, Langerhans cells recognize fungal pathogens, which drive TLR/MYD88 and dectin-1-dependent pathway and subsequently produces IL-6 mediated IL-17-producing cell development [12,37]. Blockages of IL-17 and IL-23 reduce chemokine and antimicrobial expression, and increase the risk of systemic fungal burden [38,39]. Therefore, it is assumed that humans have developed immune reactions against fungal cell components to eliminate infection and as the host immune response, and that IL-17 plays a vital role in the host defense against fungal infection.…”