The Treatment with Interleukin 17 Inhibitors and Immune-Mediated Inflammatory Diseases

Abstract

IL-17 inhibitors (IL-17i) are medicines used to treat dermatological and rheumatic diseases They belong to a class of medicines called biological disease-modifying anti-rheumatic drugs (bDMARDs). This class of drugs has had a major impact on the therapy of autoimmune diseases, being much safer and more effective than treatment with small molecules. At the same time, they have highly beneficial effects on skin and joint changes, and their efficacy has been extensively monitored and demonstrated in numerous clinical trials. More and more such drugs are still being discovered today to ensure the best possible treatment of these patients, but more frequently and relatively constantly three agents are used. Two of them (Secukinumab and Ixekizumab) inhibit IL-17A directly, and the third, Brodamulab, inhibits the IL-17A receptor. Although they are extremely effective in the treatment of these diseases, sometimes their administration has been associated with paradoxical effects, i.e., there is an exacerbation of the inflammatory process. Tough, clinical trials of IL-17i have described cases of exacerbation or even onset of inflammatory bowel disease (IBD), such as Crohn’s disease and ulcerative colitis, after administration of these drugs in patients previously diagnosed with psoriasis (PS), psoriatic arthritis (PsA), or ankylosing spondylitis (AS). The pathophysiological mechanism of action is not well understood at present. One explanation would be that this hyperreactive inflammatory process would be triggered by Interferon 1 derived from dendritic plasma cells. Even though there are many reports in the recent literature about the role of IL17i in the onset of IBD, conclusions of studies do not converge. Some of them show an increased incidence of IBD in patients treated with IL17i, while some others affirm their safety of them. In the near future we will surely have more data emerging from ongoing meta-analyses regarding safety of use IL17i in patients who are at risk of developing IBD. Clinical and paraclinical evaluation (inflammatory intestinal markers) are carefully advised before recommending treatment with IL-17i and after initiation of treatment, and prospective surveillance by clinical and biomarkers of patients treated with IL-17i is absolutely essential to capture the onset of IBD.

Have Therapeutics Enhanced Our Knowledge of Axial Spondyloarthritis?

“…IL-17 plays an important role in the defence against fungal and certain bacterial pathogens. It was first linked to human disease through a model of mouse autoimmune encephalitis in 2005 [ 75 ], heralding the discovery of IL-17 pathway dysregulation in several autoimmune and autoinflammatory diseases including axSpA [ 76 ]. The IL-17 family includes 6 known cytokines (IL-17A-IL17F) [ 77 ].…”

A shared tissue transcriptome signature and pathways in psoriasis and ulcerative colitis

“…IL-17A has demonstrated differential effects in PS and IBD: in psoriasis, it is overexpressed in baseline psoriatic skin lesions as a primary driver of the disease pathology, while in IBD, it promotes the activation of regulatory pathways and confers protection in the gastrointestinal tract 51 . Thus, inhibition of IL-17A may interfere with the protective function of IL-17A in the intestine, as evidenced by the adverse outcomes in the case studies with IL-17A inhibitors in IBD 51,52 . The above findings confirm the hypothesis of different functional effects of IL-17A in PS and IBD, including UC.…”

Interpretable Inflammation Landscape of Circulating Immune cells

“…Inflammation is a central driver in cardio-vascular 10 , autoimmune 11,12 , infectious diseases 13,14 and even cancer 15 . The success of therapies targeting inflammation underscores the importance of understanding the underlying pathways [16][17][18] . Thus, categorizing patients based on their specific inflammatory cell states in the bloodstream has significant potential for advancing disease management 19 .…”