On the other hand, contrary to IL-17 inhibition, IL-23p19 blockade does not increase the risk of candida infection, nor is it associated with inflammatory bowel disease worsening.
Serious adverse effects occur less frequently and specific to the psoriasis treatment option, such as inflammatory bowel disease and candida infections with IL-17 inhibitors, tuberculosis with certolizumab pegol, and psychiatric events with apremilast.
Up to December 2018, eight cases of new-onset inflammatory bowel disease (IBD) were reported in the literature in patients being treated with secukinumab, an interleukin-17A antagonist prescribed for dermatologic or rheumatologic indications.
This meta-analysis examined the relationship between IL-17A (rs2275913) and IL17F (rs763780 T/C) gene polymorphisms and the risk of inflammatory diseases, including periodontitis, rheumatoid arthritis (RA), and inflammatory bowel disease.
Polymorphisms in the Toll-Like Receptor and the IL-23/IL-17 Pathways Were Associated with Susceptibility to Inflammatory Bowel Disease in a Danish Cohort.
This is the first case report of de-novo severe Crohn's-like IBD in association with the use of Ixekizumab requiring rescue with escalated dosing of anti-TNF therapy and highlights the importance of close monitoring in patients being treated with IL-17 inhibitors, especially in those patients with known risk factors for inflammatory bowel disease.
After 1 year of follow-up, the odds of having IBD were 2.85 (<i>p</i> = .0213) and 1.42 (<i>p</i> = .1891) times higher in the anti-IL-17a and PDE4i cohorts, respectively, compared to the biologic-naïve cohort, and 2.86 (<i>p</i> = .0253) and 1.21 (<i>p</i> = .4978) times higher compared to the non-IBD-indicated biologic cohort.
On the other hand, safety data thus far suggest that these drugs might be devoid of some adverse effects of IL-17A blockade that seem to be class related, such as mucocutaneous Candida infections or triggering or worsening of inflammatory bowel disease.
Upregulation of Bcl-2 and IL-17 by HSPA4 would control apoptosis of inflammatory cells and immune response in the gut, which might develop treatment resistance in IBD.
However, given the complexity and probably the redundancy of pathways leading to IBD lesions, and the fact that Th17 cells may also have protective functions, neutralization of IL-17Afailed to induce any improvement in CD.
IL-23-mediated Th-17 cell activation and stimulation of IL-17-driven pro-inflammatory axis has been associated with autoimmunity disorders such as Inflammatory Bowel Disease (IBD) or Crohn’s Disease (CD).
IL-17A and the transcription factor retinoic acid receptor-related orphan receptor γt (RORγt) play fundamental roles in the pathogenesis of inflammatory bowel diseases; in human studies, we detected a dense infiltration of RORγt-dependent CD4(+) IL17A(+) T helper (Th)17 cells in specimens of CRC, ulcerative colitis, and ulcerative colitis-associated colorectal cancer.
An efficient strategy for IBD therapy is represented by the combination of IL-17A and IL-17F in acute IL-17A knockout TNBS-induced colitis, and also definite decrease of the inflammatory process in IL-17F knockout, DSS-induced colitis have been observed.
The function of these lymphocyte subpopulations in the development of IBD is well-known, since they produce a number of pro-inflammatory cytokines, such as interferon-γ and interleukin-17A, which in turn activate mucosal proteases, thus leading to the development of intestinal lesions, i.e., ulcers, fistulas, abscesses, and strictures.
IL-17-producing Th17 cells and IFN-γ and IL-17 double-producing Th1/17 cells have been identified as the pathogenic cells in inflammatory bowel disease (IBD).
Especially the identification of the strong association of a series of single nucleotide polymorphisms including interleukin (IL)-23R, CCR6, signal transducer and activator of transcription 3 (Stat3) and Stat4 with IBD susceptibility point at a critical involvement of T cells and especially of IL-17a-producing Th17 cells in the immune pathogenesis of IBD.
We sought to report adjudicated IBD cases (Crohn's disease [CD] and ulcerative colitis [UC]) in patients exposed to ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A.