Psoriasis and inflammatory bowel disease: concomitant IMID or paradoxical therapeutic effect? A scoping review on anti-IL-12/23 and anti-IL-23 antibodies

Abstract

Inflammatory bowel diseases (IBD) and psoriasis are chronic inflammatory conditions belonging to the heterogeneous group of immune-mediated inflammatory diseases (IMIDs). A significant bidirectional link between these two entities has been observed, conditioning an increased risk of IBD in patients with psoriasis and vice-versa. Biological therapies used for IBD may lead to the occurrence of psoriasis as a "paradoxical reaction." The objective of this study is to analyze the current evidence on the association between psoriasis and IBD, particularly finding case reports of the appearance or aggravation of psoriasis under therapy with interleukin-12/23 (IL-12/23) and IL-23 inhibitors. We conducted comprehensive research to identify studies examining the association between psoriasis and IBD and to find case presentations that reported the appearance or aggravation of psoriasis under biologic therapy with IL-12/23 and IL-23 inhibitors up to March 2024. Clinical trials for IL-12/23 and IL-23 inhibitors in IBD were analyzed to find cases of paradoxical psoriasis as registered adverse events. The sources of evidence are PubMed and ClinicalTrials.gov. For each included case report, data on patient characteristics concerning their age, sex, and comorbidities were selected. Moreover, information regarding the indication for biologic therapy, time to onset of paradoxical psoriasis after starting treatment, clinical presentation, and management of the paradoxical psoriasis was extracted. We found 10 reported cases of ustekinumab-induced new-onset or worsening psoriasis and one reported case of paradoxical psoriasis induced by risankizumab in the literature. Four cases of paradoxical psoriasis have been also registered in clinical trials involving ustekinumab treatment in IBD. Psoriasis can constitute a rare paradoxical adverse event of ustekinumab treatment, but further studies are needed to better clarify the cytokine imbalance that leads to this phenomenon induced by inhibition of IL-12/23 and IL-23. Still, few real-world data exist to draw any conclusions, but risankizumab may positively treat psoriasis induced by ustekinumab.

Keywords: Crohn’s disease; IBD; IMID; anti-IL-23 antibodies; psoriasis; therapy; ulcerative colitis; ustekinumab.

Figure 1.

Psoriasis of the left leg. (a) Onset during therapy with ustekinumab. (b) Resolution during therapy with risankizumab.

Figure 2.

Histopathologic findings at punch biopsy of the leg. (a) Small magnification (EE 4×). The epidermis shows moderate acanthosis and plurifocal spongiosis. Mild orthokeratosis is noted along the entire surface, and plurifocal parakeratosis is also seen at the hair infundibulum. Small and scattered intracorneal accumulations of polymorphonucleates in the context of parakeratosis. In the dermis, the presence of mixed superficial inflammatory infiltrate and capillary ectasia is predominantly in the papillary dermis. (b) Moderate magnification (EE 10×), we note psoriasiform and more regular epidermal hyperplasia, focal spongiosis, and parakeratotic scale on the surface. The inflammatory infiltrate is shown to consist of elements of chronic inflammation, small lymphocytes, and histiocytes, mixed with polymorphonucleates, with predominantly superficial pericapillary arrangement. No obvious eosinophilic granulocytic component is noted. Small extravasation of emazias. Minimal surface edema in association with capillary ectasia in the papillary dermis. Conclusion (for both): the histologic picture is consistent with the clinical hypothesis of psoriasis.

Figure 3.

IBD and psoriasis common pathogenesis. Gut epithelium (left) and skin epithelium (right). Shared inflammatory pathways are marked in red. Both innate immunity and adaptive immunity play a key role in triggering and maintaining both skin and gut chronic inflammation. Particularly, the IL-23/Th17 cells axis and its interaction with keratinocytes and intestinal mucosa cells are crucial for the pathogenesis of both psoriasis and IBDs. Hist, histamine; IFN-γ, interferon-gamma; LK, leukotriene; IL, interleukin; PGD2: prostaglandin D2; Th, T helper cells; TNF, tumor necrosis factor.

Figure 4.

Flowchart illustrating the screening process for relevant studies reporting cases of paradoxical psoriasis induced by IL-12/23 and IL-23 inhibitors. Source: Page et al.

Figure 5.

IL-23 inhibitors molecular structure and differences. Mirikizumab is a humanized IgG4 variant monoclonal antibody; guselkumab is a fully human IgG1 monoclonal antibody with a native Fc region, while risankizumab is a humanized IgG1 antibody with a mutated Fc region. Differences between anti-IL-23 therapeutic antibodies may be related to unique molecular characteristics: binding of these therapeutic antibodies to CD64 is particularly interesting since CD64+ IL-23-producing myeloid cells are increased in the inflamed colon in IBD. Atreya et al. found that guselkumab showed the strongest binding to CD64 compared with risankizumab, thus neutralizing IL-23 at its source of production. These findings may contribute to different therapeutic profiles between IL-23 inhibitors.