Case Report: Secukinumab (Interleukin-17 Inhibitor) and Ulcerative Colitis Flare – the Double-Edged Sword

Abstract

Introduction

Secukinumab is an interleukin (IL)-17A inhibitor approved for psoriatic arthritis (PsA) and ankylosing spondylitis (AS). Its use has been reported to be associated with inflammatory bowel disease (IBD) flare and new onset.

Case Presentation

We report a case of a 56-year-old woman with longstanding ulcerative colitis (UC) in remission, who developed a severe UC flare after initiating secukinumab for refractory PsA. She presented with extensive ulcerations, systemic inflammation needing hospitalization, and change of treatment to risankizumab.

Conclusion

This case highlights the emerging evidence of IL-17A blockade in IBD, potentially leading to adverse events, and adds to the growing body of evidence regarding the management of such complications with novel therapeutic approaches in severe cases. Physicians should be aware of this possibility when using IL-17A blockade in patients with pre-existing IBD.

Introduction

Secukinumab is a monoclonal antibody that targets interleukin (IL)17A, a key cytokine involved in inflammatory pathways. It is approved for the treatment of moderate to severe plaque psoriasis, psoriatic arthritis (PsA) and ankylosing spondylitis (AS), with well-established efficacy in these immune-mediated conditions [1].

Its use in patients with inflammatory bowel disease (IBD) remains controversial. A randomized, placebo-controlled trial (RCT) published in 2012 evaluated secukinumab in patients with active Crohn’s disease (CD) and found lack of efficacy and higher rate of flares and adverse events compared to placebo [2]. Since then, additional studies and case reports have described possible new onset or exacerbation of IBD, including ulcerative colitis (UC), in patients treated with IL-17A inhibitors [3, 4].

Here, we present the case of a patient with long-standing UC in sustained remission, who developed a severe disease flare shortly after initiating secukinumab for refractory PsA, needing hospitalization and change of treatment to risankizumab.

Case Report

A 56-year-old woman with a history of left sided UC diagnosed at age 30, which has been in sustained clinical, biochemical, and endoscopic remission under oral mesalamine, without previous need for corticosteroids or advanced therapy for years. The patient also had a history of breast cancer treated in 2018, as well as PsA and AS, which were challenging due to persistent disease activity. She started guselkumab in September 2023. Due to an insufficient therapeutic response, treatment was switched to secukinumab in September 2024. At this point, laboratory revealed a hemoglobin level of 128 g/L, a C-reactive protein (CRP) of 11 mg/L, and an albumin level of 48 g/L. UC was in clinical remission, with a partial Mayo Score (pMS) of 0 and earlier surveillance endoscopy proved endoscopic remission (endoscopic Mayo 0) in June 2023.

Three months after starting secukinumab, she developed severe bloody diarrhea (>10 bm per day) and weight loss (4–6 kg). She required admission to the intensive care unit. Laboratory findings were: hemoglobin 68 g/L, C-reactive protein 329 mg/L, albumin 26 g/L and fecal calprotectin >2,100 μg/g. Clostridium difficile toxins and cytomegalovirus immunohistochemistry of colonic biopsies were negative. Computed tomography (CT) showed mild to moderate proctocolitis involving the rectum and distal sigmoid. Sigmoidoscopy showed confluent, deep, and extensive ulcerations up to 30 cm from the anal verge (endoscopic Mayo 3). Histology showed diffuse moderately active proctitis. No histological signs of cytomegalovirus were observed. She needed blood transfusion and intravenous corticosteroids for 3 days, followed by a tapering regimen of prednisone, and after discussing options with the patient, therapy with an interleukin-23 antagonist (risankizumab) was initiated.

During follow-up in March and mid-May 2025, she achieved clinical remission with a pMS of 0 and showed clinical improvement on PsA related symptoms. In April, a follow-up sigmoidoscopy revealed endoscopic improvement with healing signs (shown in Fig. 1).

Fig. 1.

Endoscopic assessment of UC before, during and shortly (4 weeks) after flare. a, b Before starting secukinumab (endoscopic remission). c, d During admission to intensive care unit (Mayo 3, pictures show deep ulceration with only islands of remaining mucosa, “pseudopolypoid” appearance). e, f During early follow-up (at 4 weeks, Mayo 3, but improving, linear ulceration and edematous mucosa around the ulcers).

Discussion

To our knowledge, this is the first reported case of a secukinumab-associated UC flare requiring admission to the intensive care unit (see Table 1). Our case highlights the importance of the IL-17 pathway in the pathogenesis of IBD. The T helper 17 (Th17) lymphocytes produce IL-17 cytokines, which can exert both protective and deleterious effects in tissue-specific immunity [5]. Among them, IL-17A is recognized as a key mediator of chronic tissue inflammation. IL-23 promotes Th17 cell expansion, leading to excessive IL-17A production, which in turn stimulates the release of pro-inflammatory mediators by keratinocytes, epithelial cells, and leukocytes. In diseases such as psoriasis and AS, IL-17A inhibition has shown significant clinical efficacy [5]. Given the role of IL-17A in inflammation, its inhibition was expected to benefit patients with IBD as well.

Table 1.

Summary of prior reported cases of IBD flares associated with secukinumab

Reference	Demographics (age/sex)	IBD type	Indication for secukinumab	Severity	Management	Hospitalization	ICU
Ehrlich et al. [6] (2018)	42 M	UC	AS	Severe	DD + IV S + infliximab	Yes	No
Wang et al. [7] (2018)	41 F	UC	Psoriasis	Severe	DD+ IV S +ciclosporine	Yes	No
Shukla et al. [8] (2018)	28 F	Not specified	Psoriasis	Mild-moderate	DD + ustekinumab	Not specified; likely outpatient	No
Johnston and Veettil [9] (2019)	27 M	UC	AS	Severe	DD + IV S + infliximab	Yes	No
Achufusi et al. [10] (2019)	39 M	UC	Psoriasis	Severe	DD + S + infliximab	Yes	No
Darch et al. [11] (2020)	54 F	CD	PsA	Mild-moderate	DD+ tildrakizumab	No	No
Khouri et al. [12] (2023)	38 F	CD	PsA	Mild-moderate	DD + S + infliximab	Not specified; likely outpatient	No
Bautista-Parada et al. [13] (2023)	43 F	UC	AS	Severe	DD + IV S + mesalazine	Yes	No
Edupuganti et al. [14] (2023)	20 F	CD	Juvenile idiopathic arthritis	Severe	DD + IV S + upadacitinib	Yes	No
Ongay et al. (present case)	56 F	Severe UC flare	Psoriasis + PsA	Severe	DD + IV S + risankizumab	Yes (ICU)	Yes

DD, drug discontinuation; S, steroids; IV, intravenous; UC, ulcerative colitis; CD, Crohn’s disease.

Surprisingly, an RCT showed that IL-17 blockade led to flare of CD in a subset of patients and IBD activity in patients on secukinumab inferior to placebo (mean reduction of CDAI placebo group −63.9 vs. secukinumab −29.2). Moreover, higher rates of adverse events (74.4% secukinumab vs. 50% placebo) and more cases of disease worsening were reported in the treatment group [2, 5]. In concordance with the above finding, animal studies suggested that IL-17A may support intestinal epithelial barrier function. Its inhibition was associated with negative effects such as increased intestinal permeability and mucosal fragility [15].

In contrast, in 2015 a study of 606 patients, did not report increased rates of IBD onset or reactivation in patients with PsA [16]. Diarrhea was described as an adverse event, with similar incidence in both treatment and placebo groups [16]. Similarly, a 2016 review of 14 clinical studies concluded that secukinumab did not increase the risk of new-onset or exacerbation of IBD in AS, psoriasis, and PsA [17].

In 2018, based on accumulating post-marketing data of IBD cases, the US Food and Drug Administration (FDA) released a warning on the secukinumab highlighting a potential risk of developing or exacerbating IBD [18]. The update emphasized the importance of monitoring for gastrointestinal symptoms in patients treated with secukinumab, particularly those with a history of IBD.

In recent years, additional evidence has emerged. In 2023, Deng et al. [4] published a study analyzing adverse gastrointestinal events associated with anti-IL-17 therapy. Using data from 2015 to 2022, they reported a significantly increased odds ratio (OR = 2.13, 95% CI: 1.96–2.30) for secukinumab-related IBD. A total of 388 gastrointestinal inflammatory events were identified, of which 268 were IBD cases attributed to secukinumab (new onset or exacerbation) [4, 5]. In 2025, another study examining the clinical characteristics of secukinumab-induced IBD reported a median onset of 4 months after initiation, with clinical symptoms similarly to those observed in our case, highlighting that severity of secukinumab-induced IBD varied significantly, ranging from mild IBD-like lesions to acute fulminant colitis, hence concluding that additional clinical data are required to further elucidate the full spectrum of severity associated with secukinumab-induced IBD [1]. Our case showed an almost life-threatening UC flare associated with secukinumab requiring intensive care.

Most patients in reported cases required drug discontinuation, and change of IBD treatment including corticosteroids, TNFα inhibitors, an IL-12/23 antagonist (ustekinumab), IL-23 inhibitors (guselkumab), or JAK inhibitors. Clinical improvement was observed in the majority of cases [1]. In this patient, the decision to switch to risankizumab, an IL-23 inhibitor, was based on patient previous exposure to biologic therapy, and the concurrent long-standing symptomatic PsA, which significantly impacted her quality of life. The choice of risankizumab over ustekinumab, TNFα inhibitors and JAK inhibitors (also viable alternatives discussed that have demonstrated efficacy in both UC and PsA), was primarily guided by the presence of concomitant psoriasis, for which risankuzumab has proved higher efficacy and patient preference, given the safety profile of this agent [19]. This favorable evolution of both colonic and articular symptoms highlights the importance of selecting a therapy capable of targeting both conditions.

In conclusion, emerging evidence suggests a potential association between anti–IL-17 therapy and IBD flares, which in some cases may be severe enough to require intensive care unit admission. The present patient developed a severe UC flare shortly after starting secukinumab for PsA and AS in line with the clinical features described in recent reports. This case highlights the importance of monitoring gastrointestinal symptoms in patients under secukinumab therapy, especially in those with a prior history of IBD, in which alternative biologic agents may offer a safer therapeutic option. In addition, there is no guideline that addresses how to manage these patients and our patient was successfully treated with risankizumab, an IL-23 inhibitor that selectively targets the p19 subunit of IL-23. While this therapeutic approach has been reported with other agents in the same pharmacologic class, to our knowledge, it has not been previously reported with risankizumab specifically, and we believe this case adds to the current body of evidence. Physicians will need to factor in the therapeutic decision to choose a new therapy covering both spectrums, severe IBD as well as the other immune-mediated condition, thus a multidisciplinary approach is the most effective.

The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000547522).

Statement of Ethics

The review of the patient data did not require ethical approval in accordance with local guidelines. Patient gave written informed consent for the use of the anonymized medical data for scientific purposes and publication. Written informed consent was obtained from the patient for publication of the details of their medical case and any accompanying images.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

This study was not supported by any sponsor or funder.

Author Contributions

Joaquin Ongay and Ivanna Candel: collecting the patient data, searching the literature and original drafting the manuscript; Alain Bitton, Waqqas Afif, Talat Bessissow: reviewing and editing the manuscript; Peter L. Lakatos: concept and supervision, collecting the patient data, searching the literature and original drafting the manuscript, reviewing and editing the manuscript, and guarantor of the paper.

Funding Statement

This study was not supported by any sponsor or funder.

Data Availability Statement

The data that support the findings of this study are not publicly available due to patient confidentiality but are available from the corresponding author upon reasonable request.