Dual biologic therapy in patient with refractory ulcerative colitis and comorbidities: A case report

Abstract

BACKGROUND

Despite advances in the treatment of ulcerative colitis (UC), some patients remain refractory to the currently available treatments. Dual biologic therapy (DBT) has emerged as a promising strategy for these patients.

CASE SUMMARY

A patient with extensive UC presented with steroid dependence and contraindications (past medical history included breast cancer and previous myocardial infarction) to treatment with tumor necrosis factor and Janus kinase inhibitors. DBT of α4β7 integrin antagonist (vedolizumab) and interleukin 23p19 inhibitor (mirikizumab) resulted in a sustained clinical and biochemical remission. No adverse events were recorded during the follow-up.

CONCLUSION

This case highlighted the challenge of managing refractory UC, especially in frail patients.

Key Words: Inflammatory bowel disease; Refractory ulcerative colitis; Combination therapy; Mirikizumab; Vedolizumab; Case report

Core Tip: Dual biologic therapy (DBT) is a promising treatment option for patients with refractory ulcerative colitis (UC) who have limited therapeutic alternatives. We presented the first case of a patient with extensive UC treated with mirikizumab and vedolizumab due to contraindications to tumor necrosis factor and Janus kinase inhibitors. The combination of mirikizumab and vedolizumab led to sustained clinical and biochemical remission without adverse events. Our case highlighted the therapeutic potential and safety of DBT in selected patients, reinforcing the need for individualized treatment strategies in complex clinical scenarios.

INTRODUCTION

Biologic therapies have revolutionized the management of inflammatory bowel diseases (IBD). Tumor necrosis factor (TNF) inhibitors are the cornerstone of biologic treatment. However, some patients remain refractory to this type of treatment[1]. Therefore, new agents targeting alternative inflammatory pathways have been explored and have led to the consideration of dual biologic therapy (DBT) for selected cases. The selective interleukin (IL)-23p19 inhibitors, risankizumab, mirikizumab and guselkumab, have shown consistent safety and efficacy in IBD[2,3]. Vedolizumab, an α4β7 integrin antagonist, also has a favorable safety profile in the treatment of IBD[4,5]. Both selective IL-23p19 inhibitors and vedolizumab may be suitable candidates for DBT in complex ulcerative colitis (UC) cases. We report herein the successful treatment of a patient with refractory UC with mirikizumab and vedolizumab.

CASE PRESENTATION

Chief complaints

A 52-year-old female with extensive UC presented to our clinic for a follow-up visit in March 2025 reporting clinical worsening over the prior month. She reported experiencing an increased number of bowel movements (> 15/day) that was associated with fecal urgency and cramp-like abdominal pain.

History of present illness

The patient had been diagnosed with UC at age 45. Initial treatment with oral/topical mesalamine and azathioprine failed, and the patient required multiple courses of corticosteroids. Remission was achieved with induction and maintenance of adalimumab (40 mg every 2 weeks) and had been maintained for 4 years. At age 49 the patient was diagnosed with breast cancer, leading to discontinuation of immunosuppressants. Six months later, she experienced a disease flare that was treated with corticosteroids. Colonoscopy showed scattered rectosigmoid ulcers (Mayo Endoscopic Score: 3), and histology confirmed chronic active colitis. Vedolizumab (300 mg at weeks 0, 2, and 6, followed by every 8 weeks) was initiated, resulting in a partial clinical response and the need for an additional course of corticosteroids. The patient experienced clinical worsening after the corticosteroid tapering, and the dosing interval of vedolizumab was shortened to every 4 weeks. One month later mesalamine and tacrolimus enemas were added to the treatment regimen because fecal calprotectin level had increased significantly (2790 µg/g). After two weeks, no clinical improvement was observed, and the enemas and vedolizumab were therefore discontinued. Since she had contraindications to TNF inhibitors and Janus kinase inhibitors, treatment with ustekinumab (6 mg/kg intravenously, followed by 90 mg subcutaneously every 8 weeks) was recommended. However, ustekinumab was interrupted during hospitalization and recovery following emergency surgery for small bowel ischemia. Treatment with ustekinumab was resumed 1 month later, and the patient also received a new course of corticosteroids. Due to clinical and analytical worsening (fecal calprotectin level 840 µg/g) following the corticosteroid tapering, ustekinumab dosing was escalated to every 4 weeks and the dose of corticosteroids was escalated. Three months later, a colonoscopy revealed persistent severe endoscopic activity in the left colon and rectum (Mayo Endoscopic Score: 3). Ustekinumab was then discontinued, mirikizumab was initiated (300 mg at weeks 0, 4, and 8, followed by 200 mg subcutaneously every 4 weeks), owing to its greater specificity for the IL-23 pathway and corticosteroid tapering was initiated. The patient experienced initial improvements. However, after completing induction she experienced a new worsening of symptoms. An extended induction protocol was pursued, including three additional intravenous administrations every 4 weeks.

History of past illness

Past medical history included hypertension, prior myocardial infarction treated with coronary stenting in 2017 and breast cancer diagnosed in 2022.

Laboratory examinations

Fecal calprotectin: 64 µg/g; hemoglobin: 12.9 g/dL; white blood cells: 10.7 × 10³/µL; platelets: 428 × 10³/µL; and erythrocyte sedimentation rate: 33 mm/hour.

FINAL DIAGNOSIS

Treatment-refractory UC.

TREATMENT

Combination therapy of mirikizumab and vedolizumab was initiated in addition to a new course of corticosteroids. Two months later, although the patient showed clinical improvement, fecal calprotectin level increased again (273 µg/g). Symptom exacerbation occurred prior to the scheduled 8-week dose. Therefore, vedolizumab administration was optimized to every 4 weeks.

OUTCOME AND FOLLOW-UP

Thus far, the patient has received DBT for 6 months, consisting of vedolizumab (300 mg intravenously every 4 weeks) and mirikizumab (200 mg subcutaneously every 4 weeks), administered every 2 weeks in alternating fashion. Therapeutic modifications since the initiation of mirikizumab are summarized in Figure 1. At the most recent follow-up visit, she was in a steroid-free clinical and biochemical remission with fecal calprotectin level normalization (39 µg/g). She reported no adverse events.

Figure 1 Summary of therapeutic changes and fecal calprotectin levels since initiation of mirikizumab. CF: Fecal calprotectin; Jan: January; Mar: March; Nov: November; Sep: September.

DISCUSSION

Combination therapy for the treatment of IBD was first investigated in 2010 in the Study of Biologic and Immunomodulator Naive Patients in Crohn’s Disease. This landmark trial demonstrated that patients with moderate Crohn’s disease treated with a combination of infliximab and azathioprine were more likely to achieve corticosteroid-free remission compared with those receiving azathioprine alone[6]. In 2014 the UC-SUCCESS study included patients with moderate-to-severe UC and demonstrated that combination therapy with infliximab plus azathioprine was more effective in achieving corticosteroid-free remission compared with either agent alone[7]. Recently, DBT has been proposed as a therapeutic strategy for two clinical scenarios of IBD: (1) Patients with well-controlled luminal disease but persistent, uncontrolled extraintestinal manifestations; and (2) Patients with refractory, poorly controlled intestinal disease despite standard biologic monotherapy[5]. However, there is no consensus regarding the optimal patient selection criteria, biologic combinations, or long-term safety of DBT. Most evidence[1,5] has been limited to case reports and small case series, primarily focusing on TNF and Janus kinase inhibitor combinations, which are limited due to safety concerns[8-11]. This case highlights the successful use of DBT with mirikizumab and vedolizumab in a patient with refractory UC and multiple therapeutic limitations. In this case, the switch from ustekinumab to mirikizumab was prompted by an inadequate clinical response despite dose optimization. Mirikizumab, a selective anti-IL-23p19 antibody, was considered a rational alternative due to its distinct mechanism of action compared with ustekinumab (anti-IL-12/23p40), allowing for more specific targeting of the IL-23 pathway, which has been associated with sustained efficacy in IBD[2,3]. Vedolizumab was further incorporated into DBT in view of the patient’s previous partial response and its well-established safety profile. The strengths of this report lie in the rationale for drug selection, the achievement of clinical and biochemical remission after failure of several advanced therapies and the favorable safety profile observed. Importantly, the patient tolerated the regimen well, and no adverse events were reported during 6 months of therapy, adding further reassurance regarding safety.

CONCLUSION

We demonstrated the feasibility, potential effectiveness, and apparent safety of DBT involving IL-23p19 inhibitors and vedolizumab. Our report adds to the growing evidence of alternative therapeutic combinations that may benefit patients with difficult-to-treat IBD. However, prospective studies with large sample sizes are needed to define the optimal patient selection, timing, and long-term safety.