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The therapeutic management of patients with severe steroid-refractory ulcerative colitis still represents a critical clinical challenge. In this setting, cyclosporin is an effective and rapidly acting induction treatment that is applied in combination with maintenance therapeutic agents like thiopurines or vedolizumab. Here, we present the case of a 33-year-old ulcerative colitis patient with severe steroid-refractory ulcerative colitis who refused surgical intervention and previously demonstrated no long-term benefit to anti-TNF antibody, vedolizumab, cyclosporin, thiopurines or tofacitinib treatment. Intravenous cyclosporin therapy was re-initiated in the patient and, after signs of clinical response, therapy with ustekinumab was additionally applied. After 11 weeks of well tolerated cyclosporin and ustekinumab combination therapy, cyclosporin was discontinued upon clinical and endoscopic remission. Subsequently, ustekinumab treatment has been effective in maintaining remission during the follow-up period of 195 days.