A178 USTEKINUMAB FOLLOWING PRIMARY ANTI-TNF FAILURE AND SECONDARY LOSS OF RESPONSE TO VEDOLIZUMAB IN AN ADOLESCENT WITH ULCERATIVE PANCOLITIS

Abstract

Background: Infliximab is, to date, the only biologic therapy approved for the treatment of ulcerative colitis (UC) in paediatric patients. Although often effective, primary mechanistic failure is more common in UC than in luminal inflammatory paediatric Crohn's disease (CD). Alternate pathway biologics, specifically vedolizumab (anti-alpha4beta7 integrin) and ustekinumab (anti-interleukins 12/23) are increasingly used in adults with UC. Emerging data from head to head trials of biologics and network meta-analyses of placebo-controlled trial data are being used to guide choice and sequencing of therapeutic agents. Even among adults with UC data concerning combination biologics are very limited. Aim(s): To report the outcomes of addition of ustekinumab to vedolizumab in a patient with steroid dependent colitis, previous primary non-response to infliximab and secondary loss of response to vedolizumab monotherapy. Method(s): Case report Results: A 17 years old girl was hospitalized with acute severe colitis (PUCAI 85) developing as oral prednisone was tapered below 30 mg daily despite ongoing intensified vedolizumab therapy (300 mg q4 weekly) and per rectal steroids. First presentation 2 years earlier with UC pancolitis, responsive to oral prednisone, maintained on oral 5-ASA until first exacerbation 8 months later. Responsive then to IV steroids, but unable to maintain steroid-free remission despite intensified infliximab with therapeutic levels. Vedolizumab initiated in setting of primary mechanistic anti-TNF failure. Steroid-free clinical remission for 7 months of q 8 weekly dosing with normalization of fecal calprotectin (16, 115 mug/g) when symptoms recurred and persisted despite shortening of vedolizumab dosing interval to 4 weeks. Vedolizumab level 34 mug/mL. Symptomatic response to oral prednisone 40 mg, but unsustained with tapering. Hospitalized with up to 10 bloody stools per day, nocturnal stools, abdominal pain and anemia requiring blood transfusion. High doses of IV steroids were given with slow response. Colectomy refused by family. IV ustekinumab 390 mg given. Vedolizumab continued q 8 weekly in view of prior responsiveness. Ustekinumab subcutaneous maintenance therapy initiated at week 8 and continuing q 4 weekly (levels 3.3 mg/L). Oral prednisone tapered and discontinued. At 5 months post ustekinumab initiation, patient is in steroid-free clinical remission (PUCAI 0). Fecal calprotectin has declined from >1800 to 723 mug/g. Conclusion(s): In this patient with UC and primary failure of anti-TNF, ustekinumab has demonstrated short-term efficacy in alleviating steroid-dependency. The contribution of continued vedolizumab, to which there had previously been secondary loss of response, is unknown. Nevertheless, the safety profile of vedolizumab allows it to be combined with other therapies in selected treatment-refractory patients.