P046 Tofacitinib Induced Resolution of Severe Colitis and Reactive Atypia in an Adolescent Patient With IBD

CASE: Tofacitinib is an anti-JAK/STAT small molecule approved for treatment of adults (but not children and adolescents) with moderate to severe ulcerative colitis. Data is limited in children and teens although two major centers have shown efficacy as both mono- and dual - combination therapy using tofacitinib in pediatric patients refractory to anti-TNF agents. We present a 16-year-old female diagnosed with inflammatory ileocolonic Crohn’s disease without upper gastrointestinal involvement after presenting with several months of abdominal pain, diarrhea, and unintentional weight loss. Laboratory evaluation was notable for normal inflammatory markers, albumin and complete blood count and an elevated stool lactoferrin. Initial endoscopic evaluation revealed moderate to severe pancolitis and patchy ileitis; biopsies noted mild chronic active ileitis and moderate to severe chronic active pancolitis without dysplastic or atypical changes. She was started on infliximab for induction and maintenance therapy and dosage was increased due to suboptimal levels and marginal symptomatic improvement. However, despite increased dosing plus a course of budesonide (Uceris), she had minimal improvement in her symptoms and ongoing elevation of her lactoferrin. Given an equivocal result on a Clostridium difficile testing (GDH antigen positive only), she was started on oral vancomycin which resulted in mild improvement, but not resolution, of diarrhea and abdominal pain. This was continued after completion of a 14-day course (and subsequent negative testing) due to increased stool frequency with discontinuation of the medication and improvement with reinitiating it. She had severe pancolitis (Mayo 2 – 3) but normal TI on repeat colonoscopy 5 months after diagnosis. Biopsies (reviewed by a panel of adult GI pathologists) were notable for reactive atypia with features concerning for early dysplasia in the ascending and descending colon. Due to disease severity and rapid progression plus histologic changes concerning for possible dysplasia despite optimized therapy with infliximab and repeat negative C. difficile testing, she was started on tofacitinib 10 mg twice daily along with oral vancomycin. She had complete resolution of diarrhea, abdominal pain, and early satiety within a week; repeat fecal lactoferrin was negative (<30). She underwent repeat colonoscopy with chromoendoscopy 5 months after initiation of tofacitinib which revealed mild acute ileitis but no active colonic inflammation, atypia or dysplasia. This is the first report to our knowledge that an adolescent patient with colonic predominant Crohn’s disease has complete resolution of atypia and possible early dysplasia with tofacitinib therapy.