S4086 Successful Switch to Subcutaneous Infliximab (Zymfentra) After Development of High Titer Antibodies in a Patient With Ulcerative Colitis

Introduction: Infliximab (IFX) is a cornerstone biologic for ulcerative colitis (UC) and Crohn’s disease. Monitoring IFX levels and antibodies to IFX (ATI) is routine. ATI are associated with lower drug levels and loss of response. Six IFX biosimilars exist—only 1, IFX-dyyb (Zymfentra), is subcutaneous. Switching between biosimilars does not appear to worsen immunogenicity (PMID: 37788264). We present a case of IFX loss of response managed successfully with IFX-dyyb. Case Description/Methods: A 39-year-old undocumented man presented with 6 months of bloody diarrhea and abdominal pain. He was anemic (Hgb 7.6 g/dL), with leukocytosis (WBC 14.5 K/μL) and fecal calprotectin >4800 mcg/g. Computed tomography abdomen showed pancolitis. Flexible sigmoidoscopy revealed Mayo 3 colitis; biopsies confirmed chronic active colitis. He was diagnosed with UC and started on prednisone and IFX 5 mg/kg. At 8 weeks, proactive therapeutic drug monitoring (TDM) showed IFX level 10.2 mcg/mL and no ATI. At 6 months, he was in clinical, biochemical, and endoscopic remission, but proactive TDM showed low IFX level (3.5 mcg/mL) and ATI >100 AU. He was dose-escalated to 10 mg/kg every 4 weeks and started on azathioprine 50 mg/day. Due to cost barriers, he was unable to continue infusions but qualified for subcutaneous injections via support programs. The only available timely option was IFX-dyyb, which was initiated at 240 mg every other week, 2 months after ATI detection. After 4 doses, trough IFX level was 22.2 mcg/mL despite persistent ATI >100 AU. He remains in clinical remission. Discussion: This case highlights several key points. First, proactive TDM may not always correlate with clinical status, as this patient remained in remission despite high ATI. Second, the drop in IFX level from week 8 to month 6 supports ATI as potentially neutralizing. Third, switching to IFX-dyyb restored therapeutic levels despite persistent ATI, suggesting these antibodies may not fully neutralize the subcutaneous formulation. Although azathioprine may have influenced immunogenicity, ATI levels remained high despite improved IFX levels. To our knowledge, this is the first case describing successful transition from intravenous IFX to IFX-dyyb in the setting of high-titer ATI, with restoration of therapeutic levels and sustained remission. Subcutaneous IFX may help mitigate immunogenicity in select patients, though further studies are warranted.