Vedolizumab Treatment in Adults with Inflammatory Gastrointestinal Disorders and Underlying Immunodeficiency

Background Noninfectious gut inflammation is a common manifestation of inborn errors of immunity (IEI) and can affect various segments of the gastrointestinal tract. Vedolizumab, which selectively blocks leukocyte trafficking to the gut, is approved for treatment of inflammatory bowel disease; however, there is lack of data regarding safety and efficacy in IEI. We aim to describe the experience of patients with gut inflammation related to IEI treated with vedolizumab. Material and Methods 4 patients >18 years old with humoral or combined immunodeficiency and gut inflammation treated with vedolizumab (weeks 0, 2, and 6, and then every 8 weeks) at a tertiary center. Clinical improvement was defined as a reduction in diarrhea reported by patients with weight gain and/or improvement of malabsorption. Results Case 1: 37-year-old man, combined immunodeficiency with dysregulation due to TRAF3 haploinsufficiency. He had a long-standing enteropathy with duodenal, ileal, and colonic involvement and was corticosteroids dependent. He started vedolizumab, achieving good symptomatic control. After one year of treatment, mild endoscopic activity was observed, so he added a low dose of corticosteroids, resulting in clinical improvement. Case 2 23-year-old man, combined immunodeficiency with dysregulation, WES negative. He presented chronic diarrhea, weight loss, and malabsorption requiring hospitalizations in context of complete villous atrophy with poor response to corticosteroids. A clear clinical response was observed after induction with 3 doses of vedolizumab. Case 3 49-year-old woman, CVID with autoimmune hepatitis and chronic severe colitis refractory to topical and oral corticosteroids and azathioprine. She received four doses of vedolizumab without clinical improvement, eventually developing extensive pancolitis due to CMV. She is being considered for a subsequent treatment line with ustekinumab. Case 4 51-year-old woman, persistent agammaglobulinemia after rituximab treatment for immune thrombocytopenia and multiple other autoimmune manifestations, WES pending. Chronic diarrhea with complete villous atrophy refractory to corticosteroids. After 5 doses of vedolizumab, she exhibited clinical and endoscopic improvement and remained free of atrophy for two years. After this period, partial villous atrophy recurred. Conclusion We observed a more favorable and sustained effect of vedolizumab on duodenal atrophy compared with colitis, emerging as a safe option for patients with immunodeficiency and enteropathy. Table 1.Clinical and immunological features.Case 1Case 2Case 3Case 4Age of first symptoms (years)1513826Age of first gastrointestinal symptoms (years)17193829Extraintestinal clinical featuresRecurrent RTI, warts, penile intraepithelial neoplasia, polyarthritisRecurrent RTI, bronchiectasis, HSM, portal hypertension, Hodgkin lymphoma, short statureAutoimmune hepatitis, esophageal candidiasis, recurrent RTIITP, splenectomy, thyroiditis, vitiligo, alopecia areata, CMV pneumonia, severe COVID-19Immunoglobulin levelsIgG (800-1700 mg/dL)673<200370<200IgA (70-400 mg/dL)57<436<4IgM (50-300 mg/dL)32819<10IgE (0.1-100 UI/mL)2<0.1<0.1Antipneumococcal responseAbsentPoor responsePoor responseAbsentLymphocyte subsets (cel/uL)CD19+ (110-570 cel/uL)515 (22%)8 (0.9%)3 (0.3%)1 (1%)CD4+ (530-1300 cel/uL)196 (28%)123 (14%)281 (36%)358 (42%)CD8+ (330-920 cel/uL)413 (59%)687 (86%)337 (43%)275 (32%)CD56+ (70-597 cel/uL)70 (3%)75 (8.4%)181 (21%)221 (26%)HSM: hepatosplenomegaly. RTI: respiratory tract infection.Table 2.Endoscopic and biopsy findings before and after treatment with vedolizumab.Findings before treatmentFindings after treatmentCase 1Duodenum: complete villous atrophy (Marsh IIIc). Active duodenitisDuodenum: absence of villous atrophy. Active duodenitisIleum: follicular hyperplasia, chronic ileitisIleum: follicular hyperplasiaColon: chronic active colitisColon: absence of inflammatory activityRectum: focal active colitisCalprotectin: 2065 ug/gCalprotectin: 838 ug/gCase 2Duodenum: complete villous atrophy (Marsh IIIc). Intraepithelial lymphocytosis >25%, absence of plasmocytesPending resultsCase 3Duodenum: absence of villous atrophy and lymphocytosisColon: severe active colitis, with viral inclusionsIleum: follicular hyperplasia, active ileitisColon: severe active chronic colitis, increased apoptosis and absence of plasmocytesCalprotectin: 371 ug/gCase 4Duodenum: complete villous atrophy (Marsh IIIc). Intraepithelial lymphocytosis >30%Duodenum: absence of villous atrophy and lymphocytosisIleum: follicular hyperplasiaColon: absence of inflammatory activityColon: absence of inflammatory activityCalprotectin*: 332 ug/gCalprotectin: 203 ug/g*Normal range: 5-45 ug/g