Safety and Efficacy of Vedolizumab in Kidney Transplant Recipients With Crohn’s Disease

Crohn’s disease (CD) and ulcerative colitis are chronic idiopathic inflammatory bowel diseases, characterized by gastrointestinal symptoms such as abdominal pain, fecal urgency, diarrhea1Torres J. Mehandru S. Colombel J.F. Peyrin-Biroulet L. disease.Lancet. 2017; 389: 1741-1755https://doi.org/10.1016/S0140-6736(16)31711-1Abstract Full Text PDF PubMed Scopus (1131) Google Scholar,2Ungaro R. Allen P.B. Ulcerative colitis.Lancet. 1756-1770https://doi.org/10.1016/S0140-6736(16)32126-2Abstract (1605) Scholar; extra intestinal manifestations that may involve almost any organ including the kidney. The most common renal nephrolithiasis, tubulointerstitial nephritis, glomerulonephritis, amyloidosis. In addition, kidney damage in patients with CD result from dehydration, long-term malnutrition, anemia, side-effects of medical therapy.3van Hoeve K. Hoffman I. Renal disease: a systematic review.J Gastroenterol. 2022; 57: 619-629https://doi.org/10.1007/s00535-022-01903-6Crossref (3) Scholar management transplant (KT) recipients is extremely challenging complex; traditional treatments mesalazine, azathioprine, steroids burdened significant side effects4Cai Z. Wang Li Treatment comprehensive review.Front Med (Lausanne). 2021; 8765474https://doi.org/10.3389/fmed.2021.765474Crossref (52) newer biological drugs antitumor necrosis factor-alpha inhibitors possibly correlated increased risk infectious complications malignancy.5Garrouste C. Anglicheau D. Kamar N. et al.Anti-TNFα therapy for recipients: clinical outcomes.Med (Baltim). 2016; 95e5108https://doi.org/10.1097/MD.0000000000005108Crossref (17) Scholar,6Quinn C.S. Jorgenson M.R. Descourouez J.L. Muth B.L. Astor B.C. Mandelbrot D.A. Management tumor factor α inhibitor after transplantation: comparative analysis associated outcomes.Ann Pharmacother. 2019; 53: 268-275https://doi.org/10.1177/1060028018802814Crossref (7) Vedolizumab an antibody against α4β7 integrin, selectively blocking lymphocyte homing gut. It approved moderately to severely active not responsive standard or inhibitors.7Loftus Jr., E.V. Feagan B.G. Panaccione al.Long-safety vedolizumab disease.Aliment Pharmacol Ther. 2020; 52: 1353-1365https://doi.org/10.1111/apt.16060Crossref (54) Several studies literature show efficacy safety CD; nevertheless, data on KT (KTCD) has been reported so far. We describe our monocentric experience use 3 KTCD patients. A 50-year-old male diagnosed 1997 was treated multiple therapeutic lines, azathioprine limited benefits. 2016, he underwent deceased donor end-stage caused focal segmental glomerulosclerosis. Maintenance immunosuppressive based prednisone 2.5 mg/d, new prolonged release tacrolimus 2.25 mg/d (trough level 5–7 ng/ml) 75 mg/d. At beginning 2017, replaced mycophenolic acid 540 cellular borderline rejection. Over years, had frequent reactivation subsequent prerenal acute injury (AKI), often requiring hospitalization. After developing steroid-dependent disease, July 2021 started treatment. Intravenously 300 mg administered first 2 times every weeks induction (as per Center protocol) then bimonthly maintenance budesonide other day (is ongoing tapering completely suspend steroids). 64-year-old female autosomal dominant polycystic 2014. time diagnosis, patient 5 extended 4 720 2020, seeking specialist diarrhea diagnosis made, suspended, 50 One year later, due response, treatment prescribed. given intravenously months thereafter unique CD. 56-year-old 2003 IgA nephropathy. following onset diarrhea, discontinued no 2021, during 7.5 ng/ml). line therapy, at second administration protocol), therapy. Main characteristics summarized Table 1. followed least 12 start maintained, unchanged all No adverse events have far.Table 1Clinical demographical characteristicsCharacteristicCase 1Case 2Case 3Age506456SexMaleFemaleMaleNephropathyFSGSADPKDIgA nephropathyKidney year201620142003Maintenance starting vedolizumabPrednisone mg/dPrednisone Tacrolimus ER mg/dTacrolimus LCPT mg/dMycophenolic mg/dTherapy disease-1997–2017 mesalazine-azathioprine 2020–2021-2021 vedolizumab-2017–2021 budesonide-2021 vedolizumab-2021 + budesonideTime transplant5 yr7 yr19 yrTime diagnosis25 yr2 yr0 yrADPKD, disease; ER, release; FSGS, secondary segmentary glomerulosclerosis; LCPT, tacrolimus. Open table tab ADPKD, All showed improvement symptoms. Specifically, achieved remission, defined Harvey Bradshaw Index score ≤ 4; 1 required course oral flare follow-up period, 2o maintained remission without need CD-related (all antirejection medication low dose prednisone). On endoscopic evaluation treatment, exhibited complete mucosal healing (SES-CD 0); third yet remission. achieving also normalization C-reactive protein levels. From nephrological perspective, stabilization estimated glomerular filtration rate trough decrease AKI hospitalization; vedolizumab, none hospitalization, Supplementary S1. evaluated Coefficient Variation8van den Belt S.M. Gracchi V. de Zeeuw Heerspink H.J.L. How measure monitor albuminuria healthy toddlers?.PLoS One. 2018; 13e0199309https://doi.org/10.1371/journal.pone.0199309Crossref (2) trend levels, comparing 24 before after, obtaining results both (respectively, 25.5% vs. 4.3% 55.04% 7.28%). Data depicted Figure heterogeneous can affect organ, particular, more likely suffer require replacement their life.9Park Chun Han K.D. al.Increased nationwide population-based study.World J 24: 4798-4808https://doi.org/10.3748/wjg.v24.i42.4798Crossref (38) There lack about recipients, but few suggest undergoing shorter overall graft survival rates compared controls Particularly, one mentioned study, related higher infection rate, (conducted selected population) recurrence amyloidosis.S1 Despite absence strong evidence, suggested receive regimen, we did report on. diseases occur different pathophysiological playgrounds; hypoperfusion episodes, and/or anemia. Parenchymal be close events, amyloidosis, correlate activity disease. Moreover, some medications’ lead damage. Postrenal causes less common, mainly obstructive nephrolithiasis. Therefore, effective essential improve outcomes these patients.3van very encumbered literature. “traditional” therapies side-effects. Mesalazine nephrotoxic interstitial fibrosis papillary necrosis.3van Scholar,4Cai recent inhibitors, enhanced malignancy complications.5Garrouste monoclonal which acts preventing infiltration leukocytes submucosa. Due its gut selectivity, systemic infections malignancy.S2 GEMINI trials do include nephrotoxicity, although there case reports nephritis administration.S3 Few literature, small sample patients, shown liver CDS4,S5; recently published review nontransplant biologics solid recipient, albeit data, suggests possibility adjustment specific prophylaxis.S6 To knowledge, this experience, complications, nephrotoxicity observed same observing improvements stable value This number retrospective observation, control group, allowing finishing conclusion. Nevertheless, encouraging lay groundwork design further investigate Teaching points resumed 2.Table 2Teaching pointsCD UC IBDs, EIMs.The EIMs ScholarThe effects: mesalazine necrosis. Calcineurin cause vasoconstriction afferent arterioles thereby increasing leading TNF alpha complications.KTCD eGFR through hospitalization events.AKI, injury; CD, eGFR, rate; EIMs, manifestations; diseases; KT, transplant; KTCD, UC, colitis. AKI, authors declared competing interests. declare they obtained consent discussed report. manuscript supported research fundings Italian Health Ministry “Ministero della Salute” (Ricerca Corrente). would like acknowledge thank who provided written informed publish details cases. Download .pdf (.09 MB) Help pdf files File (PDF) References. Incidence Vedolizumab.