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. 2023 Dec 18;6(4):pbad033. doi: 10.1093/pcmedi/pbad033

Table 5.

Clinical and molecular markers in prediction of treatment response and adverse events to thiopurines and biologics.

Markers
Drugs Good response Poor response Adverse events Sample number References
Thiopurines N/A N/A TPMT; NUDT15 (myelosuppression) CD (41);
CD (253)		 [129, 130]
Infliximab Concurrent immunomodulator treatment; male; non-stricturing/penetrating phenotype; IL23R (risk-increasing variants); FasL-843 (CC/CT); ADAM17 (rs10929587, TT); SLCO1C1 (rs3794271, CC); high CRP; high DEF5; high ECP; high F. prausnitzii; high Bifidobacteriales; high Clostridium Smoking; older age at first dose; IL23R (risk-decreasing variants); caspase-9 93 (CC/CT); HLA-DQA1*05 (A>G); ATG16L1 (rs2241880, AA); PHACTR3 (rs6100556, TT); CXCL12 (rs10508884, CC/CT); p-ANCA+/ASCA-; high baseline WBC; high CATH; high FC STAT3 (rs744166) CD (169);
CD (210);
UC (90);
CD (287);
CD (131);
CD (226);
UC (56);
CD (17), UC (6), IBDU (6);
CD (36), UC (26)
JIA (18), HC (8);
CD (106);
CD (1610);
CD (152), UC (110);
CD (240), UC (93), IC (7);
UC (191);
CD (35);
CD (5)		 [131–144]
Adalimumab ATG16L1 (rs10210302, CT/TT); TLR2 (rs3804099, TC/CC); TLR4 (rs5030728, GA/AA); TNFRSF1A (rs4149570, TT); MIF (rs755622, GG); TNFa (rs361525, GG); IRGM (rs13361189, TT); high CRP*; high mTNF+ cells; high Barnesiell; high Anaerostipes; high Tyzzerella; high Lachnoclostridium; high Lachnospiraceae_unclassified; high F. prausnitzii Male; Smoking; family history of IBD; infliximab failure; EIMs; perianal disease; high CDAI; high BMI; FasL (໿rs763110, CC genotype); TNF-308 (໿rs1800629, AA/GA); IL17A (rs2275913, AA/AG); low fT3/fT4; high CD25; high IL-5; high Escherichia-Shigella N/A UC (56);
CD (1610);
CD (102);
CD (483);
CD (482), UC (256);
CD (102);
UC (64);
CD (25);
CD (115);
CD (121);
CD (997);
UC (56)		 [140, 144–152]
Vedolizumab Mayo score<9; CDAI score≤330; younger patients; longer disease duration*; Concurrent thiopurine treatment; high BLOC1S1; high TLCD1; high TMEM223; high α4β7*; high Roseburia inulinivorans; high Burkholderiales Smoking history; anti-TNF failure; active perianal lesions; ໿concomitant steroid use; ໿HBI score>10; high CRP*; low albumin; high PHLDA1; high OSBPL11; high CXCL3; high α4β1; high αEβ7; low α4β7 receptor saturation; absent α4β7 expressing cells N/A CD (161), UC (111)
CD (1115);
UC (620);
CD (18), UC (19);
CD (15), UC/IC (11);
CD (19), UC (17);
CD (42), UC (43);
CD (212);
CD (128), UC (117);
CD (173), UC (121);
CD (967), HC (148);
CD (5)		 [153–164]
Ustekinumab Colonic/ileocolonic disease; concurrent immunomodulator treatment; CRP≥10mg/L; high TNF; high TBX21; high IL-23A; high IL-6; high FOXP3; high OSM; high OSMR; high F. prausnitzii; high Bacteroides; high clostridium citroniae; high Agathobaculum butyriciproducens; high Phascolarctobacterium faecium; low FC HBI>7; structuring disease; perianal disease; intestinal resection history; current corticosteroid use; anti-TNF failure; Mayo score>6; high BMI; high albumin N/A CD (167);
CD (104);
UC (133);
CD (102);
CD (28), UC (28), NIBD (11);
CD (306);
CD (108), UC (77);
CD (439);
CD (116);
CD (1369)		 [23, 165–171]

Abbreviations: TPMT: thiopurine s-methyltransferase; NUDT15: nudix hydrolase 15; CD: Crohn's disease; STAT3: signal transducer and activator of transcription 3; IL23R: interleukin 23 receptor; UC: ulcerative colitis; FasL-843: Fas ligand-843; ADAM17: ADAM metallopeptidase domain 17; SLCO1C1: solute carrier organic anion transporter family member 1C1; ATG16L1: autophagy related 16 like 1; CRP: c-reactive protein; DEF5: defensin 5; PHACTR3: phosphatase and actin regulator 3; IBDU: inflammatory bowel disease unclassified; CXCL12: C-X-C motif chemokine ligand 12; ECP: eosinophil cationic protein; F. prausnitzii: faecalibacterium prausnitzii; p-ANCA: perinuclear anti-neutrophil cytoplasmic antibodies; ASCA: anti-Saccharomyces cerevisiae; WBC: white blood cell; CATH: cathelicidin antimicrobial peptide; FC: fecal calprotectin; FL: fecal lactoferrin; JIA: juvenile idiopathic arthritis; TLR2: Toll like receptor 2; TLR4: Toll like receptor 4; EIMs: extra-intestinal manifestations; TNFRSF1A: TNF receptor superfamily member 1A; MIF: macrophage migration inhibitory factor; TNFa: tumor necrosis factor alpha; BMI: body mass index; IL17A: interleukin 17A; fT3/fT4: free triiodothyronine-to-thyroxin; CDAI: crohn's disease activity index; HBI: harvey-bradshaw index; BLOC1S1: biogenesis of lysosomal organelles complex 1 subunit 1; IC: indeterminate colitis; TLCD1: TLC domain containing 1; TMEM223: transmembrane protein 223; α4β7: alpha 4 beta 7; PHLDA1: pleckstrin homology like domain family a member 1; OSBPL11: oxysterol binding protein like 11; CXCL3: C-X-C motif chemokine ligand 3; α4β1: alpha 4 beta 1; αEβ7: alpha E beta 7; TBX21: t-box transcription factor 21; NIBD: non-IBD; IL-23A: interleukin 23A; IL-6: interleukin 6; FOXP3: forkhead box p3; OSM: oncostatin M; OSMR: oncostatin M receptor. * controversial.