title: NOD2 polymorphism predicts response to treatment in Crohn's disease--first steps to a personalized therapy.
abstract: OBJECTIVE
  Great efforts have been made to predict disease behavior over time and the response to treatment in Crohn's disease (CD). Such understanding could personalize therapy. Early introduction of more aggressive therapies to patients at high risk and no introduction of predictable refractory treatments could become possible. We hence tested the influence of the NOD2 carrier status on treatment response.
  
  
  METHODS
  In 185 CD patients (age 45 ± 9.8 years, female n = 108, minimum disease duration 10 years), the three most common polymorphisms (p.Arg702Trp, p.Gly908Arg, p.Leu1007fsX1008) of NOD2 were tested by polymerase chain reaction and sequencing. Detailed clinical and medical history were obtained with a standardized questionnaire and by reviewing the medical charts. Treatments introduced were chosen by physicians blinded to genotype data.
  
  
  RESULTS
  The frequency of the NOD2 variant allele was about one-third (67, 30.2%) of CD patients. NOD2 carriers were more often treated with systemic and locally active steroids and with an immunosuppressant (Azathioprine/6-MP). NOD2 mutation carrier status was more often associated with systemic steroid [8.9% vs. wild-type (WT) 1.2%, P = 0.0086] and local-steroid refractory (14.9% vs. WT 3.5%; P = 0.001). The WT patients were significantly higher refractory to immunosuppressant (12.8% vs. NOD2 carriers, 0.5%, P = 0.03). Most WT patients were treated with TNF-α antagonists and remission rates were significantly higher in this group after 1 year of treatment (84% vs. NOD2 carriers, 33%, P = 0.07).
  
  
  CONCLUSIONS
  The study presents first hints for the NOD2 carrier status to be predictive for response to therapy. A higher percentage of CD patients with NOD2 mutation carrier status was steroid refractory but could be treated well with immunosuppressants. The WT status showed a higher response to steroids and remission rates within 1 year of anti-TNF-α therapy. On the way to personalized medicine, this approach should be further investigated in larger studies.
authors.affiliation: Department of Medicine I (Gastroenterology), Ulm University, Albert-Einstein-Allee 23, 89081 Ulm, Germany. jan-hendrik.niess@uniklinik-ulm.de
authors.forename: Jan Hendrik
authors.initials: JH
authors.lastname: Niess
authors.forename: Jochen
authors.initials: J
authors.lastname: Klaus
authors.forename: Johannes
authors.initials: J
authors.lastname: Stephani
authors.forename: Carolin
authors.initials: C
authors.lastname: Pflüger
authors.forename: Nadine
authors.initials: N
authors.lastname: Degenkolb
authors.forename: Ulrike
authors.initials: U
authors.lastname: Spaniol
authors.forename: Benjamin
authors.initials: B
authors.lastname: Mayer
authors.forename: Georgia
authors.initials: G
authors.lastname: Lahr
authors.forename: Georg B T
authors.initials: GB
authors.lastname: von Boyen
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D003424:Crohn Disease / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D005838:Genotype; D005938:Glucocorticoids / Q000627:therapeutic use; D006579:Heterozygote; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D057285:Precision Medicine; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D014409:Tumor Necrosis Factor-alpha