title: CCL20 and IL22 Messenger RNA Expression After Adalimumab vs Methotrexate Treatment of Psoriasis: A Randomized Clinical Trial.
abstract: OBJECTIVE
  Methotrexate is a first-line systemic agent for treating of psoriasis, although its onset of effects is slower and overall it is less effective than tumor necrosis factor blockers.
  
  
  OBJECTIVE
  To differentiate the response of psoriatic disease to adalimumab and methotrexate sodium.
  
  
  METHODS
  Single-center, randomized, assessor-blind, 2-arm clinical trial of 30 patients from the outpatient dermatology center of Tufts Medical Center, enrolled from August 18, 2009, to October 11, 2011. Patients aged 18 to 85 years with chronic plaque-type psoriasis, a minimum Physician Global Assessment score of 3 (higher scores indicate more severe disease), and a psoriatic plaque of at least 2 cm were randomized in a 1:1 fashion to receive subcutaneous adalimumab or oral methotrexate. Skin biopsy specimens obtained at baseline and weeks 1, 2, 4, and 16 were given a histologic grade by blinded assessors to evaluate treatment response. Analyses were conducted from April 16, 2013, to January 5, 2015.
  
  
  METHODS
  A 16-week course of subcutaneous adalimumab (40 mg every 2 weeks after a loading dose) or low-dosage oral methotrexate sodium (7.5-25 mg/wk).
  
  
  METHODS
  Changes in genomic, immunohistochemical, and messenger RNA (mRNA) profiles.
  
  
  RESULTS
  Methotrexate responders experienced significant downregulation of helper T-cell-related (T(H)1, T(H)17, and T(H)22) mRNA expression compared with methotrexate nonresponders. Comparisons among adalimumab-treated patients were limited by the number of nonresponders (n = 1). Between adalimumab and methotrexate responders, we found no significant differences in gene expression at any study point or in the expression of T-cell-related mRNA at week 16. Adalimumab responders demonstrated early downregulation of chemokine (C-C motif) ligand 20 (CCL20) mRNA (mean [SE] at week 2, -1.83 [0.52], P < .001; week 16, -3.55 [0.54], P < .001) compared with late downregulation for methotrexate responders (week 2, 0.02 [0.51], P = .96; week 16, -2.96 [0.51], P < .001). Similar differences were observed with interleukin 22 (IL22) mRNA showing early downregulation for adalimumab responders (week 2, -3.17 [1.00], P < .001; week 16, -3.58 [1.00], P < .001) compared with late downregulation for methotrexate responders (week 2, -0.44 [0.68], P = .64; week 16, -5.14 [0.68], P < .001). Analysis of variance findings for key mRNA and immunohistochemical marker expression over the study course were significant only for CCL20 (P = .03) and IL22 (P = .006) mRNA comparing adalimumab and methotrexate responders.
  
  
  CONCLUSIONS
  Methotrexate is an immunomodulator with effects on helper T-cell signaling in psoriasis. Similar genomic and immunohistochemical response signatures and levels of mRNA downregulation at study completion among adalimumab and methotrexate responders suggest a disease-driven instead of therapeutic-driven pathway regulation. Adalimumab and methotrexate responses are differentiated by patterns of normalization of CCL20 and IL22 mRNA expression and may explain the varied onset and degree of clinical responses by each treatment.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00932113.
authors.affiliation: Department of Dermatology, Tufts Medical Center, Boston, Massachusetts.
authors.forename: Ari M
authors.initials: AM
authors.lastname: Goldminz
authors.affiliation: Laboratory of Investigative Dermatology, The Rockefeller University, New York, New York.
authors.forename: Mayte
authors.initials: M
authors.lastname: Suárez-Fariñas
authors.affiliation: Department of Dermatology, Tufts Medical Center, Boston, Massachusetts.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Tufts Medical Center, Boston, Massachusetts.
authors.forename: Nicole
authors.initials: N
authors.lastname: Dumont
authors.affiliation: Laboratory of Investigative Dermatology, The Rockefeller University, New York, New York.
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
authors.affiliation: Department of Dermatology, Tufts Medical Center, Boston, Massachusetts.
authors.forename: Alice B
authors.initials: AB
authors.lastname: Gottlieb
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use; D054418:Chemokine CCL20 / Q000235:genetics*; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006801:Humans; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D016037:Single-Blind Method; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism; D016896:Treatment Outcome; D055815:Young Adult; D000097043:Interleukin-22
chemical_list: D000068879:Adalimumab; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D054418:Chemokine CCL20; D007378:Interleukins; D008727:Methotrexate; D012333:RNA, Messenger; D000097043:Interleukin-22; C108355:CCL20 protein, human