Biomolecular index of therapeutic efficacy in psoriasis treated with anti-TNF-α agents

G Ital Dermatol Venereol. 2018 Jun;153(3):316-325. doi: 10.23736/S0392-0488.16.05427-4. Epub 2016 Sep 14.

Abstract

Background: Clinical or quality of life assessments are currently available for psoriasis severity evaluation and therapeutic response. Laboratory scores focused to measure and follow treatment efficacy are lacking at present.

Methods: A microscopic and biomolecular score was designed to monitor skin disease severity and clinical response to anti-psoriatic treatments. A susceptibility gene analysis on cellular retinoic acid binding protein-II (CRABP-II), acting on keratinocyte differentiation, was also performed. A Molecular Index of Therapeutic Efficacy (MITE) was defined by assembling morphometric/semiquantitative measurement of epidermal thickness, immunohistochemical Ki-67, keratin 17 and CRABP-II expression of lesional and non-lesional psoriatic skin biopsies before and after anti-tumor necrosis factor (TNF) α therapies. A 0-12 MITE score was correlated with Psoriasis Area and Severity Index (PASI) and Psoriasis Disability Index (PDI) scores and inflammation. Three CRABP-II SNPs were analyzed by TaqMan assay.

Results: All parameters were highly expressed in psoriatic lesions and reduced after 12 weeks of anti-TNF-α treatments. MITE score strongly correlated with PASI and PDI values either before or after therapies (P<0.001 and P<0.001, respectively). Conversely, MITE values did not change after treatments of non-responder patients. CRABP-II did not result in a psoriatic susceptibility gene for the SNPs probes analyzed.

Conclusions: MITE score variations corresponded to the patients' clinical improvement following anti-TNF-α treatments, with significant statistical correlation among MITE, PASI and PDI scores. If confirmed in a larger series and/or in different hyperproliferative and inflammatory dermatoses, MITE score could be proposed as additional monitoring system to evaluate treatment protocols in skin disorders and targeted biomolecular pathways supporting clinical efficacy.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Biopsy
  • Cell Differentiation
  • Dermatologic Agents / pharmacology
  • Dermatologic Agents / therapeutic use*
  • Female
  • Humans
  • Keratinocytes / metabolism
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Psoriasis / drug therapy*
  • Psoriasis / genetics
  • Psoriasis / physiopathology
  • Quality of Life*
  • Receptors, Retinoic Acid / genetics
  • Severity of Illness Index
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Dermatologic Agents
  • Receptors, Retinoic Acid
  • Tumor Necrosis Factor-alpha
  • retinoic acid binding protein II, cellular