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Genetic Markers That Identify TNF-Inhibitor Responders in Psoriasis

Summary and Comment |
November 5, 2013

Genetic Markers That Identify TNF-Inhibitor Responders in Psoriasis

  1. Craig A. Elmets, MD

A first step toward personalized psoriasis therapy

  1. Craig A. Elmets, MD

Treatment of moderate-to-severe psoriasis changed dramatically with introduction of tumor necrosis factor α (TNF-α) inhibitors. However, these agents are very expensive and do not work in all patients. Investigators examined whether genetic polymorphisms in the TNF-promoter region and in the IL12B/IL23R genes might help to identify likely TNF-inhibitor responders. Psoriasis Area and Severity Index (PASI) scores were obtained prior to, and 3 and 6 months after, initiation of anti–TNF-inhibitor therapy in 109 psoriasis patients.

At 6 months, those with wildtype-238 and -1031 genotypes in the TNF-promoter region were more likely than patients with single nucleotide polymorphisms (SNPs) in those areas, although not significantly so, to achieve a PASI75 score. Patients with the -857CT or the -857TT genotype were significantly more likely than those with the -857CC genotype to attain PASI75 (P=0.006). Differences in responder versus nonresponder were the same when etanercept, adalimumab, and infliximab were analyzed separately; the difference became statistically significant with infliximab. Among TNF-inhibitor recipients, those with the wildtype IL12B/IL23R gene were more likely than those with SNPs at that locus to achieve a PASI90.

Comment

Psoriasis therapy could be optimized if effective markers were found to predict which patients will and will not respond to tumor necrosis factor inhibitors, just as estrogen receptors guide the management of breast cancer. This study is an important first attempt at identifying likely responders. Although the genetic differences evaluated here do not have sufficient sensitivity or specificity for clinical application, it is a start. The future will likely bring more studies of this nature to facilitate personalized psoriasis therapy.

  • Disclosures for Craig A. Elmets, MD at time of publication Consultant / Advisory board Astellas Pharmaceuticals Grant / research support NIH; NIH/NCI; Veteran’s Administration; Abbott Laboratories; Biogen; Clinuvel; Covan Basilea Pharmaceutica; Genentech; TenX Biopharma; University of California Editorial boards Cancer Prevention Research; Journal of the American Academy of Dermatology; Photodermatology, Photoimmunology, & Photomedicine; UpToDate Leadership positions in professional societies American Academy of Dermatology (Psoriasis Guidelines Subcommittee and Chair Designate, Clinical Guidelines and Research Committee); Photomedicine Society (Board of Directors)

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