Tumor Necrosis Factor Inhibitor Primary Failure Predicts Decreased Ustekinumab Efficacy in Psoriasis Patients

August 2015 | Volume 14 | Issue 8 | Original Article | 893 | Copyright © August 2015

Eric P. Sorensen BS,ab Kristina A. Fanucci BS,ac Ami Saraiya MD,a Eva Volf MD,a Shiu-chung Au MD,a Yahya Argobi MD,a Ryan Mansfield AS,a and Alice B. Gottlieb MD PhDa,c

aDepartment of Dermatology, Tufts Medical Center, Boston, MA bUniversity of California San Diego School of Medicine, San Diego, CA cTufts University School of Medicine, Boston, MA

BACKGROUND: Additional studies are needed to examine the efficacy of ustekinumab in psoriasis patients who have previously been exposed to tumor necrosis factor inhibitors (TNFi).
OBJECTIVE: To examine the predictive effect of TNFi primary failure and the number of TNFi exposures on the efficacy of ustekinumab in psoriasis treatment.
METHODS: This retrospective study examined 44 psoriasis patients treated at the Tufts Medical Center Department of Dermatology between January 2008 and July 2014. Patients were selected if they were treated with ustekinumab and had ≥ 1 previous TNFi exposure. The following subgroups were compared: patients with vs without a previous TNFi primary failure, and patients with one vs multiple previous TNFi exposures. The efficacy measure used was the previously validated Simple Measure for Assessing Psoriasis Activity (S-MAPA), which is calculated by the product of the body surface area and physician global assessment. The primary outcome was the percentage improvement S-MAPA from course baseline at week 12 of ustekinumab treatment. Secondary outcomes were the psoriasis clearance, primary failure, and secondary failure rates with ustekinumab treatment.
RESULTS: Patients with a previous TNFi primary failure had a significantly lower percentage improvement in S-MAPA score at week 12 of ustekinumab treatment compared with patients without TNFi primary failure (36.2% vs 61.1%, P=.027). Multivariate analysis demonstrated that this relationship was independent of patient demographics and medical comorbidities. Patients with multiple TNFi exposures had a non-statistically significant lower percentage S-MAPA improvement at week 12 (40.5% vs 52.9%, P=.294) of ustekinumab treatment compared with patients with a single TNFi exposure.
CONCLUSIONS: Among psoriasis patients previously exposed to TNFi, a history of a previous TNFi primary failure predicts a decreased response to ustekinumab independent of patient demographics and medical comorbidities.

J Drugs Dermatol. 2015;14(8):893-898.


Biologic agents have innovated the management of psoriasis. In particular, the tumor necrosis factor inhibitors (TNFi), which bind the inflammatory cytokine tumor necrosis factor α (TNFα), have become a cornerstone of psoriasis treatment. However, despite the success of TNFi, there is still a significant number of psoriasis patients who do not respond to these medications. For these people, drug failure may be characterized as primary (never achieved meaningful response), secondary (achieved, then lost meaningful response), or intolerance (experienced prohibitive adverse events).1-4 Primary drug failure may be influenced by individual differences in biologic drug metabolism,5-7 while secondary drug failure may be explained by the immunogenicity of the biologic agent and formation of anti-drug antibodies.8-13
More recently, ustekinumab, a fully human monoclonal antibody targeted to the p40 subunit shared between interleukin (IL)-12 and IL-23, has offered a new treatment option. However, the expected efficacy of ustekinumab following TNFi exposure in psoriasis patients is not clear. The ACCEPT, PHOENIX 2, and PSUMMIT 2 trials suggest that ustekinumab efficacy is reduced in patients who have been TNFi exposed compared with patients who are TNFi naïve.14-16 PSUMMIT 2 data also suggest that patients previously exposed to multiple TNFi are less likely to achieve ustekinumab responsiveness than patients exposed to a single previous TNFi.16 In contrast, clinical practice data have found no significant difference between ustekinumab efficacy in patients who are TNFi naïve vs TNFi exposed or patients previously treated with one vs multiple TNFi.17,18 However, to date no major studies in psoriasis have examined the relationship between type of previous TNFi failure and future ustekinumab response. This is relevant, as studies in rheumatoid arthritis have found that patients with a previous TNFi primary failure exhibit a decreased clinical response to a new biologic compared with patients with a previous TNFi secondary failure.4
Our study examines the efficacy of ustekinumab in psoriasis patients who were previously exposed to the TNFis at a major