Baseline anti-dsDNA concentrations and previous treatments predict response to Adalimumab and Etanercept: A retrospective investigation of 146 psoriasis patients

https://doi.org/10.1016/j.jdermsci.2014.09.003Get rights and content

Highlights

  • No method to predict response of psoriasis-patients to TNF-α antagonist-treatment is available to date.

  • We retrospectively investigated possible predictors of response to TNF-α antagonist-treatment.

  • Low baseline anti-dsDNA and few/no previous TNF-α antagonist treatments predicted good response to Adalimumab.

  • Age and baseline PASI are unlikely to predict response to TNF-α antagonists in a clinically significant manner.

Abstract

Background

Adalimumab and Etanercept are TNF-α antagonists commonly used for treatment of moderate-to-severe psoriasis and psoriatic-arthritis. Reliable instruments to assist the selection of patients for a specific treatment in a real-world scenario are unavailable.

Objective

To identify patient characteristics and baseline laboratory parameters predicting response to Adalimumab- and Etanercept-treatment.

Methods

We report a retrospective observational study including 116 and 64 psoriasis-patients treated with Adalimumab and Etanercept, respectively, at a dermatological outpatient clinic of a university hospital. Thirty four patients contributed data to both biologics. First occurrence of either loss-of-response or serious-side-effects (LOR/SSE) was chosen as clinical endpoint and predictors were identified using Cox-regression.

Results

Baseline anti-double-stranded DNA (anti-dsDNA) concentrations, number of previous treatments with TNF-α antagonists in general and previous treatment with Etanercept in particular significantly predicted LOR/SSE to Adalimumab. The predictive effect of baseline anti-dsDNA was conserved in TNF-α antagonist naïve patients. Number of previous systemic treatments other than TNF-α antagonists significantly predicted LOR/SSE to Etanercept. Age and baseline psoriasis area and severity index (PASI) did not predict response to either biologic in a clinically significant manner.

Conclusion

Our data suggests that treatment with Adalimumab may promise best results in psoriasis-patients with (A) low baseline anti-dsDNA concentrations, and (B) no previous TNF-α antagonist treatment. A clinically significant predictive effect of age and baseline PASI on response to Adalimumab and Etanercept is unlikely.

Introduction

Adalimumab, a humanized monoclonal anti-tumor necrosis factor-α (TNF-α) antibody, and Etanercept, a soluble decoy receptor for TNF-α, are two commonly used biologics to treat patients with moderate to severe psoriasis. While the treatment is beneficial for many patients, treatment itself is expensive (approximately 23,000 € per patientyear for Adalimumab and 23–28,000 € per patientyear for Etanercept for medication alone [1]), has potential serious-side-effects (SSE), and maybe subject to loss-of-response (LOR). Both, Adalimumab and Etanercept, share very common medical indications in the treatment of psoriasis patients [1], [2]. Reliable methods to select among these treatments on an individual patient level are unavailable. We previously reported baseline anti-double-stranded DNA (anti-dsDNA) concentrations and anti-nuclear antibody titers (ANA) as potential predictors for LOR to Infliximab therapy and Infliximab-antibody formation [3]. While comparable modes of action exist among the aforementioned biologics, respective data on predictors of response to Adalimumab and Etanercept-treatment is lacking to date.

The present study investigated patient characteristics, previous treatments, and baseline laboratory parameters, including autoantibodies, that might predict response to Adalimumab and Etanercept-treatment using long-term real-life data.

Section snippets

Patient selection

Data of 356 patients treated at the outpatient clinic of the department of dermatology of the University of Heidelberg between March 2003 and January 2012 were retrospectively investigated. Patients were eligible for study participation if they were (A) treated with Adalimumab or Etanercept for psoriasis vulgaris (PV), psoriasis guttata (PG), psoriasis palmoplantaris pustulosa (PPP) with or without accompanying psoriasis arthritis (PA) at our institution, and (B) gave informed consent to

Study population

One hundred forty-six psoriasis patients treated at our immunological outpatient clinic with either Adalimumab or Etanercept were included in this study. Thirty-four of these patients were consecutively treated with Adalimumab and Etanercept at our institution and contributed data to both biologics. Please refer to Table 1 for further details on our general study population. Baseline anti-dsDNA values were available for 51 patients. Patient characteristics were similar to those of the general

Discussion

This study examined possible predictors of LOR/SSE under treatment with Adalimumab and Etanercept using long-term real-life data.

Kaplan–Meier curves were chosen to describe treatment response as event-free drug survival. Cox-regression analysis was used to identify possible predictors for LOR/SSE, thus accounting for right-censoring. LOR/SSE was chosen as a surrogate for overall treatment response over PASI 75 as LOR/SSE reflects joint and skin symptoms as well as adverse events and could be

Conclusions

Our data suggests that treatment with Adalimumab may promise best results in psoriasis-patients with (A) low baseline anti-dsDNA concentrations, and (B) no previous TNF-α antagonist treatment. Furthermore, our data suggests that age and baseline PASI do not predict response to Adalimumab and Etanercept treatment in a clinically significant manner. Further prospective research, particularly on baseline anti-dsDNA and sequential treatment with Adalimumab following Etanercept, is; however,

Funding sources

None.

Conflict of interest statement

The authors have no conflict of interest to declare.

Acknowledgements

We thank Mr. Lorenz Uhlmann of the Institute for medical biometry and informatics (IMBI) of the University of Heidelberg for statistical advice.

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