Shaping Treatment Expectation to Optimize Efficacy of Interleukin 17A Antagonist Secukinumab in Psoriasis Patients

Abstract

Purpose: Patients' treatment expectations significantly influence the effectiveness of medical and pharmacological treatments. This clinical proof-of-concept study aimed to enhance treatment outcomes by targeting positive treatment expectations of psoriasis patients beginning systemic anti-psoriatic therapy with secukinumab, an interleukin (IL)-17A antagonist.

Patients and methods: We randomly assigned patients to three groups: a treatment as usual (TAU) group receiving the standard 300mg dose of secukinumab, a dose-control (DC) group with 75% dose reduction and an experimental (EXP) group receiving the same reduced dose along with a "cover story" designed to positively influence treatment expectations. We evaluated skin symptoms using the Psoriasis Area and Severity Index (PASI), the Dermatology Life Quality Index (DLQI), perceived itch, mood and plasma IL-17A levels at baseline and at 1, 2, 3, 4, 8, 12, and 16 weeks post intervention.

Results: The study included N = 120 patients (average age = 45.78 years, 34% female). A high baseline expectation level (8.1 of 10 points) was observed across all groups which could not be further increased by the EXP-group's "cover story". The EXP and DC groups did not differ with regard to reaching 75% improvement in PASI scores (PASI75), a DLQI score of 0 or 1 or at least 4 points improvement in itch. Over time, the EXP-group showed a faster decline in PASI scores and anxiety symptoms compared to the DC-group, but less improvement in quality of life. IL-17A levels significantly increased throughout the treatment, with no significant differences between groups despite the 75% dose reduction.

Conclusion: This study demonstrates an attempt to modify patients' treatment expectations to enhance the effectiveness of pharmacological therapy with secukinumab in psoriasis patients. However, verbal suggestion alone did not significantly improve clinical outcomes, suggesting that future studies should explore alternative approaches to leverage placebo effects to the benefit of patients with psoriasis.

Keywords: placebo effect; psoriasis treatment; psychodermatology.

Graphical abstract

Figure 1

Study Design. After an initial pre-check, patients were randomly allocated to one of three treatment groups: The treatment as usual (TAU) group received the full dose of secukinumab as in clinical routine (300mg) and served as pharmacological control. The dose reduction control group (DC) was administered only 75mg of secukinumab (75% reduction) during all treatment weeks. Patients in the enhanced expectation group (EXP) were treated with the same dose reduction regimen as the DC group but received an additional verbal instruction together with the ingestion of a novel tasting beverage to increase the salience of this verbal suggestion. At follow-up, all outcome parameters were measured again and continuation of treatment outside of the study was discussed with patients.

Figure 2

CONSORT Flow diagram.

Figure 3

Expectation ratings. Positive treatment expectations, assessed with the GEEE scale on a 0–10 numeric rating scale. Ratings were collected prior to (week 0) and after (week 1) the experimental intervention, involving the verbal suggestion of probable treatment success supported by a novel tasting drink for the experimental (EXP) group.

Figure 4

Absolute numbers over the course of treatment for the three primary outcomes. (A) Psoriasis Area and Severity Index (PASI) over the course of treatment; (B) Itch ratings on a visual analogue scale (VAS) ranging from 0–10; (C) Dermatology Life Quality Index (DLQI), with higher numbers indicating higher burden on quality of life; (D) Interleukin (IL)-17A measured in the blood plasma.