Itch as Major Mediator of Effect of Tofacitinib on Health-Related Quality of Life in Psoriatic Arthritis: A Mediation Analysis.

Peter C Taylor,Gil Yosipovitch,Joseph C Cappelleri,Andrew G Bushmakin,Joseph F Merola,Rebecca Germino,Pamela Young

doi:10.3390/jcm10184081

Abstract

Patients with psoriatic arthritis (PsA) experience impaired health-related quality of life (HRQoL). Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA, which has been associated with improvements in dermatologic endpoints in patients with PsA. To assess the extent to which tofacitinib affects patient HRQoL via improvements in dermatologic symptoms, including itch, data were pooled from patients with PsA who received tofacitinib in phase III studies (NCT01866668 and NCT01882439). Mediation modeling assessed the indirect effects (via Itch Severity Item [ISI] and Physician’s Global Assessment of Psoriasis [PGA-PsO]) and direct effects (via all other factors) of tofacitinib treatment on dermatology-specific HRQoL (measured by Dermatology Life Quality Index [DLQI]). In the initial model, the treatment effect on DLQI was largely mediated by itch (ISI; p < 0.0001) and PGA-PsO (p < 0.01). The model was re-specified to assess the indirect effects only of itch and PGA-PsO on DLQI. Here, 17.7% of the treatment effect on DLQI was attributable to PGA-PsO (p = 0.0006), and 82.3% to itch (p < 0.0001). Tofacitinib-dependent improvements in DLQI were primarily mediated by itch relief, in addition to improvements in PGA-PsO.

Highlights

Given that itch is considered to be a form of nociception [15], these findings provide further support of the potential for Janus kinase (JAK) inhibitors to relieve itch
In the analyses of data pooled from both OPAL Broaden and OPAL Beyond, the Overall, data for 468 patients were available for the analyses
Baseline demographics and disease charPGA-PsO (Figure 2). The majority of this indirect effect was attributable to improvements in acteristics for all patients included in both primary studies have been previously pubitch (88.5%, p < 0.0001; Figure 2a); the indirect effect mediated via improvements lished [16,17,20]

Summary

Introduction

It has been shown to substantially impact the physical and mental state of patients [7], and leads to impaired health-related quality of life (HRQoL) [8]

Methods

Results

Conclusion