Underreporting of sleep variables in psoriasis clinical trials

Abstract

Dear Editor,

The successful management of psoriasis, a chronic skin condition characterised by red, scaly plaques, may depend on consistent, high-quality sleep.¹ Numerous studies indicate that individuals without healthy sleep routines may experience more severe psoriasis symptoms.^2-4 Although the exact mechanism between sleep and psoriasis has yet to be elucidated, epidermal immune dysregulation caused by disruptions in sleep patterns is thought to be involved.⁴ Increased numbers of circulating proinflammatory molecules due to poor sleep, coupled with decreased skin healing, further aggravate symptoms.^{5, 6} Furthermore, lack of sleep can heighten anxiety and stress, psychological factors known to cause psoriasis flare-ups.^{7, 8} This necessitates the monitoring of study participants' sleep when developing psoriasis treatments, as both healthy and poor practices may modulate trial results.^{1, 3}

Literature also corroborates this need, as patients who consistently achieve sufficient sleep have lower levels of baseline inflammation, thereby complementing the anti-inflammatory effects of psoriasis medications.^{2, 3, 9} We aim to investigate how sleep is incorporated into the design of recent psoriasis clinical trials and any reporting trends over the past 10 years.

We searched clinicaltrials.gov for phase 2 and 3 psoriasis clinical trials with start dates between 1 January 2013 and 15 November 2023 using filters: all sexes, all ages, interventional design, with results. Only English language studies were included, yielding 255 trials that were screened for sleep. Psoriatic arthritis was excluded. Twenty-three studies were then extracted by two independent reviewers (G. X. and N. H.) for intervention type, date completed, country, funding, sleep outcome measures, sleep-related results, sleep analysis and incorporation into the inclusion criteria.

Our results demonstrate that only 9% of psoriasis clinical trials in the past 10 years mentioned sleep, with just 7/23 reporting sleep as an actual study outcome. In these studies, one identified sleep as a primary outcome, and six collected sleep data secondary to measures such as the dermatology life quality index. Psoriasis subtypes included nail (1/23), plaque (9/23) and unspecified (13/23). 82.6% (19/23) of studies investigated systemic therapies, whereas 17.4% examined topicals. Interestingly, no studies for lifestyle interventions included sleep. Secukinumab was the most commonly examined systemic therapy in 36.8% (7/19) of studies. 14/23 studies in the second half of the study period mention sleep, potentially indicating an upwards trend. Only one study (NCT02070965), investigating betamethasone dipropionate cream, incorporated sleep by excluding participants who had abnormal sleep schedules or worked night shifts. This is notable, as sleep-deprived subjects in topical corticosteroid trials may bias the complication rate of iatrogenic secondary adrenal insufficiency.¹⁰

The under-reporting of sleep disturbances can be attributed to several factors. Clinical trials may be preoccupied with physical outcomes rather than holistic patient well-being or lack awareness of the crucial link between sleep and psoriasis altogether. Due to its systemic inflammatory effects, psoriasis is known to be associated with sleep disorders such as obstructive sleep apnoea.¹¹ This correlation is corroborated in 11/23 of included RCTs, in which sleep apnoea is intentionally examined as an adverse event. However, the impact of psoriasis on daytime sleepiness and, by extension, road accidents and loss of productivity has been less explored.² Thus, study designs that explicitly incorporate validated sleep quality assessments such as the Epworth sleepiness scale, Athens insomnia scale or Pittsburgh sleep quality index are necessitated. Wearable devices like actigraphy, which provide continuous, noninvasive monitoring of sleep patterns may also be effective.¹²

In conclusion, researchers are encouraged to design clinical trials that explicitly incorporate sleep quality assessments and explore sleep disturbances as both a consequence of and potential causative or exacerbating factor of psoriasis.

Grace Xiong: Conception; design; extraction; analysis; interpretation; manuscript writing; correspondence. Nicholas Hua: Conception; design; extraction; interpretation; manuscript writing. Ron Vender: Conception; supervision; editing. All authors contributed significantly to this work and its intellectual content.

The authors declare no conflict of interest.

No ethics review was required for this work as it involves secondary analyses of publicly available data.