Ali Al-Janabi, MA

Credit: University of Liverpool

Paradoxical eczema risk is lowest among biologic-treated individuals with psoriasis who are given IL-23 inhibitors, according to new findings, with female sex, greater age, and eczema or hay fever history being linked to greater risk of paradoxical eczema.¹

These findings resulted from a recent prospective cohort study conducted to assess patients’ risk of paradoxical eczema depending on biologic class and to assess the different factors associated with this skin condition. The investigators noted a prior lack of clarity on whether risk of paradoxical eczema varies by class of biologics or other types of clinical features.

The research was led by Ali Al-Janabi, MA, from the Division of Musculoskeletal and Dermatological Sciences at the University of Manchester in the UK. Al-Janabi and colleagues implemented the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) for their analysis, as it had involved over 20 000 individuals with psoriasis seen at 168 centers in the UK and in Ireland.²

“We used BADBIR to undertake a prospective cohort study to assess (1) the overall and biologic class–specific incidence of paradoxical eczema, (2) whether risk of paradoxical eczema differs between TNF inhibitors and other biologic classes, and (3) the demographic and clinical factors associated with paradoxical eczema,” Al-Janabi and colleagues wrote.

Background and Findings

The investigators utilized BADBIR data which spanned from September 2007 - December 2022, and they included adults in the age range of 18 and above with diagnosed plaque psoriasis and treated with various biologics. The biologics included by the team included IL-17 inhibitors, TNF inhibitors, IL-12/23 inhibitors, and IL-23 inhibitors.

The period in which the investigators gathered their data occurred at baseline, every 6 months within the initial 3-year span, and yearly thereafter, with the data consisting of systemic therapy information, participants’ baseline comorbidities, noted adverse events, and demographic data such as self-reported ethnicity.

In their primary analysis, the investigators considered all exposure lines, with follow-up time until the onset of participants’ paradoxical eczema, switches in treatment or discontinuation, the last documented follow-up, or end of life. Continuous exposure was defined by the research team as including a treatment break of 90 days or less prior to restarting the same biologic, and exposures with concomitant therapies were also used.

The team applied a 90-day risk window, with a paradoxical eczema occurrence within this period of switching biologics being counted as an event for both of the agents. The investigators’ final sample size was determined using the number of eligible exposures.

The team also identified the paradoxical eczema events through the use of adverse event data, implementing terms such as atopy, eczema, or dermatitis. They were flagged for review and inclusion in the research, with the team excluding non-eczema events and alternative phenotypes.

Overall, among the 56,553 drug exposures examined by the investigators, there were 24,997 from 13,699 study participants. These subjects had a median age of 46 years (IQR, 36-55).

These exposures, constituting 81,441 patient-years, ended up showing that 1% of the exposures were found to be linked with paradoxical eczema. The investigators found that the adjusted incidence rates were shown to be 1.22 per 100,000 person-years for the IL-17 inhibitors, 0.80 for the IL-12/23 inhibitors, 0.94 for the TNF inhibitors, and 0.56 for the IL-23 inhibitors.

Compared to TNF inhibitors, the research team noted that IL-23 inhibitors were shown to lead to a lower risk of paradoxical eczema (HR, 0.39; 95% CI, 0.19-0.81). They added that there was no substantial association found for the IL-17 inhibitors (HR, 1.03; 95% CI, 0.74-1.42) or the IL-12/23 inhibitors (HR, 0.87; 95% CI, 0.66-1.16).

The elements shown to contribute most to the increases in risk were shown to include increasing age (HR, 1.02 per year; 95% CI, 1.01-1.03), a history of atopic dermatitis (AD) (HR, 12.40; 95% CI, 6.97-22.06), and hay fever (HR, 3.78; 95% CI, 1.49-9.53). They added that males were found to have a lower risk (HR, 0.60; 95% CI, 0.45-0.78).

“The low overall incidence of paradoxical eczema may be reassuring for patients and clinicians, but it is possible that the incidence was underestimated due to underreporting or exclusion of adverse events with insufficient detail,” they wrote.

References

1. ^{Al-Janabi A, Alabas OA, Yiu ZZN, et al. Risk of Paradoxical Eczema in Patients Receiving Biologics for Psoriasis. JAMA Dermatol. Published online December 06, 2023. doi:10.1001/jamadermatol.2023.4846.}
2. ^{Burden AD, Warren RB, Kleyn CE, et al; BADBIR Study Group. The British Association of Dermatologists’ Biologic Interventions Register (BADBIR): design, methodology and objectives. Br J Dermatol. 2012;166(3):545-554. doi:10.1111/j.1365-2133.2012.10835.x.}