Hideaki Miyachi, MD, PhD, on Treatments and Outcomes of Generalized Pustular Psoriasis

Among the different subtypes of psoriasis, generalized pustular psoriasis (GPP) affects only 2% of patients, but is the most severe form of the disease and can sometimes result in heart, respiratory, multiple organ failure, even death.

The use of systemic corticosteroids for the treatment of GPP has been replaced by newer systemic therapies, such as cyclosporin, etretinate, and methotrexate, except in patients with GPP accompanied by acute respiratory distress syndrome or capillary leak syndrome. Biological therapy and granulocyte monocyte apheresis therapy have also proven safe and effective for the treatment of GPP.

In spite of therapeutic advances, the clinical course of GPP and the outcomes associated with different treatments remain unclear, according to a research team from Japan. Results from their large retrospective analysis of national hospital administrative claims data of patients with GPP admitted to the hospital on an emergency basis showed that overall in-hospital mortality and morbidity was 4.2% and 8.4%, respectively. But patients treated with at least one biological therapy had significantly lower rates of morbidity and mortality compared with those receiving either oral agents or systemic corticosteroids alone.

"Patients with GPP who were treated with biologics demonstrated favorable outcomes compared with other treatments," Hideaki Miyachi, MD, PhD, of Chiba University Hospital in Japan, and colleagues reported in the Journal of the American Academy of Dermatology. "Our findings provide useful information for treatment decision-making for patients with GPP hospitalized in the biologics era."

The analysis included data from all 82 university hospitals in Japan. Of 1,516 patients with GPP hospitalized between July 2010 and March 2019, 294 were treated at least once with a biologic. Biological therapies included the tumor necrosis factor (TNF) inhibitors infliximab and adalimumab, the interleukin (IL)-12/IL-23p40 inhibitor ustekinumab, and the IL-17 inhibitors secukinumab, ixekizumab, and brodalumab. Another 948 patients received cyclosporine, retinoids, or methotrexate, and 274 had systemic corticosteroids alone.

Mortality rates in patients treated with a biologic were 1% compared with 3.7% in those treated with oral agents and 9.1% in those receiving systemic corticosteroids. No significant differences were observed in the number of patients in each group requiring ICU admission, central venous catheterization, mechanical ventilation, or continuous hemodiafiltration.

The analysis also revealed that 54% of patients in the biologics group received concomitant oral agents, and were more likely to receive granulocyte monocyte apheresis than patients on either oral agents or systemic corticosteroids (13%, 7.5%, and 4.7%, respectively). Notably, 52% of patients treated with biologics received concomitant corticosteroids as did 41% of patients treated with oral agents (P<0.001).

More patients receiving biologics were discharged home compared with patients in the other two groups but the biologics cohort was also in the hospital slightly longer (20 days versus 19 and 16 days, respectively), and had a higher median hospital bill ($9,705 USD compared with $6,108 in patients on oral agents and $5,602 for patients receiving systemic corticosteroids).

"Length of stay was prolonged in the biologics group, presumably because clinicians tended not to administer biologics during the first week after admission," the authors suggested. "Clinicians likely observed responses to other initial treatments such as oral agents and performed screening examinations before introducing biologics."

Miyachi, assistant professor in the department of dermatology at the Graduate School of Medicine, Chiba University, discussed the findings in greater detail.

How did your findings compare with earlier studies?

Miyachi: We were glad to observe that in-hospital mortality of patients with generalized pustular psoriasis, especially for those who received treatment with biologics, was lower in our relatively recent cohort compared with cohorts from previous studies. A study published in 1971 reported that mortality among 106 patients with GPP was 32%, and a study published in 2014 reported that mortality among 102 patients with GPP was 7%. The lower overall mortality in the current study may be the result of advances in the treatment of GPP, including biologics, in both the acute phase and during remission of the disease.

What were the characteristics of the study population overall?

More than half of the patients were male, older than 65 years of age, had a normal body mass index, and 85% were hospitalized in teaching hospitals. About half had a Charlson comorbidity index of 0.

How did patients in the different study groups compare?

Miyachi: Compared with the oral agents group and the corticosteroids-only group, the biologics group was younger (57 versus 68 years for both other groups) and had fewer comorbidities (5.4% versus 8.2% and 12%, respectively). Additionally, we found that the percentage of patients in the biologics group increased from 14% in fiscal years 2010 to 2014 to 23% in fiscal years 2015 to 2018.

You found that IL-17 inhibitor use increased over time and showed comparable in-hospital mortality and morbidity to treatment with TNF inhibitors. What could this mean clinically?

Miyachi: In the treatment of psoriasis vulgaris or plaque psoriasis, IL-17 inhibitors are now regarded as first-line treatment and have several advantages over TNF inhibitors. We showed that in patients hospitalized with GPP, the short-term outcomes were similar for both treatments. However, data on the treatment of GPP with IL-17 inhibitors are still limited. Thus, we can only assume at this point, but the advantages of IL-17 inhibitors may become more evident in the long-term treatment during remission.

In your expert opinion, should the use of biologics potentially be considered sooner in the treatment of hospitalized patients with GPP?

Miyachi: Yes, we think treating patients with biologics earlier after admission may potentially benefit patients with GPP. We are basing this on our current research findings as well as a decade of experience showing that patients with psoriasis can be safely treated with biologics.