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Many patients with generalized pustular psoriasis (GPP) flares got no specific treatment for them, despite their high risk of severe complications, according to the biggest study of these episodes to date.

Among 1,535 patients with GPP diagnoses, 271 had flares recorded in their electronic records over a 5-year period ending in June 2020 -- with a total of 513 such events. In 122 of these flare episodes, the patients received no anti-inflammatory treatments, although many were given opioids, according to Carla L. Zema, PhD, of Boehringer Ingelheim Pharmaceuticals in Ridgefield, Connecticut, and colleagues.

And for those who did get anti-inflammatory therapy, the researchers found a startlingly broad array of drugs provided, as .

These were just two results from a broad study aimed at elucidating the epidemiology and common treatment practices for GPP flares -- and perhaps to build awareness as Boehringer Ingelheim readies a new, specific therapy for the episodes.

GPP is considered rare but serious. According to Zema and colleagues, it "is characterized by intermittent flares involving the sudden and widespread formation of sterile pustules with associated erythema and pustules often coalescing to form lakes of pus." It can stand alone or appear in patients with other autoimmune conditions. (Most of the 1,535 patients identified in the study also had other forms of psoriasis, and about 7% had rheumatoid arthritis.)

Flares often come with flu-like symptoms and others such as anorexia, nausea, and severe pain, the researchers noted. "Moreover, pustules during and after a GPP flare can last for months and lead to life-threatening complications, often requiring emergency care."

However, the condition has not been well studied, with the only extant research coming as case series (often focusing solely on hospitalized patients) or from surveys.

It is surely not a coincidence that Boehringer Ingelheim wanted to pursue this topic with a published study. The company currently has a for GPP flares. The agent inhibits interleukin-36, a novel target in autoimmune disease. Phase II data reported last December and showed that the drug helped clear skin pustules just 1 week after receiving a single dose, and the benefit lasted 12 weeks.

Spesolimab reportedly ; no explanation has been given for the apparent delay in announcing a decision.

For the current study, Zema and colleagues analyzed data from Optum's database on some 89 million U.S. patients insured through private plans, Medicare, and Medicaid. Mean and median follow-up time for those with GPP diagnoses in the database was 4.3 and 2.9 years, respectively.

The 1,535 GPP patients the researchers identified were a mean 53 years old and two-thirds were women. Half had commercial insurance and most of the rest were divided evenly between Medicare and Medicaid. Most had other conditions, some likely connected to GPP and others not, at least directly. Mean Charlson comorbidity score was 2.22 across all patients.

One of the study's key findings, however, was that comorbidities were more common in patients with flares (mean Charlson score 2.80 vs 2.09 among non-flaring patients). Non-autoimmune conditions that were numerically more common were anxiety, type 2 diabetes, chronic obstructive pulmonary disease, hypertension, and obesity.

Autoimmune diagnoses were also more common in flaring patients -- most notably other forms of psoriasis, psoriatic arthritis, rheumatoid arthritis, and ulcerative colitis.

As expected, given the high risk for severe complications with GPP flares, admissions were far more frequent in flaring patients (44% vs 15%), as were emergency department visits (47% vs 24%). Those with documented flares were also more likely to have received medications of nearly every class: topical and oral steroids, oral retinoids, tumor necrosis factor and interleukin blockers, immunosuppressants such as methotrexate and tacrolimus, phosphodiesterase-4 inhibitors, and phototherapy. (Use of JAK inhibitors, B-cell depleting agents, and T-cell inhibitors was very rare.)

During flares, about 35% of patients received topical steroids, but no other anti-inflammatory treatment was used in as many as 15% of patients. Some 20% of patients, however, were prescribed opioids. Some patients also received treatments during the 30 days before and 30 days after episodes -- though at lower rates than while the flares were active.

The findings could be seen as highlighting the lack of standardized therapy for GPP flares. Moreover, said Zema and colleagues, the high rates of hospitalizations and emergency visits are evidence that these episodes can indeed be very severe.

Yet "[d]espite this high level of severity," the group asserted, "advanced treatments are very rarely used during flare episodes, leaving a significant unmet treatment need for patients with GPP and for health care professionals."

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