Spesolimab Increases Generalized Pustular Psoriasis Lesion Clearance By 1 Week

Pustular psoriasis of pregnancy (PPP) is a rare, life-threatening disease.8 It is sometimes referred to as impetigo herpetiformis, but many dermatologists consider this a misnomer because PPP is not associated with the herpes virus or bacterial infection.8 Although it is unclear whether PPP is specific to pregnancy, it typically arises early in the third trimester in affected women.3,8 Sterile erythematous plaques studded by painful pustules originate in skin folds on the trunk and back before coalescing into large dry desquamating plaques that spread to the extremities.2,8 Symptoms include fever, nausea, and diarrhea. Patients may also have neutrophilia, electrolyte abnormalities, and elevated inflammatory markers.2,8 Aggressive treatment is required and usually consists of systemic corticosteroids.8 Untreated PPP can lead to placental insufficiency, intrauterine growth restriction, and even miscarriage or stillbirth.8 Pregnant women with PPP and their fetuses should be closely monitored.2,8

Pustular psoriasis of pregnancy (PPP) is a rare, life-threatening disease.8 It is sometimes referred to as impetigo herpetiformis, but many dermatologists consider this a misnomer because PPP is not associated with the herpes virus or bacterial infection.8 Although it is unclear whether PPP is specific to pregnancy, it typically arises early in the third trimester in affected women.3,8 Sterile erythematous plaques studded by painful pustules originate in skin folds on the trunk and back before coalescing into large dry desquamating plaques that spread to the extremities.2,8 Symptoms include fever, nausea, and diarrhea. Patients may also have neutrophilia, electrolyte abnormalities, and elevated inflammatory markers.2,8

Aggressive treatment is required and usually consists of systemic corticosteroids.8 Untreated PPP can lead to placental insufficiency, intrauterine growth restriction, and even miscarriage or stillbirth.8 Pregnant women with PPP and their fetuses should be closely monitored.2,8

Treatment with interleukin (IL)-36 receptor inhibitor spesolimab was examined in patients with generalized pustular psoriasis (GPP).

Treatment with interleukin (IL)-36 receptor inhibitor spesolimab in patients with generalized pustular psoriasis (GPP) was associated with higher lesion clearance by 1 week compared with placebo, but the IL-36 receptor inhibitor was also associated with greater rates of infections and system drug reactions, according to findings from the phase 2 Effisayil 1 trial published in the New England Journal of Medicine.

The study included 53 patients with a GPP flare. Patients were randomly assigned to either a single 900-mg intravenous dose of spesolimab (n=35; mean age, 43.2±12.1 years) or placebo (n=18; mean age, 42.6±8.4 years). All patients were eligible to receive an open-label spesolimab dose on day 8, an open-label spesolimab dose as a rescue medication after day 8, or both. Patients were followed to week 12 after the open-label treatments.

Investigators assessed the rate of achievement of the GPP Physician Global Assessment (GPPGA) pustulation subscore of 0 at the end of the first week. In the GPPGA subscore, scores ranged from 0 (ie, no visible pustules) to 4 (ie, severe pustulation). A secondary endpoint was achievement of the GPPGA total score of 0 (clear skin) or 1 (almost clear skin) at the end of the first week.

At the baseline assessment, a GPPGA pustulation subscore of 3 was observed in 46% and 39% of patients in the spesolimab and placebo groups, respectively. Additionally, approximately 37% of patients in the spesolimab and 33% in the placebo arm had a pustulation subscore of 4. Overall, 19% of patients had a GPPGA total score of 4, indicating that 1 of 5 patients had severe disease.

A significantly greater percentage of patients in the spesolimab group vs the placebo group had a pustulation subscore of 0 at the end of week 1 (54% vs 6%, respectively; difference, 49 percentage points; 95% CI, 21-67; P <.001). At the end of the first week, 43% of patients in the spesolimab arm and 11% in the placebo group had a GPPGA total score of 0 or 1 (difference, 32 percentage points; 95% CI, 2-53; P =.02).

In all, 2 patients in the spesolimab group had drug reactions, with 1 of these reactions occurring alongside a drug-induced hepatic injury. In the spesolimab-treated group, 17% of patients experienced infections during the first week of treatment. By week 12, infections occurred in 47% of patients who received spesolimab at any time during the study. The investigators detected antidrug antibodies in 46% of patients who received 1 or more spesolimab doses.

Limitations of the study included its short treatment period, the small sample size, as well as its open-label nature.

Given these limitations, the researchers concluded that “longer and larger trials are warranted to determine the effect and safety of spesolimab in patients with pustular psoriasis.”

Disclosure: This clinical trial was supported by Boehringer Ingelheim. Multiple authors declared affiliations with the pharmaceutical industry. Please refer to the original article for a full list of disclosures.

Reference

Bachelez H, Choon SE, Marrakchi S, et al. Trial of spesolimab for generalized pustular psoriasisN Engl J Med. 2021;385(26):2431-2440. doi:10.1056/NEJMoa2111563