The safety and efficacy of spesolimab in Asian patients

Spesolimab is a humanized, selective antibody, which disrupts the activation of the interleukin-36 receptor.¹ The interleukin-36 pathway is involved in the pathogenesis of multiple inflammatory diseases, including generalized pustular psoriasis (GPP) in adults.

Spesolimab has been approved for use in multiple countries, including Japan, mainland China, and the European Union,¹ as well as receiving approval by the U.S. Food and Drug Administration (FDA) for the treatment of GPP flares in September 2022, as summarized by the Psoriasis and Psoriatic Arthritis Hub here.¹

The Psoriasis and Psoriatic Arthritis Hub has previously reported on the safety and frequency of adverse events following treatment with spesolimab in the GPP population from the randomized, double-blind, placebo-controlled phase II trial, Effisayil™ 1 (NCT03782792). Here, we summarize the safety and efficacy findings from the Effisayil™ 1 clinical trial in respect to the characteristics and outcomes of the 29 Asian participants, as reported by Morita et al.² in The Journal of Dermatology.

Patient characteristics

The baseline characteristics among Asian patients in the spesolimab treatment and placebo groups were comparable. However, there was a greater number of female participants in the placebo group (Table 1).

Table 1. Baseline characteristics of Asian participants*

GPPGA, Generalized Pustular Psoriasis Physician Global Assessment. *Data from Morita, et al.2 †Data are missing for one participant in the spesolimab group. ‡Present or past psoriasis could encompass any type of psoriasis including plaque psoriasis, while ongoing plaque psoriasis refers exclusively to plaque psoriasis.
Characteristic, % (unless otherwise stated)	Spesolimab (n = 16)	Placebo (n = 13)
Mean age, years	42.2	43.2
Mean body weight, kg	68.1	64.0
Sex
Female	62.5	92.3
Male	37.5	7.7
Country of enrollment
China	12.5	30.8
Japan	6.3	7.7
Malaysia	50.0	30.8
Singapore	0.0	7.7
Thailand	0.0	7.7
Taiwan	18.8	15.4
France	12.5	0.0
Present or past psoriasis†,‡	75.0	76.9
Ongoing plaque psoriasis	25.0	15.4
GPPGA total score
3	68.8	100.0
4	31.3	0.0
GPPGA pustulation subscore
2	18.8	30.8
3	43.8	46.2
4	37.5	23.1

Efficacy

The primary endpoint in this study was a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0, defined as no visible pustules at Week 1. This primary endpoint was met in 62.5% of patients in the spesolimab group compared with 7.7% in the placebo group (risk difference, 54.8; 95% confidence interval, 17.3–79.8). A secondary endpoint of a GPPGA total score of 0 or 1 (demonstrated by clear or almost clear skin) at Week 1 was met in 50.0% and 15.4% of patients in the spesolimab and placebo group, respectively (risk difference, 34.6; 95% confidence interval, −3.1 to 64.7). The comparisons of GPPGA pustulation subscore and GPPGA total score between the spesolimab and placebo groups among Asian patients and the overall population are outlined in Figure 1.

GPPGA, Generalized Pustular Psoriasis Physician Global Assessment.
*Adapted from Morita, et al.²

Safety

Among Asian patients, adverse events (AEs) were reported in 68.8% of patients in the spesolimab group compared with 61.5% of patients in the placebo group at Week 1. Common AEs in the spesolimab group included urinary tract infections and peripheral edema, occurring in 12.5% of patients. In the placebo group, the more common AEs included pyrexia and dizziness, occurring in 23.1% and 15.4% of patients, respectively. No deaths were recorded in this study. Other reported AEs are displayed in Table 2.

Table 2. Adverse events occurring in Asian patients*

AE, adverse event; RCTC, Rheumatology Common Toxicity Criteria. *Data from Morita, et al.2 †AEs reported in ≥10% of patients in any group. AE severity was graded according to the RCTC version 2.0 safety analysis set. Pustular psoriasis was excluded as an AE from this safety analysis. ‡One patient was recorded to have three serious AEs by Week 1 including urinary tract infection and symptoms that were reported as drug-induced liver injury and drug reaction with eosinophilia and systemic symptoms. However, these were not considered to be associated with spesolimab.
Event, %	Spesolimab (n = 16)	Placebo (n = 13)
Any AE	68.8	61.5
Common AE†
Urinary tract infection	12.5	0.0
Headache	6.3	7.7
Extremity pain	6.3	7.7
Diarrhea	6.3	0.0
Pyrexia	6.3	23.1
Peripheral edema	12.5	7.7
Dizziness	0.0	15.4
Nausea	6.3	0.0
Severe AE (RCTC Grade 3 or 4)	0.0	7.7
Investigator-defined drug-related AE	31.3	38.5
Serious AE‡	6.3	0.0
Serious AE requiring or prolonging hospitalization	6.3	0.0

Conclusion

Overall, the majority of characteristics and treatment outcomes among Asian patients were comparable with the overall population. Spesolimab treatment was found to improve outcomes in Asian patients compared with a placebo for GPP flares, as well as having an acceptable safety profile. The data retrieved from this analysis of the Asian participants in the Effisayil™ 1 clinical trial support the approved use of spesolimab to treat GPP in Asian patients.