Effisayil 2

21 evidence topics · 4 sources

Objective

Maintenance treatment and flare prevention

“prevents the occurrence of GPP flares” (opens the source at this quote in a new tab)

Location and study date

Geographic scope

“This multicentre, randomised, placebo-controlled, phase 2b trial was done at 60 hospitals and clinics in 20 countries.” (opens the source at this quote in a new tab)

Trial dates

Milestone	Reported date
Start	“June 8, 2020”
End	“Nov 23, 2022”

Study design

Randomized dose-finding study

“phase 2, multicenter, randomized, parallel-group, double-blind, placebo-controlled, dose-finding study” (opens the source at this quote in a new tab)

Eligibility criteria

Required flare history

“at least two GPP flares” (opens the source at this quote in a new tab)

GPPPGA total score at screening and randomization

“0 or 1” (opens the source at this quote in a new tab)

Treatment

Investigated subcutaneous spesolimab regimens

Regimen	Loading dose in mg	Maintenance dose in mg	Maintenance interval in weeks
High dose	“600”	“300”	“4”
Medium dose	“600”	“300”	“12”
Low dose	“300”	“150”	“12”

Study outcomes

Rationale for using time to first GPP flare as the primary endpoint

Flare definition for the primary endpoint through week 48

Required component	Threshold
GPPPGA pustulation subscore	“≥2”
Increase in GPPPGA total score from baseline	“≥2”

GPPGA and GPPASI validation

“the GPPGA and GPPASI are valid, reliable and responsive measures for the assessment of GPP disease severity” (opens the source at this quote in a new tab)

Statistical analysis description

Number of participants (Planned and analyzed)

Planned enrollment

Population	Participants
Total planned	“120”

Screening and randomization

Population	Participants
Screened	“157”
Randomized	“123”

Description of analysis sets

Prespecified time-to-event analyses

Analysis	Method
Hazard ratios for dose-response testing, stratified by systemic GPP medication use at randomization	“stratified Cox regression model”
Individual-dose comparison with placebo, with the same stratification	“stratified log-rank test”

Results

Participant disposition

Randomized treatment groups

Group	Participants
High-dose spesolimab	“30”
Medium-dose spesolimab	“31”
Low-dose spesolimab	“31”
Placebo	“31”

Baseline characteristics

Sex distribution

Characteristic	Participants and percentage
Female	“76 [62%]”

Efficacy results

Participants with a GPP flare by week 48

Group	Participants and percentage
High-dose spesolimab	“three (10%)”
Placebo	“16 (52%)”

High-dose spesolimab versus placebo: time to first flare

Measure	Reported value
Hazard ratio	“0·16”
95% confidence interval	“0·05-0·54”
P value	“0·0005”

Health-related quality of life and patient-reported outcomes

Definition of the symptom and quality-of-life endpoints

“Other secondary endpoints included time to worsening (defined as an increase of four points from baseline for each score) of the Psoriasis Symptom Scale (PSS) and Dermatology Life Quality Index (DLQI) up to week 48, and the occurrence of adverse events by week 48.” (opens the source at this quote in a new tab)

Time to worsening of the Psoriasis Symptom Scale

“Spesolimab reduced the risk of PSS worsening over 48 weeks compared with placebo, as demonstrated by HRs of 0·46 (95% CI 0·22–0·95, nominal p=0·0079) for the low-dose regimen, 0·56 (95% CI 0·28–1·10, nominal p=0·052) for the medium-dose regimen, and 0·42 (0·20–0·91, p=0·013) for the high-dose regimen” (opens the source at this quote in a new tab)
“A smaller proportion of patients in the low-dose (12 [39%] of 31), medium-dose (14 [45%] of 31), and high-dose (ten [33%] of 30) spesolimab groups reported a worsening of their PSS score compared with placebo (20 [65%] of 31; figure 3A and appendix p 11).” (opens the source at this quote in a new tab)
“High-dose spesolimab did not pass the significance threshold for superiority (α=0·0063) for time to worsening of PSS (p=0·013) and no further testing was done.” (opens the source at this quote in a new tab)

Time to worsening of the Dermatology Life Quality Index

“Spesolimab reduced the risk of DLQI worsening over 48 weeks, with HRs versus placebo of 0·58 (95% CI 0·30–1·14, nominal p=0·043) for the low-dose group, 0·60 (0·31–1·17, nominal p=0·048) for the medium-dose group, and 0·26 (0·11–0·62, nominal p=0·0010) for the high-dose group” (opens the source at this quote in a new tab)

Safety results

Mortality during the trial

“no deaths” (opens the source at this quote in a new tab)

Study limitations

Summary

The trial enrolled participants with a history of at least two GPP flares who had clear or almost clear skin at screening and randomization. It therefore addresses flare prevention rather than initial treatment of an active flare. The high-dose group included 30 participants and the placebo group 31, limiting precision for uncommon harms. Follow-up for the primary endpoint extended to 48 weeks. The comparator was placebo, not imsidolimab.