Efficacy and Safety of Bimekizumab in Japanese Patients with Generalised Pustular Psoriasis and Erythrodermic Psoriasis: 3-Year Results from BE BRIGHT, a Multicentre, Open-Label, Phase 3 Study

Abstract

Introduction: This study aimed to report bimekizumab (BKZ) efficacy and safety in Japanese patients with generalised pustular psoriasis (GPP) and erythrodermic psoriasis (EP).

Methods: Patients aged ≥ 18 years with plaque psoriasis, GPP, or EP received BKZ for 144 weeks; only results for GPP and EP reported here. All patients received BKZ 320 mg every 4 weeks (Q4W) at week 0, with dose adjustments for Q4W or Q8W at weeks 16 and 48, depending on Investigator's Global Assessment (IGA) 0/1 response. Efficacy outcomes assessed to week 144: IGA 0/1, Dermatology Life Quality Index (DLQI) 0/1, Clinical Global Impressions-Improvement (CGI-I), ≥ 75/90/100% improvement from baseline Psoriasis Area and Severity Index (PASI 75/90/100), ≥ 75/90/100% improvement from baseline modified Nail Psoriasis Severity Index (mNAPSI 75/90/100), and patient-reported outcomes; GPP-specific outcomes: Japanese Dermatological Association (JDA) severity index and Global Improvement Score (GIS). Treatment emergent adverse events (TEAEs) evaluated through weeks 0-144 and safety follow-up.

Results: At week 144, most patients with GPP (8/10) and EP (10/11) completed the study. At week 16, all patients reported efficacy outcomes improving with BKZ, generally persisting through week 144. At week 144 (missing visit: 1 GPP), 6/7 patients with GPP and 8/10 with EP achieved IGA 0/1; 5/7 and 9/10 patients achieved DLQI 0/1; 7/7 and 9/10 patients achieved CGI-I response ("improved"/"remission"); and 6/7 and 9/10 patients achieved PASI 90, respectively; 2/5 patients with GPP and 4/9 with EP achieved week 144 mNAPSI 100. Among patients with GPP, JDA severity index generally decreased and improvements in GIS were sustained to week 144. Serious TEAEs were observed in 2/10 patients with GPP and 5/11 with EP; BKZ was well tolerated with low incidence of TEAEs leading to study discontinuation (2 GPP, 1 EP).

Conclusions: Long-term BKZ treatment over 3 years improved signs and symptoms of GPP and EP; these were sustained through week 144. No new safety signals were identified.

Trial registration: ClinicalTrials.gov identifier, NCT03598790.

Keywords: Anti-interleukin-17; Bimekizumab; Erythrodermic psoriasis; Generalised pustular psoriasis; Japan.

Fig. 1

Study design (subgroup of BE BRIGHT). Data reported only for the subgroup of Japanese patients with GPP and EP who were directly enrolled into BE BRIGHT. ^aScreening period allowed for the washout of medications prohibited during the study and the length of the washout period was contingent on the medication/treatment in question. ^bAt week 28 and all following visits, patients on continuous treatment with BKZ for ≥ 12 weeks with a persistent IGA score ≥ 3 over at least a 4-week period were defined as non-responders and should discontinue BKZ. BKZ bimekizumab, EP erythrodermic psoriasis, GPP generalised pustular psoriasis, IGA Investigator’s Global Assessment, Q4W every 4 weeks, Q8W every 8 weeks

Fig. 2

Patient disposition to week 144 (subgroup of BE BRIGHT). Safety set. Data reported only for the subgroup of Japanese patients with GPP and EP who were directly enrolled into BE BRIGHT. ^aWeek 0 refers to the baseline of BE BRIGHT. ^bAt week 16, patients who achieved IGA 0/1 response were switched to BKZ 320 mg Q8W, while patients who did not achieve IGA 0/1 response remained on BKZ 320 mg Q4W. ^cAt week 48, patients receiving BKZ 320 mg Q8W who achieved IGA 0/1 response remained on BKZ 320 mg Q8W, while those who did not achieve IGA 0/1 response were switched back to BKZ 320 mg Q4W. ^dAt week 48, 2 patients with GPP receiving BKZ 320 mg Q8W who did not achieve IGA 0/1 response were switched back to BKZ 320 mg Q4W. BKZ bimekizumab, EP erythrodermic psoriasis, GPP generalised pustular psoriasis, IGA Investigator’s Global Assessment, Q4W every 4 weeks, Q8W every 8 weeks

Fig. 3

IGA 0/1 response to week 144 in the a GPP and b EP populations. Full analysis set (observed case). The IGA was conducted on a 5-point scale to determine the disease severity of psoriasis: clear (0), almost clear (1), mild (2), moderate (3), severe (4). IGA 0/1 response defined as an IGA score of clear (0) or almost clear (1) with at least a two-category improvement from baseline. ^aWeek 0 refers to the baseline of BE BRIGHT; patients with GPP or EP were not required to have IGA ≥ 3 for inclusion in BE BRIGHT. ^bAt week 16, patients who achieved IGA 0/1 response were switched to BKZ 320 mg Q8W, while patients who did not achieve IGA 0/1 response remained on BKZ 320 mg Q4W. ^cAt week 48, patients receiving BKZ 320 mg Q8W who achieved IGA 0/1 response remained on BKZ 320 mg Q8W, while those who did not achieve IGA 0/1 response were switched back to BKZ 320 mg Q4W. ^dBKZ was discontinued after week 16 and before week 144; or data were unavailable because of a missing visit. BKZ bimekizumab, EP erythrodermic psoriasis, GPP generalised pustular psoriasis, IGA Investigator’s Global Assessment, Q4W every 4 weeks, Q8W every 8 weeks

Fig. 4

DLQI 0/1 response to week 144 in the a GPP and b EP populations. Full analysis set (observed case). The DLQI is a skin disease-specific questionnaire that assesses the impact of disease symptoms and treatment on patients’ health-related QoL, with the total score ranging from 0 to 30 (higher scores indicating lower health-related QoL). DLQI 0/1 response defined as patients achieving a DLQI total score of 0/1, which indicates no impact of disease on health-related QoL. ^aWeek 0 refers to the baseline of BE BRIGHT. ^bAt week 16, patients who achieved IGA 0/1 response were switched to BKZ 320 mg Q8W, while patients who did not achieve IGA 0/1 response remained on BKZ 320 mg Q4W. ^cAt week 48, patients receiving BKZ 320 mg Q8W who achieved IGA 0/1 response remained on BKZ 320 mg Q8W, while those who did not achieve IGA 0/1 response were switched back to BKZ 320 mg Q4W. ^dBKZ was discontinued after week 16 and before week 144; or data were unavailable because of a missing visit. BKZ bimekizumab, DLQI Dermatology Life Quality Index, EP erythrodermic psoriasis, GPP generalised pustular psoriasis, IGA Investigator’s Global Assessment, QoL quality of life, Q4W every 4 weeks, Q8W every 8 weeks

Fig. 5

CGI-I status to week 144 in the a GPP and b EP populations. Full analysis set (observed case). The CGI-I assesses changes from baseline in findings of GPP or EP based on a 4-point scale: remission, improved, no change, or worsened. No patients had a CGI-I status of “worsened” at weeks 16, 48, 96, and 144. ^aAt week 16, patients who achieved IGA 0/1 response were switched to BKZ 320 mg Q8W, while patients who did not achieve IGA 0/1 response remained on BKZ 320 mg Q4W. ^bAt week 48, patients receiving BKZ 320 mg Q8W who achieved IGA 0/1 response remained on BKZ 320 mg Q8W, while those who did not achieve IGA 0/1 response were switched back to BKZ 320 mg Q4W. ^cBKZ was discontinued after week 16 and before week 144; or data were unavailable because of a missing visit. BKZ bimekizumab, CGI-I Clinical Global Impressions-Improvement, EP erythrodermic psoriasis, GPP generalised pustular psoriasis, IGA Investigator’s Global Assessment, Q4W every 4 weeks, Q8W every 8 weeks

Fig. 6

PASI 90 response to week 144 in the a GPP and b EP populations. Full analysis set (observed case). PASI responses were evaluated only in patients with baseline PASI score > 0 (GPP, N = 10; EP, N = 11). PASI 90 response defined as an improvement of ≥ 90% in PASI score from baseline. ^aAt week 16, patients who achieved IGA 0/1 response were switched to BKZ 320 mg Q8W, while patients who did not achieve IGA 0/1 response remained on BKZ 320 mg Q4W. ^bAt week 48, patients receiving BKZ 320 mg Q8W who achieved IGA 0/1 response remained on BKZ 320 mg Q8W, while those who did not achieve IGA 0/1 response were switched back to BKZ 320 mg Q4W. ^cBKZ was discontinued after week 16 and before week 144; or data were unavailable because of a missing visit. BKZ bimekizumab, EP erythrodermic psoriasis, GPP generalised pustular psoriasis, IGA Investigator’s Global Assessment, PASI 90: ≥ 90% improvement from baseline in Psoriasis Area and Severity Index, Q4W every 4 weeks, Q8W every 8 weeks

Fig. 7

mNAPSI 100 response to week 144 in the a GPP and b EP populations. Full analysis set (observed case). mNAPSI 100 response defined as an improvement of 100% in mNAPSI score from baseline. ^amNAPSI responses were evaluated only in patients with baseline nail psoriasis, defined as mNAPSI score > 0 (GPP, N = 7; EP, N = 10). ^bAt week 16, patients who achieved IGA 0/1 response were switched to BKZ 320 mg Q8W, while patients who did not achieve IGA 0/1 response remained on BKZ 320 mg Q4W. ^cAt week 48, patients receiving BKZ 320 mg Q8W who achieved IGA 0/1 response remained on BKZ 320 mg Q8W, while those who did not achieve IGA 0/1 response were switched back to BKZ 320 mg Q4W. ^dBKZ was discontinued after week 16 and before week 144. BKZ bimekizumab, EP erythrodermic psoriasis, GPP generalised pustular psoriasis, IGA Investigator’s Global Assessment, mNAPSI 100 100% improvement from baseline in modified Nail Psoriasis Severity Index, Q4W every 4 weeks, Q8W every 8 weeks

Fig. 8

GPP-specific efficacy outcomes to week 144: a JDA severity index score for GPP and b GIS. Full analysis set (observed case). The JDA severity index score for GPP assesses the severity of GPP based on skin symptoms (erythematous area, erythematous area with pustules, and oedematous area; each item scored from 0 to 3), and systemic symptoms and laboratory findings (fever, white blood cell count, C-reactive protein, and serum albumin; each item scored from 0 to 2), with the total score ranging from 0 (best) to 17 (worst) [34]. GIS assesses the changes from baseline in JDA severity index score for GPP in addition to other clinical criteria as very much improved, much improved, minimally improved, no change, or worsened. Data presented for patients with GPP (N = 10). ^aAt week 16, patients who achieved IGA 0/1 response were switched to BKZ 320 mg Q8W, while patients who did not achieve IGA 0/1 response remained on BKZ 320 mg Q4W. ^bAt week 48, patients receiving BKZ 320 mg Q8W who achieved IGA 0/1 response remained on BKZ 320 mg Q8W, while those who did not achieve IGA 0/1 response were switched back to BKZ 320 mg Q4W. ^cData at week 0 referred to the last valid measurement before the administration of BKZ. ^dEfficacy outcomes in patients who discontinued BKZ after week 16 and before week 144 were reported as missing. ^eNo patients had a GIS status of “worsened” or “minimally improved” at weeks 16, 48, 96, and 144. BKZ bimekizumab, GIS Global Improvement Score, GPP generalised pustular psoriasis, IGA Investigator’s Global Assessment, JDA Japanese Dermatological Association, Q4W every 4 weeks, Q8W every 8 weeks, SD standard deviation