Guselkumab,a human interleukin‐23 monoclonal antibody in Japanese patients with generalized pustular psoriasis and erythrodermic psoriasis: Efficacy and safety analyses of a 52‐week,phase 3, multicenter,open‐label study

Generalized pustular psoriasis (GPP) and erythrodermic psoriasis (EP) are the rare and severe subtypes of psoriasis, which are often difficult to treat. The aim of this phase 3, open‐label study was to evaluate efficacy and safety of guselkumab, a human interleukin‐23 monoclonal antibody, in Japanese patients with GPP and EP. Guselkumab 50 mg was administrated to GPP (n = 10) and EP (n = 11) patients at weeks 0, 4 and thereafter every 8 weeks (q8w). Beginning at week 20, patients were escalated to 100 mg q8w if they met the dose escalation criteria. The primary end‐point was the proportion of patients achieving treatment success (Clinical Global Impression score of “very much improved”, “much improved” or “minimally improved”) at week 16. Safety evaluations included assessment of treatment‐emergent adverse events (TEAE) through week 52. At week 16, the proportions of GPP and EP patients achieving treatment success were 77.8% (7/9) and 90.9% (10/11), respectively. Furthermore, guselkumab treatment consistently showed improvement in responses of secondary end‐points such as Psoriasis Area and Severity Index, Investigator's Global Assessment, Japanese Dermatological Association severity index and improvement in body surface area involvement. Improvements in quality of life, as assessed by the Dermatology Life Quality Index, were also observed through week 52. The most commonly reported TEAE was nasopharyngitis (28.6%, 6/21). Safety findings were consistent with those observed previously in other studies. In conclusion, guselkumab treatment demonstrated efficacy and showed no safety concerns in Japanese patients with GPP and EP through week 52.     

Efficacy and safety of risankizumab in Japanese patients with moderate to severe plaque psoriasis: Results from the SustaIMM phase 2/3 trial

Risankizumab, a humanized immunoglobulin G1 monoclonal antibody, selectively inhibits interleukin‐23, a key cytokine in the pathogenesis of psoriasis, by binding to its p19 subunit. In SustaIMM (ClinicalTrials.gov/NCT03000075), a phase 2/3, double‐blinded, placebo‐controlled study, Japanese patients with moderate to severe plaque psoriasis (n = 171) were stratified by bodyweight and concomitant psoriatic arthritis and randomized 2:2:1:1 to 75 mg risankizumab, 150 mg risankizumab, placebo with cross‐over to 75 mg risankizumab and placebo with cross‐over to 150 mg risankizumab. Dosing was at weeks 0, 4, 16, 28 and 40, with placebo cross‐over to risankizumab at week 16. The primary end‐point was 90% or more improvement from baseline in Psoriasis Area and Severity Index (PASI‐90) at week 16 for risankizumab versus placebo. Missing data were imputed as non‐response. All primary and psoriasis‐related secondary end‐points were met for both risankizumab doses (P < 0.001). At week 16, PASI‐90 responses were significantly higher in patients receiving 75 mg (76%) or 150 mg (75%) risankizumab versus placebo (2%). Corresponding response rates were 86%, 93% and 10% for static Physician Global Assessment (sPGA) score of clear/almost clear; 90%, 95% and 9% for PASI‐75; and 22%, 33% and 0% for PASI‐100, with significantly higher responses for both risankizumab doses versus placebo. Through week 52, PASI and sPGA responses increased or were maintained and treatment‐emergent adverse events were comparable across treatment groups. Both doses of risankizumab were superior to placebo in treating patients with moderate to severe plaque psoriasis. The safety profile was consistent with previous risankizumab trials, with no new or unexpected safety findings.     

Oral tofacitinib efficacy,safety and tolerability in Japanese patients with moderate to severe plaque psoriasis and psoriatic arthritis: A randomized,double‐blind,phase 3 study

Tofacitinib is an oral Janus kinase inhibitor that is being investigated for psoriasis and psoriatic arthritis. Japanese patients aged 20 years or more with moderate to severe plaque psoriasis and/or psoriatic arthritis were double‐blindly randomized 1:1 to tofacitinib 5 or 10 mg b.i.d. for 16 weeks, open‐label 10 mg b.i.d. for 4 weeks, then variable 5 or 10 mg b.i.d. to Week 52. Primary end‐points at Week 16 were the proportion of patients achieving at least a 75% reduction in Psoriasis Area and Severity Index (PASI75) and Physician's Global Assessment of “clear” or “almost clear” (PGA response) for psoriasis, and 20% or more improvement in American College of Rheumatology criteria (ACR20) for patients with psoriatic arthritis. Safety was assessed throughout. Eighty‐seven patients met eligibility criteria for moderate to severe plaque psoriasis (5 mg b.i.d., n = 43; 10 mg b.i.d., n = 44), 12 met eligibility criteria for psoriatic arthritis (5 mg b.i.d., n = 4; 10 mg b.i.d., n = 8) including five who met both criteria (10 mg b.i.d.). At Week 16, 62.8% and 72.7% of patients achieved PASI75 with tofacitinib 5 and 10 mg b.i.d., respectively; 67.4% and 68.2% achieved PGA responses; all patients with psoriatic arthritis achieved ACR20. Responses were maintained through Week 52. Adverse events occurred in 83% of patients through Week 52, including four (4.3%) serious adverse events and three (3.2%) serious infections (all herpes zoster). No malignancies, cardiovascular events or deaths occurred. Tofacitinib (both doses) demonstrated efficacy in patients with moderate to severe plaque psoriasis and/or psoriatic arthritis through 52 weeks; safety findings were generally consistent with prior studies.     

Efficacy and safety of guselkumab in psoriasis patients who failed ustekinumab and/or anti‐interleukin‐17 treatment: A real‐life 52‐week retrospective study

Recent major research advancements have significantly expanded our understanding of psoriasis pathophysiology, resulting in the development of highly effective, targeted therapies. Guselkumab is the first interleukin (IL)‐23 inhibitor approved for the treatment of moderate‐to‐severe‐psoriasis, providing a new therapeutical option for psoriasis. The aim of our study was to evaluate the efficacy of guselkumab in psoriatic patients who previously failed anti‐IL‐12/23 and/or anti‐IL‐17 treatment. A 52‐week single‐center retrospective study was performed enrolling moderate‐to‐severe patients attending our Psoriasis Care Center from October 2018 to May 2020. Study population included 13 patients; 46.1% have been previously treated with ustekinumab, while 69.2% have previously failed an anti‐IL‐17 treatment (38.5% secukinumab, 30.8% ixekizumab, and 38.5% both). At baseline, mean Psoriasis Area and Severity Index was 13.2 ± 6.8, reducing up to 0.5 ± 0.7 at week 52 (P < .001). Body surface area reduced from 22.3 ± 10.5 (baseline) to 0.8 ± 1.1 at week 52 (P < .001). No statistically significant differences have been found between patients previously treated with anti‐IL‐12/23 compared to anti‐IL‐17 or both. Only one patient discontinued guselkumab at week 36 due to secondary inefficacy. This is a single institution study with a relatively small sample size. Our real‐life data confirm trial results, showing guselkumab as a safe and effective option in patients with moderate‐to‐severe psoriasis even in those who previously failed ustekinumab and/or anti‐IL‐17 treatment.     

Efficacy and safety of ixekizumab treatment in Japanese patients with moderate‐to‐severe plaque psoriasis: Subgroup analysis of a placebo‐controlled,phase 3 study (UNCOVER‐1)

The present study describes a subgroup analysis of 33 Japanese patients participating in UNCOVER‐1, an international, placebo‐controlled, phase 3 study of ixekizumab in patients with moderate‐to‐severe psoriasis. Patients were randomized to a placebo (n = 13) or ixekizumab 80 mg every 4 (IXEQ4W, n = 12) or 2 (IXEQ2W, n = 8) weeks, from week 0–12. At week 12, ixekizumab‐treated patients with a static Physician Global Assessment score 0 or 1 (sPGA [0,1]; n = 16) were re‐randomized to a placebo (n = 6), ixekizumab 80 mg every 12 (IXEQ12W, n = 5) or 4 (IXEQ4W, n = 5) weeks, from week 12–60. At week 12, more ixekizumab‐treated versus placebo‐treated patients achieved sPGA (0,1) (≥66.7% vs 0%), ≥75% improvement in Psoriasis Area and Severity Index (≥75% vs 0%), and sPGA (0) or 100% improvement in Psoriasis Area and Severity Index (both ≥33.3% vs 0%), with improved symptoms and quality of life. At week 60, 100% (IXEQ4W), 40.0% (IXEQ12W) and 16.7% (placebo) had maintained sPGA (0,1). From week 0–12, treatment‐emergent adverse events were 76.9% (placebo), 75.0% (IXEQ4W) and 87.5% (IXEQ2W), and from week 12–60 were 66.7% (placebo) and 100% (IXEQ12W, IXEQ4W). Ixekizumab‐treated patients had no severe treatment‐emergent adverse events, and one serious TEAE (IXEQ4W); infection was the most frequent treatment‐emergent adverse event. In conclusion, ixekizumab for 60 weeks was effective and safe for Japanese patients with moderate‐to‐severe psoriasis, in line with the overall findings from UNCOVER‐1.     

Efficacy and safety of ixekizumab treatment for Japanese patients with moderate to severe plaque psoriasis,erythrodermic psoriasis and generalized pustular psoriasis: Results from a 52‐week,open‐label,phase 3 study (UNCOVER‐J)

Psoriasis, a chronic, immune‐mediated skin disease characterized by red, scaly plaques, affects approximately 0.3% of the population in Japan. The aim of this open‐label study was to evaluate the long‐term efficacy and safety of ixekizumab, a humanized, anti‐interleukin‐17A monoclonal antibody, in Japanese patients with plaque psoriasis (n = 78, including 11 psoriatic arthritis), erythrodermic psoriasis (n = 8) and generalized pustular psoriasis (n = 5). Ixekizumab was administrated s.c. at baseline (week 0, 160 mg), from weeks 2 to 12 (80 mg every 2 weeks), and from weeks 16 to 52 (80 mg every 4 weeks). At week 52, 92.3% of patients with plaque psoriasis achieved Psoriasis Area and Severity Index (PASI) 75, 80.8% achieved PASI 90, 48.7% achieved PASI 100, and 52.6% had remission of plaques (by static Physician Global Assessment, sPGA [0]). Difficult to treat areas of psoriasis (nail or scalp) also responded to ixekizumab. All patients with psoriatic arthritis who were assessed (5/5) achieved an American College of Rheumatology 20 response. Most patients with erythrodermic psoriasis or generalized pustular psoriasis responded to ixekizumab and the clinical outcome was maintained over 52 weeks (75% and 60% of patients achieved sPGA [0, 1] at week 52, respectively). Mostly mild or moderate treatment‐emergent adverse events were reported by 79 of 91 patients; the most common were nasopharyngitis, eczema, seborrheic dermatitis, urticaria and injection site reactions. In conclusion, 52‐week ixekizumab treatment was efficacious and well tolerated in Japanese patients with plaque psoriasis. Efficacy was also observed in patients with erythrodermic psoriasis, generalized pustular psoriasis and psoriatic arthritis.     

Tofacitinib for the treatment of moderate to severe chronic plaque psoriasis in Japanese patients: Subgroup analyses from a randomized,placebo‐controlled phase 3 trial

Tofacitinib is an oral Janus kinase inhibitor. These post‐hoc analyses assessed tofacitinib efficacy and safety in Japanese patients with psoriasis enrolled in a 52‐week global phase 3 study. Patients received tofacitinib 5 mg, tofacitinib 10 mg or placebo twice daily (b.i.d.); placebo‐treated patients advanced to tofacitinib at week 16. Primary efficacy end‐points were the proportions of patients with 75% or more reduction from baseline Psoriasis Area and Severity Index (PASI‐75) and Physician's Global Assessment (PGA) of “clear” or “almost clear” (PGA response) at week 16. Other end‐points included: Itch Severity Item (ISI), Dermatology Life Quality Index (DLQI) score and Nail Psoriasis Severity Index (NAPSI). Adverse events (AEs) were recorded throughout the study. Overall, 58 Japanese patients were included in this analysis (tofacitinib 5 mg b.i.d., n = 22; 10 mg b.i.d., n = 24; placebo, n = 12); 29 completed the study. At week 16, significantly more patients receiving tofacitinib 5 and 10 mg b.i.d. versus placebo achieved PASI‐75 (50% and 75% vs 0%, P < 0.01) and PGA response (59% and 75% vs 0%, P < 0.001). Substantial improvements in ISI, DLQI and NAPSI score were observed with both tofacitinib doses. Over 52 weeks, similar rates of AEs were reported across treatment groups; one serious AE occurred with tofacitinib 10 mg b.i.d. Herpes zoster occurred in three patients receiving tofacitinib 10 mg b.i.d. No deaths, serious infections, malignancies or gastrointestinal perforations were reported. Results were generally consistent with global analysis, suggesting sustained efficacy and a manageable safety profile, with increased herpes zoster incidence, of tofacitinib in Japanese patients with psoriasis.     

Secukinumab efficacy and safety in Japanese patients with moderate‐to‐severe plaque psoriasis: Subanalysis from ERASURE,a randomized,placebo‐controlled,phase 3 study

Secukinumab, a fully human anti‐IL‐17A monoclonal antibody, neutralizes IL‐17A, a key cytokine in the pathogenesis of psoriasis. Efficacy and safety of secukinumab was evaluated in Japanese patients with moderate‐to‐severe plaque psoriasis as part of a large Phase 3 global study (ERASURE). In this 52‐week, double‐blind study (ClinicalTrials.gov Identifier: NCT01365455, JapicCTI‐111529), 87 patients from Japan (11.8% of 738 patients randomized in the overall study population) were equally randomized to receive secukinumab 300 mg or 150 mg, or placebo once weekly at baseline and at Weeks 1, 2, 3 and 4, then every 4 weeks. Co‐primary endpoints (Week 12) were ≥75% improvement in psoriasis area‐and‐severity index (PASI 75) from baseline and a score of 0 (clear) or 1 (almost clear) on a 5‐point Investigator's Global Assessment scale (IGA mod 2011 0/1) versus placebo. PASI 75 and IGA mod 2011 0/1 responses at Week 12 were superior with secukinumab 300 mg (82.8% and 55.2%, respectively) or 150 mg (86.2% and 55.2%, respectively) versus placebo (6.9% and 3.4%, respectively; P < 0.0001 for all). Greater than 90% improvement in PASI (PASI 90) was also superior with secukinumab 300 mg (62.1%) or 150 mg (55.2%) versus placebo (0.0%) at Week 12 (P < 0.0001 for both). Clinical responses were sustained up to Week 52 in the majority of patients. During a 12‐week induction period, adverse event incidences were 48.3% with secukinumab 300 mg, 55.2% with 150 mg, and 41.4% with placebo. Secukinumab showed robust and sustainable efficacy in symptom reduction for moderate‐to‐severe plaque psoriasis in the Japanese patients.     

Adalimumab in Japanese patients with moderate to severe chronic plaque psoriasis: Efficacy and safety results from a Phase II/III randomized controlled study

Incidence of psoriasis vulgaris in Asians is estimated at 0.05–0.3%. Studies in North America and Europe demonstrated that adalimumab, a fully human, recombinant, immunoglobulin G₁ monoclonal antibody, was efficacious and well‐tolerated in patients with chronic plaque psoriasis. This 24‐week, placebo‐controlled study evaluated the efficacy and safety of three different dosing regimens of adalimumab in Japanese patients with moderate to severe chronic plaque psoriasis (n = 169). Patients were randomized to receive adalimumab 40 mg every other week (eow), adalimumab 80‐mg loading dose at week 0 followed by adalimumab 40 mg eow starting at week 2, adalimumab 80 mg eow, or placebo eow given as s.c. injections. The primary efficacy endpoint was the percentage of patients achieving a 75% or greater improvement in Psoriasis Area and Severity Index (PASI 75) score at week 16. At week 16, PASI 75 response rates were significantly greater for all three adalimumab groups (40 mg eow: 57.9%, P < 0.001; 40 mg eow plus loading dose: 62.8%, P < 0.001; 80 mg eow: 81.0%, P < 0.001) versus placebo (4.3%). As early as week 4, the 40‐mg eow plus loading dose and 80‐mg eow groups achieved significantly greater PASI 75 response rates compared with placebo. Injection‐site reactions and hepatic events occurred in greater percentages of adalimumab‐treated patients compared with placebo. Adalimumab therapy demonstrated efficacy and safety at all three dosage regimens. Rapid response rate in patients receiving 40 mg eow plus loading dose supports using an 80‐mg loading dose in the treatment of psoriasis.     

Effectiveness of anti‐interleukin 23 biologic drugs in psoriasis patients who failed anti‐interleukin 17 regimens. A real‐life experience

Among the most recent biologic drugs available for psoriasis therapy, those targeting interleukin‐17 (secukinumab and ixekizumab) or its receptor (brodalumab) have been shown to be quickly effective. However, in those patients who failed one or more of the above‐cited drugs, real‐life data on the effectiveness of switching to one anti‐interleukin‐23 biologic (guselkumab, risankizumab, or tildrakizumab) are very scarce. Here, we report our experience in treating 12 multi‐failure psoriatic patients, prospectively followed‐up over 6 months, who showed a significant improvement in their psoriasis after switching from an anti‐interleukn‐17 to an anti‐interleukin‐23 drug.     

Efficacy and safety of topical WBI‐1001 in patients with mild to moderate psoriasis: results from a randomized double‐blind placebo‐controlled,phase II trial

Background There is a need for the development of novel non‐steroidal topical drugs for the treatment of psoriasis. Objective To assess the efficacy and safety of topical 1.0% WBI‐1001 in patients with mild to moderate plaque psoriasis. Methods A total of 61 patients with 1–10% body surface area (BSA) covered with plaque psoriasis and a physician’s global assessment score (PGA) of 2–4 were randomized (2 : 1) to receive either 1% WBI‐1001 in a cream formulation or placebo, applied twice daily for 12 weeks. Efficacy was evaluated using PGA, BSA and Psoriasis Area and Severity Index (PASI). The primary endpoint was the change from baseline (Day 0) in PGA at week 12. Results The improvement in PGA at week 12 was 62.8% for patients randomized to WBI‐1001 when compared with 13.0% for patients randomized to placebo (P < 0.0001). At week 12, the proportion of patients who achieved a PGA of clear or almost clear and the mean improvement in BSA were 67.5% and 79.1%, respectively, for patients randomized to WBI‐1001, when compared with 4.8% (P < 0.0001) and an increase of 9.4% (P < 0.0001), respectively, for patients randomized to placebo. More application site adverse drug reactions were observed in patients randomized to WBI‐1001 than in those randomized to placebo. These adverse drug reactions were all mild or moderate in intensity. Conclusion Topical WBI‐1001 induces rapid and significant improvement in patients with plaque psoriasis.     

Efficacy and safety of apremilast in subjects with moderate to severe plaque psoriasis: results from a phase II,multicenter, randomized,double‐blind,placebo‐controlled,parallel‐group,dose‐comparison study

Background Apremilast, a small molecule specific inhibitor of phosphodiesterase 4, works intracellularly to modulate pro‐inflammatory and anti‐inflammatory mediator production. Objective Assess apremilast efficacy and safety in moderate to severe plaque psoriasis. Methods Phase II, 12‐week, multicenter, double‐blind, placebo‐controlled, parallel‐group, dose‐comparison study of 259 subjects randomized 1 : 1 : 1 to placebo, apremilast 20 mg QD or apremilast 20 mg BID. Results More subjects receiving apremilast 20 mg BID achieved ≥ 75% reduction in Psoriasis Area and Severity Index (PASI‐75) vs. placebo (24.4% vs. 10.3%; P = 0.023). A similar proportion of subjects receiving apremilast 20 mg QD and placebo achieved PASI‐75 at week 12 [9/87 (10.3%, each group)]. Mean per cent reduction in PASI from baseline was 17.4% for placebo, 30.3% for apremilast 20 mg QD (P = 0.021 vs. placebo) and 52.1% for apremilast 20 mg BID (P < 0.001). Apremilast 20 mg BID significantly decreased mean body surface area involvement vs. placebo (30.8% vs. 3.2%; P < 0.001). The most common adverse events were headache, nasopharyngitis, diarrhoea and nausea. Most events (> 90%) were mild to moderate and did not lead to study discontinuation. Serious adverse events occurred in four placebo subjects (panic attack, hospitalization for rehabilitation, hospitalization for alcoholism, worsening psoriasis), one receiving apremilast 20 mg QD (knee surgery) and in one receiving apremilast 20 mg BID (worsening psoriasis). The panic attack was considered treatment‐related; both cases of worsening psoriasis occurred after medication discontinuation. No deaths or opportunistic infections were reported. Conclusion Apremilast 20 mg BID for 12 weeks was effective and well tolerated in subjects with moderate to severe plaque psoriasis.     

Safety profile of intravenous and subcutaneous siplizumab,an anti‐CD2 monoclonal antibody,for the treatment of plaque psoriasis: results of two randomized,double‐blind,placebo‐controlled studies

Several biologics targeting different cytokines and receptors, including T‐cell receptors, have been approved for psoriasis treatment. Siplizumab, a humanized anti‐CD2 monoclonal antibody, may potentially provide an alternative therapy for psoriasis. Its safety profile and immunogenicity was examined in adults with plaque psoriasis. Two multicenter phase II randomized, double‐blind, placebo‐controlled studies: one tested two intravenous (I.V.) doses (0.012 and 0.04 mg/kg) of siplizumab every 2 weeks × 8 doses (124 patients); the second study tested three subcutaneous (S.C.) dose regimens of siplizumab (5 mg × 12 weeks, 5 mg × 6 weeks + placebo × 6 weeks, 7 mg × 4 weeks + placebo × 8 weeks), and placebo × 12 weeks (420 patients). Adverse events (AEs) and laboratory values were monitored. Immunogenicity was determined by anti‐siplizumab antibodies quantification. In both studies, siplizumab exhibited an acceptable safety profile; most common AEs judged to be siplizumab related were lymphopenia, chills, and headache, reported at a higher frequency in the siplizumab‐treated vs. placebo group. Siplizumab‐related reductions in absolute lymphocyte count did not result in clinical evidence of immune suppression. Anti‐siplizumab antibodies were detected after exposure to siplizumab; however, there was no evidence of an association between antibody development and AEs. Siplizumab exhibited an acceptable safety profile in adult patients with plaque psoriasis when administered as multiple I.V. or S.C. doses. Higher, clinically relevant doses of siplizumab would need to be tested to fully assess its safety.     

Efficacy and safety of Risankizumab in moderate to severe psoriasis: A systematic review and meta‐analysis

Monoclonal antibodies are explored for their therapeutic potential in Psoriasis. To evaluate Risankizumab in the moderate to severe psoriasis with regard to efficacy, tolerability, and safety PubMed, Cochrane Central Register of Controlled Trials (CENTRAL) and clinicaltrials.gov , databases were searched for relevant RCTs. The reference lists of relevant publications were also scanned manually to identify any further studies not indexed in the searched databases. Only RCT aiming to evaluate the role of Risankizumab in the treatment of moderate to severe psoriasis were considered eligible for this systematic review. Intervention group was patients taking Risankizumab and placebo or other monoclonal antibody was considered as control group. Cochrane review manager 5 (RevMan) version 5.3 was used for data synthesis and meta‐analysis. Quality assessment of included randomized controlled trials was done with Cochrane Collaboration risk of bias assessment tool, version 2.0 (ROB‐2). Overall Grading of evidence for study objectives was performed with GRADE Pro GDT software. A total of seven studies were included in analysis with total of 1533 and 710 patients in Risankizumab and standard care groups, respectively. Statistically significant increase in percentage of individual achieving PASI90 (OR = 11.01 (95% CI = 8.67‐13.99), DLQI‐01 (OR = 6.95 (95% CI = 5.53‐8.75), sPGA‐01 (OR = 14.22 (95% CI = 11.10‐18.22); sPGA‐0 (OR = 6.39 (95% CI = 4.79‐8.54) in risankizumab group as compared with control, with high quality of evidence. Increased risk of infections with risankizumab as compared with placebo (OR = 1.44 [95% CI = 1.13‐1.83], high quality evidence), while no difference in SAE among two groups. Analysis of all outcome data from RCTs. In the light of evidence from systematic review on effectiveness of Risankizumab, we propose treatment with risankizumab for psoriasis patients not responding to available treatment.     

Long‐term efficacy and safety of secukinumab in Japanese patients with moderate to severe plaque psoriasis: 3‐year results of a double‐blind extension study

Secukinumab, a fully human monoclonal antibody neutralizing interleukin‐17A, has been shown to have significant efficacy in the treatment of moderate to severe psoriasis. Long‐term (3‐year) efficacy and safety of secukinumab in Japanese patients with moderate to severe psoriasis were evaluated in an extension study of a large phase 3 global study (SCULPTURE). In the core study, 52 Japanese patients with 75% improvement of Psoriasis Area and Severity Index (PASI‐75) response at week 12 were re‐randomized to a fixed interval (FI; every 4 weeks) schedule and retreatment as needed (RAN), in which patients received placebo until start of relapse, at which time secukinumab was reinitiated. Fifty Japanese patients completed the 52‐week core study, and 47 patients entered the extension study with the same double‐blind regimens up to week 152. All patients in the secukinumab 300 mg FI and seven patients in 150 mg FI groups completed 3 years of treatment. PASI‐90 and ‐100 at the end of year 3 were achieved in 69.2% and 53.8%, respectively, in 300 mg FI and 42.9% and 42.9%, respectively, in 150 mg FI, indicating high sustained response in 300 mg FI. Mean absolute PASI was continually low in 300 mg FI and numerically higher in 150 mg FI. Dermatology Life Quality Index of 0/1 was maintained by approximately two‐thirds of 300 mg FI patients, and all EuroQoL 5‐Dimension Health Questionnaire domain measures were also improved. FI dosing was consistently more efficacious than RAN. The safety profile of secukinumab remained favorable, with no new safety concerns identified.     

Efficacy and safety of secukinumab in the treatment of moderate‐to‐severe plaque psoriasis: a randomized,double‐blind,placebo‐controlled phase II dose‐ranging study

Background Conventional systemic therapies for plaque psoriasis have not fully met the needs of patients, and although current biologic treatments are generally well tolerated, concerns exist with respect to long‐term safety. Interleukin (IL)‐17A is believed to be an important effector cytokine in the pathogenesis of psoriasis and is produced by Th17 cells, a class of helper T cells that act outside the established Th1/Th2 paradigm for regulation of innate and adaptive immunity. Objectives To assess the efficacy and safety of different doses of secukinumab, a fully human anti‐IL‐17A IgG1κ monoclonal antibody, in patients with moderate‐to‐severe plaque psoriasis. Methods Patients (n = 125) were randomized 1 : 1 : 1 : 1 : 1 to receive subcutaneous doses of placebo (n = 22) or secukinumab [1 × 25 mg (n = 29), 3 × 25 mg (n = 26), 3 × 75 mg (n = 21) or 3 × 150 mg (n = 27)] at weeks 0, 4 and 8. After the 12‐week treatment period, patients entered a follow‐up period of 24 weeks. The primary efficacy outcome was at least 75% improvement from baseline in the Psoriasis Area and Severity Index score (PASI 75); secondary outcomes included the Investigator’s Global Assessment (IGA) and PASI 90 and 50 response rates. Results After 12 weeks of treatment, secukinumab 3 × 150 mg and 3 × 75 mg resulted in significantly higher PASI 75 response rates vs. placebo (82% and 57% vs. 9%; P < 0·001 and P = 0·002, respectively). Higher PASI 75 response rates compared with placebo were maintained throughout the follow‐up period with these dosages [week 36, 26% (n = 7) and 19% (n = 4) vs. 4% (n = 1), respectively], with a gradual decline of PASI 75 response over time after the dosing period. IGA response rates were significantly higher in the 3 × 150 mg group vs. placebo at week 12 (48% vs. 9%; P = 0·005) and were consistently higher for the 3 × 150 mg and 3 × 75 mg groups vs. placebo at all time points from week 4 onward. The PASI 90 response rate was significantly higher in the 3 × 150 mg group vs. placebo (52% vs. 5%) at week 12 and remained higher during the follow‐up period. Secukinumab was well tolerated. Two cases of neutropenia (≤ grade 2) were reported in the 3 × 150 mg cohort. Conclusions Treatment with subcutaneous secukinumab 3 × 75 mg and 3 × 150 mg met the primary outcome of PASI 75 response achievement after 12 weeks, demonstrating efficacy in moderate‐to‐severe psoriasis.