Achieved Psoriasis Area Research Articles

Superior effect of adalimumab versus secukinumab on ultrasound-confirmed synovitis in psoriatic arthritis: comprehensive evidence from musculoskeletal ultrasound and clinical assessments

Background and objectives: Psoriatic arthritis (PsA) is a chronic inflammatory musculoskeletal disorder affecting 30% of psoriatic patients. Effective treatment, especially with biologics like IL-17 and TNF inhibitors, is vital for improving patient outcomes. This study aimed to compare the efficacy of secukinumab and adalimumab in PsA patients through clinical and ultrasonographic evaluations.Materials and methods: We enrolled 116 PsA patients, with 58 patients receiving secukinumab and 58 receiving adalimumab. Regular follow-ups were conducted at weeks 4, 12, 24, and 52. The primary outcome was the proportion of patients achieving at least a 20% improvement in the ACR response (ACR20) at week 12, with additional evaluations for axial arthritis, enthesitis, skin involvement, minimal disease activity, health assessment questionnaire, and ultrasound changes.Results: There was no significant difference in ACR20 response between the two groups at week 12 (OR: 0.59, 95% CI: 0.26–1.37, p = 0.22). However, secukinumab demonstrated superior efficacy in achieving Psoriasis Area and Severity Index (PASI)90 (OR: 2.25, 95%CI: 1.07–4.74, p = 0.03), while adalimumab showed better improvement in ultrasound synovitis count (β: 0.94, 95%CI: 0.09–1.79, p = 0.03) and synovitis PD signal (β: 0.20, 95%CI: 0.03–0.36, p = 0.02).Conclusions: In conclusion, both treatments were highly effective for PsA, with secukinumab being more suitable for severe skin involvement and adalimumab for significant ultrasound-confirmed synovitis.

Real-world data on the effectiveness of brodalumab in patients with moderate-to severe plaque psoriasis in the Greek clinical setting (the BrIDGE study).

Despite that brodalumab's efficacy and safety have been assessed in randomized clinical trials, real-life data remain scarce. BrIDGE was an observational, prospective, single-cohort, multicentre study that recruited patients with moderate-to severe plaque psoriasis in Greece. The primary objective was to assess the proportion of patients who achieved Psoriasis Area and Severity Index (PASI)100 after 24 weeks. Other endpoints included: the maintenance of PASI90/100 through to 104 weeks, the short-term response [PASI75/90/100 and static Physician's Global Assessment (sPGA) 0/1] to brodalumab at 12-16 weeks and time to complete clearance. Moreover, we explored the change in quality of life [Dermatology Life Quality Index (DLQI) 0/1] and adherence to brodalumab. Two hundred patients who were initiating treatment with or switching to brodalumab, were recruited. Analyses were conducted using the as observed data and three imputation approaches were also applied for the missing data (last observation carried forward, 'worst case' and 'best case' scenario). Continuous variables were reported using summary statistics, whereas categorical variables were reported in frequency tables. Based on the 'as observed data', 42.0% of patients achieved PASI100 at Week 24 after 25.9 ± 3.5 weeks and 65% of patients attained PASI100 at Week 104. In total, 70.2%, 47.5% and 32.0% achieved PASI75/90/100, respectively, whereas 72.6% of patients achieved sPGA 0/1, at Weeks 12-16. With respect to sPGA status 82.8%, 89.2% and 92.5% of patients achieved sPGA 0/1 at Weeks 24, 52 and 104, respectively. The time to achieve PASI100 at Weeks 12-16 was 13.7 ± 1.3, 52.1 ± 3.4 weeks at Week 52 and 105.5 ± 4.8 weeks at Week 104. Mean DLQI and Psoriasis Symptom Inventory (PSI) scores decreased by 11.4 ± 7.0 and 15.4 ± 6.5 points from baseline to Week 104, respectively. Adherence to treatment was equal to 98.9%. Brodalumab confers rapid and durable responses, as well as improvements in the quality of life of moderate-to-severe psoriasis patients.

Five-year Maintenance of Clinical Response and Consistent Safety Profile for Guselkumab in Asian patients with Psoriasis from VOYAGE 1 and VOYAGE 2.

Guselkumab is a human monoclonal antibody against IL-23 used in the treatment of moderate-to-severe psoriasis. This post-hoc analysis evaluated the efficacy and safety of guselkumab in the Asian subpopulation of VOYAGE 1 and VOYAGE 2 through 5years. The proportions of guselkumab-treated Asian patients (VOYAGE 1 and 2) achieving Psoriasis Area and Severity Index (PASI) 90 and PASI 100, Investigator's Global Assessment (IGA) scores of 0/1 and 0, and Dermatology Life Quality Index (DLQI) scores of 0/1 (week 100 through week 252) were assessed. Non-responders were patients who met the treatment failure rules. Efficacy endpoints were analyzed using the as-observed methodology (no missing data imputation) for both studies and using non-responder imputation (for patients with any missing data) in VOYAGE 1. Safety outcomes were based on pooled data through week 252. Response rates through week 252 for 199 Asian patients in the guselkumab group in VOYAGE 1 and VOYAGE 2, respectively, were 76.8% and 80.6% (PASI 90), 26.8% and 38.7% (PASI 100), 64.3% and 87.1% (IGA 0/1), and 26.8% and 45.2% (IGA 0). DLQI (0/1) at week 252 was achieved by 52.7% of patients in VOYAGE 1 and 61.3% in VOYAGE 2, while DLQI (0) at week 252 was achieved by 32.7% of patients in VOYAGE 1 and 40.3% in VOYAGE 2. The safety profile was similar to the global population and remained consistent through 5years. Asian patients were followed for a total of 814 patient-years (PY). Over 85% of the guselkumab-treated patients continued treatment through week 264. The rate of serious adverse events (AEs) at week 252 was 3.07/100 PY. Rates of AEs of interest were low: serious infections, 0.74/100 PY; nonmelanoma skin cancer (NMSC), no patients; malignancies other than NMSC, 0.12/100 PY; and no major adverse cardiovascular events (MACE). These analyses confirm a continuous response over 5years, indicating that guselkumab shows therapeutic longevity in Asian patients requiring long-term treatment for moderate-to-severe psoriasis. ClinicalTrials.gov identifiers: VOYAGE 1 [NCT02207231] and VOYAGE 2 [NCT02207244].

PS14 Bimekizumab response up to 3 years in patients with moderate-to-severe plaque psoriasis who responded at week 16: post hoc results from the BE BRIGHT open-label extension trial

Abstract Treatment with the interleukin-17A/F inhibitor bimekizumab (BKZ) has demonstrated maintenance of efficacy and health-related quality of life (HRQoL) outcomes over 2 years. The objective of this analysis was to assess the long-term response in patients with moderate-to-severe plaque psoriasis who achieved Psoriasis Area and Severity Index (PASI) ≤ 2, a key treat-to-target outcome, after 16 weeks of BKZ treatment over 3 years. Patients who completed a 52- (BE VIVID) or 56-week (BE SURE and BE READY) phase III feeder study were eligible to enrol in the BE BRIGHT open-label extension (OLE) (NCT03370133, NCT03412747, NCT03410992 and NCT03598790). Upon OLE entry, patients received BKZ 320 mg Q4W or Q8W based on feeder study treatment and week 52/56 PASI 90 (≥ 90% improvement in PASI) response. Patients switched from BKZ Q4W to Q8W at OLE week 24 (based on investigator discretion and PASI 90 response), or OLE week 48/next scheduled visit (all patients). Achievement of body surface area (BSA) ≤ 1% and PASI 0 (all studies), and Dermatology Life Quality Index (DLQI)0/1 (BE SURE and BE READY only due to schedule differences) is reported among week 16 PASI ≤ 2 responders through year 1 (feeder study week 52/56) and year 3 (OLE week 96). Analysed patients were randomized to BKZ, received BKZ maintenance dosing from feeder study week 16 and entered the OLE, including a subset who received BKZ Q4W through to week 16 then continuous BKZ Q8W (Q4W/Q8W/Q8W). Missing data were imputed using modified nonresponder imputation (mNRI): patients who discontinued treatment due to lack of efficacy or treatment-related adverse events were considered nonresponders; multiple imputation was used for all other missing data. The week 16 responder rate is also reported (NRI). At baseline, 989 patients were randomized to BKZ; 87.8% (n = 868) achieved PASI ≤ 2 at week 16. Of these, 694 entered the OLE. Among week 16 PASI ≤ 2 responders (n = 694), 91.9% and 82.3% achieved BSA ≤ 1% and PASI 0 after year 1 (52 weeks), and 88.6% and 74.1% after year 3, respectively. Among week 16 PASI ≤ 2 responders (n = 445), 87.8% and 86.8% achieved DLQI 0/1 after year 1 (56 weeks) and year 3, respectively. Of the week 16 PASI ≤ 2 responders who received BKZ Q4W/Q8W/Q8W (n = 189), 95.2% and 87.6% achieved BSA ≤ 1% and PASI 0 after 1 year (52 weeks), and 93.4% and 79.7% after 3 years, respectively. Among the Q4W/Q8W/Q8W patients, 94.1% and 91.2% achieved DLQI 0/1 after year 1 (56 weeks) and year 3, respectively. The BKZ provided long-term efficacy and HRQoL benefits. Among week 16 PASI ≤ 2 responders, the vast majority sustained high levels of clinical and HRQoL responses through 3 years of BKZ treatment, including those who received BKZ Q4W/Q8W/Q8W. Funding: UCB Pharma. Medical writing: Costello Medical.

Estimate of the cost per responder for treatment with biological therapies of moderate-to-severe plaque psoriasis in Colombia for first-year and maintenance periods

ABSTRACT Introduction Psoriasis is a chronic systemic inflammatory disease manifesting as erythematous and desquamative dermatoses. Objectives This study estimated the cost per responder (CPR) for the treatment of moderate-to-severe plaque psoriasis with biologic therapies approved by the Colombian regulatory agency. Methods This secondary study used a modeling based CPR estimation to evaluate psoriasis therapies in Colombia. We calculated CPR of achieving Psoriasis Area and Severity Index (PASI) scores of 75, 90, and 100 for biological treatments based on the number needed to treat (NNT), reported in previously published network meta-analyses. We calculated CPR for the first year and for the maintenance period. We ranked alternatives using the estimated CPR from each literature source using the Borda count method. Results Adalimumab, infliximab and etanercept were the least expensive alternatives. Ixekizumab, guselkumab and secukinumab were the treatments with the lowest NNT for PASI 75, 90, and 100. For both first year and maintenance periods, adalimumab, infliximab, guselkumab and ixekizumab had the lowest CPR. Sensitivity analyzes showed consistent results. Conclusions The application of CPR analysis of biologics to treat plaque psoriasis demonstrated that adalimumab, infliximab, guselkumab, and ixekizumab had the lowest CPR in the first year of treatment and during the maintenance period.

Efficacy, Safety and Pharmacokinetics of IL-17 Monoclonal Antibody Injection (AK111) in Patients with Moderate-to-Severe Plaque Psoriasis: A Randomized, Double-Blinded, Placebo-Controlled Phase Ib Multidose Escalation Clinical Study.

To evaluate the safety, tolerability, immunogenicity, and induced expression of skin biomarkers of AK111 injection after multiple administrations in subjects with moderate-to-severe plaque psoriasis. This study is a randomized, double-blinded, placebo-parallel-controlled study using a dose escalation mode of multiple doses. A total of 48 subjects were sequentially randomized to receive each AK111 dose regimen (75mg, 150mg, 300mg, 450mg) or the corresponding placebo. All subjects were treated with the study drug at weeks0, 1, 4, and 8 and were unblinded at week 12, with the placebo group ending and the AK111 group being followed up to 20weeks. At week12, compared with placebo, the percentage of subjects achieving Psoriasis Area and Severity Index 75 (PASI75) and static Physician Global Assessment (sPGA) 0/1 in the AK111 75mg-450mg dose groups was significantly increased, and higher PASI90 was achieved in the 150mg, 300mg, and 450mg dose groups than in the 75mg group. All efficacy indicators were maintained at week 20. The incidence of treatment-emergent anti-drugantibodies (ADAs) was 0% (0/48). Neutralizing antibodies (NAbs) were not detected in any subject. The proportion of subjects who reported any treatment-emergent adverse event (TEAE) was 75.0% in the AK111 group, similar to the 66.7% in the placebo group. The most commonly reported adverse events were hyperglycemia, elevated blood pressure, and hypokalemia. The AK111 pharmacokinetics showed approximate dose proportionality with regard to the maximum observed concentration (Cmax) and area under the curve from 0 to the time of the last quantifiable concentration (AUC0-t) following subcutaneous injection doses of 150-450mg. After moderate-to-severe plaque psoriasis subjects received multiple subcutaneous AK111 injections of 150-450mg, AK111 exposure increased in a roughly dose-proportional relationship. AK111 was safe and tolerable. In subjects with moderate-to-severe plaque psoriasis, AK111 demonstrated encouraging preliminary efficacy, which was sustained for a relatively long time after the last dose administration. The clinical trial identification number is NCT05504317.

Effectiveness and Safety of Secukinumab in Latin American Patients with Moderate to Severe Plaque Psoriasis: PURE Registry 12-Month Data.

The efficacy and safety of secukinumab in patients with psoriasis has been established in randomised clinical trials. However, data on effectiveness and safety of secukinumab in Latin American real-world settings are scarce. To evaluate the effectiveness and safety of secukinumab in real-world settings in patients with psoriasis in Latin America. PURE is an ongoing multinational, prospective, observational study in patients with moderate-to-severe chronic plaque psoriasis in Canada and Latin America assessing the real-world safety and effectiveness of secukinumab and other approved therapies. The study enrolled (1:1) patients treated with secukinumab versus other approved therapies (other Tx) per local standard of care from 81 community- and hospital-based speciality sites (21 in Latin America). Here, we report effectiveness and safety outcomes with secukinumab and other Tx for plaque psoriasis for up to 12months in a Latin American population. Overall, 187 patients were included in the analysis, 89 of whom initiated secukinumab treatment and 98 of whom received other Tx. At month12, 84.4%, 71.1% and 53.3% of patients treated with secukinumab achieved Psoriasis Area and Severity Index (PASI) 75/90/100, respectively, compared with 66.7%, 47.9% and 29.2% of patients who received other Tx. Investigator Global Assessment (IGA) 0/1 responders in secukinumab versus other Tx were 78.3% versus 36.7% at month3 and 81.8% versus 66.7% at month12, respectively. Overall, the proportion of patients achieving Dermatology Life Quality Index (DLQI) 0/1 improved from 6.9% at baseline to 76.5% at month12 in patients treated with secukinumab versus 5.6% at baseline to 54.5% at month12 in patients on other Tx. No unexpected adverse events were reported during the 12-month observation period. Secukinumab demonstrated real-world effectiveness and improved dermatology quality-of-life in chronic plaque psoriasis patients from Latin America. PURE: NCT02786186.

34660 Deucravacitinib, an oral, selective tyrosine kinase 2 (TYK2) inhibitor, versus placebo and apremilast in moderate to severe plaque psoriasis: Achievement of absolute PASI thresholds in the phase 3 POETYK PSO-1 and PSO-2 trials

Background: Deucravacitinib is an oral selective inhibitor of TYK2, which mediates signaling of key cytokines in psoriasis immunopathogenesis. The efficacy of deucravacitinib in achieving Psoriasis Area and Severity Index (PASI) disease control thresholds in 2 Phase 3 trials was compared versus placebo and apremilast.

34820 Real-world treat-to-target skin clearance with risankizumab in patients with moderate to severe psoriasis from the CorEvitas Psoriasis Registry

Objective: Risankizumab is efficacious in the treatment of plaque psoriasis, with a reported 73%–75% of patients receiving risankizumab vs 2%–5% receiving placebo achieving Psoriasis Area Severity Index ≥90% improvement at week 16. This analysis assessed real-world effectiveness of risankizumab in achieving National Psoriasis Foundation (NPF)-defined treatment targets. Methods: CorEvitas’ Psoriasis Registry is an independent, prospective, observational cohort of patients ≥18 years diagnosed with psoriasis by a dermatologist and recruited from practices in US and Canada. Adult patients with moderate-to-severe plaque psoriasis (Investigator’s Global Assessment ≥3) at baseline, who initiated risankizumab at baseline visit and had persistent use at 12-month ( ± 3 months) follow-up were included. The achievement of NPF-defined target response (body surface area [BSA] ≤1%) or acceptable response (BSA ≤3% or BSA improvement ≥75% from baseline) at 12 months after initiation was assessed (3). Results: Among 137 patients, mean (SD) age was 48.7 (14.0) years, 59.9% were male, and mean (SD) psoriasis duration was 15.3 (13.0) years at baseline. Mean (SD) BSA involvement was 13.8% (12.8%) and 62.0% of patients had prior biologic use at baseline. At 12 months (n = 136), 70.4% of patients achieved NPF-defined target and 90.4% achieved NPF-defined acceptable response. NPF-defined target and acceptable responses were achieved by 80% and 94% of biologic-naive patients (n = 52) and 64% and 88% of biologic-experienced patients (n = 85), respectively, at 12 months. Conclusion: Persistent 12-month risankizumab use was highly effective in achieving NPF-defined patient-centered treatment targets among patients with moderate-to-severe psoriasis in a real-world setting.

Secukinumab treatment demonstrated high drug survival and sustained effectiveness in patients with severe chronic plaque psoriasis: 21-month analysis in Australian routine clinical practice (SUSTAIN study).

BackgroundDrug survival measures the rate and duration of adherence to a given therapeutic agent and evaluates its long‐term effectiveness, safety, and real‐world utility. The SUSTAIN study sought to establish the drug survival and effectiveness of secukinumab for patients with severe chronic plaque psoriasis (CPP) in the Australian clinical setting.MethodsData of all patients (aged ≥18 years) from Australasian Psoriasis Registry (APR) treated with secukinumab were analysed. The primary objective was to describe the drug survival of secukinumab at 9 months. Key secondary objectives included drug survival of secukinumab at 3, 6, 15, and 21 months, stratified by biologic‐naïve vs biologic‐experienced patients; proportion of patients achieving Psoriasis Area and Severity Index (PASI) 75/90/100 responses; and changes in health‐related quality of life over time utilising the Dermatology Life Quality Index (DLQI).ResultsOf 294 patients included in this analysis, 110 (37.4%) were biologic‐naïve and 184 (62.6%) biologic‐experienced. Kaplan–Meїer drug survival rates in biologic‐naïve vs biologic‐experienced patients were 0.92 vs. 0.86 (9 months) and 0.82 vs. 0.68 (21 months), respectively. The proportion of patients with PASI 75/90/100 responses for biologic‐naïve vs. biologic‐experienced was 100/87.7/38.4 vs 98.5/61.5/27.2 (9 months) and 100/81.0/41.7 vs. 98.4/62.0/24.2 (21 months), respectively. The mean (standard deviation [SD]) DLQI in biologic‐naïve vs. experienced patients was 2.2 (4.1) vs. 3.1 (5.2) (9 months) and 1.4 (2.5) vs. 3.1 (5.3) (21 months). No new safety signals were observed.ConclusionsSecukinumab demonstrated high drug survival and sustained effectiveness in Australian real‐world setting, in biologic‐naïve and biologic‐experienced patients with severe CPP.

Associations between HLA-Cw1 and Systemic Treatment Response of Asian Psoriasis Patients.

Psoriasis is a chronic inflammatory disease with a strong genetic background, particularly the human leukocyte antigen (HLA). HLA-Cw6 has been shown to be the major disease susceptibility locus and affects the phenotypes and treatment response in psoriasis; however, the prevalence of HLA-Cw6 is far lower than HLA-Cw1 in some Asian countries. The aim of this study was to determine whether HLA-Cw1 predisposes psoriasis patients to different treatment responses of biologics and other systemic therapy. This retrospective case-control study included 126 patients with moderate to severe plaque-type psoriasis who had been genotyped and treated in a special psoriasis clinic. HLA-Cw1-positive and -negative patients were compared. Our results showed that HLA-Cw1-negative patients were significantly more likely to respond (achieve Psoriasis Area and Severity Index [PASI]75 after a 12- to 16-week treatment course) to biologics (including etanercept, adalimumab, ustekinumab, secukinumab, ixekizumab, and guselkumab; odds ratio [OR] 1.99, 95% confidence interval [CI] 1.17-3.44, p=0.0122) and especially to ustekinumab (OR 3.27, 95% CI 1.03-11.30; p=0.0496). An HLA-Cw1 allele dose effect was also found. The results remained after multivariate logistic regression analysis. HLA-Cw1-negative patients also showed significantly greater improvement of PASI in ustekinumab and biologics (p=0.0044 and p=0.0064, respectively), with other biologics showing non-significant trends. HLA-Cw1 status did not affect the treatment responses of non-biologic systemic treatment, including phototherapy. There is an association between HLA-Cw1 and treatment response to biologics, but not to non-biologics, in our Asian population of patients with moderate to severe psoriasis; however, the exact mechanism and role of HLA-Cw1 remain to be investigated.

Circulating Brodalumab Levels and Therapy Outcomes in Patients With Psoriasis Treated With Brodalumab

Given the possible treatment modalities in psoriasis management, little is known about whether drug monitoring is associated with response rate. To determine whether drug monitoring is associated with response to brodalumab therapy. A multicenter case series study of patients with psoriasis treated with brodalumab whose treatment with previous IL-17A inhibitor therapy failed. Patients were recruited from the Departments of Dermatology at Gentofte and Aarhus University Hospitals, Denmark, between 2018 and 2020. Patient visits were conducted after 4 and 12 weeks of therapy. Patients not achieving Psoriasis Area and Severity Index 75% improvement from baseline (PASI 75) after 12 weeks were discontinued and considered nonresponders. Patients maintaining PASI 75 response were followed up for up to 52 weeks. Treatment with brodalumab, 210 mg, at weeks 0, 1, 2, then every 2 weeks. Outcome measures were PASI reductions vs brodalumab levels and antibrodalumab antibodies. Twenty patients with psoriasis (13 [65%] were male; median age, 50 years [range, 19-66 years]) were included. After 12 weeks of therapy, patients with quantifiable levels of brodalumab (≥0.05 μg/mL) experienced significantly higher PASI reductions than those without (median, 93%; range, 61%-100% vs median, -3; range, -49% to 94%, respectively; P = .006). After 12 weeks of therapy, 4 of 5 patients (80%) not achieving PASI 75 had subquantifiable drug levels (<0.05 μg/mL), although this finding was seen for only 3 of 14 PASI 75 responders (21%). None of 7 patients (35%) with subquantifiable drug levels after 12 weeks of therapy maintained response. No antibrodalumab antibodies were detected in any of the tested samples. Results of this case series study suggest that circulating brodalumab level is a factor associated with clinical treatment response. Monitoring patient levels of circulating brodalumab may aid clinical decision-making and help prevent ineffective therapy.

Secukinumab dosing every 2 weeks demonstrated superior efficacy compared with dosing every 4 weeks in patients with psoriasis weighing 90 kg or more: results of a randomized controlled trial.

Obesity is a common comorbidity of psoriasis and can attenuate response to biologic treatment. To investigate the efficacy, safety and tolerability of secukinumab 300 mg every 2 weeks (Q2W) vs. secukinumab 300 mg every 4 weeks (Q4W) in patients with a higher bodyweight. In this multicentre, double-blind, parallel-group trial, 331 patients with moderate-to-severe chronic plaque psoriasis weighing ≥ 90 kg were randomized to receive secukinumab 300 mg Q2W or secukinumab 300 mg Q4W. Patients who did not achieve Psoriasis Area and Severity Index (PASI) 90 at week 16 on the Q4W regimen were reallocated to remain on the Q4W regimen or uptitrate to Q2W. At week 16, Q2W dosing (n = 165) led to significantly higher PASI 90 responses vs. Q4W [n = 166; 73.2% vs. 55.5%, one-sided P-value = 0.0003, odds ratio estimate (95% confidence intervals): 2.3 (1.4-3.8)]. At week 52, higher efficacy responses were maintained in the Q2W arm (n = 165) vs. Q4W (n = 83); PASI 75: 88.9% vs. 74.8%; PASI 90: 76.4% vs. 52.4%; PASI 100: 46.7% vs. 27.3%; Investigator's Global Assessment 0/1: 75.9% vs. 55.6% and Dermatology Life Quality Index 0/1: 66.1% vs. 48.8%. PASI 90 nonresponders at week 16 who uptitrated to Q2W (n = 31) showed higher efficacy responses at week 32 (16 weeks post-uptitration, PASI 90: 38.7% vs. 16.5%) vs. those who remained on Q4W (n = 40). Safety results were comparable across treatment arms and consistent with the established secukinumab safety profile. Secukinumab 300 mg Q2W demonstrated superior and sustained efficacy compared with Q4W in patients with moderate-to-severe plaque psoriasis weighing ≥ 90 kg. PASI 90 nonresponders derived additional benefits from uptitration to a Q2W regimen (ClinicalTrials.gov identifier: NCT03504852). What is already known about this topic? Obesity is a common comorbidity of psoriasis and can attenuate response to biologic treatment. Secukinumab is a fully human monoclonal antibody that selectively neutralizes interleukin-17A in the treatment of moderate-to-severe plaque psoriasis. Subgroup analyses of previous study results and pharmacokinetic/pharmacodynamic modelling data suggest that heavier patients may benefit from higher exposure to secukinumab through an increased dosing frequency [300 mg every 2 weeks (Q2W) vs. every 4 weeks (Q4W)]. What does this study add? Over 52 weeks, secukinumab 300 mg Q2W demonstrated superior efficacy compared with secukinumab 300 mg Q4W in patients with moderate-to-severe plaque psoriasis weighing ≥90 kg, with comparable safety results, consistent with the established secukinumab safety profile. In patients who did not achieve PASI 90 at week 16 on the Q4W regimen, uptitration to the Q2W regimen at week 16 resulted in improved efficacy responses through week 52 after switching.

Oral tyrosine kinase 2 inhibitor PF-06826647 demonstrates efficacy and an acceptable safety profile in participants with moderate-to-severe plaque psoriasis in a phase 2b, randomized, double-blind, placebo-controlled study

Psoriasis treatments lack durable efficacy and have inconvenient administration, highlighting the need for new therapies. To evaluate the efficacy and safety of tyrosine kinase 2 inhibitor, PF-06826647, in moderate-to-severe plaque psoriasis. This phase 2b, double-blind study randomized participants to oral, once-daily PF-06826647 (1:1:2:2:2) 50:100:200:400mg:placebo (16weeks), then 200 or 400mg (24weeks) (NCT03895372). The primary end point was a proportion of participants achieving psoriasis area severity index (PASI) 90 at week 16. Secondary end points (PASI50/75/90/100; Physician's Global Assessment) and safety were assessed to week 40. Overall, 178 participants were treated. A significantly greater proportion of participants (risk difference % [90% CI]) achieved PASI90 in the 200-mg (33.0 [18.0, 47.1], P=.0004) and 400-mg (46.5 [30.6, 60.6], P<.0001; week 16) groups versus placebo. Significant increases from placebo were observed for all secondary end points (200 and 400mg; weeks 6-16; P<.05); increases were evident to week 40 (categorical data). PF-06826647 was well tolerated and most treatment-emergent adverse events were mild/moderate. Eighteen participants discontinued due to treatment-emergent adverse events (14 arising from laboratory abnormalities). Limitations included the large proportion of White males and non-placebo-controlled extension. PF-06826647 200 and 400mg once daily showed significant efficacy versus placebo at week 16 and was well tolerated over 40weeks.

Number Needed to Treat Network Meta-Analysis to Compare Biologic Drugs for Moderate-to-Severe Psoriasis.

IntroductionNumber needed to treat (NNT) estimates are a practical metric to help identify the most effective therapies. Our objective is to compare 11 biologic drugs for moderate-to-severe psoriasis in terms of NNT.MethodsThe NNT data were obtained from a Bayesian network meta-analysis of 42 double-blind, randomized, phase 3 clinical trials for 11 biologics (adalimumab, brodalumab, certolizumab pegol, etanercept, guselkumab, infliximab, ixekizumab, risankizumab, secukinumab, tildrakizumab, and ustekinumab). We determined NNT to achieve Psoriasis Area and Severity Index (PASI) 75/90/100 responses at weeks 4, 8, 12, 16, and 48/52 and Dermatology Life Quality Index (DLQI) response 0, 1 at week 12.ResultsHighest efficacy (lowest NNT) was with brodalumab and ixekizumab for PASI 90 at weeks 4, 8, and 12; ixekizumab for PASI 90/100 at week 16; and brodalumab for PASI 100 at week 12. After 48/52 weeks, risankizumab had the highest efficacy for PASI 90/100 overlapping with guselkumab, brodalumab, and ixekizumab for PASI 90 and with brodalumab and ixekizumab for PASI 100. Ixekizumab had the highest efficacy for DLQI (0,1) at week 12.ConclusionsBrodalumab and ixekizumab had the lowest NNTs for achieving PASI responses at early time points and were not significantly different than risankizumab and guselkumab after 48/52 weeks.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-022-02065-w.

Effectiveness and Safety of Secukinumab for Psoriasis in a Real-World Clinical Setting in the Asia-Pacific and Middle East Regions: Results from the REALIA Study.

IntroductionSecukinumab has demonstrated sustained long-term efficacy with a favourable safety profile in various manifestations of psoriatic disease. We investigated effectiveness and safety of secukinumab, other biologics and conventional systemic therapies in patients with chronic plaque psoriasis in a real-world setting.MethodsREALIA was a non-interventional, multicentre, prospective, parallel group study. Eligible patients were ≥ 18 years old with chronic plaque psoriasis commencing a new treatment with a biologic agent or conventional systemic therapies.ResultsAt baseline, 541 patients were divided into three cohorts based on treatment initiated: conventional systemics (173), secukinumab (184) and other biologics (184). A significantly higher proportion of patients achieved almost clear to clear skin based on physician’s judgement in secukinumab versus conventional systemics at month 3 (64.7% versus 22.8%, P < 0.001) and month 6 (61.8% versus 20.8%, P < 0.001). At month 12, clear to almost clear skin was achieved by 52.1% of the patients in secukinumab versus 35.8% in conventional systemics (P = 0.066). The proportion of patients achieving Psoriasis Area Severity Index (PASI) 90 on conventional systemics, secukinumab and other biologics was 18.8%, 59.7% and 40.0% at month 3 and 35.3%, 60.8% and 50.0% at month 12, respectively. Secukinumab patients showed significantly higher change in PASI total score from baseline versus conventional systemics at month 3 {least squares [LS] mean [standard error (SE)]: −14.49 [0.648] versus −8.48 [1.149], P < 0.001} and numerically higher [LS mean (SE): −13.60 (0.475) versus −10.84 (1.733), P = 0.122] at month 12. The proportion of patients with Dermatology Life Quality Index 0/1 score on conventional systemics, secukinumab and other biologics was 22.6%, 65.0% and 41.6% at month 3 and 32.0%, 63.5% and 41.3% at month 12, respectively. Safety profile was comparable across cohorts.ConclusionsSecukinumab is effective and well tolerated in patients with chronic plaque psoriasis in a real-world setting in an Asia-Pacific and Middle East population, and these results are in agreement with clinical outcomes of secukinumab reported in randomised clinical trials.Trial registration number170803-001645.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13555-021-00675-w.

Clinical efficacy, speed of improvement and safety of apremilast for the treatment of adult Psoriasis during COVID-19 pandemic.

Time to improvement is a crucial characteristic for effective treatments of chronic inflammatory conditions, such as psoriasis. Apremilast is a recently approved drug, belonging to the small molecule phosphodiesterase 4 inhibitors, whose optimal safety and efficacy profile is somewhat affected by slow activity rate in clinical trials. Real world case series are suggesting a more consistent improvement, and with this additional personal investigation on 48 patients, we signal that 58% of patients achieved Psoriasis Area and Severity Index (PASI) 50, and 19% PASI 75 improvement in the first 8 weeks of treatment. Results at 16‐week are remarkable, with overall 55% of patients achieving PASI 75, 21% PASI 90 and 14% PASI 100. Only 8 patients (18, 6%) had slightly improved, although satisfied with the regimen, and determined to continue. Noteworthy, our population was rather problematic in terms of comorbidities (86%), and resistance to other treatments, with only 28% naïve to systemics, including biologics. Moreover, the observation period includes the Italian outbreak of COVID‐19 epidemic, and further information on apremilast safety are provided, no one of the patients having stopped treatment. In such a critical period, the apremilast satisfactory speed of therapeutic response in a real‐world setting has further strengthens patient's compliance to remain safely at home, which is the best strategy to limit contagion.

AB0026 SELECTIVE INHIBITION OF TYROSINE KINASE 2 WITH AN ORAL AGENT, BMS-986165, COMPARED WITH JANUS KINASE INHIBITORS

Background:BMS-986165 is an oral, selective inhibitor of tyrosine kinase 2 (TYK2) with a unique mode of binding to the pseudokinase domain of the enzyme rather than the active site within the kinase domain. This unique mode of binding provides high functional selectivity for TYK2 versus other tyrosine kinases (TYKs) in cellular and other in vitro assays.1This approach may provide robust efficacy with a differentiated safety profile due to decreased off-target activity on other kinases. In a 12-week, placebo-controlled Phase 2 trial in patients with moderate to severe plaque psoriasis,2BMS-986165 had a favorable safety profile, and 67%–75% of patients achieved Psoriasis Area and Severity Index 75 (PASI 75) after 12 weeks at doses ≥3 mg twice daily versus 7% with placebo. BMS-986165 is currently under investigation in multiple autoimmune disorders such as psoriatic arthritis, psoriasis, and systemic lupus erythematosus.Objectives:To understand the selectivity of BMS-986165 compared with JAK inhibitors, such as tofacitinib (Tofa), upadacitinib (Upa), and baricitinib (Bari), at clinically relevant doses and plasma concentrations.Methods:In vitro whole blood assays were developed to measure the activity of common pairings of JAKs (JAK 1/3, JAK2/2, and TYK2/JAK2) and concentrations providing half-maximal inhibition (IC50) for BMS-986165, Tofa, Upa, and Bari were determined. The whole blood IC50values were plotted against pharmacokinetic profiles of these agents at approved doses and/or doses evaluated in their respective Phase 2/3 trials. The time that concentrations were &gt;IC50and projected average daily inhibition were evaluated.Results:At clinically relevant doses and exposures, BMS-986165 plasma concentrations were higher than the TYK2 whole blood IC50value for a considerable part of the dosing interval. Additionally, the maximal plasma concentration (Cmax) of BMS-986165 was approximately &gt;9- to 18-fold lower than the JAK 1/3 whole blood IC50value and &gt;52- to &gt;109-fold lower than JAK2/2 whole blood IC50, indicating lack of meaningful inhibition of the JAK 1-3 pathways by BMS-986165 at therapeutic doses. At clinically relevant doses, projected Cmaxvalues of Tofa, Upa, and Bari were many-fold lower than TYK2 IC50, indicating minimal or no meaningful inhibition of the TYK2 pathway. As expected, Tofa, Upa, and Bari had varying degrees of inhibition against JAK1/3 (daily average inhibition range: 70%–94%) and JAK2/2 pathways (daily average inhibition range: 24%–67%) at clinically relevant doses and exposures.Conclusion:These results demonstrate the high TYK2 functional selectivity of BMS-986165 at clinically relevant doses and plasma concentrations compared with Tofa, Upa, and Bari and indicate that BMS-986165 is in a different class compared with JAK 1–3 inhibitors. Ongoing studies in psoriasis and other conditions may confirm the expected safety of BMS-986165 based on the above results. The daily average inhibition of JAK1 and JAK2 likely explains some common laboratory observations and adverse events reported for the JAK1–3 inhibitors.

Efficacy and Safety of Ixekizumab Through 5 Years in Moderate-to-Severe Psoriasis: Long-Term Results from the UNCOVER-1 and UNCOVER-2 Phase-3 Randomized Controlled Trials.

IntroductionIxekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A, is approved for treatment of moderate-to-severe plaque psoriasis. Our objective was to evaluate the long-term efficacy and safety of ixekizumab in moderate-to-severe plaque psoriasis through 5 years.MethodsData were integrated from the UNCOVER-1 and UNCOVER-2, randomized, double-blinded, phase-3 trials. Patients who continuously received the labeled ixekizumab dose, were static Physician’s Global Assessment (sPGA) (0,1) responders at Week 12 and completed 60 weeks of treatment could enter the long-term extension (LTE) period. Patients could escalate to every-2-week dosing per investigator opinion. Efficacy and health outcomes included proportion of patients achieving Psoriasis Area and Severity Index (PASI) 75/90/100, sPGA (0,1) and (0), absolute PASI ≤ 5/ ≤ 3/ ≤ 2/ ≤ 1 and Dermatology Life Quality Index (DLQI) (0,1). Results exclude patients who escalated to every-2-week dosing. A modified non-responder imputation method was used to account for missing data. Supplemental analyses include patients who escalated to every-2-week dosing and observed and multiple imputation results. Exposure-adjusted safety outcomes are also reported.ResultsOf 206 patients who entered the LTE periods, 172 completed treatment. At Week 60, PASI 75/90/100 responses were 94.7%, 85.0% and 62.1%, respectively, and at year 5 were 90.3%, 71.3% and 46.3%, respectively. Similarly, meaningful responses were achieved for the other efficacy and health measures. Among patients with PASI 100 through 5 years, 92% achieved DLQI (0,1), indicating no impact of skin disease on quality of life. During the LTE period, exposure-adjusted incidence rates were 31.4 per 100 patient-years for treatment-emergent adverse events and 6.8 per 100 patient-years for serious adverse events. No deaths were reported. No new or unexpected safety findings were noted.ConclusionsThe results demonstrate 80 mg ixekizumab maintains long-term efficacy and a safety profile consistent with previous data in patients with moderate-to-severe plaque psoriasis through 5 years of treatment.Trial RegistrationClinicalTrials.gov identifier, UNCOVER-1: NCT01474512, UNCOVER-2: NCT01597245.Electronic Supplementary MaterialThe online version of this article (10.1007/s13555-020-00367-x) contains supplementary material, which is available to authorized users.

Real-world Efficacy and Safety of Apremilast Monotherapy in the Management of Moderate-to-severe Psoriasis.

Introduction:Apremilast is the new oral drug in the management of moderate-to-severe plaque psoriasis with well-established effectiveness and safety in long-term clinical trials and a few real-world studies. However, its effectiveness and safety in Indian setup have not been reported yet.Materials and Methods:This was retrospective, single-center, longitudinal, observational cohort study where the total study period was 24 weeks. Effectiveness parameters were the proportion of patients achieving psoriasis area and severity index (PASI) 50, 75, 90, and 100 response at week 16 and 24. Safety was measured as the proportion of patients reporting ≥1 adverse event (AE) during the study period.Results:Data of a total of 70 patients were included in our study. At week 16, 76.92%, 41.53%, 15.38%, and 6.15% patients achieved PASI 50, 75, 90, and 100, respectively. At week 24, 81.53%, 58.46%, 29.23%, and 10.76% patients achieved PASI 50, 75, 90, and 100, respectively. Mean percentage reduction in PASI was 67% at week 24 and DLQI score was reduced significantly to 3.4 from mean baseline DLQI score of 10.8 (P < 0.001). 40% of patients reported ≥1 AE during the study period. 5 out of 70 patients discontinued apremilast due to AE. Nausea was most common AE reported by 21.4% patients followed by diarrhea (18.57%), headache (17.4%), vomiting (8%), weight loss (7.69%), myalgia (6.15%), and gastritis (6.15%). Most of the AEs were of mild-to-moderate severity.Conclusion:The results of this study support the long-term use of apremilast monotherapy as an efficacious and safe treatment option for the management of moderate-to-severe plaque psoriasis.