Absolute PASI Research Articles

Bimekizumab efficacy and safety in patients with moderate-to-severe plaque psoriasis who switched from adalimumab, ustekinumab or secukinumab: results from phase III/IIIb trials.

Discontinuation of biologics is common among patients with psoriasis due to treatment failure or adverse events. To achieve improvements in disease management, patients and clinicians may choose to switch biologics. To evaluate the efficacy and safety of switching to bimekizumab from adalimumab, ustekinumab and secukinumab. Data are reported for up to 80 weeks after patients switched to bimekizumab from adalimumab at week 24 in BE SURE, ustekinumab at week 52 in BE VIVID [upon entry into the BE BRIGHT open-label extension (OLE)] and secukinumab at week 48 in BE RADIANT (upon entry into the BE RADIANT OLE). Efficacy outcomes are reported by number of weeks after switching to bimekizumab and were split based on whether patients had achieved a ≥90% improvement from baseline in Psoriasis Area and Severity Index (PASI 90) at the time of switch. Treatment-emergent adverse events (TEAEs) are reported using exposure-adjusted incidence rates (EAIRs) per 100 patient-years. Trial registration: BE SURE (NCT03412747), BE VIVID (NCT03370133), BE BRIGHT (NCT03598790), BE RADIANT (NCT03536884). Rapid and durable improvements in clinical responses and benefits in health-related quality of life were observed among PASI 90 nonresponders who switched to bimekizumab. Most PASI 90 nonresponders achieved PASI 90 4 weeks after switching to bimekizumab from adalimumab (67%), ustekinumab (79%) and secukinumab (53%). After 48 weeks of bimekizumab, 91%, 90% and 79% of PASI 90 nonresponders had achieved PASI 90 after switching from adalimumab, ustekinumab or secukinumab, respectively. Durable improvements were also observed for PASI 100, Investigator's Global Assessment score 0/1, body surface area affected by psoriasis ≤ 1%, absolute PASI ≤ 2, and Dermatology Life Quality Index 0/1. Among PASI 90 responders, existing treatment responses were maintained or improved after switching to bimekizumab. The majority of TEAEs were mild or moderate. EAIRs were generally similar between active-comparator treatment periods and after switching to bimekizumab. EAIRs typically decreased with a longer duration of bimekizumab exposure. High proportions of patients who did not adequately respond to adalimumab, ustekinumab or secukinumab achieved high levels of skin clearance after switching to bimekizumab. Bimekizumab was well tolerated and there were no new safety findings.

Risankizumab: Efficacy, Safety, and Survival in the Mid-Term (52 Weeks) in Real Clinical Practice in Andalusia, Spain, According to the Therapeutic Goals of the Spanish Psoriatic Guidelines.

Risankizumab is a humanized monoclonal antibody of the immunoglobulin G1 (IgG1) type that binds selectively, and with high affinity, to the p19 subunit of interleukin-23 (IL-23), resulting in the inhibition of inflammation and clinical symptoms associated with psoriasis. Its introduction has managed to increase the levels of efficacy and safety (improving upon those previously presented by the anti-IL-23 class). Retrospective analysis of a multicenter, observational study of real clinical practice, including patients with moderate-to-severe plaque psoriasis in treatment with risankizumab. This cross-sectional analysis includes information on patients from May 2020 to June 2022. A total of six tertiary hospitals in Andalusia (Spain) participated in this study. Analyses were performed "as observed" using GraphPad Prism version 8.3.0 for Windows. Regarding the percentage of patients who reached PASI 90 or PASI 100 at week 52, 92.5% achieved the therapeutic goal of PASI 90, and 78.5% reached PASI 100. When analyzing the results by absolute PASI, we found that 78.5% (n = 33) obtained PASI 0, 85.7% (n = 36) obtained PASI ≤ 1, and all patients achieved PASI ≤ 3 (disease control). Risankizumab has shown promising results in the control of psoriasis in the long-term, with a high percentage of patients (>80%) maintaining PASI 90 and PASI 100 up to 52 weeks of treatment. No abnormal safety findings have been reported, and risankizumab appears to be a solid treatment in the different scenarios analyzed.

Secukinumab long-term efficacy and safety in psoriasis through to year 5 of treatment: results of a randomized extension of the phase III ERASURE and FIXTURE trials.

In the long-term extension study of the ERASURE and FIXTURE trials, the efficacy of secukinumab (a fully human anti-interleukin-17A monoclonal antibody) was demonstrated to have been maintained through to year 3 of treatment in moderate-to-severe plaque psoriasis. To assess the efficacy and safety of secukinumab through to year 5 of treatment in moderate-to-severe plaque psoriasis. Responders with ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) from two core trials - ERASURE and FIXTURE - were randomized 2 : 1 at year 1 (end of core trials) to either the same dose (300 or 150 mg, continuous treatment) or placebo (treatment withdrawal) every 4 weeks, until year 3 or relapse (> 50% reduction in maximal PASI from core study baseline). Partial responders (achieving PASI 50 but not PASI 75) at year 1 continued at the same dose as in the core trials. At year 3, all patients received open-label secukinumab treatment, with those on secukinumab 300 mg continuing on their dose, while those on secukinumab 150 mg or placebo received secukinumab 150 or 300 mg based on the physician's discretion. The study is registered on ClinicalTrials.gov with the identifier NCT01544595. Most patients randomized to placebo at year 1 relapsed, but the response was rapidly recaptured upon reinitiation of treatment. PASI responses were sustained with secukinumab through to year 5. The PASI responses for the 300 mg responders + partial responders group at year 1 (PASI 75/90/100: 86.8%/72.8%/45.9%) trended downwards until year 3 (PASI 75/90/100: 82.3%/58.4%/32.7%) and then remained stable through year 4 (PASI 75/90/100: 83.3%/60.1%/32.2%) until year 5 (PASI 75/90/100: 81.1%/62.8%/35.1%). Dermatology Life Quality Index showed sustained benefit up to year 5. Absolute PASI responses were maintained throughout the study. The most common adverse events (AEs) were infections and infestations, nasopharyngitis, and upper respiratory tract infections (URTIs). The overall exposure-adjusted incidence rate (EAIR; with 95% confidence interval) for all AEs was 139.9 (130.3-149.9). EAIRs for Crohn's disease and neutropenia were 0.1 (0.0-0.3) and 0.5 (0.3-0.8), respectively. The 4-year extension of two pivotal phase III trials demonstrated that secukinumab treatment was effective through to year 5 and improved quality of life in patients with moderate-to-severe plaque psoriasis. The most common AEs were infections and infestations, nasopharyngitis, and URTIs. The safety profile was consistent with that in the secukinumab phase II/III clinical development programme.

Tildrakizumab: Efficacy, Safety and Survival in Mid-Term (52 Weeks) in Three Tertiary Hospitals in Andalucia (Spain).

Tildrakizumab (TIL) binds selectively to the p19 subunit of interleukin 23. Its introduction has managed to increase the levels of efficacy, safety (improving that previously presented by the anti-IL-12/23 class) and survival. Retrospective analysis of a multicenter, observational study of real clinical practice including patients with moderate-to-severe plaque psoriasis in treatment with TIL. This cross-sectional analysis includes information of patients between February 2019 to February 2022. A total of three tertiary hospitals in Andalusia (Spain) participated in this study. Analyses were performed “as observed” using IBM SPSS v28 for Windows. A total of 61 patients were included in the analysis. The mean age of our patients was 49.5 years; 50.18% of the patients were female and 34.42% of the patients had a BMI greater than 30. It was notable that 44.26% of our patients had scalp involvement. Almost 35% of the patients had psoriatic arthropathy, although skin involvement was predominant. At week 52 (n = 34), 68% of the patients presented an absolute PASI equal to or less than 1. Regarding the drug survival, eight patients discontinued treatment due to inefficacy: five primary and three secondary failures, and one death due to causes not drug related showing survival of 86% at week 52. In the analysis of subgroups of patients, we found that scalp involvement determined greater survival (94%), as well as a shorter duration of the disease (91.7% vs. 84.4% in those with less than 10 years versus more than 15 years of evolution) and with a lower number of previous biological therapies (100% naïve, 90% in those who have used one line of biological therapy and 82.1% in those who have completed two or more lines of biological treatment. Tildrakizumab showed excellent results in the control of psoriasis in the mid-term with an elevated number of patients maintaining treatment after 52 weeks. There were no statistically significant differences in the efficiency, safety or survival results of TIL between patients coming from previous therapies.

Long-Term Dose Optimization of Adalimumab via Dose Spacing in Patients with Psoriasis.

Dose spacing (DS) can be useful for optimizing treatment with biologics in psoriasis patients. However, interval prolongation might increase the production of anti-drug antibodies (ADA) and, therefore, reduce the drug’s effectiveness. The long-term effects of DS with adalimumab in psoriatic patients have not been reported. The goal of our study was to evaluate the long-term follow-up of psoriatic patients after adalimumab DS regarding the clinical course and determination of circulating adalimumab, TNFα levels, and anti-adalimumab antibodies. We retrospectively included seven patients treated with adalimumab for moderate-to-severe psoriasis and benefiting from DS from 2010 to 2021. The dose interval of adalimumab was extended to three weeks for all patients and then to four weeks for three of the seven patients. Adalimumab trough levels, TNFα levels, and ADA against adalimumab were measured. For six of the seven patients, absolute PASI values remained below 3 throughout the follow-up period (median = 8.0 years; range: 1.7–11.5) after DS. All the patients were satisfied with the effectiveness of their treatment regime. Within the follow-up period, an average of 63 doses of adalimumab per patient were spared. The median adalimumab trough levels were 4.7 µg/mL (range: 1.9–12.5). TNFα levels remained under 10 pg/mL (undetectable) in all except one patient. ADA against adalimumab remained negative (<10 µg/mL) during the follow-up in all patients. Our data indicate that therapeutic drug monitoring, including the measurement of trough concentrations and ADA, together with the clinical response and patient’s preference, can be helpful for clinical decision making and treatment optimization in psoriasis.

Comparative effectiveness of biologics in clinical practice: week 12 primary outcomes from an international observational psoriasis study of health outcomes (PSoHO).

Clinical trials study treatment outcomes under stringent conditions, capturing incompletely the heterogeneity of patient populations and treatment complexities encountered in real-world practice. To compare the effectiveness of anti-interleukin (IL)-17A biologics relative to other approved biologics in patients with moderate-to-severe psoriasis. The Psoriasis Study of Health Outcomes (PSoHO) is an ongoing 3-year observational cohort study in adults with chronic moderate-to-severe plaque psoriasis initiating or switching to a new biologic. Primary study endpoint is the proportion of patients achieving 90% improvement in Psoriasis Area and Severity Index (PASI 90) and/or static Physician Global Assessment (sPGA) 0/1 at Week 12 (W12) in the anti-IL-17A cohort (ixekizumab [IXE], secukinumab) vs. all other approved biologics. Secondary outcomes include the proportion of patients who achieve PASI 75/90/100, absolute PASI scores ≤5, ≤2 and ≤1, Dermatology Life Quality Index (DLQI) score of 0/1 at W12 between the two cohorts and among the individual biologics. Comparative effectiveness analyses were conducted using Frequentist Model Averaging (FMA), a novel causal inference machine learning approach. Missing data for binary outcomes were imputed as non-response. Patient profiles in the anti-IL-17A cohort and other biologics cohort were similar, with more frequent comorbid psoriatic arthritis and less frequent exposure to conventional treatments in the patients receiving anti-IL-17A biologics. At W12, 71.4% of patients who received an anti-IL-17A biologic achieved PASI 90 and/or sPGA 0/1 compared to 58.6% of patients who received other biologics (odds ratios [OR], 1.9; 95% confidence intervals [CI], [1.6, 2.4]). Similar findings were observed for secondary outcomes. These results reflect the high efficacy and early onset of skin clearance of IL-17A inhibitors observed in randomized clinical trials and confirm the effectiveness of anti-IL-17A biologics in the real-world setting.

Secukinumab demonstrated sustained retention, effectiveness and safety in a real-world setting in patients with moderate-to-severe plaque psoriasis: long-term results from an interim analysis of the SERENA study.

Randomized controlled trials of secukinumab have shown sustained efficacy and a favourable safety profile in multiple manifestations of psoriatic disease. To assess the long-term, real-world retention, effectiveness and safety of secukinumab in routine clinical practice for the treatment of moderate-to-severe plaque-type psoriasis (PsO). SERENA (CAIN457A3403) is a large, ongoing, longitudinal, observational study conducted at 438 sites and 19 countries for an expected duration of up to 5 years in adult patients with moderate-to-severe PsO, psoriatic arthritis and ankylosing spondylitis. Patients received ≥16 weeks of secukinumab treatment before enrolment. This interim analysis presents data from PsO patients, who were enrolled in the study between October-2016 and October-2018 and were observed for ≥2 years. In total, 1756 patients (67.3% male) with a mean age of 48.4 years and body mass index of 28.8 kg/m2 were included in the analysis. The secukinumab treatment retention rates after 1, 2 and 3 years in the study were 88.0%, 76.4% and 60.5%, respectively. Of the 648 patients who discontinued the study, the most common reasons included lack of efficacy (42.6%), adverse event (17.4%), physician decision (12.2%) and subject decision (11.6%). Mean ± SD absolute PASI was 21.0 ± 13.0 at the start of treatment (n = 1,564). At baseline, the mean ± SD PASI score reduced to 2.6 ± 4.8 and remained low at Year 1 (2.3 ± 4.3), Year 2 (1.9 ± 3.6) and Year 3 (1.9 ± 3.5). The safety profile of secukinumab during the SERENA study was consistent with its known safety profile, with no new safety signals reported. Particularly, low rates of inflammatory bowel disease (0.3%; Incidence Rate [IR]:0.15), candida infections (3.1%; IR:1.43) and MACE (0.9%; IR:0.37) were observed. Secukinumab showed high treatment persistence, sustained effectiveness and a favourable safety profile up to 3 years of follow-up in the real-world population of PsO patients observed in SERENA.

Tildrakizumab in moderate-to-severe plaque psoriasis: A multicenter, retrospective, real-life study.

New biologic agents targeting interleukin (IL)23/T‐helper17 axis, such as tildrakizumab, have been developed for the treatment of plaque psoriasis. To analyze the efficacy and safety of tildrakizumab in a real life setting of patients affected by moderate‐to‐severe psoriasis over a 28‐week treatment period. A multicentric retrospective study was conducted in patients who initiated tildrakizumab between February 2020 and March 2021. Psoriasis Area and Severity Index—PASI was measured at baseline and after 4, 16 and 28 weeks. The percentage change in PASI value from baseline to the considered time‐points, proportion of patients with absolute PASI <3 at week 28 and the percentages of achieving a PASI75 or PASI90 response were assessed. Data about potential safety issues and adverse events (AEs) were collected. Statistical analysis were performed for establish clinical efficacy and for variables predicting clinical response. Fifty nine patients with psoriasis were included. Overall mean PASI percentage reduction was of 88% from baseline to week 28 and 47 out of 59 patients (79.7%) at week 28 had an absolute PASI <3. PASI75 and PASI90 responses at week 28 were achieved by 48 (81.40%) patients and 38 (64.4.0%) patients, respectively. No substantial associations between gender, body mass index ‐ BMI, PASI at baseline and prior exposition to biological therapies and the efficacy endpoints were retrieved. No serious safety issues or discontinuations related to adverse events were reported. In our real‐life study, tildrakizumab showed high efficacy and a favorable safety profile, regardless of patient‐ and disease‐related factors.

Long-term efficacy and safety of brodalumab in moderate-to-severe plaque psoriasis: a post hoc pooled analysis of AMAGINE-2 and -3.

Brodalumab is a monoclonal antibody that blocks multiple interleukin (IL)-17 family cytokines by binding to the shared A subunit of the IL-17 receptor. In Phase 3 trials, brodalumab provided high levels of skin clearance through 52 weeks in patients with moderate-to-severe psoriasis and was generally well tolerated. To assess efficacy response rates and safety outcomes through 120 weeks for patients with moderate-to-severe psoriasis who received brodalumab. Safety and efficacy data were pooled for patients from AMAGINE-2 and -3 who received continuous brodalumab 210 mg every 2 weeks, or brodalumab 210 mg every 2 weeks after receiving either brodalumab 140 mg or placebo through Week 12. Efficacy data are presented using observed data, non-responder imputation (NRI) and a combination of NRI and missing at random assumption to account for missing data. Absolute PASI scores are presented using mixed-effect model repeated measure modelling and multiple imputation. Based on observed data at Week 120, 86% of the continuous brodalumab 210 mg group achieved PASI 90 and 74% achieved PASI 100. At Week 12, 58% of this group achieved absolute PASI ≤1; this proportion increased to approximately 80% at Week 52 and persisted through Week 120. Among patients receiving continuous brodalumab 210 mg, median duration of brodalumab exposure was 747 days and the overall exposure-adjusted event rate of treatment emergent adverse events per 100 patient-years was 329. Safety through 120 weeks was comparable to the results of the primary AMAGINE-2 and -3 studies. Patients who switched to brodalumab 210 mg after receiving either brodalumab 140 mg or placebo through Week 12 showed similar skin clearance and safety profiles. Brodalumab treatment was well tolerated and resulted in high levels of skin clearance that were rapidly achieved and maintained through Week 120, supporting its long-term efficacy and safety profile.

Super responders to guselkumab treatment in moderate-to-severe psoriasis: a real clinical practice pilot series.

The term super responders defines a subset of patients with moderate-to-severe psoriasis that present a rapid and higher rate of response to biological treatments in comparison to the general population. Little scientific evidence to explain the behavior and clinical characteristics of these psoriatic patients has been published thus far. Its characterization could be important to improve therapeutic optimization and to identify the profile of patients that will respond efficiently to biological treatments. The main objective of this study was to evaluate and characterize the proportion of super-responder patients (who achieved PASI = 0 at week 12 and 24) in a total of 87 patients with moderate-to-severe psoriasis treated with guselkumab. Also, our intent was to analyze and evaluate differences in response to guselkumab in absolute PASI, PASI 75, PASI 90, PASI 100, BSA, VAS pruritus, and DLQI between groups. A total of 14 out of 87 patients treated with guselkumab were characterized as SR. No differences in demographic characteristics were found. The percentage of patients reaching PASI 75, PASI 90, and PASI 100 were numerically greater for SR than N-SR at week 12, 24, 36, and 52. These differences were more pronounced for PASI 100 > PASI 90 > PASI 75. SR performed better and faster to guselkumab treatment as assessed by absolute PASI, BSA, VAS pruritus, and DLQI. Statistically significant differences were found in absolute PASI, BSA, VAS pruritus, and DLQI between groups along the 52 weeks of study. No differences in drug survival were found between groups (P = 0.3326). Our study demonstrated for the first time, in a real clinical practice setting, the presence of a subpopulation of patients that super respond to guselkumab at week 12 and 24 and maintain this efficacy for 52 weeks. Further research must be performed to identify basal specific characteristics of this SR population.

Which PASI Outcome Is Most Relevant to the Patients in Real-World Care?

In psoriasis treatment, there is a high need to define meaningful endpoints and differences from the patient perspective to analyze patient-relevant differences of frequently used outcome methods for psoriasis under real-world conditions. A sample of 3116 patients from the German Psoriasis-Registry PsoBest was analyzed for clinical as well as patient-reported outcomes (PRO) after 3- and 6-month treatment. The parameters PASI, DLQI, and PBI were intercorrelated and related to two anchoring variables: (1) patient satisfaction with treatment and (2) perceived complete clearance. Baseline data were as follows: PASI 10.5 ± 9.1, DLQI 12.4 ± 3.4, and PBI 2.7 ± 0.3. There was an almost linear relationship between “complete patient satisfaction” and the relative differences in PASI in the range from PASI 25 to PASI 90. However, there was no additional benefit between PASI 90 and PASI 100. The same finding resulted from the anchoring variable “perception of complete healing”. When related to DLQI outcomes, relative PASI changes as well as absolute changes and PASI at 3 and 6 months showed relevant differences between the PASI classes 25 to 90 but not between PASI 90 and PASI 100. Under real-world conditions, changes in PASI and DLQI reflect patient-relevant benefits.

P70: Real‐world effectiveness of guselkumab in achieving absolute PASI thresholds and mean DLQI scores in patients with moderate‐to‐severe plaque psoriasis: analysis of the BADBIR registry following 6 months of treatment

P70: Real‐world effectiveness of guselkumab in achieving absolute PASI thresholds and mean DLQI scores in patients with moderate‐to‐severe plaque psoriasis: analysis of the BADBIR registry following 6 months of treatment

Is apremilast for psoriasis as effective and safe as reported in clinical trials? Five-year experience from a Greek tertiary hospital: long-term real-life efficacy and safety of apremilast in Greece.

Apremilast has been approved as an effective and safe treatment for psoriasis, but clinical trial results may differ from real-life data. This retrospective cross-sectional study evaluated the long-term efficacy and safety of apremilast in a Greek cohort of adult patients with psoriasis who had received at least one dose of apremilast between March 2016 and January 2021. The primary endpoint was the percentage of patients who achieved 75% reduction in Psoriasis Area Severity Index (PASI75) at Week 16. Absolute PASI, PASI90 (90% reduction) and adverse events were also recorded at various timepoints. In total, 102 patients (29.4% women, 70.6% men) with a mean ± SD age 55.94 ± 15.21 years were included. PASI75 and PASI90 were achieved by 20.8% and 1.98% of patients, respectively, at Week 16. According to our results, PASI90 achievement was significantly lower than that reported in clinical trials. The efficacy of apremilast increased gradually until Week 24, with further improvement noted in good responders up to Week 52.

P189 Comparison of secukinumab versus adalimumab efficacy on skin outcomes in psoriatic arthritis: 52-week results from the EXCEED study

Abstract Background/Aims Psoriatic arthritis (PsA) is a heterogeneous disease comprising musculoskeletal and dermatological manifestations, especially plaque psoriasis. Secukinumab, an interleukin17A inhibitor, provided significantly greater PASI75/100 responses in two head-to-head trials versus etanercept or ustekinumab, a tumour necrosis factor inhibitor (TNFi), in patients with moderate-to-severe plaque psoriasis. The EXCEED study (NCT02745080) investigated whether secukinumab was superior to adalimumab, another TNFi, as monotherapy in biologic-naive active PsA patients with active plaque psoriasis (defined as having ≥1 psoriatic plaque of ≥ 2 cm diameter, nail changes consistent with psoriasis or documented history of plaque psoriasis). Here we report the pre-specified skin outcomes from the EXCEED study in the subset of patients with ≥3% body surface area (BSA) affected with psoriasis at baseline. Methods In this head-to-head, Phase 3b, randomised, double-blind, active-controlled, multicentre, parallel-group trial, patients were randomised to receive subcutaneous secukinumab 300 mg at baseline and Weeks 1-4, followed by dosing every 4 weeks until Week 48, or subcutaneous adalimumab 40 mg at baseline followed by the same dosing every 2 weeks until Week 50. The primary endpoint was superiority of secukinumab versus adalimumab on ACR20 response at Week 52. Pre-specified outcomes included the proportion of patients achieving a combined ACR50 and PASI100 response, PASI100 response, and absolute PASI score ≤3. Missing data were handled using multiple imputation. Results Overall, 853 patients were randomised to receive secukinumab (n = 426) or adalimumab (n = 427). At baseline, 215 and 202 patients had at least 3% BSA affected with psoriasis in the secukinumab and adalimumab groups, respectively. At Week 52, more patients achieved simultaneous improvement in ACR50 and PASI100 response with secukinumab versus adalimumab (30.7% versus 19.2%, respectively; P = 0.0087). Greater efficacy was demonstrated for secukinumab versus adalimumab for PASI100 responses and for the proportion of patients achieving absolute PASI score ≤3 (Table 1). Conclusion In this pre-specified analysis, secukinumab provided higher responses compared with adalimumab in achievement of combined improvement in joint and skin disease (combined ACR50 and PASI100 response) and in skin-specific endpoints (PASI100 and absolute PASI score ≤3) at Week 52. P189 Table 1:Skin-specific outcomes at Week 52Endpoints, % responseSEC 300 mg (N = 215)ADA 40 mg (N = 202)P value (unadjusted)PASI10046300.0007Combined ACR50 and PASI10031190.0087Absolute PASI score ≤379650.0015P value vs ADA; unadjusted P values are presented. Multiple imputation was used for handling missing data. ADA, adalimumab; ACR, American College of Rheumatology; N, number of patients in the psoriasis subset; PASI, Psoriasis Area and Severity Index; SEC, secukinumab. Disclosure A. Gottlieb: Grants/research support; A.G. has received research support, consultation fees or speaker honoraria from Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB. F. Behrens: Consultancies; F.B. is a consultant for Pfizer, AbbVie, Sanofi, Lilly, Novartis, Genzyme, Boehringer Ingelheim, Janssen, MSD, Celgene, Roche and Chugai. Grants/research support; F.B. has received grant/research support from Pfizer, Janssen, Chugai, Celgene, Lilly and Roche. P. Nash: Consultancies; P.N. is a consultant for AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer Inc., Roche, Sanofi and UCB. Member of speakers’ bureau; for AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer Inc., Roche, Sanofi and UCB. Grants/research support; P.N. has received research support from AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi and UCB. J. Merola: Consultancies; J.F.M. is a consultant for Merck, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB Pharma, Celgene, Sanofi, Regeneron, Arena, Sun Pharma, Biogen, Pfizer, EMD Sorono, Avotres and LEO Pharma. P. Pellet: Corporate appointments; P.P. is an employee of Novartis. Shareholder/stock ownership; P.P. is a shareholder of Novartis. L. Pricop: Corporate appointments; L.P. is an employee of Novartis. Shareholder/stock ownership; L.P. is a shareholder of Novartis. I. McInnes: Consultancies; I.M. is a consultant for AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer and UCB. Grants/research support; I.M. has received grant/research support from Bristol Myers Squibb, Celgene, Eli Lilly and Company, Janssen and UCB.

The Impact of ANxA6 Gene Polymorphism on the Efficacy of Methotrexate Treatment in Psoriasis Patients

Background: There are great interindividual variations in the clinical efficacy of methotrexate (MTX) treatment and patients’ genetic background seems promising in its explanation. Objectives: The study aimed to test whether the polymorphism of annexin A6 (ANxA6) gene, a susceptibility factor for psoriasis, was associated with the clinical response to MTX therapy. Methods: A total of 325 patients enrolled in the study received oral MTX treatment, of whom 310 completed the 1-year study and performed the genotype analysis. They were defined as responders (a reduction of Psoriasis Area and Severity Index [PASI] score ≥75%) and nonresponders (a reduction of PASI <50%) compared to baseline after 12 weeks of short-time therapy. On 1-year treatment, they were defined as responders if they achieved PASI75 and absolute PASI ≤3, otherwise as nonresponders. The genotypes of 4 single-nucleotide polymorphisms (SNPs) in the ANxA6 gene were verified using the Sequenom platform. Potential predictors associated with the treatment outcome of MTX were assessed by binary logistic regression. Results: We found significant associations for the ANxA6 SNPs of rs11960458, rs960709, and rs13168551 with psoriasis severity. Patients with rs11960458 CC genotype and rs960709 GG genotype showed higher percentages of PASI75 and improvement rates of PASI at 12 weeks. And on 1-year treatment, statistical difference occurred in rs11960458 rather than other SNPs compared between responders and nonresponders that the frequency of CC genotype was higher in responders (p = 0.019). After adjustment for potential confounders, patients with rs11960458 TT/CT genotype (at 12 weeks: OR 0.483, 95% CI 0.245–0.951, p = 0.035; at 1 year: OR 0.483, 95% CI 0.280–0.833, p = 0.009) were significantly more likely to not respond to MTX both on the short-term and long-term treatment, while rs960709 and rs13168551 polymorphisms were only associated with the short-term efficacy of MTX (p = 0.018 and p = 0.036, respectively). Conclusions: The CC ge­notype of ANxA6 (rs11960458) was significantly associated with a better response when compared to those patients with the TT/CT genotype, thus being a potential predictor for the clinical efficacy of MTX.

Treat-to-Target Approach for the Management of Patients with Moderate-to-Severe Plaque Psoriasis: Consensus Recommendations.

IntroductionTreat-to-target strategies are used in several chronic diseases to improve outcomes. Treatment goals have also been suggested for psoriasis, but there is currently no consensus on targets, and guidance is needed to implement this strategy in clinical practice. The project ‘Treat to Target Italia’ was launched by a scientific board (SB) of 10 psoriasis experts to generate expert consensus recommendations.MethodsOn the basis of the published literature, their clinical experience, and the results of a survey among Italian dermatologists, the SB identified four relevant topics: (1) clinical remission; (2) quality of life; (3) abrogation of systemic inflammation; (4) safety. They drafted 20 statements addressing these four topics and submitted them to a panel of 28 dermatologists, in a Delphi process, to achieve consensus (greater than 80% agreement).ResultsConsensus was reached on all statements. Treatment goals defining clinical remission should include a 90% improvement from baseline in the Psoriasis Area and Severity Index (PASI90 response) or an absolute PASI score of less than or equal to 3. Patient’s quality of life and satisfaction are important targets. If PASI targets are achieved, there should be no or very low impact of psoriasis on quality of life [Dermatology Life Quality Index (DLQI) score less than or equal to 3]. If PASI or DLQI goals are not achieved within 3–4 months, treatment should be changed. Abrogation of systemic inflammation may be crucial for preventing or delaying inflammatory comorbidities. Safety is an equally important target as efficacy.ConclusionThese 20 consensus statements define the parameters of a treat-to-target strategy for psoriasis in Italy. It is hoped that use of these in the management of patients with psoriasis will improve treatment outcomes and patient health-related quality of life.

Therapeutic goals and treatment response evaluation in moderate to severe psoriasis: an experts opinion document

Objective To critically analyse and define therapeutic objectives, response to treatment evaluation and related decisions in psoriasis. Methods Expert consensus meetings, a systematic and narrative reviews and a collaborative Delphi procedure were carried out. A steering committee from the Spanish Group of Psoriasis was established who based on the reviews generated a set of related statements. Subsequently, a group of 40 experts tested their agreement with the statements, through 3 Delphi rounds. Results We found a great variability in clinical guidelines regarding to the definition of treatment goal and the response. In general, treatment failure was considered if a PASI50 is not achieved. The panel of experts agreed on (1) clearly differentiate between ideal and a realistic goals when establishing the therapeutic goal in moderate to severe psoriasis; (2) treatment goals should be in general established regardless of the type of drug for psoriasis; (3) treatment failure if PASI75 response is not reached; (4) an absolute PASI is in general preferred to the rate of PASI improvement from baseline; (5) disease characteristics, patients and physicians opinions/needs and treatment adherence influence treatment goals. Conclusions A clear treatment decision making framework is vital to improve management of psoriasis. KEY MESSAGES Psoriasis characteristics, patients and physicians opinions/needs and treatment adherence influence treatment goals. Different disease indexes could be used to assess treatment response but absolute PASI is preferred In general psoriasis treatment failure should be considered if PASI75 response is not reached

14998 Reductions in absolute PASI over 144 weeks of treatment with certolizumab pegol in patients with plaque psoriasis: Pooled analysis from two phase 3 trials (CIMPASI-1 and CIMPASI-2)

Background: Certolizumab pegol (CZP) is an Fc-free, PEGylated anti–tumor necrosis factor. Here, we report the proportions of patients with moderate to severe plaque psoriasis (PSO) achieving clinically relevant absolute PASI thresholds over 144 weeks’ CZP treatment.

18239 Secukinumab treatment results in sustained improvement in absolute PASI and drug survival: 24-month follow-up from the British Association of Dermatologists Biologics and Immunomodulators Register

Introduction: Secukinumab (SEC) is an anti–IL-17A monoclonal antibody for moderate to severe psoriasis. The British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR), an ongoing UK and Republic of Ireland prospective longitudinal pharmacovigilance registry, is an ideal resource to assess real world drug survival and effectiveness.

Secukinumab 2-weekly vs. 4-weekly dosing in patients with plaque-type psoriasis: results from the randomized GAIN study.

Secukinumab is a fully human monoclonal antibody that selectively neutralizes interleukin-17A and shows long-lasting efficacy and safety in plaque psoriasis. More evidence is required to optimize secukinumab dosing according to clinical response. GAIN compared the efficacy and safety of secukinumab 300mg every 2weeks (q2w) with 300mg every 4weeks (q4w) in patients achieving≥75% improvement in Psoriasis Area and Severity Index (PASI 75) but not PASI 90 after 16weeks. In total, 772 patients with moderate-to-severe plaque psoriasis received secukinumab 300mg subcutaneously at baseline and weeks 1, 2, 3 and 4, then q4w until week 16. At week 16, patients with PASI≥75 to PASI<90 were randomized 1:1 to continue q4w dosing (n=162) or switch to q2w (n=163) to week 32. The primary endpoint was superiority of q2w to q4w dosing for PASI 90 response at week 32. PASI 90 response at week 32 was numerically greater with secukinumab 300mg q2w than with secukinumab 300mg q4w in suboptimal responders, but this did not reach statistical significance (64·4% vs. 57·4%; odds ratio 0·64, 95% confidence interval 0·39-1·07; P=0·087). Although the primary endpoint was not met, absolute PASI was significantly lower at week 32 in q2w vs. q4w patients (2·11 vs. 2·84, P=0·024). Significantly more patients with q2w vs. q4w dosing showed minimal disease activity (Investigator's Global Assessment score 0 or 1: 73·0% vs. 64·1%, P<0·05) and improved quality of life (Dermatology Life Quality Index score 0 or 1: 58·9% vs. 50·6%, P<0·05) at week 32. No new or unexpected safety signals arose. Most patients achieved PASI 90 response with secukinumab q4w. There was potential benefit of q2w dosing in some suboptimal responders. Continued q4w treatment can improve response even after 16weeks.