Absolute PASI Research Articles

Genetic polymorphisms to identify patients with an optimal response to tildrakizumab in psoriasis patients from real-life clinical practice.

Detecting the association of genetic variants to the response of biological therapy represents an important advance in developing a personalized therapy. The aim of this work was to study the association of polymorphisms with an optimal response to tildrakizumab in patients with psoriasis in a real-life clinical practice. Ninety patients with plaque psoriasis recruited from-Spanish hospitals receiving tildrakizumab for at least 24 weeks were genotyped for 180 polymorphisms. Optimal response to tildrakizumab was evaluated by absolute PASI ≤1 at 6 and 12 months. Polymorphisms corrected for weight and disease duration with an FDR <0.15 were included in a multiple regression model. Sixty three percent of patients achieved an absolute PASI ≤1 at 6 months, while 71% did so after 12 months. Disease duration (>27 years) and weight (>76 kg) were associated with treatment response; after correcting by these factors, no association (FDR >0.15) was found for any polymorphism and response to tildrakizumab at 6 months. The analysis at 12 months identified the genotype GG for rs610604 (TNFAIP3), CT for rs9373839 (ATG5), and delCTGT/delCTGT for rs72167053 (PDE4D) as risk factors to not achieve an optimal response (PASI ≤1), while CT for rs708567 (IL17RC) was protective, independently of weight and disease duration (FDR <0.15). The final multivariable model at 12 months showed an AUC of 0.90 (95% CI 0.82 to -0.98). We identified a set of polymorphisms that could be helpful to identify psoriatic patients with an optimal response to tildrakizumab at 12 months in real-world practice conditions.

Ixekizumab trough concentrations in psoriasis: Paving the way towards personalised therapy: A cohort study

AbstractBackgroundBiologics for psoriasis demonstrate varying clinical outcome in real‐world practice, implying potential under‐ and overexposure.ObjectivesIn this prospective cohort study we aimed to develop and validate an in‐house sandwich‐type enzyme‐linked immunosorbent assay (ELISA) for ixekizumab (IXE), and to explore whether there is an exposure‐response relationship in standard maintenance dose for IXE, and whether patient factors influence IXE exposure and clinical outcome.MethodsThis was a prospective, multicentric, cohort study in psoriasis patients treated with IXE according to standard dosing regimen (BIOLOPTIM‐IXE). IXE trough concentrations (TCs) in sera collected at multiple timepoints were measured using an in‐house immunoassay.ResultsUsing MA‐IXE117E12 and MA‐IXE100F5‐biotin as the capture and detection antibodies, respectively, an ELISA was developed with an exposure‐response curve ranging from 10 to 0.16525 ng/mL. One hundred‐fifteen steady‐state serum samples from 48 patients (17 [35.4%] bio‐experienced; median body weight, 81.5 kg) were measured. Optimal responders (Psoriasis Area and Severity Index [PASI] ≤ 2) had significantly higher TCs than suboptimal responders (PASI &gt; 2) (median TCs, 4.4 and 3.0 μg/mL, respectively; p = 0.026). Median cohort IXE TC was 4.1 µg/mL [2.8−6.1]. An optimal steady‐state IXE TC of 3.4 µg/mL was identified for clinical outcome defined by absolute PASI. Median TCs and absolute PASI were significantly lower and worse, respectively, in patients ≥ 90 kg (p &lt; 0.001 and p = 0.013, respectively) and in bio‐experienced subjects (p &lt; 0.001 and p = 0.029, respectively).ConclusionsThis study identified an IXE exposure‐response relationship and an optimal effective steady‐state TC of 3.4 µg/mL in real‐world psoriasis patients, revealing the potential of therapeutic drug monitoring in optimising IXE use.

Exposure-response relationship of guselkumab and the potential of serum proteomics in identifying predictive biomarker candidates in psoriasis.

Response to biologics in psoriasis varies in real-world settings. Serum biomarkers could aid biologic selection and dose modifications to improve patient outcomes while encouraging cost-effective care. To explore the exposure-response relationship for guselkumab (GUS), to define a GUS concentration target for optimal response and to evaluate the potential of serum protein levels as predictive biomarker candidates. This is a prospective, multicentric, cohort study in psoriasis patients treated with GUS. Serum GUS trough concentrations (TCs) collected at multiple timepoints were measured using an in-house immunoassay. Next, proximity extension assay technology (Target 96 Inflammation Panel Olink®) was used to measure serum protein levels in a subcohort including 38 GUS patients (week 0 and week 4), six psoriasis patients naive for systemic treatment and four healthy controls. Seventy-five patients participated and 400 samples were collected. Guselkumab TCs and clinical response were correlated at week 4, week 12 and in steady-state (≥20 weeks). Optimal responders (Psoriasis Area and Severity Index [PASI] ≤ 2) had significantly higher TCs than suboptimal responders from week 4 onwards in treatment. An optimal steady-state TC of 1.6 μg/mL was defined. Although TC and absolute PASI were lower and worse, respectively, in patients weighing ≥90 kg, clinical outcomes referred to desirable to excellent PASI ranges. Therefore, we do not recommend systematically higher GUS doses in obese patients. We could not reveal early differentially expressed proteins to distinguish future optimal from suboptimal responders. We demonstrated an exposure-response relationship for GUS and an optimal steady-state TC of 1.6 μg/mL in real-world psoriasis patients. Hereby, we deliver more evidence that therapeutic drug monitoring poses a promising strategy in optimizing GUS treatment. No biomarker candidates were identified through serum proteomics. We propose protein screening should be repeated in larger cohorts to continue the quest for predictive biomarkers.

Management of moderate to severe psoriasis with brodalumab-Real-world evidence from the LIBERO study.

Brodalumab, a fully human monoclonal immunoglobulin IgG2 antibody that binds the human interleukin 17 receptor subunit A, is available for the treatment of moderate-to-severe plaque psoriasis in Europe since September 2017, but so far there are only a few studies on its use in real-world conditions. To assess the management of moderate-to-severe psoriasis with brodalumab 210 mg in daily practice after 12 and 52 weeks (W). In addition, patient profiles and treatment pathways are described. LIBERO is a prospective, multicenter, non-interventional study including adult patients with plaque psoriasis treated with brodalumab 210 mg. In total, 638 patients (65% male, mean age: 49.3 ± 14.4 years) from 148 sites in Germany were enrolled. The majority suffered from severe (51.1%) or very severe (13.1%) psoriasis according to physician global assessment (PGA0-5). When starting with brodalumab, 58.5% were biologic naïve and 41.5% were previously treated with another biologic, mainly adalimumab (18.5%) and secukinumab (17.9%). About 74.0% of patients met the primary endpoint of an absolute PASI ≤3 at ~W12 (n = 618, LOCF). The mean PASI was reduced significantly as of ~W2 from 17.2 (±11.7) to 9.7 (±8.8) and improved further to 3.3 (±6.3) at ~W12 (p < 0.001). At ~W52 85.5% of patients reached a PGA0/1-response (primary endpoint) and 54.1% patients were assessed as completely clear (PGA0) (both n = 399, as observed). Effectiveness of brodalumab was confirmed in relevant subgroup analysis by previous treatment regimen. Most frequently reported adverse events were nasopharyngitis (4.6%), psoriasis (4.6%) and arthralgia (4.1%), new safety signals were not detected. This representative, non-interventional study confirms the short- and long-term effectiveness and safety profile of brodalumab in the management of psoriasis in daily practice as well as in relevant treatment pathways.

Impact of Oral, Selective, Allosteric Tyrosine Kinase 2 Inhibitor, Deucravacitinib, on Psoriasis in Patients with Active Psoriatic Arthritis: Results from a Phase 2 Trial

Introduction: Deucravacitinib (DEUC), an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in the US, EU, and other countries for treatment of adults with moderate-to-severe plaque psoriasis (PsO) who are candidates for systemic therapy. DEUC was superior to apremilast and placebo (PBO) in two phase 3 trials in patients with moderate to severe PsO. DEUC was efficacious on multiple measures of arthritis severity vs PBO in a phase 2 trial in patients with active psoriatic arthritis (PsA) who had ≥1 PsO lesion (≥2 cm). In patients with body surface area (BSA) involvement ≥3% at baseline (80% of patients in this trial), a greater proportion achieved PASI 75 with DEUC (6 mg QD: 42.4%, P=0.01; 12 mg QD: 59.6%, P&lt;0.0001) vs PBO (20.4%) at Week 16. This analysis evaluated the impact of DEUC on PsO in patients with PsA in the phase 2 trial (NCT03881059).&#x0D; Methods: The phase 2 double-blind PsA trial randomized patients (N=203) 1:1:1 to PBO, DEUC 6 mg once daily (QD), or DEUC 12 mg QD. After Week 16, patients could enroll in an optional, double-blind period until Week 52. DEUC-treated patients achieving minimal disease activity at Week 16 continued DEUC to Week 52. PsO disease activity measurements were assessed.&#x0D; Results: Baseline PsO characteristics were comparable across groups. At Week 16, significant decreases from baseline in mean PASI were observed with DEUC vs PBO in patients with baseline BSA ≥3%-&lt;10% or PASI ≤12 even with very low baseline PASI scores, and also in those with baseline BSA ≥10% and PASI &gt;12. Significant decreases in PASI from baseline were observed with DEUC vs PBO in patients with background csDMARD use (DEUC 6 mg, -4.0 and 12 mg, -4.9 vs PBO, -2.3; both P&lt;0.05) and those without csDMARD use (-3.7 and -4.0 vs -2.5, respectively; both P&lt;0.001). At Week 16, greater proportions of DEUC vs PBO patients achieved PASI ≤1 with baseline BSA ≥3% (DEUC 6 mg: 32.2%; DEUC 12 mg: 44.2%; PBO: 18.5%) and in patients with baseline BSA ≥10% and PASI &gt;12 (23.1%; 28.6%; 0.0%). In patients with baseline BSA ≥3%, decreases in mean PASI at Week 16 were maintained through Week 52 in patients continuing DEUC 6 mg (absolute PASI score, Week 16: 2.39, Week 52: 1.22) and 12 mg (Week 16: 0.64, Week 52: 0.24).&#x0D; Conclusion: DEUC significantly improved PsO in patients with PsA, regardless of baseline PsO severity and background csDMARD use. Improvement was comparable to that observed in the phase 3 POETYK PSO-1 trial.&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D;

Effectiveness and safety of deucravacitinib treatment for moderate-to-severe psoriasis in real-world clinical practice in Japan

Background Deucravacitinib is a selective oral tyrosine kinase 2 (TYK2) inhibitor recently approved for psoriasis. Objectives We aimed to evaluate the real-world effectiveness and safety of deucravacitinib for psoriasis. Methods We analyzed 33 Japanese patients with psoriasis (23 with plaque psoriasis, eight with psoriatic arthritis, and two with erythrodermic psoriasis) from January 2023 to October 2023. All patients received deucravacitinib 6 mg daily until week 16. Results At week 8, 12, or 16, the achievement rate of PASI 75 was 60.9%, 73.9%, or 78.3%, that of PASI 90 was 13.0%, 39.1%, or 52.2%, that of PASI 100 was 0%, 8.7%, or 13.0%, that of absolute PASI ≤2 was 34.8%, 65.2%, or 78.3%, respectively. The achievement rate of dermatology life quality index 0/1 at week 16 was 42.9%. Fourteen patients (42%) complained pruritus. Peak pruritus-numerical rating scale in patients with pruritus decreased by median [interquartile] 71.4 [50–80] % of baseline at week 2. Adverse events occurred in 18.2% of patients, which were mild and manageable. Conclusions Deucravacitinib for patients with psoriasis was well-tolerated and gave favorable therapeutic effects in the real-world practice. Deucravacitinib treatment rapidly reduced pruritus.

Drug survival, effectiveness, and safety of brodalumab for moderate-to-severe psoriasis up to 3 years.

Brodalumab is a monoclonal antibody and IL-17 RA inhibitor that is approved for the treatment of moderate-to-severe psoriasis. The present study aims to estimate the drug survival (DS), effectiveness, and safety of brodalumab over a period of 156 weeks. The primary objectives were: (i) to determine the treatment response rate at Weeks 16, 28, 52, 78, 104, and 156 as defined by PASI100, PASI90, and an absolute PASI ≤ 3 and (ii) long-term DS. Secondary objectives included the evaluation of possible predictive factors associated with the achievement of response outcomes, and possible predictive factors associated with lower DS. The treatment response was rapid, with 80.3% of patients achieving PASI ≤ 3, 66% PASI90, and 54.3% the complete clearance of disease at Week 16. The response improved at Week 28, when a plateau was achieved with mild loss of response at later time points, in particular for PASI100 and PASI90 in 55.2 and 65.5% of patients, respectively, at Week 156. After 156 weeks of treatment, 66.22% of patients were still on therapy, and the previous use of IL-17 inhibitors appeared to be associated with an increased risk of treatment discontinuation (HR: 2.51, CI: 1.06-5.98, P = 0.037), and achievement of PASI ≤ 3 until Week 16 with less risk (HR: 0.27 CI: 0.14-0.51, P < 0.001). Bio-naïve status was favorably associated with treatment response, while high BMI negatively affected the achievement of outcomes. Our study confirms the good effectiveness and favorable safety profile of brodalumab in a real-world setting for up to 3 years of treatment.

Reactivation Risk of Latent Tuberculosis or Inactive Hepatitis B Virus Infection and Effectiveness of Ustekinumab in Chinese Plaque Psoriasis Patients: A 28-Week Retrospective, Observational Study.

This study observed the effectiveness of ustekinumab and reactivation risk of concurrent latent tuberculosis infection (LTBI) and inactive hepatitis B virus (HBV) infection in Chinese mainland psoriasis patients on ustekinumab treatment. This retrospective, multicenter, observational study was conducted in three centers in China. Adult patients with moderate to severe plaque psoriasis were treated with ustekinumab for 28 weeks. The effectiveness endpoint included 75% and 90% improvement in Psoriasis Area Severity Index (PASI75/90) response rate, percentage of PASI improvement, change of absolute PASI score and body surface area involvement (BSA) score, absolute PASI ≤1/3 and Physicians' Global Assessment (PGA)=0/1, as well as Dermatology life quality index (DLQI)=0/1 response rate at week 4, 16 and 28. Screening of tuberculosis and hepatitis were performed at baseline and week 28. A total of 82 patients were enrolled between March 2021 and May 2023 and the number of patients combined with LTBI and inactive HBV infection was 20 and 21 respectively. The PASI75 and PASI90 response rate at week 28 was 95.1% and 81.7% respectively. The mean PASI score decreased from 14.93 ± 12.07 at baseline to 0.78 ± 1.86 at week 28, and the mean BSA score decreased from 21% ± 18% at baseline to 1% ± 2% at week 28 (both P<0.001 compared with baseline). DLQI 0/1 response rate at week 28 was 73.2%. No reactivation of LTBI and inactive HBV infection and also no new-onset tuberculosis and hepatitis B occurred in patients without LTBI and inactive HBV infection at baseline. Ustekinumab demonstrated great effectiveness in Chinese plaque psoriasis patients and good safety in psoriasis concurrent with LTBI and inactive HBV infection under the real-world setting.

Pharmacogenetic biomarkers for secukinumab response in psoriasis patients in real-life clinical practice.

Prediction of the response to a biological treatment in psoriasis patients would allow efficient treatment allocation. To identify polymorphisms associated with secukinumab response in psoriasis patients in a daily practice setting. We studied 180 SNPs in patients with moderate-to-severe plaque psoriasis recruited from 15 Spanish hospitals. Treatment effectiveness was evaluated by absolute PASI ≤3 and ≤1 at 6 and 12 months. Individuals were genotyped using a custom Taqman array. Multiple logistic regression models were generated. Sensitivity, specificity and area under the curve (AUC) were analysed. A total of 173 patients were studied at 6 months, (67% achieved absolute PASI ≤ 3 and 65% PASI ≤ 1) and 162 at 12 months (75% achieved absolute PASI ≤ 3 and 64% PASI ≤ 1). Multivariable analysis showed the association of different sets of SNPs with the response to secukinumab. The model of absolute PASI≤3 at 6 months showed best values of sensitivity and specificity. Four SNPs were associated with the capability of achieving absolute PASI ≤ 3 at 6 months. rs1801274 (FCGR2A), rs2431697 (miR-146a) and rs10484554 (HLCw6) were identified as risk factors for failure to achieve absolute PASI≤3, while rs1051738 (PDE4A) was protective. AUC including these genotypes, weight of patients and history of biological therapy was 0.88 (95% CI 0.83-0.94), with a sensitivity of 48.6% and specificity of 95.7% to discriminate between both phenotypes. We have identified a series of polymorphisms associated with the response to secukinumab capable of predicting the potential response/non-response to this drug in patients with plaque psoriasis.

Bio‐experienced psoriasis patients treated with anti‐interleukin monoclonal antibodies are less likely to achieve PASI 90, PASI 100, PASI ≤ 1 and ≤3: Results from a cohort of 305 patients

AbstractBackgroundMonoclonal antibodies (mAbs) directed against tumour necrosis factor alpha (TNF‐α) and interleukin (IL)‐17 and ‐23 represent the ultimate therapeutic strategy in treating psoriasis patients, but scientific literature still does not provide conclusive results regarding the possible influence of previous biological therapies on real‐life therapeutic response.ObjectivesThe objective of our work was to investigate any putative difference in the achievement and maintenance of PASI 75, 90 and 100, as well as the probability to achieve absolute PASI ≤ 1 and ≤3, between 305 bio‐naïve and bio‐experienced patients treated with anti‐IL mAbs.MethodsA comparison between previous biologic and clinical factors, including relative and absolute PASI, was carried out through chi square test. Survival curves for the achievement of PASI 75, 90 and 100 and their differences were evaluated, performing a multivariate analysis (confidence interval 95%; p &lt; 0.0.5).ResultsPrevious biologic therapy resulted associated with a lower rate of PASI 75 (hazard ratio [HR]: 1339; p = 0.034), 90 (HR: 1365; p = 0.0031) and 100 achievement (HR 1596; p = 0,007). The survival curves showed how bio‐experienced patients were less likely to reach and maintain PASI 90 (naïve vs. anti‐IL: p = 0.001; naïve vs. anti‐TNF + anti‐IL: p &lt; 0.001) and PASI 100 (naïve vs. anti‐TNF‐α: p = 0.014; naïve vs. anti‐IL: p &lt; 0.001; naïve vs. anti‐TNF‐α + anti‐IL: p &lt; 0.001). Moreover, bio‐naïve patients showed a greater probability to achieve both absolute PASI ≤ 3 and ≤1 (p &lt; 0.001).ConclusionsOur results represent a real‐life analysis on the impact of previous biologic therapy in the clinical efficacy of anti‐IL. Even if further studies with bigger samples are needed to extrapolate absolute considerations, we provided the first evidence on the burden of the bio‐naïve condition for a greater achievement of both PASI 90, 100 and the probability to achieve PASI ≤ 1 and ≤3.

39861 Deucravacitinib, a Selective, Allosteric Tyrosine Kinase 2 Inhibitor, in Japanese Patients With Psoriasis: Absolute PASI Outcomes in a Phase 3 Trial

39861 Deucravacitinib, a Selective, Allosteric Tyrosine Kinase 2 Inhibitor, in Japanese Patients With Psoriasis: Absolute PASI Outcomes in a Phase 3 Trial

Ixekizumab is effective in the long-term management in moderate-to-severe plaque psoriasis: results from an Italian retrospective cohort study (the LOTIXE study)

PurposeIxekizumab is a high-affinity monoclonal antibody that selectively targets interleukin (IL)-17A approved for the treatment of moderate-to-severe plaque psoriasis. The objective of this study was to describe the real-world long-term effectiveness of ixekizumab in patients with plaque psoriasis in Italy.Materials and MethodsA retrospective study was conducted in patients affected by moderate-to-severe plaque psoriasis who were continuously treated with ixekizumab for at least 12 months. Patient data was obtained at 4-weeks, 12-weeks and 6-, 12-, 18- and 24-months after baseline (June 2017 and September 2019) from 10 sites. Results were analyzed by complete case approach, with sensitivity analysis performed to evaluate the impact of missing data.ResultsA total of 198 patients were enrolled in the study. At Month 24, 94.3% of patients achieved PASI75 response, while 85.1 and 71.8% achieved PASI90 and PASI100, respectively; and 91.1% of the patients achieved absolute PASI score ≤2. Patients experienced psoriasis improvement at 4 weeks after starting treatment, and improvement was maintained with continued ixekizumab use. The quality of life of patients also improved significantly starting at Week 12, with sustained effect in the long term.ConclusionThis 24-month observational cohort study confirmed that ixekizumab is effective in the long-term management of patients with moderate-to-severe plaque psoriasis.

Effectiveness and safety of brodalumab in the treatment of plaque, scalp and palmoplantar psoriasis: A multicentre retrospective study in a Spanish population.

The data in clinical practice regarding the effectiveness and safety of brodalumab in psoriasis are scarce, especially at scalp and palmoplantar locations. The main objective was the percentage of patients achieving absolute PASI ≤3/ ≤1/ =0 for plaque psoriasis and the percentage of patients achieving an IGA 0-1/IGA 0 for the special locations at Week 52 of treatment. Observational retrospective multicentre study in 28 Spanish Hospitals that included adult patients with plaque psoriasis treated with brodalumab, from September 2018 until March 2021. A total of 200 patients were included. The mean baseline PASI was 10.97 (±6.28) with a mean basal scalp (n = 58) and palmoplantar (n = 40) IGA of 2.10 (±0.97) and 2.15 (±1.26), respectively. At Week 52, 93.98%/75.90%/68.67% of patients reached an absolute PASI ≤3/ ≤1/ =0 in plaque psoriasis (n = 83), with a percentage of patients achieving scalp (n = 27) and palmoplantar (n = 19) IGA 0-1/IGA 0 of 96.3%/88.9% and 100%/88.9%, respectively. Fifteen per cent of patients reported any adverse events with candidiasis being the most reported (6%), but only 6% of the adverse events required the withdrawal. Brodalumab demonstrated high PASI and IGA responses and was well tolerated in clinical practice in plaque, scalp and palmoplantar psoriasis.

Biological therapy optimization in patients with psoriasis by reducing the dose or increasing the time interval, in a specialized centre in Colombia

IntroductionPsoriasis is treated with biological therapy, which has led to low disease activity or even clinical clearance. The optimization (dose-tapping) process seeks to reduce biological therapy while maintaining the risk–benefit ratio. ObjectivesTo determine relapse rate in psoriasis optimization strategy (dose tapering) patients. Material and methodsCohort study (October 2015 to February 2021) of patients with psoriasis in a specialized multicentre health institution in Colombia. Selection criteria included being at least 18 years old with biological therapy and having a sustained response (DLQI=0–5; absolute PASI <3 or BSA <1) for at least 12 months. The optimization strategy was dose reduction or interval application increase. PASI >10 was defined as relapse. Rates were estimated by medication using Kaplan–Meier. ResultsOf the 467 patients with psoriasis in the cohort, 467 received biologic therapy. 12.2% (n=57) of those who met the inclusion criteria were men, with a median age of 57 years (IQR: 44–66), disease evolution time of 15 years (IQR: 5–30), and time in optimization of 8 months (IQR: 1.54–13.2). Because of the increased application interval, the optimization strategy was 85.8%; 24.5% (n=14) received ustekinumab, 35% (n=20) received adalimumab, 15.8% (n=9) received secukinumab, 14% (n=8) received ixekizumab, 5.2% (n=3) received etanercept, and 5.2% (n=3) received guselkumab. A total of 14% (8 patients) relapsed, the relapse rate was 7.4 cases per 100 person-years (95% CI: 3.4–14). ConclusionsEighty-six percent of patients in the optimization strategy remain relapse-free after 8 months. The optimization strategy was effective, with a low relapse rate.

P89 Real-world effectiveness of guselkumab in patients with psoriasis with and without concomitant psoriatic arthritis: retrospective data from the British Association of Dermatologists Biologics and Immunomodulators Register

Abstract Guselkumab is a monoclonal antibody that inhibits interleukin (IL)-23 signalling by binding to its p19 subunit and is approved to treat adults with moderate-to-severe plaque psoriasis and active psoriatic arthritis (PsA). BADBIR collects UK and Eire real-world observational data and includes patients receiving biologic treatments for psoriasis, with PsA being one of the recorded comorbidities at the time of enrolment. Absolute PASI (aPASI) scores can be used to quantify treatment effectiveness in routine clinical practice, and it has been suggested that an aPASI ≤ 2 represents a relevant disease endpoint to inform treat-to-target psoriasis-management strategies. This retrospective analysis evaluated the 1-year, real-world effectiveness of guselkumab on aPASI response in patients with moderate-to-severe plaque psoriasis and the subset of patients with and without concomitant PsA within BADBIR. Analyses were carried out on data collected up to the September 2021 data cutoff. Data were obtained from patients who had initiated guselkumab treatment and had recorded measurements for aPASI at baseline and 12-month follow-up was analysed. Measures of treatment effect for psoriasis included mean aPASI response, as well as the proportion of patients achieving an aPASI score of ≤ 1, ≤ 2, ≤ 3 and ≤ 5. Incomplete data collection limited the sample size of patients available for analysis. Five patients receiving guselkumab were excluded due to stopping treatment prior to the 12-month cutoff. Stratified by diagnosis, 36 (30.8%) patients had a concomitant diagnosis of PsA vs. 81 (69.2%) who did not. In the overall guselkumab-treated cohort (n = 117), mean (SD) aPASI at baseline and the following 12 months of treatment were 11.85 (8.95) and 2.45 (4.24), respectively. Following 12 months of guselkumab treatment in the cohort of patients with psoriasis (without concomitant PsA), 48 (59.3%) achieved an aPASI ≤ 1, 56 (69.1%) an aPASI ≤ 2, 64 (79.0%) an aPASI ≤ 3 and 69 (85.2%) an aPASI ≤ 5. In the concomitant PsA group, 19 (52.8%) achieved an aPASI score of ≤ 1, 22 (61.1%) achieved an aPASI score of ≤ 2, 28 (77.8%) achieved an aPASI ≤ 3 and 30 (83.3%) achieved an aPASI ≤ 5. Over 50% of guselkumab patients achieved an aPASI ≤ 1 at 12 months, supporting the effectiveness of targeting IL-23 with guselkumab for the treatment of psoriasis over 1 year. These results demonstrate that comparable responses were achieved for the treatment of psoriasis with guselkumab in patients with and without a concomitant PsA diagnosis within a real-world cohort.

Biological therapy optimization in patients with psoriasis by reducing the dose or increasing the time interval, in a specialized centre in Colombia

IntroductionPsoriasis is treated with biological therapy, which has led to low disease activity or even clinical clearance. The optimization (dose-tapping) process seeks to reduce biological therapy while maintaining the risk–benefit ratio. ObjectivesTo determine relapse rate in psoriasis optimization strategy (dose tapering) patients. Material and methodsCohort study (October 2015 to February 2021) of patients with psoriasis in a specialized multicentre health institution in Colombia. Selection criteria included being at least 18 years old with biological therapy and having a sustained response (DLQI=0–5; absolute PASI <3 or BSA <1) for at least 12 months. The optimization strategy was dose reduction or interval application increase. PASI >10 was defined as relapse. Rates were estimated by medication using Kaplan–Meier. ResultsOf the 467 patients with psoriasis in the cohort, 467 received biologic therapy. 12.2% (n=57) of those who met the inclusion criteria were men, with a median age of 57 years (IQR: 44–66), disease evolution time of 15 years (IQR: 5–30), and time in optimization of 8 months (IQR: 1.54–13.2). Because of the increased application interval, the optimization strategy was 85.8%; 24.5% (n=14) received ustekinumab, 35% (n=20) received adalimumab, 15.8% (n=9) received secukinumab, 14% (n=8) received ixekizumab, 5.2% (n=3) received etanercept, and 5.2% (n=3) received guselkumab. A total of 14% (8 patients) relapsed, the relapse rate was 7.4 cases per 100 person-years (95% CI: 3.4–14). ConclusionsEighty-six percent of patients in the optimization strategy remain relapse-free after 8 months. The optimization strategy was effective, with a low relapse rate.

Bimekizumab maintenance of response through 3 years in patients with moderate-to-severe plaque psoriasis: results from the BE BRIGHT open-label extension trial

Given the chronic nature of psoriasis and the loss of response that can be observed with therapies over time, it is important to understand the long-term efficacy of new treatments. To evaluate maintenance of Week 16 responses with bimekizumab (BKZ) treatment through Year 3, in patients with moderate-to-severe plaque psoriasis. Data were pooled from BKZ-treated patients in the 52-week (BE VIVID) and 56-week (BE READY and BE SURE) phase III studies, and their ongoing open-label extension (OLE), BE BRIGHT. Efficacy outcomes are reported through 3 years of BKZ treatment in patients with an efficacy response at Week 16. Missing data were imputed primarily using modified nonresponder imputation (mNRI), with nonresponder imputation and observed case data also reported. A total of 989 patients were randomized to BKZ at baseline in BE VIVID, BE READY and BE SURE. At Week 16, 693 patients achieved ≥ 90% reduction from baseline in Psoriasis Area and Severity Index (PASI 90), 503 achieved 100% reduction from baseline in PASI (PASI 100), 694 achieved absolute PASI ≤ 2 and 597 achieved body surface area (BSA) ≤ 1%, and continued into the OLE. Of these, 93.0% maintained PASI 90, 80.8% maintained PASI 100, 94.0% maintained PASI ≤ 2 and 90.3% maintained BSA ≤ 1% responses through to 3 years of BKZ treatment (mNRI). Among Week 16 PASI 90 responders, 96.8% and 72.5% also achieved Investigator's Global Assessment 0/1 and PASI 100 at Week 16, respectively, and 92.2% and 73.4% achieved these responses at Year 3 (mNRI). Among Week 16 PASI 100 responders, 76.3% also achieved Dermatology Life Quality Index (DLQI) 0/1 at Week 16, and DLQI 0/1 response increased with continuous BKZ treatment to 89.0% at Year 3 (mNRI). High levels of clinical response were maintained through to 3 years of BKZ treatment in the vast majority of Week 16 responders. Long-term treatment with BKZ was efficacious, with important benefits for health-related quality of life, in patients with moderate-to-severe plaque psoriasis.

Brodalumab in plaque psoriasis: Real-world data on effectiveness, safety and clinical predictive factors of initial response and drug survival over a period of 104 weeks.

Brodalumab, a fully human IgG2k antibody blocking the receptor of IL17, is characterized by a rapid onset of action with high skin clearance rates in clinical trials. Since setting PASI90/100 or absolute PASI ≤ 3 as treatment goals have become attainable, evaluating the effectiveness and safety profile of biologic agents, such as brodalumab, in a real-world setting is essential. The aim of this study was to evaluate the effectiveness and safety profile of brodalumab over a period of 104 weeks in everyday practice. Clinical predictive factors of initial (week 12/16) response to treatment and long-term drug survival were also investigated. In this monocentric, retrospective study, PASI90/100 and absolute PASI ≤ 1/3 were assessed in 91 patients with moderate-to-severe skin psoriasis under brodalumab at weeks 12/16, 24, 52 and 104 of treatment. At week 12/16, patients with an absolute PASI ≤ 3 were defined as 'initial responders' and ≤1 as 'super-responders'. Clinical parameters, such as age, gender, BMI, comorbidities and previous systemic treatment, were assessed in order to predict 'super-responders'. Drug survival and its prognostic factors were also evaluated. PASI90/100 has reached 81.1/66.0% in week 12/16. This response rate increased at week 104, where 87.1/80.7% had PASI90/100 and 84.9% had absolute PASI ≤ 1. The presence of >3 comorbidities, prior treatment with >2 systemic agents and obesity tended to be negative predictive factors of 'super-response'. Previous exposure to IL17 inhibitors had no impact on both PASI < 1 and PASI < 3 initial response. One- and two-year drug survival probability was 87.6% and 77.32%, respectively. 'Initial responders' and anti-IL17 drug-naïve patients had better drug survival. Drug discontinuation occurred in 24.2%, mostly due to secondary failure, and arthralgia was the most common adverse event that led to discontinuation. Our study confirms the high effectiveness and good safety profile of brodalumab in the real-world setting.

Is it possible to optimize biologic therapy in patients with psoriasis?

Introduction/ObjectiveThe purpose of this study was to evaluate patients in clinical remission of psoriasis for at least for one year, who maintained therapeutic goals after initiating optimization of biologic therapy. Materials and methodsA descriptive, observational study was conducted on patients with a diagnosis of moderate–severe psoriasis in treatment with biologic therapy who were started on optimization of biologic therapy. ResultsA total of 29 patients started therapeutic optimization, of these, 27 patients were in the target range with absolute PASI less than 3. Only one patient failed therapeutic optimization with final PASI 3.6 and there was a case of a patient who lost continuity of management due to an accident and had a final PASI 3.8. Most of the patients were male, with an average age of 53 years, married, employed, residing in urban areas, with psoriasis of more than ten years of evolution, without associated morbidities, and without previous biologic treatment, the most frequently used being etanercept and adalimumab. ConclusionOptimizing biologic therapy in patients with moderate–severe psoriasis may be viable. We seek to share this experience to propose a protocol to reduce the possibility of adverse events due to the prolonged use of this type of therapy, preserving clinical response and reducing costs to the health system.

Long-Term Effectiveness and Drug Survival of Secukinumab in Vietnamese Patients with Psoriasis: Results from a Retrospective ENHANCE Study.

Psoriasis (PsO), an immune-mediated inflammatory skin disorder, has substantial negative impact on patients' quality of life. Secukinumab, an approved treatment for moderate-to-severe plaque PsO, has an established long-term efficacy and safety profile. This study aims to provide real-world evidence of long-term effectiveness and retention rate of secukinumab in Vietnamese patients with PsO. This retrospective, observational study collected medical records of adult patients with moderate-to-severe PsO receiving secukinumab treatment from Ho Chi Minh City Hospital of Dermato-Venereology. The primary objective was to evaluate secukinumab effectiveness in PsO as measured by 75% improvement in psoriasis area and severity index (PASI 75) at month 12. Secondary objectives were PASI 90/100, absolute PASI ≤ 3 and ≤ 5, Dermatology Life Quality Index (DLQI), and retention rate over 48months. In total, 232 patients with moderate-to-severe PsO met inclusion criteria; 68.1% were male, with median age and age of onset of 39 and 27.5years, respectively. Median time from onset of PsO to secukinumab treatment was 120months, 95.3% were prior biologics/disease-modifying antirheumatic drugs naive and 41.4% received concomitant therapies for PsO; 82.3% had national insurance coverage. At month 12, 93.9% of patients achieved PASI 75 (primary endpoint); 80.2/56.9% achieved PASI 90/100; 91.4 and 84.8% patients achieved absolute PASI ≤ 5 and ≤ 3, respectively. The response was sustained over 48months, with 91.9%/78.0%/52.0% of patients achieving PASI 75/90/100, 89.5% and 82.1% patients achieving absolute PASI ≤ 5 and ≤ 3, respectively. At month 12, 61.4% of patients achieved DLQI 0/1 which was sustained up to month 48 (69.2%). Secukinumab adherence rate of 84.9% at month 12 dropped to 34.2% at month 48. Patients receiving concomitant therapy and national insurance showed higher adherence rate. Secukinumab demonstrated long-term effectiveness in real-world Vietnamese patients with moderate-to-severe PsO, with treatment adherence being higher in patients having concomitant therapies and national insurance.