Psoriasis Area And Severity Index Improvement Research Articles

Complete Skin Clearance is Associated with the Greatest Benefits to Health-Related Quality of Life and Perceived Symptoms for Patients with Psoriasis.

With newer biologics, the achievement of complete skin clearance has become an attainable treatment goal for patients with plaque psoriasis. We evaluate how improvements in Psoriasis Area and Severity Index (PASI) responses, particularly at incremental improvements approaching complete skin clearance (PASI 100), translate into improvements in health-related quality of life (HRQoL) and patient-perceived symptoms. Data from the BE RADIANT phase 3b trial (NCT03536884) and its open-label extension (OLE), pooled across all study visits and treatments over 16weeks (randomised patients) and 2years (patients entering the OLE), were analysed using mixed-effects logistic regression models. Proportions of patients achieving a Dermatology Life Quality Index (DLQI) of 0/1, DLQI item scores of 0, and Psoriasis Symptoms and Impacts Measure (P-SIM) item scores of 0 for itching, scaling, and skin pain at specific PASI improvement levels were estimated. Seven hundred andforty-three patients were randomised to treatment; 654 entered the OLE. Using 16-week pooled data, there were incremental improvements in the proportions of patients estimated by our model to achieve DLQI 0/1 with PASI 100 compared with 95% (PASI = 95%) and 90% (PASI = 90%) improvements in PASI (93.0%, 89.3%, and 83.8% achieving DLQI 0/1, respectively). Estimated proportions achieving DLQI item scores of 0 had the greatest increases at higher PASI improvement levels for Items 1 (itchy, sore, painful, or stinging skin), 2 (embarrassment), and 4 (choice of clothing). Estimated proportions of patients achieving P-SIM = 0 were also higher for PASI 100 (itching: 61.7%; scaling: 82.2%; skin pain: 96.9%) than for PASI = 95% (50.8%; 72.3%; 95.7%) and PASI = 90% (39.8%; 59.5%; 94.0%). Similar benefits of incremental PASI improvements were estimated using 2-year data. Complete skin clearance translated into the greatest benefits to HRQoL and patient-perceived symptoms, over and above skin clearance between 90% and 100%, highlighting the importance of targeting PASI 100 as a treatment outcome for patients with psoriasis. NCT03536884.

Direct and Indirect Effect of Guselkumab on Anxiety, Depression, and Quality of Life in Patients with Moderate-to-Severe Plaque Psoriasis: A Mediation Analysis.

Treating plaque psoriasis (PsO) with guselkumab (GUS) promotes skin clearance and is associated with improvements in health-related quality of life (HRQoL), anxiety, and depression. It is unclear whether improvements in patient-reported outcomes are due to resolution of skin symptoms or the direct result of GUS treatment. Two phase3, placebo- and active-comparator-controlled studies randomized patients with moderate-to-severe PsO to GUS, placebo (crossing over to GUS at week16), or adalimumab. Posthoc mediation analyses examined direct and indirect effects of GUS, versus adalimumab, on Dermatology Life Quality Index (DLQI) or Hospital Anxiety and Depression Scale (HADS) after adjusting for indirect effects mediated by skin clearance, evaluated via Psoriasis Area and Severity Index (PASI), to determine the direct effect of GUS on dermatology HRQoL, depression, and anxiety. Compared with adalimumab, the natural direct effect (NDE) of GUS on change in DLQI from baseline was - 2.04 (P < 0.001), using PASI improvement as a mediator, indicating 89.2% of the total treatment effect was due to direct effects of GUS; using PASI90 as a mediator, NDE of GUS was - 1.43 (P < 0.001), with 62.2% of the total treatment effect attributed to direct effects of GUS. Compared with adalimumab, 25.5% of change in HADS anxiety score was mediated through PASI improvement (NDE - 0.74; P = 0.002), indicating 74.5% of the total effect was independent of PASI improvement. Similarly, 24% of treatment effect was mediated through PASI90 (NDE - 0.76; P = 0.002). Comparable proportions of the total improvement in HADS depression scores were due to direct and indirect effects of GUS mediated through PASI improvement (direct, 50.2%; indirect, 49.8%) or PASI90 (direct, 59.5%; indirect, 40.5%). GUS-mediated improvements in anxiety, depression, and overall HRQoL are not solely mediated by resolution of PsO signs, suggesting GUS use has a potential direct effect on anxiety and depression.

Real-life Effectiveness and Safety of Guselkumab in Moderate-to-Severe Plaque Psoriasis: A 104-Week Retrospective Single-Center Study.

Guselkumab is a monoclonal antibody approved for treating moderate-to-severe plaque psoriasis. Long-term data on the effectiveness and safety of guselkumab in a real-world setting are still limited. We conducted a 104-week monocentric retrospective study on 102 psoriasis patients, all treated with guselkumab for at least 16 weeks. At each visit, we used the Psoriasis Area and Severity Index (PASI): effectiveness endpoints were the percentages of patients achieving 75%/90%/100% (PASI 75/90/100) improvement in PASI compared with baseline. The Kaplan-Meier curve was used to assess the drug survival. At week 16, PASI 90 and PASI 100 were achieved by 49.02% and 32.35% of patients. At week 52, PASI 90 and PASI 100 were achieved by 71.58% and 55.79% of patients. After 2 years, PASI 90 and PASI 100 were achieved by 79.63% and 61.11% of patients. Obese and overweight patients had comparable PASI 90 and PASI 100 responses throughout the study. At week 104, no significant differences were observed between bio-na&iuml;ve and bio-experienced patients regarding all effectiveness endpoints. No significant safety signals were reported in our study. After 24 months, 91.57% of our cohort was still on treatment with guselkumab. Our findings, although limited by the study's retrospective nature, confirm that guselkumab is a safe and effective therapeutic option for a "real-life" cohort of patients with psoriasis. J Drugs Dermatol. 2024;23(8):632-639.&nbsp; doi:10.36849/JDD.7486R1.

Impact of residual skin lesions and previous biologic treatment failure on patient-reported outcomes in patients with psoriasis receiving biologic treatment.

Recent advances in biologic treatments have made clear skin a realistic treatment goal for psoriasis. However, clear skin may not uniformly translate to an absence of impact on patients' quality of life. This retrospective observational study aimed to elucidate the factors influencing patient-reported outcomes in patients with psoriasis who have demonstrated successful clinician-reported outcomes on using biologics. A total of 96 patients who have achieved a ≥75% improvement in Psoriasis Area and Severity Index (PASI) scores with ≥6 months of biologic treatment were included. Their median PASI score was 0.4, with 37.5% having achieved PASI 100 (clear skin). Furthermore, 47.9% reported no impact of psoriasis on their quality of life (Dermatology Life Quality Index [DLQI] score 0 or 1), while 52.1% reported a negative impact (DLQI score ≥2). Notably, 28.1% of the participants had a history of biologic treatment failure, defined as the inability to achieve or sustain a 75% PASI improvement with the previously used biologic agent. Multivariable logistic regression analysis revealed a positive association between achieving PASI 100 and reporting no impact of psoriasis on quality of life (adjusted odds ratio [aOR] 3.88, 95% confidence interval [CI] 1.49-10.91, P = 0.007). Conversely, prior biologic treatment failure was negatively associated with reporting no impact of psoriasis on quality of life (aOR 0.13, 95% CI 0.02-0.65, P = 0.023). Furthermore, among patients with clear skin, those with experience of previous biologic treatment failure reported significantly lower quality of life than those without such experience (P = 0.033). In conclusion, minimal residual skin lesions and prior biologic treatment failure were associated with poorer patient-reported outcomes in patients with psoriasis. Opting for a biologic agent with the highest predicted efficacy, rather than pursuing a "step-up" approach with a higher possibility of treatment failure, may be a more suitable strategy in the biologic treatment of psoriasis.

Insulin resistance impairs biologic agent response in moderate-to-severe plaque psoriasis: insights from a prospective cohort study in China.

Psoriasis and insulin resistance (IR) are closely related, but it remains unclear whether IR affects the treatment of patients with psoriasis. To investigate whether IR impairs the treatment response to biologic agents in patients with moderate-to-severe plaque psoriasis. This project was based on a prospective cohort study design. Data were collected from the Shanghai Psoriasis Effectiveness Evaluation CoHort (SPEECH), which is a prospective cohort exploring treatment strategies for psoriasis in China. IR was assessed using triglyceride glucose-body mass index (TyG-BMI). Psoriasis severity was assessed using Psoriasis Area and Severity Index (PASI) and Physician Global Assessment (PGA). Multiple logistic regression was used to explore the differences between patients with high and low levels of IR. Subgroup and sensitivity analyses were performed to examine the robustness of the study results. A total of 290 patients were included in the analysis. Based on median TyG-BMI, the patients were divided into two groups: high and low IR. The high IR group exhibited a higher prevalence of diabetes, a higher BMI, and higher fasting blood glucose and triglyceride levels than the low IR group. Further analysis of treatment efficacy revealed that patients in the high IR group had lower PASI 75 [≥ 75% improvement in Psoriasis Area and Severity Index (PASI)], PASI 90 (≥ 90% improvement in PASI) and PGA 0/1 ('clear' or 'almost clear') response rates after 12 weeks of treatment. In the low IR group, 81.9% of patients achieved PASI 75, 58.3% achieved PASI 90 and 75.7% achieved PGA 0/1. However, the proportion of responses at each endpoint was significantly lower in the high IR group compared with the low IR group. The reduced PGA 0/1 response rate was more significant in the high IR group, indicated by lower odd ratios. Subsequent subgroup and sensitivity analyses produced consistent results. IR is associated with lower effectiveness of biologics in patients with psoriasis.

Roflumilast Cream 0.3% in Patients With Chronic Plaque Psoriasis: Individual Patient PASI and PASI-HD Responses: Pooled DERMIS-1 and DERMIS-2 Phase 3 Trials

Background: Roflumilast cream 0.3% is a highly potent phosphodiesterase 4 inhibitor approved as a nonsteroidal, once-daily treatment for patients with plaque psoriasis. Pooled efficacy and safety results from two Phase 3 clinical trials (DERMIS-1 and DERMIS-2) have been presented previously. The Psoriasis Area and Severity Index (PASI) is used to assess the severity of plaque psoriasis in clinical trials; however, PASI is not precise when the area of involvement is &lt;10% of a given anatomic region. A modified version of the PASI, the PASI-high discrimination (PASI-HD), allows more precise assessment of psoriasis in body regions where &lt;10% area is affected. We present individual patient responses using PASI and PASI-HD.&#x0D; Methods: Patients aged ≥2 years with at least mild plaque psoriasis involving 2-20% body surface area were randomized 2:1 to apply roflumilast cream 0.3% or vehicle cream once daily for 8 weeks. The primary efficacy endpoint was Investigator Global Assessment (IGA) Success (score of Clear or Almost Clear plus ≥2-grade improvement from baseline) at Week 8. PASI and PASI-HD were used to measure disease severity; individual patient PASI and PASI-HD responses were plotted graphically. Safety and tolerability were also evaluated and were reported previously.&#x0D; Results: Roflumilast- and vehicle-treated patients had similar baseline demographic and disease characteristics. At Week 8, statistically significantly more roflumilast- than vehicle-treated patients achieved IGA Success (39.9% vs. 6.5%; P&lt;0.0001). Statistically significant differences favoring roflumilast were observed at Week 8 for percentages of patients achieving a 50% reduction in PASI (72.1% vs. 25.5%; P&lt;0.0001), 75% reduction (40.3% vs. 6.5%, P&lt;0.0001), 90% reduction (19.7% vs 2.3%; P&lt;0.0001), and 100% reduction (12.3% vs 0.8%; P&lt;0.001). Likewise, statistically significant differences favoring roflumilast were observed at Week 8 for percentages of patients achieving 50% reduction in PASI-HD (79.4% vs. 33.1%; P&lt;0.0001), 75% reduction (59.9% vs. 17.9%, P&lt;0.0001), 90% reduction (39.9% vs 9.1%; P&lt;0.0001), and 100% reduction (12.3% vs 0.8%; P&lt;0.0001). Roflumilast cream demonstrated low rates of application-site adverse events (AEs), treatment-related AEs, and discontinuations due to AEs, comparable to vehicle. At the first application of roflumilast cream 0.3% (day 1), 96% of patients reported no or mild sensation, increasing to 99% of patients at Weeks 4 and 8.&#x0D; Conclusions: Roflumilast cream 0.3% provided greater improvement in IGA Success, PASI, and PASI-HD versus vehicle with favorable safety and tolerability in patients with psoriasis in two Phase 3 trials. PASI-HD provided higher discrimination of effects of treatment in areas with &lt;10% involvement than the traditional PASI.&#x0D; ClinicalTrials.gov Identifiers: DERMIS-1: NCT04211363; DERMIS-2: NCT04211389&#x0D; Financial Disclosures: Arcutis Biotherapeutics, Inc.

Pulse azathioprine and low-dose methotrexate vs. standard-dose methotrexate in treatment of patients with moderate-to-severe psoriasis: a randomized controlled trial.

Psoriasis is a common chronic, immune-mediated inflammatory skin disease. Despite the availability of several systemic therapeutic agents, treatment of psoriasis remains a challenge because of the associated adverse effects and/or the financial burden of these medications, given the chronicity of the disease. We aimed to compare the efficacy and safety of combined pulse azathioprine (AZA) and low-dose methotrexate (MTX) vs. a conventional dose of MTX in patients with chronic plaque psoriasis. In this randomized controlled trial, 67 patients with moderate-to-severe plaque psoriasis were randomized into two groups, receiving either combined pulse AZA (300 mg weekly dose) and low-dose MTX (10 mg weekly) or conventional-dose MTX (0.3 mg kg-1 per week) for 16 weeks. Patients were assessed for treatment response using the Psoriasis Area and Severity Index (PASI) score and for the development of any adverse effects at weeks 12 and 16, and for a further 3 months after stopping treatment. A statistically significantly higher proportion of the patients receiving combined pulse AZA and low-dose MTX achieved ≥ 90% improvement in PASI and 100% improvement (PASI 100) at week 12, and PASI 100 at week 16, compared with those receiving the conventional dose of MTX as monotherapy. No serious adverse events were reported during the entire study period in the two groups. Combination therapy using pulse AZA and low-dose MTX can be an efficacious treatment for moderate-to-severe plaque psoriasis, with a relatively good safety profile.

Bimekizumab: Short-Term Effectiveness and Safety in Real Clinical Practice in Andalucia, Spain.

Introduction: Psoriasis, a chronic inflammatory skin disease, affects 2-10% of the population globally. Bimekizumab (BMK), a monoclonal antibody targeting IL-17, is a dual inhibitor of IL17 A and F that has shown efficacy in treating moderate to severe plaque psoriasis. This real-world evidence (RWE) study aims to assess BMK's efficiency and safety in naïve and refractory patients. Material and methods: A retrospective analysis of a multicenter observational study included 22 patients treated with BMK from April 2023 to February 2023 in five Andalusian hospitals. Ethical approval was obtained, and patients provided informed consent. Assessment criteria encompassed Psoriasis Area and Severity Index (PASI), body surface area (BSA), VAS pruritus, Dermatology Life Quality Index (DLQI), and minimum disease activity (MDA) at 0, 4, 12, and 24 weeks. Results: Patients, predominantly with plaque psoriasis, exhibited significant improvements in PASI (baseline 15.7 to 0.4 at week 16), BSA (baseline 20.7 to 0.43 at week 16), DLQI (baseline 17.93 to 0.43 at week 16), and pruritus (baseline 7.12 to 0.4 at week 16). At week 16, 95.4% achieved MDA. No safety concerns or treatment discontinuations were reported. Discussion: This RWE study aligns with pivotal clinical trials, confirming BMK's efficacy and safety. Notably, BMK demonstrated rapid and sustained psoriasis clearance, even in challenging areas. The study's limitations include a small sample size, suggesting the need for further exploration of patient-reported outcomes. Conclusion: Bimekizumab exhibited optimal efficacy and safety profiles in treating moderate to severe plaque psoriasis in a real-world setting. Rapid response, sustained clearance, and favorable safety outcomes contribute to improved patient experiences. Future research could delve into patient-reported outcomes and expand sample sizes to enhance the understanding of BMK's real-world effectiveness.

Roflumilast Cream 0.3% in Patients with Chronic Plaque Psoriasis: Individual Patient Response from the Pooled DERMIS-1 and DERMIS-2 Phase 3 Trials

Roflumilast cream 0.3% in patients with chronic plaque psoriasis: individual patient response from the pooled DERMIS-1 and DERMIS-2 phase 3 trials&#x0D; &#x0D; James Del Rosso1 on behalf of the authors&#x0D; &#x0D; INTRODUCTION: Roflumilast cream 0.3% is a highly potent phosphodiesterase 4 inhibitor approved as a nonsteroidal, once-daily treatment for patients with plaque psoriasis. The efficacy and safety of the pooled results of two Phase 3 clinical trials (DERMIS-1 and DERMIS-2) in patients aged ≥2 years with plaque psoriasis have been previously presented. We present individual patient responses using the Psoriasis Area and Severity Index (PASI).&#x0D; METHODS: Patients aged ≥2 years with at least mild plaque psoriasis involving 2-20% of body surface area were randomized 2:1 to apply roflumilast cream 0.3% or vehicle cream once daily for 8 weeks. The primary efficacy endpoint was Investigator Global Assessment (IGA) Success (score of Clear or Almost Clear plus ≥2-grade improvement from baseline) at Week 8; IGA of Clear or Almost Clear was a secondary endpoint. PASI was used to measure disease severity; individual patient PASI responses were plotted graphically. Safety and tolerability were also evaluated and have been previously reported.&#x0D; RESULTS: Roflumilast- and vehicle-treated patients had similar baseline demographic and disease characteristics. At Week 8, statistically significantly more roflumilast- than vehicle-treated patients achieved IGA Success (39.9% vs. 6.5%; P&lt;0.0001) and IGA of Clear or Almost Clear (48.0% vs. 9.5%; nominal P&lt;0.0001). Statistically significant differences favoring roflumilast were observed at Week 8 for percentages of patients achieving a 50% reduction in PASI (72.1% vs. 25.5%; P&lt;0.0001), 75% reduction (40.3% vs. 6.5%, P&lt;0.0001), 90% reduction (19.7% vs 2.3%; P&lt;0.0001), and 100% reduction (12.3% vs 0.8%; P&lt;0.001). At the first post-treatment timepoint evaluated (Week 2), 85.7% of roflumilast-treated patients had a measurable improvement in PASI, increasing to 95.0% by the last timepoint (Week 8). Roflumilast cream demonstrated low rates of application-site adverse events (AEs), treatment-related AEs, and discontinuations due to AEs, comparable with vehicle. Approximately 96% of patients reported no or mild sensation after the first application of roflumilast cream 0.3%, improving to more than 99% of patients at Week 4 and Week 8, similar to vehicle.&#x0D; CONCLUSIONS: Roflumilast cream 0.3% provided greater improvement in IGA Success, IGA of Clear or Almost Clear, and PASI versus vehicle with favorable safety and tolerability in patients with psoriasis in two Phase 3 trials.&#x0D; Sponsored by Arcutis Biotherapeutics, Inc.&#x0D; ClinicalTrials.gov Identifiers: DERMIS-1: NCT04211363; DERMIS-2: NCT04211389

Outcomes for Psoriasis by Self-Identified Racial Groups in Ixekizumab Clinical Trials: A Pooled Analysis.

Biologics have shown promising outcomes in psoriasis clinical trials. However, there is a paucity of data exploring the potential differences in outcomes between self-identified racial groups. To evaluate treatment response to ixekizumab in patients with psoriasis across different self-identified racial subgroups. This study analyzed pooled data from 5 clinical studies (UNCOVER-1, UNCOVER-2, UNCOVER-3, IXORA-R, and IXORA-S) with patients of different self-identified racial subgroups, who were treated with an on-label dose of ixekizumab for psoriasis through 12 weeks. Treatment response to ixekizumab was assessed using the Psoriasis Area and Severity Index (PASI) and static Physician&rsquo;s Global Assessment response rates. Patient Global Assessment of Disease Severity, Itch Numeric Rating Scale, Skin Pain Visual Analog Scale, and Dermatology Life Quality Index were used to evaluate the patient-reported outcomes (PROs) and impact on quality of life (QoL). A total of 1825 ixekizumab-treated patients from 5 pooled studies were included. Consistent with the clinical outcomes from the overall population, all self-identified racial groups showed rapid improvement in PASI through Week 12, although the response was somewhat slower in American Indian/Alaska Native patients. Differences in PROs and QoL assessments were observed among racial groups, especially in patients who identified as Black/African American and American Indian/Alaska Native. Ixekizumab is effective through 12 weeks of treatment for psoriasis across different self-identified racial groups. Sample sizes for some racial groups were small (N&le;12), therefore, further research is required to understand potential differences in psoriasis treatment with ixekizumab between various racial groups.J Drugs Dermatol. 2024;23(2):17-22.&nbsp; doi:10.36849/JDD.7672.

Time to Onset of a Minimal Clinically Important Difference in DLQI with Guselkumab Treatment in VOYAGE 1

Introduction Psoriasis (PsO) is a chronic inflammatory disease of the skin. While skin clearance, as measured by the Psoriasis Area and Severity Index (PASI), is a clinical goal, PsO patients also suffer from reduced health-related quality of life (HRQoL). In the Phase 3 VOYAGE 1 trial, guselkumab (GUS) demonstrated improvements on patient reported outcomes compared with placebo (PBO) and adalimumab (ADA). Here we report an analysis of the estimated time to onset of the minimal clinically important difference (MCID) in HRQoL, as measured by the Dermatology Quality of Life Index (DLQI) and associated PASI response in GUS-treated patients from VOYAGE 1.&#x0D; Methods The VOYAGE 1 trial enrolled patients with moderate-to-severe PsO who were randomized to receive PBO, GUS, or ADA. The DLQI is a self-report measure for HRQoL ranging from 0 (no impact) to 30 (maximum impact) that assesses the effect of skin problems on 6 HRQoL domains. An accepted MCID in DLQI is 4, previously reported as the smallest difference in DLQI total score that patients’ rate as beneficial. DLQI score and PASI improvement (percent change from baseline) were analyzed at Weeks 0, 8, 16, and 24 for the subset of VOYAGE 1 patients with a baseline DLQI score &gt;4. Earliest time to onset of MCID in mean DLQI and corresponding mean PASI improvement were estimated using linear interpolation for the GUS group between Weeks 0 and 8.&#x0D; Results Among patients randomized to GUS, n=279 (85%) had DLQI &gt;4 at baseline. By first assessment at Week 8 (W8), we observed a reduction in the mean DLQI score from 15.6 (baseline) to 5.0 (W8) with median DLQI decreasing from 15.0 (baseline) to 3.0 (W8). The interpolated onset of MCID in DLQI occurred at 21.1 days (W3) following the initial GUS dose. In GUS-treated patients, the estimated mean PASI improvement corresponding to the onset of MCID in mean DLQI occurring at Week 3 was 29.2%.&#x0D; Conclusions These data indicate that the onset of clinically meaningful improvements in mean DLQI occur as early as after the first dose of GUS in patients with moderate-to-severe PsO.

The Effect of an Interdisciplinary Dermatological-Rheumatological Consultation on the Outcome of Patients with Psoriasis with Musculoskeletal Pain: A Prospective, Single-Center Cohort Study.

Psoriatic arthritis (PsA), a disease with complex inflammatory musculoskeletal manifestations, complicates psoriasis in up to 30% of patients. In this study, we aimed to determine the effect of an interdisciplinary dermatological-rheumatological consultation (IDRC) for patients with psoriasis with musculoskeletal symptoms. This prospective study enrolled 202 patients with psoriasis. Patients with musculoskeletal pain (MSP) (n = 115) participated in an IDRC 12weeks after enrollment. The outcome was evaluated after 24weeks. In 12/79 (15.2%) patients seen in the IDRC, the prior diagnosis was changed: eight with a first diagnosis of PsA, four with a diagnosis of PsA rescinded. Treatment was modified in 28% of patients. Significant improvements in Psoriasis Area and Severity Index (PASI) (from 5.3 to 2.0; p < 0.001) and Dermatology Life Quality Index (DLQI) (from 6.7 to 4.5; p = 0.009) were observed. By comparing changes in PASI and DLQI over the study period, an improvement in PASI of 0.7 ± 1.4 points (p = 0.64) and in DLQI of 2.9 ± 1.5 points (p = 0.051) could be attributed to participation in the IDRC. An IDRC of patients with psoriasis with MSP leads to a valid diagnosis of PsA and improvement in quality of life. Based on these results, an IDRC is a valuable and time efficient way for psoriasis patient with MSP to receive optimal care.

Acuerdo de riesgo compartido basado en resultados de salud para el tratamiento de psoriasis moderada-grave con certolizumab pegol

ObjectiveTo provide evidence of the effectiveness of certolizumab pegol (CZP) in real clinical practice in adult patients with moderate-to-severe plaque psoriasis (PsO) in the context of a risk-sharing agreement (RSA). MethodsRetrospective observational study based on variables collected in the RSA for treatment with CZP of adult patients with moderate-severe plaque PsO. Ten Spanish hospitals where the RSA was implemented participated. The percentage of patients who achieved the target clinical response of the RSA at the follow-up visit (week 16) was evaluated: absolute Psoriasis Area and Severity Index (PASI) value ≤3 for biologic naïve population, and ≤5 in case of previous failure to a single biologic drug. In addition, the improvement in the scores of other scales included in the study was analyzed: Body Surface Area (BSA), Dermatology Life Quality Index (DLQI), Physician's Global Assessment (PGA), and Nail Psoriasis Severity Index (NAPSI). A descriptive analysis was performed for the total population and by patient subgroups (naive vs. non-naive to biologic, male vs. female, and with vs. without discontinuation). ResultsSixty-six patients were included, 12 men and 54 women. 90.9% achieved the target clinical response, with a mean reduction of 8 (−78.4%) absolute PASI points. Improvement was observed in BSA, PGA, NAPSI and DLQI, with a reduction of 11.3 (−80.6%), 1.9 (−65.5%), 3.3 (−30.7%) and 9.0 (−66.4%) absolute value points, respectively. Despite not achieving the therapeutic target set in the RSA in six patients (9%) (the cost of the drug was assumed by the laboratory), only two (3%) discontinued treatment. ConclusionOur study shows that CZP is effective in real clinical practice in patients with moderate-severe plaque PsO, with an improvement in absolute PASI and DLQI, as well as other scales, both for the total population and in the subgroups analyzed. Nearly 91% of patients reached the therapeutic target fixed in the RSA. Implementing this type of agreement can provide a direct or indirect benefit for all the agents involved in the process, providing valuable information for decision-making.

Genetic Polymorphisms of rs9949644 in MAPK4 Are Associated with Clinical Response to Methotrexate in Patients with Psoriasis

Background: The study aimed to investigate the relationship of MAPK4 genetic variants with the efficacy of methotrexate (MTX) in psoriasis patients. Methods: Patients treated with MTX were classified as responders or nonresponders if the Psoriasis Area and Severity Index (PASI) at week 12 was reduced to greater than 75% or lower than 75%, respectively. The genotypes of 14 MAPK4 single-nucleotide polymorphisms in 310 patients were analyzed. The expression levels of MAPK4 protein were detected by Western blot. Results: Only rs9949644 polymorphisms were associated with the efficacy after adjusting for the confounding factors. Patients with the rs9949644 AG or GG genotype had a better clinical response compared to patients with the AA genotype. Rs9949644 polymorphisms were significantly associated with the PASI improvement rate. Besides, the protein level of MAPK4, positively associated with the psoriasis severity, was higher in patients. There were no significant differences of MAPK4 protein levels among the three groups. While after treatment, MAPK4 levels in the AG or GG group showed a significantly down-regulated trend. Conclusion: By demonstrating the significant association of MAPK4 with the efficacy of MTX, this study indicates that MAPK4 may be involved in the psoriasis progression and act as a predictor of therapeutic response.

Randomized, double-blind, multicenter study to evaluate efficacy, safety, tolerability, and immunogenicity between AVT04 and the reference product ustekinumab in patients with moderate-to-severe chronic plaque psoriasis

ABSTRACT Background This study compared efficacy, safety, tolerability, pharmacokinetics (PK), and immunogenicity between AVT04 and reference product (RP) ustekinumab (Stelara®) in patients with moderate-to-severe chronic plaque psoriasis (PsO). Patients and methods This multicenter, double-blind, 52-week study randomized patients in 1:2 ratio to AVT04 or RP. At week 16, responsive patients (≥50% improvement in psoriasis area and severity index (PASI)) previously on AVT04 continued on AVT04, while those on RP were re-randomized 1:1 to switch to AVT04 or stay on RP. The primary endpoint was a percent improvement in PASI from baseline to week 12. Therapeutic equivalence was demonstrated if the confidence interval (CI) for the adjusted difference in means was contained within the equivalence margins; ±10% (90%CI). Results Of the 581 patients initially randomized (AVT04:RP, 194:387), 575 completed week 16 and 544 completed end of study visit. The percent PASI improvement for AVT04 vs RP was 87.3% vs 86.8% (CI: −2.14%, 3.01%); study met its primary endpoint. Efficacy, safety and PK profiles were comparable across treatment arms throughout the entire study duration, and the incidence of antibodies to ustekinumab had no clinically meaningful impact. Conclusion This study demonstrates the therapeutic equivalence between AVT04 and RP in patients with moderate-to-severe chronic PsO, with similar safety and tolerability. Trial registration NCT04930042; EudraCT Number: 2020-004,493-22

Brodalumab for the treatment of plaque psoriasis in a real-life setting: a 3 years multicenter retrospective study-IL PSO (Italian landscape psoriasis).

Brodalumab is a monoclonal antibody that targets the subunit A of the interleukin-17A receptor (IL17RA), inhibiting the signaling of various isoforms of the IL-17 family. It has been approved for the treatment of moderate-to-severe plaque psoriasis after being evaluated in three Phase-3 trials. However, long-term data on brodalumab in a real-life setting are still limited. The aim of this study was to evaluate the long-term effectiveness and safety of brodalumab in psoriasis. We also assessed the drug survival of brodalumab in a 3 years timespan. We conducted a retrospective multicenter study on 606 patients followed up at 14 Italian dermatology units, all treated with brodalumab according to Italian guidelines. Patients' demographics and disease characteristics were retrieved from electronic databases. At baseline and weeks 12, 24, 52, 104 and 156, we evaluated the psoriasis area and severity index (PASI) score and investigated for adverse events. The proportions of patients reaching 75, 90 and 100% (PASI 75, PASI 90 and PASI 100, respectively) improvement in PASI, compared with baseline, were also recorded. At week 12, 63.53% of the patients reached PASI 90 and 49.17% PASI 100. After 3 years of treatment, 65.22% of patients maintained a complete skin clearance, and 91.30% had an absolute PASI of 2 or less. Patients naïve to biological therapies had better clinical responses at weeks 12, 24 and 52. However, after 2 years of treatment, no significant differences were observed. Body mass index did not interfere with the effectiveness of brodalumab throughout the study. No new safety findings were recorded. After 36 months, 85.64% of our patients were still on treatment with brodalumab. Our data confirm the effectiveness and the safety of brodalumab in the largest real-life cohort to date, up to 156 weeks.

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.

P80 Real-world evidence of the effectiveness of secukinumab in patients with psoriasis with and without scalp involvement from the British Association of Dermatologists Biologics and Immunomodulators Register

Abstract Secukinumab is a fully human anti-interleukin-17A monoclonal antibody approved for the treatment of moderate-to-severe plaque psoriasis in adults, adolescents and children aged ≥ 6 years. The British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) is an ongoing prospective observational registry that collects long-term data from patients receiving biologics for psoriasis in the UK and the Republic of Ireland. We report the clinical effectiveness, drug survival and patient-reported outcomes of secukinumab treatment in patients from BADBIR with psoriasis with and without scalp involvement. Patients aged ≥ 18 years who had one or more follow-up visit(s) after enrolment in BADBIR and were receiving secukinumab according to label (300 mg weekly loading dose for 5 weeks, followed by monthly dosing) were included (data cutoff 31 August 2021). Baseline Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores recorded between 4 and 8 months and 10 and 14 months of secukinumab initiation were used as 6- and 12-month time points, respectively. Overall mean drug survival was calculated at 12, 24 and 36 months for patients with and without scalp involvement. Outcomes of interest were the proportion of patients with PASI scores of ≤ 2 and DLQI scores of 0/1. Drug survival up to 36 months (Kaplan–Meier method) was defined as the duration between the date of first exposure to secukinumab and date of stopping secukinumab or the end of the study censoring period. The analysis included 1298 patients with psoriasis with scalp (n = 883; 68.0%) and without scalp (n = 415; 32.0%) involvement. The mean duration of follow-up was 2.9 and 2.8 years in patients with and without scalp involvement, respectively. The majority were male (60.4% and 61.5%), mean age was 45.9 and 49.5 years, mean age at disease onset was 24.7 and 26.8 years, mean baseline PASI scores were 15.2 and 14.5, and mean baseline DLQI scores were 17.4 and 17.0 in patients with and without scalp involvement, respectively. Overall, the drug survival rates at 12, 24 and 36 months were 86%, 73% and 63% and 86%, 77% and 69% in patients with psoriasis with and without scalp involvement, respectively. At 6 and 12 months of treatment, 73.9% and 70.4% and 72.1% and 68.4% of patients with and without scalp involvement, respectively, achieved PASI scores ≤ 2. At 6 and 12 months of treatment, 56.9% and 59.2% and 52.0% and 55.4% of patients with and without scalp involvement, respectively, achieved DLQI scores of 0/1. This analysis of real-world data from BADBIR shows that treatment with secukinumab resulted in high drug survival and sustained and consistent improvements in PASI and DLQI in most patients with psoriasis with and without scalp involvement.

P85 Switching from adalimumab originator to biosimilar: a 3-year retrospective cohort analysis

Abstract Biological drugs have revolutionized the treatment of immune-mediated inflammatory diseases. Clinical experience and evidence suggest that biosimilars can be used as safely and effectively as their originator. However, patients’ perceptions of biosimilars are that they are inferior to the originator. Currently, few studies have assessed the tolerability and efficacy of switching from the adalimumab originator to a biosimilar in patients with well-controlled moderate-to-severe psoriasis. Our objective was to describe the clinical experience of switching patients from the adalimumab originator to a biosimilar and that of switching back to the originator for those intolerant to biosimilars. A single-centre, retrospective cohort study was conducted to identify patients with moderate-to-severe psoriasis who had switched from the adalimumab originator (Humira®) to a biosimilar (Amgevita® or Imraldi®) from 2018 to 2022. Patient data were obtained from a combination of patient records and databases, including the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) and the National High Tech Prescribing Hub. Patients were excluded from the study if their treatment duration on an adalimumab biosimilar was &amp;lt; 16 weeks or if they were being treated for an indication other than psoriasis. From 2018 to 2022, 100 patients who switched from the adalimumab originator to a biosimilar were identified. At week 16, 81 patients (81%) maintained their initial switch from the adalimumab originator to biosimilar. Nineteen (19%) patients who were switched to an adalimumab biosimilar were switched back to the originator secondary to adverse events. Maintenance or improvement in baseline Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) was observed in 91% and 90%, respectively, in patients who remained on a biosimilar. For those intolerant to biosimilars, maintenance or improvement in baseline PASI and DLQI was still observed although in fewer patients: 63% and 47%, respectively. Our study demonstrates that drug efficacy was recaptured and adverse events were ameliorated for all patients switched from an adalimumab biosimilar back to the originator. For patients who did not tolerate biosimilar switch, reasons for switching back to the originator mirrored those reported in the literature. All patients who switched back to the originator from a biosimilar recovered from loss of efficiency and the adverse events they had reported. Physicians should be confident in switching patients with well-controlled psoriasis to adalimumab biosimilars. For the small proportion of patients who experienced loss of efficacy or adverse events, all were recaptured by either switching to an alternative adalimumab biosimilar or switching back to the adalimumab originator.

Efficacy and Safety of Cream Containing Dipotassium Glycyrrhizinate, Vaccinium myrtillius, Epigallocatechin Gallatyl Glucoside, and Tamarindus indica Compared with Triamcinolone Acetonide Cream in Eczema and Psoriasis

Background: Topical corticosteroids are the main treatment in eczema and psoriasis. However, long-term use of corticosteroids causes unwanted adverse effects. Dipotassium glycyrrhizinate (DPG) HERB cream, containing DPG, Vaccinium myrtillius, epigallocatechin gallatyl glucoside, and Tamarindus indica, has an anti-inflammatory and antioxidant effect by inhibiting histamine release and proinflammatory cytokine production so a natural herbal cream is required for alternative treatment. Objective: To evaluate the efficacy and safety of DPG-HERB. Materials and Methods: The present study was a right-left, double-blinded, randomized clinical trial in participants with eczema or plaque psoriasis on both sides of the body. DPG-HERB was applied to the lesion on one side of the body, while 0.1% triamcinolone acetonide (TA) cream was applied to the lesion on the other side, twice daily for four weeks. Disease severity as eczema area and severity index (EASI) in eczema, and psoriasis area and severity index (PASI) in psoriasis, skin biophysics as corneometry and transepidermal water loss (TEWL), and clinical assessments as erythema, scale or excoriation, and lichenification or thickness, were evaluated at baseline, week 2 and week 4 after treatment. The dermatology life quality index (DLQI) was performed at baseline and week 4. Adverse effects were recorded during each visit. Results: The evaluation of the 75 patients with 150 lesions in the present study, DPG-HERB and TA cream showed significant improvement in all the evaluated characteristics of eczema (p&lt;0.05), however, in psoriasis, both creams showed significant improvement in skin biophysics, PASI, scale, and thickness (p&lt;0.05), but DPG-HERB was less effective in decreasing erythema (DPG-HERB, p=0.31 and TA, p&lt;0.05) and less improving TEWL compared with 0.1% TA cream (DPG-HERB, p=0.051 and TA, p&lt;0.05). No side effects in the short-term period were reported in either group. Conclusion: DPG-HERB is safe and efficacious in eczema, but less effective in psoriasis comparing to TA cream. Keywords: Eczema; Plaque psoriasis; Dipotassium glycyrrhizinate acid