Psoriasis Area And Severity Index Improvement Research Articles

P115 Real-world experience of bimekizumab for plaque psoriasis in adult patients with prior exposure to interleukin-23 inhibitors: a 52-week multicentre retrospective review

Abstract For adult patients with plaque psoriasis, limited information exists on switching between classes from an IL-23 inhibitor (IL-23i) to bimekizumab. We conducted a real-world, multicentre, retrospective study of bimekizumab following IL-23i exposure. Twenty-three subjects with prior exposure to an IL-23i were identified. Effectiveness outcomes included Investigator Global Assessment (IGA), psoriasis area and severity index (PASI), body surface area (BSA), and IGA × BSA scores. Safety was assessed via treatment-related adverse events (AEs). For 23 patients included, the mean age was 43 (range: 20–73) years, with 56.5% (13/23) being male. Prior IL-23i exposures included guselkumab only (52.2%, 12/23), risankizumab only (21.7%, 5/23), and both guselkumab and risankizumab (26.1%, 6/23). Reasons for discontinuation included lack of efficacy (95.7%, 22/23) and persistent psoriatic arthritis (4.3%, 1/23). Primary non-response to prior IL-23i was defined as lack of IGA 0/1 and/or 75% improvement in PASI (PASI75) at Week 16, whereas secondary non-response to prior IL-17i was defined as loss of IGA 0/1 and/or PASI75 response at any point afterwards. At Weeks 52 ± 6: IGA 0/1 was achieved by 66.7% (12/18); mean PASI, BSA, and IGA × BSA improvements from baseline were 69.6% (8.5–0.8), 71.8% (8.2–0.7%), and 74.6% (22.6–1.4), respectively; 65.2% (15/23), 56.5% (13/23), and 47.8% (11/23) achieved PASI75, 90% improvement in PASI (PASI90), and 100% improvement in PASI (PASI100), respectively; 78.3% (18/23), 69.6% (16/23), and 65.2% (14/23) achieved absolute PASI scores <3, <2, and <1; and 73.9% (17/23) achieved BSA <1%. In prior IL-23i primary non-responders (n = 6), 83.3% (5/6) achieved IGA 0/1 and/or PASI90 and 50% (3/6) achieved PASI100 with bimekizumab at Week 52 ± 6. In prior IL-23i secondary non-responders (n = 12), 66.7% (8/12) achieved IGA 0/1 and/or PASI90 and 50% (6/12) achieved PASI100 with bimekizumab at Week 52 ± 6. Four treatment-related AEs occurred (17.4%, 4/23), including oral candidiasis (8.7%, 2/23) and bacterial folliculitis (4.3%, 1/23). There were 3 (13%) treatment-related discontinuations [lack of efficacy (n = 2); AE: anxiety (n = 1)]. While our real-world results of patients with prior IL-23i exposure demonstrated lower achievement of effectiveness endpoints (IGA 0/1: 66.7%; PASI90: 56.5%; PASI100: 47.8%) at Week 52 ± 6 as compared with clinical trials, the discrepancy between clinical trials and this study may be explained by a more difficult-to-treat population with multiple biologic failures (56.5% utilized >3 biologics and 26.1% used several IL-23i). Our real-world study also included patients with >1 biologic failure, while Phase III clinical trials excluded this population. Our results highlight the long-term utility of bimekizumab in the setting of prior IL-23i exposure. Study limitations include its small sample and retrospective nature.

P117 Dose optimization of bimekizumab for adult patients with plaque psoriasis: an interim analysis of data from a real-world, multicentre, retrospective review

Abstract The standard bimekizumab dosing regimen for adult patients with plaque psoriasis is 320 mg administered as a subcutaneous injection at Weeks 0, 4, 8, 12, and 16, then every 8 weeks (Q8W) thereafter. However, dose optimization may be required due to variability in treatment response. We conducted a real-world, multicentre, retrospective review of bimekizumab dose optimization for plaque psoriasis in adults. From a total cohort of 91 patients, we identified 15 (16.5%) that underwent dose optimization from Q8W to every 4 weeks (Q4W; 93.3%, 14/15) or every 6 weeks (Q6W; 6.7%, 1/15) in the maintenance period. All patients underwent dose optimization due to lack of efficacy. Mean age was 47.7 (range: 23–74) years, with 60% (9/15) being female. Mean time to dose optimization was 42.4 (range: 15.6–99) weeks. At the time of dose escalation (n = 15), mean psoriasis area and severity index (PASI) score was 3.4 (mean improvement from baseline: 50.5%) and mean body surface area (BSA) was 3.2% (mean improvement from baseline: 51%), with Investigator Global Assessment (IGA) scores of 1 (33.3%, 5/15), 2 (46.7%, 7/15), 3 (13.3%, 2/15), and 4 (6.7%, 1/15). Prior to dose escalation, there were 33.3% (5/15), 46.7% (7/15), and 20% (3/15) of IGA 0/1, 75% improvement in PASI (PASI75), and 90% improvement in PASI (PASI90) responders. Following a mean follow-up period of 17.5 (range: 2.9–35.6) weeks after dose optimization, there were 86.7% (13/15), 66.7% (10/15), 66.7% (10/15), and 60% (9/15) responders in IGA 0/1, PASI75, PASI90, and PASI100. From the time of dose escalation, mean improvement in PASI and BSA were 79.2% (85.2% from baseline) and 81.2% (90.6% from baseline), respectively. There was 1 (6.7%) discontinuation due to persistent lack of efficacy following dose optimization. Five treatment-related adverse events (AEs) occurred, including candidiasis (13.3%, 2/15), folliculitis (6.7%, 1/15), recurrent cellulitis (6.7%, 1/15), and recurrent urinary tract infection (UTI; 6.7%, 1/15). Of these, only the UTI patient (6.7%, 1/15) experienced an AE following dose escalation. There were no safety-related treatment discontinuations, nor any serious infections, suicidal ideation/behaviour, malignancies, hypersensitivity reactions, major adverse cardiac events, or hepatic abnormalities. In Phase III clinical trials, while IGA 0/1 and PASI90 rates were comparable between dosing regimens, Q4W maintenance dosing of bimekizumab was associated with a higher PASI100 rate than Q8W dosing [73.5–83% (Q4W) vs. 66–70.8% (Q8W)] at 1-year. Furthermore, AEs were comparable between dosing regimens with slightly higher rates of oral candidiasis and UTI with Q4W dosing. Our real-world results show increased achievement of IGA 0/1, PASI90, and PASI100 with dose optimization and no new safety signals. Study limitations include its small sample and retrospective nature.

P113 Real-world experience of bimekizumab for plaque psoriasis in adult patients with prior exposure to interleukin-23 inhibitors: a 16-week multicentre retrospective cohort study

Abstract For adult patients with plaque psoriasis, limited information exists on switching between classes from an IL-23 inhibitor (IL-23i) to bimekizumab. We conducted a real-world, multicentre, retrospective study of bimekizumab use in the setting of prior IL-23i exposure. A total of 26 patients with prior IL-23i exposure were identified. Effectiveness outcomes included Investigator Global Assessment (IGA), psoriasis area and severity index (PASI), body surface area (BSA), and IGA × BSA scores. Safety was assessed via treatment-related adverse events (AEs). Mean age was 44.0 (range: 18–76) years, with 57.7% (15/26) being female. Prior IL-23i exposures included guselkumab only (46.2%, 12/26), risankizumab only (34.6%, 9/26), and both guselkumab and risankizumab (19.2%, 5/26). All 26 patients discontinued the IL-23i agent due to inefficacy. Primary non-response to IL-23i was defined as lack of IGA 0/1 and/or 75% improvement in PASI (PASI75) at Week 16, whereas secondary non-response to prior IL-17i was defined as loss of IGA 0/1 and/or PASI75 at any point afterwards. At Weeks 16 ± 6: IGA 0/1 was achieved by 82.6% (19/23); mean PASI, BSA, and IGA × BSA improvements from baseline were 77.5% (7.2–0.9), 81.8% (6.8–0.9%), and 86.9% (19.4–1.3), respectively; 73.1% (19/26), 53.9% (14/26), and 30.8% (8/26) achieved PASI75, 90% improvement in PASI (PASI90), and 100% improvement in PASI (PASI100), respectively; 96.2% (25/26), 92.3% (24/26), and 69.2% (18/26) achieved absolute PASI scores <3, <2, and <1; and 73.1% (19/26) achieved BSA <1%. In prior IL-23i primary non-responders (n = 4), 100% (4/4) achieved IGA 0/1 and/or PASI90; however, none achieved PASI100, with bimekizumab at Week 16 ± 6. In prior IL-23i secondary non-responders (n = 16), 75% (12/16) achieved IGA 0/1 and/or PASI90 and 43.8% (7/16) achieved PASI100 with bimekizumab at Week 16 ± 6. Three treatment-related AEs occurred (11.5%, 3/26), including oral candidiasis (7.7%, 2/26) and folliculitis (3.8%, 1/26); none led to discontinuation. In comparison to clinical trials and an Italian real-world study of biologic-experienced patients (n = 103), our study of bimekizumab in IL-23i-exposed patients demonstrated lower response for PASI90 [85–91% (trials) vs. 87.9% (Italian study) vs. 53.9% (our study)] and PASI100 [59–83% (trials) vs. 74.1% (Italian study) vs. 30.8% (our study)]. This discrepancy may be explained by a more difficult-to-treat population with multiple biologic failures [42.3% utilized >3 biologics (our study) vs. 18.6% with >2 biologics (Italian study)] and IL-23i secondary failures [61.5% (our study)]. Our study included patients with >1 biologic failure, while Phase III clinical trials excluded this population. We highlight the utility of bimekizumab despite IL-23i exposure. Study limitations include its small sample and retrospective nature.

P116 Real-world experience of bimekizumab for plaque psoriasis in adult patients with prior exposure to interleukin-17 inhibitors: a 52-week multicentre retrospective review

Abstract For adult patients with plaque psoriasis, evidence remains sparse regarding switching within class from another interleukin-17 inhibitor (IL-17i) to bimekizumab. We conducted a real-world, multicentre retrospective study of bimekizumab use following prior IL-17i exposure. We identified 40 patients from 4 centres initiated on bimekizumab following prior IL-17i exposure. Effectiveness outcomes included Investigator Global Assessment (IGA), psoriasis area and severity index (PASI), body surface area (BSA), and IGA × BSA scores. Safety was assessed via treatment-related adverse events (AEs). Mean age was 44.5 (range: 18–62) years, with 52.5% (21/40) being female. Prior IL-17i agents included secukinumab (60%, 24/40), ixekizumab (42.5%, 17/40), and brodalumab (42.5%, 17/40); 37.5% (15/40) utilized ≥2 IL-17i agents. Reasons for prior IL-17i discontinuation included lack of efficacy (87.5%, 35/40), patient preference (5%, 2/40), psoriatic arthritis flare (5%, 2/40), and adverse event (AE; 2.5%, 1/40). Primary non-response to prior IL-17i was defined as lack of IGA 0/1 and/or 75% improvement in PASI (PASI75) response at Week 16, while secondary non-response to prior IL-17i was defined as loss of IGA 0/1 and/or PASI75 response at any point afterwards. At Weeks 52 ± 6: IGA 0/1 was achieved by 72.4% (21/29); mean PASI, BSA, and IGA × BSA improvements from baseline were 93.9% (9.9–1.0), 87.3% (9.5–1.0%), and 89.7% (26.1–2.6), respectively; 77.5% (31/40), 67.5% (27/40), and 60% (24/40) achieved PASI75, 90% improvement in PASI (PASI90), and 100% improvement in PASI (PASI100); 77.5% (31/40), 70% (28/40), and 60% (24/40) achieved absolute PASI scores <3, <2, and <1, respectively; and 70% (28/40) achieved BSA <1%. In prior IL-17i primary non-responders (n = 14), 57.1% (8/14) achieved IGA 0/1 and/or PASI90 and 50% (7/14) achieved PASI100 with bimekizumab treatment at Week 52 ± 6. In prior IL-17i secondary non-responders (n = 12), 66.7% (8/12) achieved IGA 0/1 and/or PASI90 and 41.7% (5/12) achieved PASI100 with bimekizumab treatment at Week 52 ± 6. Eleven AEs occurred (27.5%, 11/40), including candidiasis (10%, 4/40) and folliculitis (7.5%, 3/40). Five patients (12.5%) discontinued treatment [AEs: anxiety (n = 1); inflammatory bowel disease (n = 1); inefficacy (n = 2); pregnancy (n = 1)]. The BE RADIANT open-label extension study demonstrated IGA 0/1 (73.6%), PASI90 (73.6%), and PASI100 (47.2%) responses at Week 48 for secukinumab PASI90 non-responders switched to bimekizumab following a 48-week randomization period. Our real-world study at Week 52 ± 6 is comparable to these results. Notably, prior IL-17i primary non-responders and patients with multiple biologic failures were included in this analysis, but excluded from Phase III clinical trials. We highlight the long-term utility of bimekizumab for IL-17i-exposed patients. Study limitations include its small sample and retrospective nature.

P25 Genome-wide association study and predictive models for the efficacy and safety of NB-UVB phototherapy in psoriasis

Abstract Background Psoriasis is a chronic inflammatory skin disease affecting ∼125 million individuals worldwide. Although the treatment of psoriasis has entered an era of biological agents and small molecule drugs, narrowband ultraviolet B (NB-UVB) phototherapy still represents an effective, cost-efficient, and safe therapeutic option for patients with plaque psoriasis. However, the clinical and genetic predictors of NB-UVB treatment response remain limited. Objective We aimed to detect single nucleotide polymorphisms (SNPs) associated with the efficacy of NB-UVB in treating psoriasis and its adverse events (AEs), in order to establish predictive models for the efficacy and safety of NB-UVB phototherapy. Methods A total of 252 patients with moderate-to-severe plaque psoriasis were enrolled in this study and underwent 12 weeks of NB-UVB phototherapy. Psoriasis area and severity index (PASI) and the AEs of NB-UVB treatment were recorded during follow-up. Whole blood samples were collected from the participants, and extracted DNA was genotyped using Infinium Global Screening Array-24 v3.0 BeadChip. Genome-wide association studies (GWASs) were performed to identify SNPs related to NB-UVB treatment response. Predictive models for the efficacy and safety of NB-UVB therapy, which involved SNPs along with clinical parameters, were developed utilizing logistic regression and further validated by receiver operating characteristic (ROC) curve and calibration curve. Results After 4 weeks of NB-UVB phototherapy, 40.8% of patients achieved PASI50. Through GWASs, we discovered that SLC7A13 rs35314286 TA allele [odds ratio (OR) = 2.631, P = 5.96 × 10−6] and DYNC1H1 rs941636 A allele (OR = 3.066, P = 3.15 × 10−6) were significantly correlated with better efficacy of 4-week NB-UVB treatment. After 12 weeks of treatment, 61.4% of patients achieved PASI75. Seven ATP2B2 SNPs and 11 PSMB7 SNPs significantly impacted 12-week PASI75 achievement. During the treatment, 29.8% of patients experienced AEs that included pruritus, sting, numbness, erythema, vesicles, desquamation, hyperpigmentation, and photosensitivity. Two KCNA2 SNPs, seven THSD7B SNPs and one TENM4 SNP were considerably associated with the occurrence of AEs. Based on the clinical parameters (body mass index, smoking history, PASI score, and the percentage of PASI improvement at Week 4) and NB-UVB relevant SNPs, predictive models for the efficacy and safety of NB-UVB phototherapy were established, demonstrating excellent predictive capacities with area under the curve (AUC) value being 0.81 for 4-week efficacy, 0.80 for 12-week efficacy, and 0.85 for AE development. Conclusion Multiple gene SNPs were identified to be correlated with the efficacy and safety of NB-UVB phototherapy. Moreover, predictive models of NB-UVB treatment response were subsequently established. Our findings might contribute to the advancement of precision phototherapy in psoriasis. Clinical trial registration (www.chictr.org.cn), identifier (ChiCTR2000036186).

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. Complete skin clearance is associated with the greatest benefits to health-related quality of life and perceived symptoms for patients with psoriasis: KeyResults and Conclusions (MP4 72828 kb).

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