Baseline Psoriasis Area Severity Index Research Articles

Certolizumab pegol effectiveness, survival and safety in patients with psoriasis: A multicenter retrospective analysis in daily clinical practice by the Spanish Psoriasis Group.

Certolizumab is an Fc-free PEGylated tumor necrosis factor-alpha (TNFα) inhibitor recently approved for the treatment of moderate-to-severe plaque psoriasis, although there is limited real-world evidence on the effectiveness and safety in patients with plaque psoriasis treated with certolizumab. The objective of this article is to determine the effectiveness, drug survival, and safety, including pregnancy, childbirth, and lactation, of certolizumab in moderate-to-severe plaque psoriasis under real-world conditions. This is a retrospective, multicenter, observational study performed in 15 hospitals in Spain. It evaluates the effectiveness and safety of certolizumab in plaque psoriasis in the clinical practice setting. A total of 67 patients (73% female) were evaluated with a mean baseline Psoriasis Area Severity Index (PASI) of 8.9. At Week 12, the mean PASI was 2.3 (n = 67), 1.3 (n = 57) at Week 24 and 1.3 at Week 52 (n = 34). Absolute PASI < 3 was achieved in 69, 86, and 92% of patients at Weeks 12, 24, and 52, respectively, as observed. For its part, using the under-response imputation analysis, PASI < 3 at Weeks 12, 24, and 52 were achieved by 69, 73, and 49% of the patients, respectively. A total of 35 patients (52%) had concomitant psoriatic arthritis, and, in 24 of them, Disease Activity in Psoriatic Arthritis Score (DAPSA) was recorded at baseline, with a mean value of 17.9 which decreased to 8.2 at Week 12 (n = 22) and to 3.6 at Week 24 (n = 18). Certolizumab treatment was discontinued in 14 out of 67 patients (21%), due to lack/loss of cutaneous or articular effectiveness (n = 11) or patient decision (n = 2) or adverse event in only one patient who developed active tuberculosis. A lower baseline PASI [hazard ratio (HR): 1.12 (1.02-1.23); P = 0.023] and a more significant reduction in PASI at Week 12 [HR: 1.16 (1.07-1.27); P < 0.001] and Week 52 [HR: 1.47 (1.11-1.96); P = 0.007] was shown to be significantly related with better survival for the entire follow-up period. Fourteen patients were treated during pregnancy and/or lactation without reporting adverse events in either the patient or the newborn. Certolizumab consistently showed high effectiveness and drug survival rates in this real-life cohort. The safety demonstrated in clinical trials during pregnancy and lactation seems to be confirmed in clinical practice.

The Relationship of Hematological Parameters and C-reactive Protein (CRP) With Disease Presence, Severity, and Response to Systemic Therapy in Patients With Psoriasis.

Systemic inflammation has an important role in psoriasis, which is a chronic disease with an increasing prevalence and is associated with comorbidity. Our aim is to investigate the relationship of hematological parameters and C-reactive protein (CRP) with the presence and severity of the disease in patients with psoriasis. It is also to investigate whether it can be used as a biomarker in monitoring the response to systemic treatment. This retrospective study was conducted with the participation of 139 psoriasis patients receiving biological therapy (BT) and conventional therapy (CT) and 140 healthy controls. Demographic, clinical, and laboratory data of patients and controls were examined and all parameters were compared with the psoriasis area severity index (PASI) score. In addition, the changes in these parameters before the treatment and in the third month of the treatment were examined in the patient groups who received BT and CT. White blood cell (WBC), neutrophil, monocytes, platelet (PLT), plateletcrit, red blood cell, neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) monocyte-lymphocyte ratio (MLR), red cell distribution width (RDW), CRP and erythrocytesedimentation (ESR) levels were higher compared to the healthy control group in psoriasis patients (p<0.05). Baseline PASI values were positively correlated with WBC, neutrophils, monocytes, NLR, MLR, and CRP. WBC, neutrophil, NLR, CRP, and ESR levels decreased in all patients in the third month of treatment (p<0.05). WBC, PLT, neutrophil, and NLR in patients receiving BT; while WBC, neutrophil, NLR, CRP, and ESR levels decreased in patients receiving CT, RDW levels increased (p<0.05). Adalimumab; NLR and basophil, methotrexate; WBC, NLR, neutrophil, and ESR levels caused a significant decrease (p<0.05). The fact that increased WBC, neutrophils, monocytes, NLR, MLR, and CRP levels are associated with the severity of psoriasis indicates that these parameters reflect systemic inflammation in psoriasis. In addition, the decrease in these parameters after BT and CT suggests that they can be considered simple and reliable markers that can be used as a complement to the PASI score in assessing disease severity and response to treatment.

Translation and validation of the Self-Assessment Psoriasis Area Severity Index (SAPASI).

The Self-Assessment Psoriasis Area Severity Index (SAPASI) is a patient-administered psoriasis assessment tool for which we present a validated translation from English to Swedish. Validity was evaluated in this single-centre study using the Psoriasis Area Severity Index (PASI) as the standard. Test-retest reliability was assessed using repeated SAPASI measurements. Significant correlations (P<0.0001) using Spearman's correlation coefficient (r) were found between PASI and SAPASI scores (r=0.60) for 51 participants (median baseline PASI 4.4, interquartile range [IQR] 1.8-5.6) and repeated SAPASI measurements (r=0.70) among 38 participants (median baseline SAPASI 4.0, IQR 2.5-6.1). Bland-Altman plots showed generally higher SAPASI scores than PASI scores. The translated version of SAPASI is valid and reliable, although patients generally tend to overrate their disease severity compared to PASI. Keeping this limitation in mind, SAPASI has the potential of being implemented as a time- and cost-efficient assessment tool in a Scandinavian context.

Comparison of overall efficacy and safety of oral versus subcutaneous methotrexate in severe psoriasis.

Subcutaneous (SC) methotrexate (MTX) is considered to be associated with a higher and predictable linear bioavailability as compared to oral MTX. Although various studies have reported SC MTX to be safe and effective in psoriasis, prospective head-to-head comparative trials on oral versus SC MTX are limited. To compare the efficacy and safety of SC versus oral MTX in severe psoriasis. It was a prospective, single-blinded, randomized controlled trial, in 100 eligible, adult patients of severe psoriasis randomized into two groups. Group-A (n= 50) patients were started on oral MTX at a full dose of 0.3mg/kg/week (maximum 25 mg/week) given for 12 weeks or till achieving PASI90 [90% reduction in Psoriasis Area Severity Index (PASI) from baseline], whichever was earlier and group-B (n= 50) patients received SC MTX in the same dose and duration. MTX was then tapered gradually at 5mg every 2 weeks and stopped. All patients were followed-up for 24 weeks post-treatment with monthly assessment of PASI and Dermatology Life Quality Index (DLQI) scores. Baseline demographic profiles of patients in both the groups were comparable. The mean ±SD baseline PASI scores were group-A: 15.1± 3.2 versus group-B:15.7± 3.3 (p= 0.35). The number of patients that achieved PASI90 at or before 12 weeks of treatment was numerically higher in group-B (39/50, 78%) versus group-A (31/50, 62%; p= 0.08) and the time to achieve PASI90 was significantly lesser (p< 0.001).Also, the percentage(%) decline in DLQI was significantly higher in group-B(p= 0.003). The overall side-effect profile was comparable between groups (p= 0.31), but the frequency of gastrointestinal side-effects was significantly less in group-B (p= 0.04). Among those patients who achieved a PASI90 response by week12, relapse rates were comparable during the subsequent 24-week follow-up period [group-A: 12/31 (39%), group-B: 11/39 (28%), and p-value=0.33]. SC MTX results in a significantly faster achievement of PASI90 and greater reduction in DLQI as compared to oral MTX in patients who are candidates for systemic therapy with a comparable safety profile. CTRI/2018/01/011373, date of registration: 15 January, 2018; trial registered prospectively.

Efficacy and safety of isotretinoin in comparison to methotrexate in the patients suffering from moderate-to-severe plaque psoriasis: A prospective cohort study

Background: Psoriasis is a common dermatological disorder with both inflammatory and genetic etiology. In India, the incidence of psoriasis is on the verge of rise. Very less data is available on the efficacy of isotretinoin versus methotrexate in patients suffering from plaque psoriasis. Aims and Objective: In this prospective cohort study, we aimed at comparing the efficacy and safety of systemic isotretinoin with systemic methothotrexate in patients suffering from moderate to severe plaque psoriasis in a tertiary care medical college hospital in eastern India. Materials and Methods: It was a prospective cohort study conducted in the dermatology and pharmacology department of Burdwan Medical College between December 1, 2020, and August 31, 2021, on 60 patients suffering from moderate to severe plaque psoriasis. Patients receiving methotrexate and isotretinoin as systemic therapy of psoriasis from the dermatology outpatient department at the time of the study constituted the methotrexate and isotretinoin group, respectively. Each group had 30 patients. Psoriasis area severity index (PASI) score and dermatology life quality index (DLQI) score were utilized for evaluation of improvement in disease severity and quality of life, respectively. Different laboratory parameters and patients reported side effects were noted for evaluation of safety. Results: Fifty-eight patients completed the study (28 patients from methotrexate group and 30 patients from isotretinoin group). Both drugs were effective in managing psoriasis. 100% patients in the methotrexate group and 89.28% patients in the isotretinoin group had reached the threshold for a minimal response (25% reduction from baseline PASI score after 12 weeks of treatment). The mean percentage reduction in PASI score was 70.23±6.78 and 52.78±7.34 in methotrexate and isotretinoin group respectively at the end of 12 weeks therapy. This difference was statistically significant. Methotrexate was more effective in improving quality of life. The mean percentage reduction in DLQI score were 60.02±5.04 and 28.49±4.84 in methotrexate and isotretinoin group respectively at the end of 12 weeks therapy. This difference was statistically significant. Isotretinoin group showed fewer patient-reported side effects and lower fluctuation of laboratory parameters. Conclusions: Methotrexate is more efficacious than isotretinoin in disease remission and improving quality of life in patients suffering from mild to moderate plaque psoriasis. Isotretinoin is safer than methotrexate.

Severity of periodontitis and salivary interleukin-1β are associated with psoriasis involvement

Both psoriasis and periodontal diseases are characterized by an exaggerated immune response to the microbiota residing on epithelial surfaces. This study aimed to explore the associations between the severity of psoriasis and periodontal destruction in patients with psoriasis. Thirty-three patients diagnosed with psoriasis were referred from the dermatology clinic of National Taiwan University Hospital. Full-mouth periodontal examination was performed and saliva was collected after patients signed informed consent forms. The Psoriasis Area Severity Index (PASI) as well as clinical periodontal parameters including probing depth (PD), plaque index (PI), gingival index (GI), and clinical attachment level (CAL) were evaluated. Salivary cytokines including interleukin (IL)-1β, IL-12, IL-17, interferon-γ, and tumor necrosis factor (TNF)-α were tested with the Luminex Bio-Plex system. Anti-inflammatory medication, tobacco use, and underlying comorbidities were included in the analysis. Baseline PASI was significantly associated with PI. PASI at follow-up was positively correlated with CAL ≥4mm (%) and saliva IL-1β levels. Psoriasis patients who used non-steroidal anti-inflammatory drugs or topical steroids had significantly lower GI, PD≥4mm (%), and saliva IL-1β and TNF-α levels. Moreover, a history of tobacco use was associated with higher PD≥4mm (%). PI, CAL, and salivary IL-1β were associated with PASI. Periodontal severity was associated with psoriasis involvement. Periodontal inflammation in psoriasis may be modified by anti-inflammatory medication and tobacco use. Additional large-scale longitudinal and mechanistic studies are needed.

Efficacy and Safety of Sunflower Oil for Mild to Moderate Plaque-type Psoriasis: A Double-blind, Randomized Controlled Trial

Background: Psoriasis is a chronic, complex, inflammatory disease that needs safe and effective treatment options to decrease its disease burden. Objectives: To determine the efficacy and safety of sunflower oil in mild to moderate plaque-type psoriasis at the outpatient department of a tertiary hospital. Methods: This was an 8-week, single-center, randomized, double-blind controlled trial that compared the efficacy and safety of sunflower oil + placebo cream (Group SO), betamethasone valerate cream + placebo oil (Group BC), sunflower oil + betamethasone valerate cream (Group SO-BC) in mild to moderate plaque-type psoriasis. Psoriasis Area Severity Index (PASI) was used to measure the extent of psoriasis by assessing the erythema, induration, scaling, and body surface area involvement. The difference from baseline PASI was recorded. The Dermatology Life Quality Index (DLQI) questionnaire was used to measure the impact of psoriasis on the patient’s quality of life. Results: Fifty-one patients were randomized and blinded to three treatment arms; evaluated at baseline, week 4 and 8. The proportion of patients who achieved PASI ≥50 at week 4 was 29% in Group SO, 38% in Group BC, and 60% in Group SO-BC. By week 8, Groups SO and BC achieved 80% while Group SO-BC achieved 93%. There was significant decline of PASI at week 4 and week 8 compared to baseline. The mean percentage change of PASI was highest at Group SO-BC followed by Group BC and lastly Group SO at week 4 and week 8. The mean reduction in score for scaling was significantly higher in Group SO-BC. Mean reduction in induration and erythema was not statistically significant across the three groups. There was 40-50% improvement in DLQI scores in all groups. There were no adverse events. Conclusion: This study showed that sunflower oil is effective and safe in mild to moderate plaque-type psoriasis.

Real-world effectiveness of guselkumab in patients with psoriasis: Health-related quality of life and efficacy data from the noninterventional, prospective, German multicenter PERSIST trial.

Psoriasis is a common, chronic inflammatory skin disorder negatively impacting health-related quality of life (HRQoL). Guselkumab, targeting interleukin-23 (IL-23), is an approved biologic therapy for psoriasis. PERSIST is an ongoing prospective, noninterventional, long-term, German multicenter study evaluating the effect of guselkumab on HRQoL, and its efficacy and safety in patients with moderate-to-severe psoriasis in a real-world setting. The primary endpoint is the proportion of patients with a Dermatology Life Quality Index (DLQI) score≤1 at week 28. Of 303 patients enrolled and treated with guselkumab, mean age and disease duration were 49.7 and 21.0years, respectively, and 51.2% (n=155) of patients had received ≥1 prior biologic therapy. Mean baseline DLQI score was 13.7, and mean symptom and sign scores in the Psoriasis Symptoms and Signs Diary (PSSD) were 51.9 and 60.8, respectively. Baseline Psoriasis Area Severity Index (PASI) and body surface area (%) scores were 16.4 and 27.5. Following 28weeks of guselkumab treatment, the mean DLQI score decreased to 2.8, and 56.8% of patients (n=150) achieved DLQI≤1. Mean PSSD symptom and sign scores also improved, decreasing to 12.5 and 15.9, respectively. At week 28, PASI 90 response was 55.3%; significant improvement was observed in patients with psoriasis in difficult-to-treat areas. Overall, analyses demonstrated that guselkumab was effective in the real-world setting, as measured by HRQoL and skin improvements, even in patients with a high burden of disease and those who have received multiple biologic therapies. No new safety signals were observed.

25991 Application of the statistical method to convert published PASI 50/75/90/100 into absolute PASI response rate in patients with moderate-to-severe plaque psoriasis treated with tildrakizumab based on data from two pivotal phase 3 studies (reSURFACE 1/2)

Introduction: Improvement from baseline Psoriasis Area Severity Index (PASI) is a common efficacy endpoint in psoriasis trials. This analysis tested a published method to estimate proportion of patients reaching absolute PASI responses from 50%/75%/90%/100% improvement from baseline (PASI 50/75/90/100) response rates using clinical data from two phase 3 tildrakizumab trials, reSURFACE 1 (NCT01722331) and reSURFACE 2 (NCT01729754).

Clinical outcomes in adult patients with plaque psoriasis treated with ustekinumab under real-world practice in Korea: A prospective, observational, multi-center, postmarketing surveillance study.

Postmarketing surveillance is conducted to establish drug safety and effectiveness under real-world practice. We aimed to validate the effectiveness and safety of ustekinumab in the treatment of adult Korean patients with plaque psoriasis under real-world practice. This was a prospective, observational, and multi-center study. Subjects aged 18years or older who were treated with ustekinumab for plaque psoriasis were enrolled. We enrolled 977 patients; 654 (66.9%) were men, with mean body surface area (BSA, ± standard deviation) of 27.0±18.3% and mean psoriasis area severity index (PASI) score of 18.1±9.7. The effectiveness analysis was performed in 581 patients who had at least one follow-up assessment and met treatment criteria per local label and reimbursement guidelines. Of these patients, 287 had effectiveness data for visit 6 at 53.7±2.1weeks. At visit 6, 91.6% (263/287), 51.2% (147/287), and 9.4% (27/287) patients achieved PASI 75, 90, and 100 responses, respectively. Adverse events (AEs) occurred in 112 of the 977 (11.5%) patients with an incidence rate of 21.5 per 100 patient-years (PYs). Serious AEs occurred in eight (0.8%) patients with an incidence rate of 1.2 per 100 PYs. The estimated 1-year drug survival rate was 87.7%. The multiple logistic regression analysis showed that higher baseline PASI score and no prior biologic exposure were significant predictors for PASI 90 response at visit 6. Ustekinumab was effective and safe, and displayed a high survival rate in the treatment of adult Korean patients with plaque psoriasis in real-world practice.

A trial to compare two treatments for psoriasis: Guselkumab and fumaric acid esters

British Journal of DermatologyVolume 183, Issue 2 p. e35-e35 Plain Language Summary Free Access A trial to compare two treatments for psoriasis: Guselkumab and fumaric acid esters First published: 02 August 2020 https://doi.org/10.1111/bjd.19269 AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat Abstract Plaque psoriasis is a common skin disease characterized by skin scales and red patches. It affects about 2% of all people. A complete cure is not possible, but several drugs can improve symptoms. This study, from Germany, aimed to compare a new drug called “guselkumab” with “fumaric acid esters (FAE)” that are commonly used in Germany to treat psoriasis. Psoriasis patients received, by random allocation, either guselkumab or FAE, and after 24 weeks the researchers evaluated how well the drugs worked (efficacy) and how well they were tolerated (safety). The Psoriasis Area Severity Index (PASI) is used to record the redness, thickness and scaling of a patient's psoriasis and to measure how well a treatment works, as a reduction in the PASI score means a reduction in these symptoms. For example, if a patient achieves PASI 75, it means they had a 75% or more reduction in their PASI score from the start. In this study, at week 24, 82% of guselkumab patients and 14% of FAE patients improved their baseline PASI score by at least 90% (PASI 90 response). This means that more patients in the guselkumab group had great relief in symptoms than patients in the FAE group. Patients answered the “Dermatology Life Quality Index (DLQI)” questionnaire to measure the impact of their skin disease on different aspects of their quality of life, like symptoms and feelings, daily activities, leisure, personal relationships and side effects of treatment. After 24 weeks of treatment, more guselkumab patients (62%) reported that their psoriasis no longer bothered them at all (DLQI score of 0/1) than FAE patients (17%). Undesired harmful incidents or side effects, called adverse events, occurred less often in the guselkumab group. In conclusion, guselkumab was more effective as a treatment for plaque psoriasis and better tolerated than FAE after 24 weeks. Linked Article: Thaçi et al. Br J Dermatol 2020; 183:265–275. Volume183, Issue2August 2020Pages e35-e35 RelatedInformation

Ixekizumab Survival in Heavily Pretreated Patients with Psoriasis: A Two-year Single-centre Retrospective Study.

The long-term effect of intra-anti-interleukin-17-class switch on drug survival is unclear. The aim of this study was to evaluate the efficacy and long-term survival of ixekizumab in bio-experienced psoriatic patients with and without previous exposure to anti-interleukin-17 treatment. Retrospective search of a tertiary medical centre database for 2017 to 2019 yielded 73 patients treated with ixekizumab: 50 previously exposed to secukinumab and 23 anti-interleukin-17-naïve. Median baseline Psoriasis Area Severity Index (PASI) was 23.0. Median number of received biologics was 4. Mean drug survival was 16.4 and 16.8 months in the anti-interleukin-17-exposed and naïve groups, respectively (p = 0.878). There was no between-group difference in proportion of patients achieving ≥ 75 PASI response. At study end, 25 anti-interleukin-17-exposed patients (50.0%) and 17 anti-interleukin-17-naïve patients (73.9%) were still on ixekizumab. The use of multiple previous biologic treatments was associated with substantially reduced ixekizumab survival. In conclusion, previous anti-interleukin-17-exposure was associated with an initially favourable response and did not further reduce ixekizumab survival.

Ixekizumab Effectiveness and Safety in the Treatment of Moderate-to-Severe Plaque Psoriasis: A Multicenter, Retrospective Observational Study.

Ixekizumab (anti-IL-17A) is a biological agent used for the treatment of moderate-to-severe psoriasis. Real-life data on the effectiveness and safety of ixekizumab are currently scarce. The objective of this study was to evaluate the effectiveness and safety of ixekizumab in a cohort of psoriatic and psoriatic arthritis patients. We conducted a retrospective study involving 201 patients affected by moderate-to-severe psoriasis and treated with ixekizumab at seven Italian University centers. Data analysis focused on 110 patients who started ixekizumab at baseline and completed at least 24weeks of treatment. Significant reduction of mean (± standard deviation) baseline Psoriasis Area Severity Index (PASI) score (14.3 ± 5.8) was detected at 4weeks of ixekizumab therapy (4.9 ± 4.2, p < 0.001), with a further significant improvement at weeks 12 and 24 (1.9 ± 2.9 and 0.9 ± 1.6, respectively) (p < 0.001). Our analysis showed 90%, 72%, and 57% of patients achieving PASI75, 90, and 100 responses (75%, 90%, and 100% reduction in PASI score), respectively, after 24weeks' therapy. For patients with arthritis (28%), a significant reduction in the mean (± standard deviation) baseline Disease Activity Score (DAS)-28 score (4.6 ± 5.1) was detected at week4 (2.5 ± 3.9, p < 0.01), with a further significant improvement at weeks 12 and 24 (2.1 ± 1.2 and 1.4 ± 0.9, respectively) (p < 0.001). The bio-naïve group showed significantly higher PASI90 and 100 response rates at week12 than the bio-exposed one (p < 0.05). This trend in terms of PASI100 response was also maintained at week24 (p < 0.05). Furthermore, PASI90 responses were significantly higher in anti-interleukin (IL)-17A-naïve patients at week24 than in anti-IL-17A-experienced ones (p < 0.05). The dropout rate for adverse events (AEs) was as low as 2% (2/110), while AEs that did not cause treatment interruption were observed in 6% (7/110). Patients withdrawing from the study were defined as non-responders according to the non-responder imputation method. The retrospective design of the study does not allow missing data to be retrieved or homogeneous patient selection. The present study illustrates ixekizumab in real-world clinical practice, confirming its usefulness and safety in the management of psoriasis and psoriatic arthritis.

Outcome of cutaneous psoriasis in hepatitis C virus-infected patients treated with Direct-Acting Antiviral therapy.

Apart from chronic liver disease, hepatitis C virus (HCV) may be responsible for several extra-hepatic manifestations. Its involvement in psoriasis development is still controversial. The aim of this study was to evaluate the possible effect of anti-HCV direct-acting antiviral (DAA) treatment on cutaneous psoriasis. Thirty-seven consecutive HCV patients with cutaneous psoriasis underwent efficacious DAA treatment, and all of them were efficiently cured as shown by HCV RNA negativity 24weeks after stopping therapy (PT24W). An expert dermatologist evaluated the skin lesions at baseline, end of treatment (EOT) and PT24W using the psoriasis area severity index (PASI) scoring system. The impact on quality of life was measured with the Dermatologic Quality of Life Index (DLQI). Six patients had a stable disease throughout the study period, whereas 31/37 patients (83.8%) showed a significant improvement of the skin lesions at EOT (P<.0001). However, 24 of these 31 patients (77.4%) had a dramatic worsening of the psoriatic lesions at PT24W compared with EOT (P<.001), with lesion severity comparable to baseline. The outcome of psoriasis during and after treatment was independent of baseline PASI score, age, sex, HCV genotype, liver disease stage and of the presence of arterial hypertension, diabetes and autoimmune diseases. In conclusion, DAA-based HCV cure has only a transient effect on skin lesions of patients with concomitant cutaneous psoriasis.

028 The activation status of nuclear factor κB in type 2 conventional dendritic cells before therapy correlates with clinical response to adalimumab

Biologic therapies have revolutionised the treatment of psoriasis. Nevertheless, clinical response to therapy is unpredictable. Thus, there is a need to identify biomarkers predictive of response to enable patient stratification. Here, we investigate the effects of adalimumab (TNF-inhibitor) on the activation of nuclear factor κB (NF-κB) in the immune cells of psoriasis patients during the early phase of therapy. We hypothesize that monitoring the activation of the transcription factor downstream of the cytokine neutralized by a biologic can guide in the discovery of predictive biomarkers. Whole blood (n=16) and peripheral blood mononuclear cells (n=30) samples, obtained from psoriasis patients at baseline and weeks 1, 4 and 12 after commencing treatment, were stimulated with TNF or LPS; NF-κB nuclear translocation was quantified by imaging flow and NF-κB phosphorylation by phospho-flow cytometry. Clinical response was defined as 75% reduction in baseline psoriasis area severity index (PASI75) at week 12. TNF induced NF-κB translocation in T cells, dendritic cells (DCs), monocytes and neutrophils, while LPS, activated monocytes, DCs and neutrophils at baseline. In patients receiving adalimumab, TNF activation was significantly inhibited at each time point in T cells (92% at week 1, p<0.01), and to a lesser extent, in DCs (55% at week 1, p<0.05) compared to baseline but did not change in monocytes or neutrophils. As expected, adalimumab did not affect LPS-induced NF-κB translocation. However, we observed increased LPS-induced NF-κB translocation at baseline in the DC of patients who did not reach PASI75, as compared to patients reaching PASI75 (FDR<0.01). Importantly, this finding was replicated in an extended cohort of patients receiving adalimumab, where we detected increased LPS-induced NF-κB phosphorylation at baseline in type 2 conventional DC (cDC2) of patients not reaching PASI75 (FDR<0.001). Taken together, these data suggest that clinical response to adalimumab may depend on the baseline NF-κB activation status of cDC2.

Safety and Efficacy of Methotrexate for Chinese Adults With Psoriasis With and Without Psoriatic Arthritis

It is necessary to determine whether psoriasis responds to methotrexate in the same manner in patients with and without psoriatic arthritis. To evaluate the effectiveness and safety of methotrexate in treating patients with psoriasis with and without psoriatic arthritis. In this prospective, single-arm, interventional study, a total of 235 patients with psoriasis, 107 without psoriatic arthritis and 128 with psoriatic arthritis who were receiving methotrexate therapy from April 1, 2015, to December 31, 2017, were recruited from the outpatient department of a hospital at a large Chinese university. There were no significant demographic or clinical differences between the subgroups with the exception of diabetes. A 12-week course of low-dosage oral methotrexate (7.5-15 mg weekly). Changes in disease severity, adverse events, blood cell counts, and liver and renal function. A total of 235 patients with psoriasis (166 male [66.0%]; mean [SD] age, 49.6 [15.1] years) received methotrexate treatment for 12 weeks. The 90% reduction from baseline Psoriasis Area Severity Index response was significantly lower in patients with psoriatic arthritis than in patients without psoriatic arthritis at week 8 (4 0f 128 [3.1%] vs 12 of 107 [11.2%]; P = .02) and week 12 (19 of 128 [14.8%] vs 27 of 107 [25.2%]; P = .049). Furthermore, the incidence of adverse events, including dizziness (12 of 128 [9.4%] vs 1 of 107 [0.9%]; P = .007), gastrointestinal symptoms (32 of 128 [25.0%] vs 13 of 107 [12.1%]; P = .01), and hepatoxicity (34 of 128 [26.6%] vs 16 of 107 [15.0%]; P = .04), was significantly higher in patients with psoriatic arthritis than in patients without psoriatic arthritis. Methotrexate-induced elevation of alanine aminotransferase levels was associated with body mass index (mean [SD] body mass index, 26 [4] in patients with [P = .04] vs 26 [4] in those without [P = .005] psoriatic arthritis) and smoking (17 of 34 [50.0%] in patients with [P = .02] vs 9 of 16 [56.3%] in those without [P = .04] psoriatic arthritis). In this study, methotrexate was well tolerated and effective in treating psoriasis. It was more effective, with fewer adverse effects, in patients with psoriasis who did not have psoriatic arthritis than in patients who presented with both psoriasis and psoriatic arthritis. Therefore, methotrexate can be recommended as first-line treatment for psoriasis without arthritis.

Real-life experience of secukinumab injection in difficult chronic plaque-type psoriasis: a multicenter experience

Background Secukinumab, a fully human monoclonal antibody that selectively targets interleukin-17A, has been proven highly efficacious in the management of moderate to severe psoriasis with early response and sustained effects in many phase III clinical trials. However, data on real-life experience is lacking. Patients and methods A multicentric, retrospective study in routine clinical setting was conducted in cases of chronic plaque type of psoriasis during November 2016 to December 2017. Patients who had received 300-mg secukinumab injection subcutaneously at 0, 1, 2, 3, and 4 months and then every 4 weekly for at least 6 months were recruited for the study. Assessment of severity of psoriasis was done by psoriasis area severity index (PASI) and dermatological life quality index (DLQI). Results A total of 32 patients, comprising 24 males and 8 females, with mean age of 42.31 years (SD 11.32) and mean baseline PASI of 20.72 (SD 7.53) and DLQI of 15.31 (SD 5.25), were studied. Achievement of PASI 75/90/100 at 12 weeks was 81.25/59.37/9.3, respectively. PASI 75 at the end of 52 weeks was maintained at 65.62. DLQI reduced to 2.56 (SD 5.19) (16.72% of baseline) at the end of 12 weeks. Differences between baseline scores and each subsequent visit were statistically significant (P Conclusion Secukinumab is a very promising new molecule in the management of chronic plaque type of psoriasis that is resistant to conventional modalities in routine clinical setting even in an Indian scenario. A retrospective analysis, with few cases, was inherent limitation of this study.

PSS12 - Cost-Effectivess Analysis of Brodalumab in Moderate-To-Severe Plaque Psoriasis in Canada

To assess the cost-effectiveness of brodalumab versus available biologics and best supportive care (BSC) in adult patients with moderate-to-severe plaque psoriasis from a Canadian public payer perspective. A decision tree followed by a Markov model was developed to compare brodalumab with etanercept, adalimumab, infliximab, ustekinumab 45mg, ustekinumab 90mg, secukinumab, ixekizumab, infliximab subsequent entry biologic, and BSC. Psoriasis Area Severity Index (PASI) response was assessed at the end of the induction period (10-16 weeks) for each comparator. Responders (defined as at least 75% reduction in baseline PASI score) continued initial therapy and maintained their PASI response until treatment discontinuation or death. Non-responders switched to BSC. Comparative efficacy data were informed by a network meta-analysis. EQ-5D utility values associated with each PASI health state were derived from the brodalumab AMAGINE-1 study. Drug costs were obtained from the Ontario Drug Benefit Formulary and unit costs from the Ontario Health Insurance Plan. A 10-year time horizon was employed with 1.5% annual discount rate for costs and outcomes. Probabilistic analyses were conducted for base case and all scenario analyses. The base case analysis demonstrated that brodalumab had an ICER of $118,741 per quality-adjusted life year versus BSC. The ICER for ixekizumab versus BSC is $152,703. All other comparators were either dominated or subject to extended dominance. The results were robust across a range of scenario analyses. The model concluded that brodalumab is the most cost-effective option compared with publicly funded biologics for the treatment of moderate-to-severe plaque psoriasis in Canada. As such, the reimbursement of brodalumab will benefit the Canadian public by introducing a highly effective and most likely costs-savings alternative to the public payer system.

PSS3 - Efficacy of Brodalumab in the Treatment of Moderate-To-Severe Psoriasis: A Network Meta-Analysis

This network meta-analysis (NMA) compares the relative efficacy of brodalumab to other biologic agents in the treatment of moderate-to-severe plaque psoriasis based on randomized controlled trials (RCTs) evidence. A systematic literature review of RCTs published to October 2017 was conducted to populate the NMA. Relevant comparators included were ixekizumab, secukinumab, infliximab, adalimumab, etanercept, ustekinumab, guselkumab, and placebo according to their doses approved by Health Canada. The primary efficacy outcome measure was the Psoriasis Area Severity Index (PASI) response. A random effects Bayesian multinomial likelihood and probit link model was used to analyze PASI 50, 75, 90, and 100 responses at the end of the induction period (10-16 weeks). Inconsistency and heterogeneity were assessed in the network. Sensitivity analyses were conducted to explore potential effect modifiers such as baseline PASI score, age, weight, Dermatology Life Quality Index score, duration of psoriasis, and prior biologics exposure. A total of 43 RCTs were included in evidence network. The analysis showed that brodalumab 210mg had significantly better PASI response than ustekinumab, secukinumab, etanercept, adalimumab, and guselkumab and comparable PASI responses to infliximab and ixekizumab. Relative risk of PASI 75 response for brodalumab varied from 1.72 (1.54 to 1.96, p<0.05) to 0.99 (95%CI: 0.95 to 1.05, ns) when compared to etanercept and ixekizumab. This trend was similar across PASI 50, 90, and 100 outcomes, but a larger relative risk between brodalumab and all comparators except ixekizumab was observed for PASI 100 response. No significant heterogeneity or inconsistencies were identified and the results were consistent across all the sensitivity analyses, indicating robustness of the results. Based on the findings of this NMA, brodalumab 210 mg can be considered a superior alternative to most biologic agents currently used for the treatment of moderate-to-severe plaque psoriasis.

A multicenter, prospective, observational study examining the impact of risk factors, such as BMI and waist circumference, on quality of life improvement and clinical response in moderate-to-severe plaque-type psoriasis patients treated with infliximab in routine care settings of Greece.

Obesity has been associated with moderate-to-severe plaque psoriasis severity and PASI 75 response attainment of biologic therapies, but findings are inconsistent. This study aimed to examine the association of body mass index (BMI) and waist circumference (WC) on disease severity, to identify potential patient characteristics associated with response attainment and to assess the impact of infliximab on the patients' health-related quality of life (HRQoL) among infliximab-treated patients in the routine care setting of Greece. This was a multicenter, prospective, observational study of adult moderate-to-severe plaque psoriasis patients who had initiated treatment with originator infliximab within 2weeks prior to enrolment. Postenrolment visits occurred at 14±4, 30±4 and 54±4weeks following treatment onset. Between October 2012 and June 2014, 136 eligible patients (62.5% males) with a median age of 48.6years, BMI of 29.6kg/m2 and WC of 107.0cm at enrolment were recruited by 21 dermatology hospital/private offices. All patients had received prior psoriasis treatment(s); 62.5% were biologic-naïve. Mean baseline psoriasis area severity index (PASI) and Dermatology Quality of Life Index (DLQI) scores were 23.4±13.6 and 15.0±8.3, respectively. A low correlation was observed between WC at enrolment and baseline PASI [ρ=0.324 (P<0.001)]. Over a median 48.4weeks of infliximab exposure, 89.3% of the per protocol set achieved a PASI 75 response. At 14, 30 and 54weeks, the PASI 75 attainment rate was 66.4%, 74.8% and 76.6%, respectively; the clinically meaningful DLQI improvement (≥5 point decrease) rate was 68.9%, 75.7% and 69.8%, respectively. BMI category and abdominal obesity at enrolment did not impact PASI 75 or DLQI improvement rate attainment. In the routine care of Greece, infliximab reduced disease activity and improved the quality of life of moderate-to-severe psoriasis patients through 1year of treatment, independent of their BMI and WC.