Risankizumab for the treatment of moderate-to-severe psoriasis: A multicenter, retrospective, 1 year real-life study.

Several new biologic agents targeting IL23/Th17 axis, such as risankizumab, have been developed for the treatment of psoriasis. The aim of the present study was to analyze the efficacy and safety of risankizumab in patients with moderate-to-severe psoriasis over a 52-week period. A multicentric retrospective study was conducted in patients who initiated risankizumab between July 2019 and December 2020. Psoriasis Area and Severity Index-PASI was measured at baseline and after 4, 16, 28 and 52 weeks. Clinical responses were evaluated by PASI75, PASI90 and PASI100 at the same timepoints. Potential safety issues and adverse events (AEs) were collected. Univariable and multivariable logistic regressions were performed for variables predicting clinical response. One hundred and twelve patients with psoriasis were included. PASI90 response was achieved by 17.86% of patients at week 4, 72.22% at week 16, 91.0% at week 28 and 95.24% at week 52 (as observed analysis). No associations between the considered variables and the efficacy endpoints were retrieved, influence of variables such as Body Mass Index (BMI), baseline PASI or previous biologics were not shown. No serious safety issues or discontinuations related to adverse events were reported. Risankizumab showed high efficacy and a favorable safety profile, regardless of patient- and disease-related factors.

A linear forehead lesion caused by intralesional injection of triamcinolone acetonide and treated with hyaluronic acid filler: Case report.

Intralesional steroid injection is a treatment method frequently used to resolve a large number of orthopedic, rheumatological, dermatological, and neurological disorders. Although this treatment is very effective, it is not without possible side effects, both systemic and local, among which we can mention pain, bleeding, ulceration, atrophy, pigmentary changes, calcification, secondary infections, formation of granulomas, allergic reactions and, in very rare cases, the development of linear atrophy, and hypopigmentation. Here, we present a case of frontal linear skin atrophy after intralesional steroid injection for the treatment of alopecia areata (AA) in a 29 year-old patient, successfully treated with a hyaluronic acid filler.

Efficacy and safety of adalimumab in difficult-to-treat psoriasis.

Psoriasis is a chronic immune-mediated inflammatory skin disorder, with a prevalence of 2% to 3% worldwide. Psoriatic lesions affecting scalp, nails, palms, and soles are considered difficult-to-treat and require specific management. When psoriasis involves these areas, it may be considered more severe even if the lesions are not extensive. Adalimumab (Humira) is a fully human monoclonal antibody against tumor necrosis factor (TNF), administered via subcutaneous injection. It has already been used in the treatment of adults and children with moderate-to-severe chronic plaque psoriasis. In literature, few studies investigated its efficacy in difficult-to-treat areas, hence we conducted an observational prospective study of 24 weeks to assess its role in patients with difficult to treat psoriasis. We found out a significant improvement in nail and scalp psoriasis, while palmoplantar and genital psoriasis showed an improvement though not statistically significant. Therefore, adalimumab can be used in difficult-to-treat areas with great results, also allowing an improvement in the quality of life of affected patients, both adults and children.

Paradoxical Psoriasis Induced by Anti-TNFα Treatment: Evaluation of Disease-Specific Clinical and Genetic Markers.

Paradoxical psoriasis (PP) may occur during treatment with anti-tumor necrosis factor-alpha (TNF-α) drugs in various chronic immune-mediated diseases, mainly inflammatory bowel diseases (IBD) and psoriasis. In this study, clinical and genetic characteristics of PP arising in IBD and psoriatic patients were investigated to identify disease-specific markers of the paradoxical effect. A total of 161 IBD and psoriatic patients treated with anti-TNF-α drugs were included in the study. Of these patients, 39 developed PP. All patients were characterized for the main clinical-pathologic characteristics and genotyped for six candidate single nucleotide polymorphisms (SNPs) selected for their possible role in PP susceptibility. In IBD patients, the onset of PP was associated with female sex, presence of comorbidities, and use of adalimumab. IBD patients with PP had a higher frequency of the TNF-α rs1799964 rare allele (p = 0.006) compared with cases without the paradoxical effect, and a lower frequency of the human leucocyte antigen (HLA)-Cw06 rs10484554 rare allele (p = 0.03) compared with psoriatic patients with PP. Overall, these findings point to specific clinical and genetic characteristics of IBD patients with PP and provide data showing that genetic variability may be related to the paradoxical effect of anti-TNF-α drugs with possible implications into clinical practice.

One drug and two diseases: A case of multidrug-resistant hidradenitis suppurativa and psoriasis treated with apremilast.

Hidradenitis suppurativa and psoriasis are chronic inflammatory skin disorders. The onset of these pathologies is due to the interaction between genetic, environmental, and immunological factors making them classifiable as immuno-mediated inflammatory diseases, deriving from immunological deregulation. The coexistence of hidradenitis suppurativa (HS) and psoriasis in the same patient is rare and choosing the right therapy to treat both the conditions can be challenging. Here, we report the case of a patient affected by multidrug-resistant psoriasis and HS who reached a complete healing with apremilast, suggesting its possible therapeutic role in patients showing both the diseases.

Adalimumab in severe plaque psoriasis of childhood: A multi-center, retrospective real-life study up to 52 weeks observation.

The objective of this study is to determine drug effectiveness and safety of the tumor necrosis factor-alpha blocker monoclonal antibody adalimumab in a real-life cohort of 54 children and/or adolescents with severe plaque psoriasis. Retrospective, multicenter analysis over a 52-week period is discussed in this study. Efficacy was determined by the percentage of patients achieving Psoriasis Area Severity Index (PASI 75) and PASI 90 at weeks 16, 24, and 52 and the response in biologic-naïve versus non-naïve patients. Safety was assessed by the number of patients experiencing at least one adverse event. At week 16, 29.6% of patients achieved a 90% PASI score reduction (PASI 90), while 55.5% of patients achieved a 75% PASI score reduction (PASI 75). Effectiveness was sustained through week 24, since PASI 90 response increased to 55.5% and PASI 75 response increased to 74.0% of patients. The PASI response rates did not differ between biologic-naïve and non-naïve patients. The drug was well tolerated and no serious infections were observed. Adalimumab was effective and safe in this cohort of children with severe plaque psoriasis in a 52-week observation. Effectiveness did not differ between biologic-naïve and non-naïve patients.

Use of biological drugs in patients with psoriasis and psoriatic arthritis in Italy: Results from the PSONG survey.

This Italian multicenter retrospective study compared the drug survival and efficacy of different anti-TNF agents in psoriasis (PsO) and psoriatic arthritis (PsA) patients. A database of PsO/PsA patients treated with adalimumab, etanercept, and infliximab from May 2013 to May 2014 was analyzed. PASI 75, 90, and 100 was calculated at each time point to evaluate efficacy. Drug survival rate and probability of maintaining PASI response were evaluated. The impact of dependent variables on probability of PASI 75 loss was evaluated by logistic regression. 1,235 patients were included, 577 with PsO and 658 with PsA. Highest survival rates were observed with adalimumab followed by etanercept and infliximab in PsO and PsA patients. The probability of maintaining PASI response was significantly higher for adalimumab followed by infliximab. For PsO patients, the odds of losing PASI 75 was higher in etanercept-treated patients (OR: 8.1; 95% CI: 4.2-15.6, p < .001) or infliximab (OR: 6.6; 95% CI: 2.6-16.3, p < .001) vs. adalimumab. Likewise, for PsA patients the odds of losing PASI 75 was higher in etanercept-treated patients (OR: 2.3; 95% CI: 1.4-3.8, p = .01) or infliximab (OR: 2.2; 95% CI: 1.1-4.1, p = .018) vs. adalimumab. Adalimumab could be the best therapeutic option over other anti-TNF agents for the treatment of PsO and PsA patients.

Detection of adalimumab and anti-adalimumab levels by ELISA: clinical considerations.

Psoriasis (Ps) is a common and stigmatizing chronic inflammatory skin disease that may cause other chronic inflammatory conditions with overlapping pathology, such as rheumatoid arthritis (RA). Tumor necrosis factor (TNF) is a proinflammatory cytokine that plays a pivotal role in chronic inflammatory and autoimmune diseases such as uveitis, multiple sclerosis, systemic lupus, arthritis, Ps, and Crohn's disease. The TNF superfamily and receptors represent active targets for drug development. Anti-TNF biological therapies, such as infliximab, adalimumab (ADL), and etanercept, are effective in treating RA, spondyloarthritis, Ps, and inflammatory bowel diseases, but long-term treatment can induce anti-drug antibody (ADA) formation associated with lower drug levels and clinical nonresponse. An investigation of the relationship between serum ADL/anti-adalimumab antibody (AAA) concentration, and clinical response in moderate to severe Ps, confirmed an association between ADL and AAA levels and response. Although the detection of ADAs can be used to determine the cause of nonresponse and aid therapy decisions, the contrary observation of long-term responders with low drug levels and detectable ADA suggests that another mechanism is also involved.

Effectiveness of risankizumab for the treatment of psoriatic arthritis: a multicenter, real-world study.

BACKGROUND: IL-23 inhibitors were recently approved for the treatment of skin psoriasis and psoriatic arthritis (PsA). Risankizumab, a humanized monoclonal antibody that specifically binds the p19 subunit of IL-23, has proven effective on PsA in two randomized controlled trials. To date, only a few real-world data are available on this topic. METHODS: Our study aimed to prospectively evaluate the effectiveness of risankizumab in patients with PsA in a real-world setting. For this purpose, both rheumatologic and dermatologic assessments were performed at baseline and after 28-40 weeks of continuous risankizumab administration. Moreover, joint and entheses ultrasound assessment was performed at the mentioned time points. The rheumatologic assessment was carried out by means of the following scores: (i) clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA); (ii) Leeds Enthesitis Index (LEI); (iii) Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and (iii) Bath Ankylosing Spondylitis Functional Index (BASFI). The degree of skin involvement was measured by both the Psoriasis Area and Severity Index (PASI) and Physician Global Assessment (PGA). Quality of life was assessed by the Health Assessment Questionnaire (HAQ) and Dermatology Life Quality Index (DLQI). Ultrasound assessment of joints and entheses was performed on the basis of the EULAR-OMERACT score. RESULTS: After treatment, cDAPSA decreased from a mean value of 12.9 ± 7.6 to 7.0 ± 6.1 (P < 0.001), and the median PD score significantly decreased from baseline (3; range 1-8) to TP1 (1; range 0-7) (P < 0.001). PASI score also decreased from 8.4 ± 4.9 to 0.3 ± 0.5 (P < 0.001), and PGA from 3.1 ± 1.0 to 0.4 ± 0.5 (P < 0.001). CONCLUSION: We can conclude that risankizumab led to substantial improvement in both skin and joint involvement.

Frequency of melanocytic nevi in psoriatic patients is related to treatment and not to disease severity.

BACKGROUND: Few data exist on the relationship between psoriasis and melanocytic lesions. OBJECTIVES: We sought to investigate number of melanocytic nevi in psoriatic patients compared with control subjects and its relationship with disease severity and treatment. METHODS: We performed a prospective study in 189 psoriatic patients and 189 control subjects. Sociodemographic and clinical data were recorded for all participants. RESULTS: As compared with control subjects, patients had fewer nevi overall [χ(2)(5) = 52.24, P < .001], fewer nevi less than 5 mm [χ(2)(4) = 60.28, P < .001], and fewer congenital nevi [χ(2)(1) = 10.41, P = .002]; no differences in atypical nevi and family history of cancer, including melanoma, were observed. Among psoriatic patients, number of biologics used was a risk factor for a higher nevus count [odds ratio 1.35 (95% CI 1.04-1.76), P = .02] whereas disease severity did not correlate with number of nevi. LIMITATIONS: Low number of psoriatic patients naïve to systemic therapies was a limitation. CONCLUSIONS: Psoriatic patients have fewer nevi than control subjects. Frequency of nevi in psoriatic patients is related to treatment, not to disease severity.

Effectiveness of risankizumab in the treatment of palmoplantar psoriasis: a 52-week Italian real-life experience.

Background: Data on the treatment of palmoplantar psoriasis (PP) are scarce, representing a therapeutic challenge. This study aims to assess the efficacy and safety of risankizumab in a population of patients with psoriasis with a palmoplantar involvement, over a 52-week treatment period. Methods: We performed a retrospective analysis in a cohort of patients with PP, with or without involvement of other skin sites. Palmoplantar Psoriasis Area and Severity Index (ppPASI) was assessed at baseline and after 4, 16, 28 and 52 weeks, to evaluate the PP severity. Results: Sixteen patients were enrolled. The rates of ppPASI90 responses constantly increased during the period of observation and were 18.7%, 62.2%, 75.0% and 81.2% at weeks 4, 16, 28 and 52, respectively. Only two patients suspended treatment because of ineffectiveness at week 16. Conclusion: Our data from a series of 16 patients reveal that risankizumab could represent an effective and safe therapeutic choice in patients with PP.

Efficacy and safety of subcutaneous anti-tumor necrosis factor-alpha agents, etanercept and adalimumab, in elderly patients affected by psoriasis and psoriatic arthritis: an observational long-term study.

BACKGROUND: In elderly patients the management of psoriasis is challenging due to contraindications and a higher risk of side effects. OBJECTIVE: Our retrospective study aimed to evaluate the long-term efficacy and safety profile of subcutaneous anti-tumor necrosis factor (anti-TNF) agents in elderly psoriatic patients. METHODS: The study included 89 patients (aged ≥65 years) with plaque-type psoriasis and psoriatic arthritis treated with the subcutaneous anti-TNF-α agents etanercept or adalimumab as monotherapy for a long-term continuous period. RESULTS: Efficacy results were consistent and stable over long-term observation, as expressed by mean Psoriasis Area and Severity Index (PASI) score variation, percentage of patients achieving PASI50 and PASI75 and by the improvement of articular indices, pain visual analogue scale (Pain-VAS) and 44-Joint Disease Activity Score (DAS44-ESR). The proportion of patients achieving PASI50 was 91.80 and 82.14% at week 156 with etanercept and adalimumab treatment, respectively, while the proportion of patients achieving PASI75 was 83.61 and 71.43% at week 156 when treated with etanercept and adalimumab, respectively. The mean DAS44-ESR score decreased from 5.80 to 0.89 and from 3.43 to 1.44 at week 156 and the mean Pain-VAS score decreased from 75.10 to 3.15 and from 71.30 to 18.26 at week 156 with etanercept and adalimumab treatment, respectively. Both treatment adherence and safety profile were good. CONCLUSIONS: Our study demonstrates that subcutaneous anti-TNF-α agents are appropriate in the long-term management of elderly patients.

Improvement of Psoriasis Using Oral Probiotic Streptococcus salivarius K-12: a Case-Control 24-Month Longitudinal Study.

Psoriasis is a common chronic skin disease, associated with an important physical and physiological involvement for any age. There is a strong link between psoriasis and streptococcal infection, particularly that of the tonsils. There are many therapies to treat psoriasis including topical, systemic, and biologic agents but these treatments are not free from side effects. Streptococcus salivarius K-12 is an oral probiotic product useful for the prophylaxis and treatment of tonsillar infections in children and adults, now tested here for the first time for control of psoriasis. Our retrospective analysis was conducted on 198 patients affected by mild to moderate psoriasis: 100 patients were first treated for 90 days with Streptococcus salivarius K-12, while 98 did not receive any probiotics and were the control group. The patients treated with S. salivarius K-12 exhibited a significant improvement of their psoriasis from the baseline condition: 83.7% patients treated achieved a 100% improvement of the PASI score at 24 weeks and efficacy continued to improve with longer treatment, maintaining same result also during follow-up observation. In all patients, the treatment was well tolerated, and no adverse events have been observed. Our data show that oral preparations containing Streptococcus salivarius may provide a beneficial option for the prevention and cure of pediatric and adult psoriasis.

Psoriasis in difficult to treat areas: treatment role in improving health-related quality of life and perception of the disease stigma.

BACKGROUND: When psoriasis affects scalp, nails, palms and soles, it is considered difficult to treat and causes severe impairment of life quality. OBJECTIVE: We evaluated which difficult site most impacts on the patient's quality of life and how quality of life changes during treatment. METHODS: We conducted a prospective observational study in patients receiving adalimumab over a 24 weeks period, through assessment at weeks 0, 4 and 24 using PASI, PAIN VAS, ITCH VAS, DLQI, NAPSI, PSSI. Pearson correlation was used to evaluate the relationship between the various measurements on the basis of three different deltas (between T0 and T24, between T0 and T4, between T0 and average between T4 and T24). RESULTS: The correlation matrix between T0 and T24 shows a significant correlation between delta PASI and delta ITCH and delta ITCH and delta DLQI and a significant correlation between ITCH delta and DLQI delta and a correlation close to significance between DLQI and NAPSI. CONCLUSION: We identified itching as a mediator between the cutaneous extension of psoriasis and the impact on quality of life. We also documented the predominant role of nail psoriasis in defining the impact on the quality of life of the psoriatic patient.

Skin advanced glycation end products as a diagnostic and monitoring tool among psoriatic patients: how the therapy helps reduce cardiovascular disease risk.

BACKGROUND AND AIMS: Psoriasis is a disturbing and burdensome inflammatory skin disorder, with a global prevalence of 2-3%. An increased risk of cardiometabolic disease between psoriatic patients has been recently demonstrated. This is probably due to the psoriasis systemic inflammation and the increased levels of inflammatory cytokines, such as IL-17, IL-23, and TNF-α. Advanced glycation end products (AGEs) are the products of nonenzymatic glycation and oxidation of proteins and lipids which modify their structure and function. They have a significant role in the pathogenesis of diabetic nephropathy, atherosclerosis, and cardiovascular diseases of diabetic adults and children. The accumulation of AGEs can be measured by skin autofluorescence (SAF). Adalimumab (Humira ®) is a fully human monoclonal antibody, administered via subcutaneous injection, which binds the tumor necrosis factor (TNF) and is used to treat moderate-to-severe chronic plaque psoriasis. We performed an observational prospective study of 24 weeks to assess the reduction of AGEs through SAF measurement during treatment with adalimumab. METHODS: SAF measurements in patients were performed at T0 and after 24 weeks of therapy. Adalimumab efficacy was assessed using Psoriasis Area and Severity Index (PASI), Visual Analogue Scale (VAS) for pain, and erythrocyte sedimentation rate (ESR). RESULTS: ESR, AGEs, PASI, and VAS for pain decreased throughout the study period. CONCLUSION: Adalimumab reduced AGEs in psoriatic patients. Biologic therapies may also prevent cardiovascular disease, suggesting a new approach of combined therapy for psoriasis and cardiovascular diseases.

Prevalence of Atherosclerosis in Psoriatic Patients Detected with Epiaortic Color Doppler Ultrasound and Computed Tomography Angiography.

INTRODUCTION: Psoriasis (PsO), a chronic inflammatory, multisystemic, and multifactorial disease can cause endothelial dysfunction, artery calcification, and atherosclerotic disease. A higher incidence of vascular occlusive events has been observed in psoriatic patients compared to healthy controls, and multiple studies confirm the association between moderate-severe PsO and atherosclerosis, coronary artery calcification, and higher cardiovascular risk. OBJECTIVE: We sought to analyze atherosclerotic disease prevalence in epiaortic vessels of psoriatic and non-psoriatic patients to understand if PsO could represent an independent risk factor predisposing to atherosclerotic disease. METHODS: We evaluated 47 psoriatic patients without cardiovascular risk factors with color Doppler ultrasound (CDUS). If atheromatous plaques were detected, a computed tomography angiography (CTA) was performed. We evaluated 47 non-psoriatic patients without cardiovascular risk factors with CDUS. Atherosclerosis prevalence in both groups were statistically analyzed. CDUS performance was compared to CTA. RESULTS: In the psoriatic group (mean age 50.9 years), 6 had atheromatous plaques and 12 had an intima-media thickness (IMT) > 1 mm (overall prevalence of atherosclerotic disease: 38.2%). All plaques detected with CDUS were confirmed at CTA. In the control group (mean age 51.3 years), CDUS revealed atheromatous plaques in 4 patients and IMT > 1 mm in 4 ones (overall prevalence of 17%). The difference of atherosclerotic disease prevalence between the groups was statistically significant (P < 0.05). CONCLUSION: Our results highlight that PsO could be considered a predisposing factor for atherosclerotic disease development in epiaortic vessels, as it causes an increased IMT, that is also considered an independent cardiovascular risk factor.

Predictive factors of lack of response to adalimumab among bio-naive patients suffering from moderate-to severe psoriasis: analysis of a multicenter data collection in Italy.

INTRODUCTION: Efficacy of anti-TNF-a agents seems inferior to IL-17 and IL-23 inhibitors. Nevertheless, after biosimilars approval, anti TNF-a agents are recommended as first-line for psoriatic patients, for economic reasons. METHODS: Predictive factors of response or non-response to adalimumab in bionaive patients who started adalimumab (originator or biosimilar) over 12 years in 9 dermatologic centers in Italy. Effectiveness was assessed with Psoriasis Area and Severity Index (PASI75 and PASI90) at weeks 12, 24 and 48. Multiple logistic regressions were used for variables predicting clinical response; Kaplan-Meier survival curves and Cox regression for drug survival. RESULTS: The drug survival analysis showed reduced hazard ratio of overall discontinuation with male gender and scalp localization. In contrast, baseline PASI and genital psoriasis were significantly associated with increased risk of overall discontinuation. Predictive factors of non-response seemed elevated in patients with baseline PASI, older age groups, previously treated patients with phototherapy, females or patients with palmo-plantar while scalp psoriasis, previous cyclosporine and acitretin appeared as a positive predictive factor. CONCLUSIONS: This real-life analysis might be useful for clinicians in case of bio-naive patients with moderate-to-severe psoriasis and various comorbidities.