PASI Score Research Articles

Comparative Effectiveness of Biologic Classes in Clinical Practice: Month 12 Outcomes from the International Observational Psoriasis Study of Health Outcomes (PSoHO).

Studies directly comparing the effectiveness of different biologics over long observation periods are lacking. As many treatment guidelines are formulated based on drug class, there is a particular need to compare drug classes rather than specific biologic agents. This post hoc analysis compares the effectiveness and durability of biologics that target the interleukin (IL)-17 A ligands or the IL-17 receptor A (IL-17RA) relative to other approved drug classes in patients with moderate-to-severe plaque psoriasis, through 12months in a real-world setting. In the Psoriasis Study of Health Outcomes (PSoHO) (N=1981), patients treated with anti-IL-17A/RA resulted in a higher proportion of patients who achieved the primary outcome [proportion of patients who had at least a 90% improvement in Psoriasis Area and Severity Index score (PASI90) and/or a score of 0 or 1 in static Physician Global Assessment (sPGA)] compared to anti-IL-23-, anti-IL-12/23-, and tumor necrosis factor (TNF)-α-treated patients at week 12, month 6, and month 12, except versus anti-IL-23 at month 12. Similar trends were observed for a 100% improvement in PASI score (PASI100), PASI90, and Dermatology Life Quality Index score of 0 or 1 [DLQI (0,1)]. At month 12, the unadjusted response rates across the drug classes were 53.5-69.1% for the primary outcome, 27.6-40.8% for PASI100, 41.7-55.9% for PASI90, and 31.8-33.0% for DLQI (0,1). Regarding the durability of effectiveness, anti-IL-17A/RA patients had the highest response rate, and for the adjusted analysis, using Frequentist Model Averaging (FMA), patients had 1.4-2.6 times higher odds of achieving the primary durability outcome compared to patients treated with any other drug class. Overall, anti-IL-17A/RA had the highest effectiveness of achieving early response to treatment and maintaining that response through 12months compared to other drug classes. The study was registered at the European Network of Centers for Pharmacoepidemiology and Pharmacovigilance (ENCEPP24207).

Innovative Topical Therapy for Extensive Psoriasis: A New Approach to Treatment

We present a case of a patient with extensive psoriasis successfully treated with “Psorisbye,” our newly developed foamy lotion. A 36-year-old male presented to our outpatient clinic with extensive psoriatic lesions affecting the chest, abdomen, back, arms, and forearms. His past medical history was unremarkable. The patient’s primary concern was severe itching associated with the psoriatic lesions. Upon examination, extensive erythrodermic psoriatic lesions were observed, covering approximately 50% of the head and neck, 70% of the trunk, and 70% of both upper and lower limbs. He was advised to use our newly patented lotion, “Psorisbye,” once daily for one month, during which he applied a total of 480 ml over 28 days. No antihistamine was administered during this treatment period. After 28 days of using “Psorisbye,” the patient returned to the clinic, reporting significant improvement in itching and noticeable remission of the red lesions. A comparison of the lesions before and after 28 days of treatment showed a remarkable reduction in his PASI score, improving from 43.7 to 2.8. Our case report demonstrated promising results in treating extensive erythrodermic psoriatic lesions with “Psorisbye.” However, clinical trials with a larger sample size and longer follow-up are essential to further evaluate remission periods and assess any potential adverse effects of applying this innovative topical therapy to large body surface areas.

Management of Plaque Psoriasis with Multimodal Treatment of Ayurveda - A Case Report

Psoriasis is the immune system problem that causes skin to revitalize at faster rate. It’s the chronic disease that has psychological and social impact on patient’s life. This condition had been narrated many decennium ago but proper aetiology and its cure remain under researched. In Ayurveda this multifaceted etiology disease needs multimodal treatment. The modern treatment provides only temporary relief with too many serious side effects. The treatment embraced here was in accordance with ayurvedic Samprapti. This case report details the successful management of plaque psoriasis in a 32-year-old female patient using a multimodal treatment approach, which incorporated Panchakarma, a traditional Ayurvedic detoxification therapy. The patient presented with erythematous plaques on forehead, neck region, lateral surface of legs and at arms along with itchy and burning skin. Auspitz sign and Koebner phenomenon was positive. Diagnosis made on the basis of Sign and Symptoms. After a thorough evaluation of the patient's constitution and the nature of the disease, a customized Panchakarma protocol was devised involving Virechana (Purgation) followed by Basti (medicated enema) along with Shamana Chikitsa (Internal Medication). The results revealed a remarkable improvement in the patient's psoriasis lesions, with a significant reduction in PASI scores, reduction in scaling, erythema, and in duration. The patient reported a substantial reduction in itching and discomfort. This case report emphasizes the potential of Panchakarma as an adjunctive therapy for plaque psoriasis, highlighting the holistic and personalized approach of Ayurveda in managing chronic skin conditions. Further research and larger-scale studies are warranted to confirm the effectiveness of Panchakarma in the treatment of psoriasis and to observe its long-term benefits and safety profile.

Stilbene-enriched extract from the leaves of Cajanus cajan attenuates psoriasis in imiquimod-induced psoriatic mice by targeting Aryl hydrocarbon receptor and chemokines.

The leaves of Cajanus cajan (L.) Millsp., an Asian traditional folkloric medicine, have been used to treat inflammatory conditions since ancient times. In Southern China, these leaves have been employed to alleviate the symptoms associated with various skin diseases. However, the therapeutic effects and the underlying mechanisms of Cajanus cajan leaves in the treatment of psoriasis remain poorly understood. This study aims to investigate the efficacy of stilbene-enriched extract from C. cajan leaves (termed as "EXT") in treating imiquimod (IMQ)-induced psoriatic mice and to elucidate its possible underlying mechanism in psoriasis treatment. The coumpounds of EXT was analyzed through a UPLC-MS system, the MS survey scan was conducted across the mass range of m/z 100∼1000 Da. The activation of aryl hydrocarbon receptor (AhR), a potential therapeutic target, by EXT in HaCaT cells was assessed using RT-qPCR and immunofluorescence. Subsequently, EXT was administrated to IMQ-induced psoriatic mice once daily for 10 days. The efficacy of EXT in treating psoriasis was evaluated through pathological analysis including change of weight, PASI score, Baker score, epidermal thickness, and H&E staining of lesion skin. Additionally, transcriptomic analysis of lesion skins was conducted to identify the potential therapeutic targets and possible mechanisms of EXT in psoriasis treatment. It was identified that the primary stilbenes present in EXT were 3.10% pinosylvin monomethyl ether (PME), 12.32 % cajaninstilbene (CSA), 4.54 % ongistylin A (LGA) and 2.43 % longistylin C (LGC). In cellular tests, the addition of 2.5 μg/ mL EXT to HaCaT cells enhanced the expression of AhR and its nuclear translocation. In vivo tests of EXT in IMQ-induced psoriasis mouse model, 50 mg 1.0 % EXT reduced PASI and Baker score of lesion skin to 2.67 and 4.5, respectively. In addition, the epidermis thickness of lesion skin induced by IMQ returned to normal following the application of 50 mg 1.0 % EXT in psoriatic mice. Transcriptomic profiling revealed significant downregulation of numerous chemokines (Ccl2, Ccl20, and Cxc5, etc.), pro-inflammatory cytokines (Il17a, Il19, Il22, and Il23, etc.), and genes associated with keratinocyte differentiation (Lce and Sprr family genes). Conversely, AhR and genes of the cytochrome P450 family were activated. This study is the first to demonstrate that the ethyl acetate (EtOAc) extract enriched with stilbenes from Cajanus cajan leaves (EXT) effectively alleviates symptoms in IMQ-induced psoriatic mice. The mechanism involves the activation of the aryl hydrocarbon receptor (AhR) and a subsequent reduction in the production of various inflammatory chemokines and cytokines. These findings suggest that EXT holds significant potential as a plant-derived therapeutic agent for the treatment of psoriasis.

A CLINICAL STUDY TO EVALUATE THE EFFECTIVENESS OF VAMANA KARMA AND SHAMANA CHIKITSA IN THE MANAGEMENT OF EKA KUSHTHA (PSORIASIS)

Eka kushtha comes under Kshudra Kushtha division of Kushtha roga in Ayurvedic texts and primarily involves an imbalance of Vata and Kapha Doshas. This condition is characterized by symptoms such as Asvedanam (lack of sweating), Mahavastu (extensive areas of the body affected), Matsyashakalopamam (scaling resembling fish scales), Krishna Aruna Varna (dark or reddish-brown skin lesions), Kandu (itching), and Rukshata (dryness). In contemporary terms, it can be related to Psoriasis, which is chronic, non-communicable disease (NCD), with inflammatory changes in skin, this disease having no cure causing negative impact on patients quality of life (QoL). The World Health Organization (WHO) reported a global prevalence of Psoriasis in countries vary between 0.09% and 11.4%, in most developed countries, prevalence ranges between 1.5 and 5%. India showing a prevalence range between 0.44% and 2.88%. Psoriasis causes physical, mental and social burden leading to impaired quality of life in patients, making psoriasis a serious health concern. According to Acharya Charaka, the treatment for Eka kushtha should address the excessive Doshas involved. Since Eka kushtha is considered a Bahudosha (excessively aggravated Dosha) and Chirkari (chronic) condition, Shodhana Chikitsa (purificatory treatments) are recommended along with shamana chikitsa (palliative treatments). This study evaluated the effectiveness of Vamana Karma following Shamana Chikitsa in the management of Eka kushtha. A total of 33 patients with Eka kushtha (Psoriasis) were enrolled in the study and undergone Vamana Karma as Shodhana Chikitsa followed by local application of Vajrak Tail and Ayaskriti Paan as Shamana Chikitsa . The study depicted statistically significant improvement in PASI Score (71.28% improvement) and other subjective parameters like matsyashaklopamam, kandu, aswedan, bahalatva, mandal and rukshta were also reduced significantly within the sample. Overall improvement % after 50 days of study period shows that this treatment regimen (Shodhanottar Shamana Chikitsa) is highly effective with 82% markedly improved patients.

Effectiveness of tildrakizumab 200 mg: an Italian multicenter study

Introduction: Psoriasis is a chronic immune-mediated disease that can be challenging to treat, especially in patients with severe disease or high body weight. Tildrakizumab is a monoclonal antibody which inhibits IL-23, approved for moderate-to-severe psoriasis with a standard 100 mg dose. A 200 mg dose may provide greater efficacy for patients over 90 kg or with high disease burden. Methods: This multicenter, prospective study evaluated the effectiveness and safety of tildrakizumab 200 mg in patients with moderate-to-severe psoriasis, focusing on those with specific challenges: body weight over 90 kg, baseline PASI ≥20, and difficult-to-treat areas. The study also compared bio-naive versus bio-experienced and male versus female patients. Adults received tildrakizumab 200 mg subcutaneously at weeks 0 and 4, then every 12 weeks. Results: Clinical improvements were assessed using PASI, DLQI, genital PASI, and NAPSI scores. After 24 weeks, the mean PASI score dropped from 14.6 to 0.4, with PASI 90 and PASI 100 scores exceeding 80% (100.0% and 80.3%, respectively). DLQI scores improved from 14.2 to 1.8, and significant improvements were seen in genital PASI and NAPSI scores. No significant adverse events occurred. Conclusions: Tildrakizumab 200 has been shown to be an effective therapeutic option, particularly for patients with high body weight, significant disease burden, and involvement of sensitive areas with no new safety signals.

Eucalyptus oil nanoemulsion for enhanced skin deposition of fluticasone propionate in psoriatic plaques: A combinatorial anti-inflammatory effect to suppress implicated cytokines.

Psoriasis is a chronic inflammatory skin disease that affects patients' quality of life. This study aimed to enhance the efficacy of topical application of fluticasone propionate (FP) using a eucalyptus oil-based nanoemulsion, an oil possessing anti-inflammatory activity and extracted from the leaves, fruits, and buds of Eucalyptus globulus or Eucalyptus maidenii, to improve the skin deposition of FP and aid its anti-inflammatory effect. Box-Behnken design was employed to optimize NE formulations, which were characterized for globule size, zeta potential, polydispersity index, rheological behavior, microscopic morphology, ex vivo skin permeation/deposition, and in vivo efficacy using imiquimod-induced psoriatic lesions. The optimized formulation depicted a droplet size of 188 ± 22.4 nm, a zeta potential of -17.63 ± 1.66 mV, and a viscosity of 204.9 mPa s. In addition to the increased FP retention in different skin layers caused by the NE and the reduced PASI score compared to the marketed cream, the levels of inflammatory cytokines IL-1α, IL-6, IL17a were markedly lowered, indicating the improved anti-psoriatic curable efficacy of the optimized formulation in comparison to the FP-marketed product.

Prospective Real-Life Multicenter Study of Tildrakizumab 200 mg for Moderate-to-Severe Psoriasis: Who Is the Ideal Patient?

Introduction: Tildrakizumab, a humanized monoclonal antibody targeting the p19 subunit of interleukin-23 (IL-23), has shown promise in the management of moderate-to-severe plaque psoriasis, offering potential improvements in clinical outcomes and quality of life. Objectives: The study aimed to identify patient characteristics that indicate the initiation of a 200-mg dosage of tildrakizumab in a real-world setting, focusing on factors that enhance treatment efficacy and safety. Methods: This prospective study included 54 adult patients with moderate-to-severe plaque psoriasis treated with tildrakizumab 200 mg from March 2023 to March 2024 across 13 Italian Dermatology Units. Data collected included demographics, disease duration, comorbidities, and previous treatments. PASI, BSA, and DLQI scores were recorded at baseline, week 4, 16, and 28. Safety was assessed through adverse event reporting. Univariate analysis was performed to identify baseline characteristics significantly associated with achieving PASI ≤ 5 at week 16. Results: Significant reductions in PASI scores were observed at week 4 (9 ± 6.9, p<0.001), with further improvements at weeks 16 (3.9 ± 4.2, p<0.001) and 28 (2.9 ± 4.4, p<0.001). Univariate analysis showed that obese patients (BMI > 30) had higher odds (OR = 4.333, p < 0.05) of achieving PASI ≤ 5. Longer disease duration and starting with a 100 mg dose also correlated with better outcomes. The safety profile was favorable, with minimal adverse events reported. Conclusions: Tildrakizumab 200 mg is effective and safe for moderate-to-severe psoriasis, particularly in obese patients. These findings support its use as a long-term treatment option.

The impact of tildrakizumab on quality of life in patients suffering from moderate-to-severe psoriasis: a 36-week prospective, monocentric, real-life, observational study.

Psoriasis may significantly impact on patients' health related quality of life (HRQoL). Clinical assessment has been combined with HRQoL scores to evaluate the ways that cutaneous disease is a burden to patients. Tildrakizumab is a humanized IgG1 monoclonal antibody targeting interleukin-23 p19 and is approved for the management of moderate-to-severe plaque psoriasis. The aim of our study was to evaluate the impact of tildrakizumab treatment on psychological field in patients affected by moderate-to-severe plaque psoriasis. a 36-weeks observational study was carried out enrolling psoriasis patients who initiated treatment with tildrakizumab 100 mg. DLQI and Skindex-16 questionnaire were administered at baseline, week 12, week 24 and week 36. PASI, BSA and pruritus (p)-VAS were also assessed at baseline and at each follow-up. A total of 34 patients were enrolled. Baseline PASI and BSA score were 28.4±5.6 and 38.8±21.4, respectively. Similarly, the impact of psoriasis on HRQoL was collected (DLQI: 26.4±3.2, Skindex-16: 68±5.8, p-VAS: 8.2). Clinical improvement was assessed since week 12 (PASI: 12.4±4.2; BSA: 16.5±7.3), continuing to week 24 (PASI: 4.2±2.8; BSA: 6.1±3.1) and 36 (PASI: 3.6±3.2; BSA: 4.2±1.37). Clinical improvement was accompanied by an improvement in quality of life at week 16 (DLQI: 15.5±2.9; Skindex-16: 28.2±4.2; p-VAS: 3.8) , 24 (DLQI: 8.2±1.4, Skindex-16: 16.2; p-VAS: 2.6) and 36 (DLQI: 3.1±2.4; Skindex-16: 9.3±2.8; p-VAS: 2.8). Our study also confirmed the safety of tildrakizumab in real life settings, with no treatment discontinuation for inefficacy or adverse events reported during the study. our results confirm tildrakizumab as an effective option for the improvement of psoriasis patients' HRQoL.

Tofacitinib treatment for plaque psoriasis and psoriatic arthritis: A meta-analysis of randomised controlled trials.

Objectives Tofacitinib is used as an oral Janus-associated kinase (JAK) inhibitor acting on JAK1 and JAK3, in treating psoriatic disease. However, there is still no consensus on the optimal dosage and duration of tofacitinib. In this study, we aimed to evaluate the effects of tofacitinib in treating psoriatic disease. Methods and Materials A literature search was done utilising Cochrane library, Medline, EMBASE, Wiley Online library, Web of Science and BIOSIS Previews through December 18, 2022. We performed a meta-analysis of published original studies to assess the impact of tofacitinib in plaque psoriasis or psoriatic arthritis therapy based on seven randomised controlled trials (RCTs) involving 2,672 patients (receiving tofacitinib) and 853 controls (receiving placebo). Results Compared with placebo, the treatment of 5 mg twice-daily (BID) tofacitinib for 12 weeks is sufficient to significantly alleviate the main clinical manifestations of psoriasis [≥75% decrease in Psoriasis Area and Severity Index score (PASI 75): Risk ratio (RR)=4.38 (95% Confidence interval (CI) 2.51 to 7.64); ≥90% decrease in PASI score (PASI 90): RR=21.68 (95% CI 4.20 to 111.85); Physician's Global Assessment of 'clear' or 'almost clear' (PGA 0/1): RR=3.93 (95%CI 3.03 to 5.09)]. Interestingly, there was no significant difference in improvement in PGA 0/1 with 5 mg BID tofacitinib given for 16 weeks when compared with 5 mg BID tofacitinib for 12 weeks [RR=1.11 (95%CI 0.98 to 1.25)]. Additionally, the 5 mg BID tofacitinib for 16 weeks treatment schedule significantly increased the incidence of upper respiratory tract infection (URTI) [RR=1.89 (95%CI 1.06 to 3.38)] as compared to 5 mg BID tofacitinib for 12 weeks treatment schedule [RR=1.15 (95%CI 0.60 to 2.20)]. Conclusion The 5 mg BID tofacitinib for 12 weeks treatment significantly improved psoriasis without causing too many specific adverse events. This indicated that tofacitinib is an effective treatment plan for psoriatic disease by reasonably controlling dosage and dosing time.

Predicting the Time to Relapse Following Withdrawal from Different Biologics in Patients with Psoriasis who Responded to Therapy: A 12-Year Multicenter Cohort Study.

For patients with psoriasis, discontinuation of biologics following remission has become more common in daily practice. We aimed to identify predictors and construct a predictive model for time to relapse following withdrawal from biologics. This 12-year, multicenter, observational cohort study was performed in six dermatology centers between February 2011 and February 2024. We identified biological treatment episodes in patients with moderate-to-severe psoriasis and included only treatment episodes in which a clinical response (≥50% reduction in Psoriasis Area and Severity Index score [PASI 50] from baseline) was achieved and the patient withdrew from biological therapy with a well-controlled status (PASI <10 and ≥50% improvement in PASI from baseline). The primary outcome was time to relapse, which was defined as the period from the last biologic administration to relapse. An extended multivariate Cox proportional hazards analysis (Prentice-Williams-Peterson Gap time model) was used to predict relapse and generate a predictive model. This study screened 1613 biological treatment episodes, and 991 treatment episodes were enrolled. The time to relapse decreased significantly as the number of previous withdrawals from biological treatment increased (p < 0.001). Similarly, the time to relapse decreased significantly as the number of previous biologics used increased (p < 0.001). The maximum PASI improvement during biological treatment decreased and the PASI score at withdrawal of biological treatment increased in parallel as the number of prior withdrawals from biologics increased. The time to relapse following withdrawal was longest for interleukin (IL)-23 inhibitors (IL-23i), followed by the IL-12/23i, IL-17 inhibitors (IL-17i), and tumor necrosis factor-α inhibitors. After adjustment, multivariate Cox regression identified the following significant predictors of relapse following withdrawal: the mechanisms of action of biologics (hazard ratio [HR] for IL-17i vs IL-12/23i, 1.59; HR for IL-23i vs IL-12/23i, 0.60), number of previous withdrawals from biological treatment (HR 1.23; 95% confidence interval [CI] 1.13‒1.33), time to achieve PASI 50 (HR 1.01; 95% CI 1.00‒1.02), maximum PASI improvement on biologics (HR 0.98; 95% CI 0.98‒0.99), and PASI at the end of therapy (HR 1.03; 95% CI 1.01‒1.05). The model had good predictive and discriminative ability. These results have the potential to help physicians and patients make individualized treatment decisions; information on the risk of relapse of psoriasis at specific timepoints following the withdrawal of biologics is particularly valuable for patients considering discontinuation of biologics or as-needed biologic therapy. However, the benefit and risk of repeated withdrawals of biologics should be carefully weighed, as the treatment efficacy and duration of remission decline as the number of withdrawals increases.

Uncovering the Differences: How DLQI and WHO-5 Scores Vary in Moderate-to-Severe Psoriasis Patients Treated with Tildrakizumab 100 mg vs. 200 mg?

Background/Objectives: Psoriasis (PsO) is a chronic inflammatory skin disease that severely impacts patients' quality of life (QoL). Its global prevalence is about 2%, with significant regional variations. PsO manifests in the form of erythematous and scaly plaques, causing intense pruritus and discomfort and limiting daily activities. The condition often includes comorbidities such as psoriatic arthritis, cardiovascular diseases, and metabolic syndrome, further deteriorating QoL. Psychological well-being is notably affected, with high levels of depression and anxiety due to the visible lesions, leading to social stigma and isolation. QoL indexes like WHO-QoL and SF-36 assess various well-being aspects, while patient-reported outcomes (PROs) provide a comprehensive understanding of PsO's impact. However, there are no universally shared PROs in outpatient practice to fully understand the impact of the disease and associated therapies. This study aims to evaluate differences between DLQI and WHO-5 in adult patients with moderate-to-severe PsO treated with tildrakizumab 100 mg or 200 mg. Methods: The study was conducted at the University Hospital of Siena, Italy, from May 2023 to April 2024. Data from 15 patients treated with tildrakizumab 200 mg and 15 patients treated with tildrakizumab 100 mg, observed for at least 28 weeks, were recorded. Demographic data, PASI, DLQI, and WHO-5 scores were analyzed. Patients in the 100 mg group (G100) were selected to match the demographic characteristics of the 200 mg group (G200). Reduction rates of DLQI and WHO-5 were assessed at baseline values and after 4, 16, and 28 weeks. Results: Both groups experienced improvements in QoL. The group treated with 200 mg showed more pronounced and rapid reductions in DLQI and WHO-5 scores compared to the 100 mg group. WHO-5 demonstrated faster improvements in overall well-being than DLQI, indicating its greater sensitivity to changes in mental well-being and overall QoL. No differences in adverse events were observed between the two groups, with no major adverse events reported. Conclusions: In our study, WHO-5 proved more sensitive than DLQI in capturing well-being changes in PsO patients treated with tildrakizumab. However, a combined use of both WHO-5 and DLQI questionnaires should be encouraged in clinical practice. Furthermore, this study confirmed the superior QoL improvement associated with tildrakizumab 200 mg compared to 100 mg. Future research should explore the long-term impact on QoL and comparative effectiveness among other biologic therapies in diverse patient populations.

Efficacy and safety of biotechnological drugs for the treatment of moderate-to-severe psoriasis in the elderly population: a single-center, Italian experience.

Demographic changes impose a number of issues regarding the biological treatment of elderly patients with moderate-to-severe psoriasis. A retrospective, single-center study was conducted on patients aged 65 years or older with moderate-severe psoriasis who had been undergoing treatment with biologic drugs for at least 60 weeks. A total of 168 patients aged 65 years or older with moderate-to-severe psoriasis undergoing biologic therapy were retrieved: 45 were women and with a mean age of 73.23 ± 6.53 years. The decline in mean PASI, BSA, DLQI and NAPSI values over the 60 weeks of treatment was found to be statistically significant at each interval (p < 0.05). Multivariate statistical analysis showed that nearly all the considered independent variables did not influence the response to therapy in terms of PASI score reduction, except for psoriatic arthritis (p = 0.03). We observed a better response by YOs, with 72.84% of subjects achieving PASI 75 and 71.6% achieving PASI 90 and 100 at the 60th week of treatment. The worst result was obtained by the MOs, with 60 percent of subjects reaching PASI 75 at the end of follow-up, while the OOs had a more mixed performance. The results obtained seem to indicate greater efficacy of anti-TNFα drugs, followed by the other classes of interleukin inhibitors. These results could provide a starting point for new and larger studies and guidelines for biologic treatment.

Antipsoriatic Effect of Silymarin NLCs Based Gel: In Vitro and In Vivo Activity.

Psoriasis is a chronic inflammatory disorder affecting over 100 million people, requires long-term therapy. Current treatments offer only symptomatic relief. However, phytoconstituents-based therapies like Silymarin (SLM) have shown promising effects. The study aims to develop, optimize, and evaluate a novel stable SLM NLC gel to improve anti-psoriatic activity by enhancing its permeability and retention into the dermal layer. SLM NLC formulation was prepared and optimized using 32 full factorial designs. The formulation was evaluated for the particle size, PDI, zeta potential, and % entrapment efficiency, evaluated by Transmission electron microscopy and thermal analysis. The freeze dried and prepared NLC-loaded gel was evaluated for physicochemical parameters, ex-vivo, and in-vivo studies. SLM-loaded NLC shows 624nm particle size, 0.41 PDI, 92.95% entrapment efficiency, and -31.6mV zeta potential. The sphere form of NLCs was confirmed using TEM. Controlled drug release was observed in ex vivo studies, low PASI score compared to disease control. Further, the levels of IL-6, TNF-α, and NF-κB were also reduced. The results are supported by histopathology showing minimal parakeratosis indicated in the SLM NLC-treated group. Prepared NLC-based shows enhance topical penetration and decrease the thickness of psoriatic plaques in the in vivo study.

Effects of topical isoxsuprine ointment on imiquimod-induced psoriasiform skin inflammation in mice.

This study assesses the potential positive impact of a 0.05% isoxsuprine ointment on psoriasiform skin inflammation generated by imiquimod in mouse models. Thirty-two male albino mice were allocated into four groups: the control group (which received topical emollients twice daily for 16days), the induction group (which received imiquimod cream (5%) for 8days, twice daily followed by petrolatum gel (15%) for another 8days), and the other two groups, which received imiquimod cream (5%) for 8days followed by either clobetasol ointment (0.05%) or isoxsuprine ointment (0.05%) twice daily for an additional 8days. At the end of the experiment, mice were sacrificed by ethical standards, and levels of TNF-α, IL-6, IL-17A, IL-23, and VEGF were measured; PASI and Backer's score were examined, in addition to the histopathology of skin tissue. Each clobetasol and isoxsuprine group displayed a significant reduction in tissue homogenate levels of TNF-α, IL-6, IL-17A, IL-23, and VEGF, besides increments in IL-10 compared to the induction group. Some markers (IL-17A, IL23, and VEGF) showed no significant difference between clobetasol and the isoxsuprine group. In contrast, the other markers (TNF-α, IL6, and IL10) showed significant differences between clobetasol and isoxsuprine groups. Isoxsuprine ointment showed comparable efficacy to clobetasol ointment in treating imiquimod-induced psoriasiform skin inflammation in mice models, probably due to its possible effect of anti-inflammatory and immunomodulatory activities.

Efficacy and Safety of Secukinumab in the Treatment of Psoriasis in Patients with Skin Phototypes IV to VI.

There is a paucity of data on the treatment of psoriasis in patients with skin of color &ndash; a diverse population among whom variations in clinical features and higher quality of life impact have been reported. This single-center, open-label clinical study evaluated the safety and efficacy of secukinumab in the treatment of moderate-to-severe plaque psoriasis in adults with Fitzpatrick skin types IV-VI. A total of 20 male and female subjects (ages &ge; 18, BSA &ge;10%, PASI Score &ge; 12, IGA &ge; 3) completed this study. The total study duration was 28 weeks. During the treatment period, subjects received secukinumab 300 mg subcutaneously at weeks 0, 1, 2, 3, and 4, then monthly through week 20. 73% of patients achieved at least 90% improvement in PASI score (PASI90) at week 16 compared to baseline (P=0.0592). There was a statistically significant proportion of patients achieving PASI75, IGA of clear or almost clear, and a change from baseline in DLQI total score at weeks 12, 16, and 24. A statistically significant reduction in IGAxBSA-75 score was achieved between week 16 and baseline. The sample size was small and underpowered to detect statistically significant changes in some endpoints. Furthermore, the study period was interrupted by the COVID-19 pandemic, which contributed to numerous missing data points. Secukinumab 300 mg administered monthly was safe, well-tolerated, and efficacious in treating skin of color patients with psoriasis and improving health-related quality of life. Larger studies involving skin of color populations with psoriasis are warranted. J Drugs Dermatol. 2024;23(8):600-606. doi:10.36849/JDD.8128.

The Impact of Statins on Disease Severity and Quality of Life in Patients with Psoriasis: A Systematic Review and Meta-Analysis.

Psoriasis, a chronic autoimmune condition, imposes significant burdens on patients' well-being. While corticosteroid medications are commonly used, their prolonged use presents risks. Statins, known for their immunoregulatory and anti-inflammatory properties, have emerged as potential alternatives. Previous reviews indicated that statins might improve psoriasis symptoms but showed inconsistent results and lacked meta-analyses that generated pooled effect estimates. Therefore, this study addresses this gap by providing a comprehensive overview of the impact of statins on psoriasis severity and quality of life (QoL) for patients with psoriasis. A thorough search of four electronic databases (PubMed, Cochrane Central Register of Controlled Trials, Scopus, and Science Direct) was conducted for relevant studies published before April 2024. Seven studies involving 369 patients were included. This meta-analysis showed a statistically significant reduction in PASI scores at week 8 with statin treatment (MD = -1.96, 95% CI [-3.14, -0.77], p = 0.001). However, no statistically significant difference was found between statins and placebo at week 12 (MD = 0.19, 95% CI [-0.18, 0.55]). Additionally, DLQI scores indicated a significant improvement in quality of life with statins compared to placebo (MD = -3.16, 95% CI [-5.55, -0.77]). Statins can improve disease severity and quality of life in psoriasis patients, suggesting the potential benefits of statin therapy. However, further research is needed to determine the optimal treatment duration, address outcome heterogeneity, and explore additional benefits such as cholesterol and triglyceride reduction.

Increased serum ATG5 as a marker of autophagy in psoriasis vulgaris patients: a cross-sectional study.

Psoriasis (PsO) is a prevalent chronic inflammatory skin disease. It is a complex condition that is affected by environmental and hereditary variables. Numerous pathogens, including viruses, bacteria, and even fungi, have been linked to PsO. One of the mechanisms that clears infections is autophagy. The mechanism by which a cell feeds itself is called autophagy by reusing cytoplasmic components in the lysosome. The autophagy-related (ATG) proteins are essential components of the system that control the strictly regulated process of autophagy. Among these 41 proteins, ATG5 is one that is required in order for autophagic vesicles to develop. This research aimed to compare ATG5 levels in serum among those suffering from psoriasis vulgaris and healthy controls. This cross-sectional research was carried out on 45 individuals with vulgaris psoriasis and 45 healthy, sex and age-matched control subjects. All participants underwent a clinical examination, a laboratory investigation, and a history taking, including lipid profiles and serum ATG5. The mean age of the control and PsO were 40.6 ± 9.6, and 43.7 ± 9.3 years respectively. The mean total PASI score was 13.9 ± 8.9, with a median of 11.7 (8.8). According to the PASI score, about 38% (n = 17) had mild disease (PASI < 10), and about 62% (n = 28) had moderate/severe disease (PASI ≥ 10). There was a significantly higher median (IQR) (25th-75th) ATG5 level in PsO 206 (97) (145-242) ng/ml than in the control 147 (98) (111-209) ng/ml (p = 0.002). An insignificant higher median level (IQR) was observed in PsO with mild disease 207(95) compared with those with moderate/severe disease 183(98.5) (p = 0.057). Dissimilarly, the median (IQR) ATG5 level was significantly lower in PsO individuals with metabolic syndrome 170(72) compared with those without 207(104) (p = 0.044). Four predictors were identified following sex and age adjustments, in the final linear regression model: PASI score, triglyceride, High-Density Lipoprotein, and presence of metabolic syndrome. There can be a connection between autophagy as measured by ATG5 and psoriasis vulgaris. ATG5 was elevated in the serum of individuals with psoriasis vulgaris. However, it decreased in patients with metabolic syndrome. No relation was found between serum ATG5 and PASI score. Psoriasis vulgaris patients may benefit from using an autophagy enhancer as a potential treatment target.

Biologic treatment sequences in moderate-to-severe psoriasis.

The advent of novel biologics has led to an increase in biologic-switching as patients and clinicians pursue improved clinical outcomes. However, guidance on treatment sequencing in an Australian setting is sparse. This study examines the patterns of care across two tertiary centres in Australia and characterizes the factors contributing to biologic-switching. A retrospective study of patients who attended the outpatient Dermatology biologic clinics across two tertiary hospitals was conducted. Data on treatment sequencing and patients' PASI at every visit from April 2006 to December 2020 were collected. Patterns of biologic-switching were examined. The speed of treatment response for each biologic was determined by the time to achieve PASI-90 and -100 for each treatment course. A total of 440 treatment courses were analysed. Ustekinumab and adalimumab were the most frequently prescribed first-line biologics. The highest proportion of biologic-switching was observed among patients on TNF-α inhibitors (63.8%). After 2015, more patients were prescribed IL-12/23 and IL-17 inhibitors in favour of TNF-α inhibitors. IL-17 inhibitors demonstrated the most rapid treatment response and low PASI scores relative to other biologics. Patients who did not switch biologics had lower rates of psoriatic arthritis and lower BMI, compared to patients who switched biologics. The median PASI on discontinuation generally exceeded 3.0, while on continuation, it was less than 1.2, reflecting patients' and clinicians' thresholds for biologic-switching. This study demonstrates an increased uptake of more novel biologics as they become available, due to improved safety profiles and clinical outcomes.

Momordin Ic ameliorates psoriasis skin damage in mice via the IL-23/IL-17 axis.

Psoriasis, a chronic and easily recurring inflammatory skin disease, causes a great economic burden to the patient's family because the etiology and mechanism are still unclear and the treatment cycle is long. In this study, the function and related mechanisms of Momordin Ic in psoriasis were investigated. The IMQ-induced mouse psoriasis model was constructed. The protective effects of different doses of Momordin Ic on psoriasis skin damage in mice were detected by PASI score, HE staining and Ki-67 staining. A psoriasis-like keratinocyte model was established at the cellular level using M5 (IL-17A, IL-22, oncostatin M, IL-1α, and TNF-α) triggered HaCaT. The effects of Momordin Ic upon HaCaT cell biological behavior were examined using MTT and CCK-8 assays. In terms of mechanism, the expression level of each inflammatory factor was assessed using IHC staining and/or ELISA, qRT-PCR, the expression of oxidative stress-related indicators was detected biochemically, and western blot was performed to detect the levels of key proteins of the Wnt signaling and VEGF. As the results shown, at the in vivo level, Momordin Ic significantly alleviated skin damage, reduced PASI score and inhibited hyperproliferation of keratinized cells in psoriasis mice. At the cellular level, Momordin Ic also significantly reversed M5-induced hyperproliferation of HaCaT keratinocytes. In terms of mechanism, Momordin Ic significantly inhibited the IL-23/IL-17 axis, dramatically elevated the levels of intracellular antioxidants including SOD, GSH-Px, and CAT, and significantly down-regulated the levels of the indicator of oxidative damage, malondialdehyde (MDA). In addition, Momordin Ic also significantly inhibited the level of β-catenin, a pivotal protein of the Wnt signaling, C-Myc, a target gene of the Wnt signaling, and VEGF, a critical protein of angiogenesis. Inconclusion, Momordin Ic can be involved in the skin-protective effects of psoriasis by multiple mechanisms, including inhibition of the Wnt signaling pathway and the IL-23/IL-17 axis, and suppression of oxidative damageand VEGF expression. Momordin Ic has been proven to be an underlying therapeutic drug for the treatment of psoriasis.