This study looked at liver fibrosis in psoriasis patients treated with Tremfya (guselkumab)

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Psoriasis is associated with comorbidities like metabolic syndrome and nonalcoholic fatty liver disease, increasing the risk of liver fibrosis.

This study evaluated the long-term effects of guselkumab on liver fibrosis in 154 psoriasis patients using the Fibrosis-4 (FIB-4) index, a noninvasive marker of fibrosis, over 3 years.

Patients were stratified by baseline FIB-4 (≥ 1.3 or < 1.3) and age (35–65 years). Mean FIB-4 values remained stable across all subgroups, with no significant changes observed. High-risk patients (FIB-4 ≥ 1.3) showed minor, nonsignificant fluctuations, while low-risk patients (FIB-4 < 1.3) exhibited a mild, age-related upward trend.

Disease duration emerged as a key factor influencing FIB-4, highlighting the importance of early treatment. These findings suggest guselkumab does not contribute to liver fibrosis progression in psoriasis patients.

Further research with advanced methods like imaging or biopsy is needed to confirm the long-term hepatic safety of IL-23 inhibitors like guselkumab.

Scientists at the university of Birmingham have shown that a sequence of just three amino acids may reduce the severity of psoriasis when applied topically in an emollient cream.

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The researchers identified the smallest part of a peptide (small protein) called PEPITEM, which occurs naturally in the body and regulates inflammation.

The study also showed that both PEPITEM and the three amino acid (tripeptide) sequence delivered a significant reduction in the severity of psoriasis, that is comparable to a steroid cream.

In its native state, PEPITEM consists of a chain of 14 amino acids, but in this most recent study, researchers led by Professor Ed Rainger from the University of Birmingham and Professor Francesco Maione from the University of Naples Federico II, looked for, and identified the smallest parts of the PEPITEM molecule that influence immune cells and inflammation in psoriasis.

Work by the Birmingham scientists identified two sequences of three amino acids that showed biological activity comparable to the full-length PEPITEM molecule.

The scientists then optimised these tripeptides to improve their stability in the body, and tested their ability to reduce immune cell activation and migration, which are hallmarks of inflammatory disease. Their findings showed these two sequences had at least the same activity as the original PEPITEM molecule.

They then selected the sequence with the greatest biological activity and researchers from the University of Naples Federico II trialled its effectiveness in psoriasis, using an animal model of disease.

They found that topical application directly to the skin every day for seven days in an emollient cream resulted in a clear reduction in disease compared to untreated animals, and their findings were confirmed using PASI (Psoriasis Area and Severity Index) scoring, which is used in clinical practice to measure the extent and severity of psoriasis.

Importantly, the study also showed that both PEPITEM and the tripeptide sequence reduced the PASI score by 50%, making it comparable to the steroid cream Clobetasol Proprionate 0.05%.

Professor Ed Rainger said: “While there are a number of therapies for psoriasis, there is a clear need for new therapeutic agents that can be used continuously, and without the risk of excessive side effects, to prevent psoriasis flares. Our findings raise the possibility of using PEPITEM derived peptides for the treatment of psoriasis.”

“This study also raises the interesting possibility that PEPITEM derived peptides could be used in combination with other psoriasis therapies, allowing lower dosing for longer durations, for example, a ‘steroid sparing’ approach, to reduce the side effects associated with prolonged use of such agents.”

University of Birmingham Enterprise has filed several patent families related to PEPITEM and the components of the PEPITEM molecule responsible for maintaining a normal immune response.

The research team is now seeking investment, licensing, partnering and/or collaborative research opportunities.

This study looked at the use of Cosentyx (secukinumab) in Japanese patients with generalised pustular psoriasis (GPP)

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Secukinumab is one of the human monoclonal antibodies recommended in the Japanese guidelines for patients with psoriasis, but few case reports and clinical studies on secukinumab for pustular psoriasis are available because of the rarity of the disease.

This was an open-label, multicenter, uncontrolled, single-arm, prospective observational surveillance conducted in a clinical practice setting to evaluate the safety and effectiveness of secukinumab in Japanese patients with generalized pustular psoriasis (GPP).

Patients were monitored for 1 year after starting secukinumab and followed up for an additional 2 years. Of 99 patients from 71 sites, 95 were included in safety and 82 in effectiveness analysis. The mean (standard deviation) observation period was 346.2 (64.87) days, and 91.58% of patients were observed over 52 weeks.

Adverse events, serious adverse events, and adverse reactions were reported in 51.58%, 12.63%, and 35.79% of patients, respectively. Safety evaluations showed no significant difference in the incidence of events based on the history of biologics The proportion of patients with either “complete response” or “partial response” was ~90% from week 2 and remained stable until week 52.

The proportion of patients with “remission (no symptom)” in the Japanese Dermatological Association total score increased from week 4 (22.22%) to week 52 (47.83%). The mean Psoriasis Area and Severity Index score decreased from week 1 (17.26) to week 16 (1.18), with the mean percentage change decreasing from −28.07% to −90.18%. The mean Dermatology Life Quality Index (DLQI) total score decreased from 8.7 at the start of secukinumab treatment to 1.9 at week 52. At week 52, the proportion of patients with DLQI total score of 0/1 was 57.14%.

No new safety signals for secukinumab in long-term treatment were observed from this surveillance, and no additional measures needed to be taken. Moreover, secukinumab showed sustained effectiveness in patients with GPP in Japan.

This study suggests higher c-reactive protein (CRP) levels were associated with future development of psoriatic arthritis (PsA)

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Objective:
We aimed to assess whether high sensitivity c-reactive protein (hsCRP) could predict the development of psoriatic arthritis (PsA) in patients with psoriasis.

Methods:
We analyzed data from a prospective cohort of patients with psoriasis without PsA at enrollment. Participants were assessed annually by a rheumatologist for signs and symptoms of PsA. Information on patient demographics, psoriasis features, medications and musculoskeletal symptoms was collected. hsCRP levels were measured in serum samples collected at baseline using standard commercial assays. The association between hsCRP levels and risk of development of PsA was assessed using multivariable Cox proportional hazards model adjusted for age, sex, psoriasis severity and duration, nail lesions, body mass index (BMI), fatigue, and medication use.

Results:
A total of 589 patients with psoriasis followed from 2006 to 2019 were analyzed. 57 patients developed PsA during the follow up period. Mean level of hsCRP was 3.1±5.5 mg/L (hsCRP levels in incident PsA cases: 5.4±13.1). Significantly higher levels of hs-CRP at baseline were found in patients with arthralgia, obesity and in females. Higher hs-CRP levels were associated with future development of PsA in multivariable analysis (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.01, 1.07, p=0.007). Similar effect size was seen in males and females. No significant interaction was found between hsCRP and sex or BMI.

Conclusion:
Higher levels of systemic inflammation, as measured by hsCRP, are associated with future development of PsA.

This retrospective cohort study evaluated the clinical outcomes of HIV-positive patients undergoing anti-IL-23 therapy in real-world settings at the Dermatology Units of four leading reference centres in Northern Italy for the treatment of psoriasis.

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HIV-positive patients with psoriasis often face delays in accessing biologic therapies due to their exclusion from clinical trials and concerns about the impact of immunomodulatory drugs on viral replication.

Anti-IL-23 therapies, such as risankizumab and guselkumab, have shown great promise thanks to their strong efficacy and favourable safety profiles.

A case series from four Italian centres reported sustained effectiveness of these drugs, with no observed effects on viral replication or immune parameters in HIV-positive patients. Although the number of cases is limited, these therapies appear to be a compelling option for patients with extensive or treatment-resistant psoriasis.

Hi there , I hope you can assist me in some way please with some advice , I have had Pustular psoriasis since 2016 and my latest GPP is ongoing since 23rd January 2025 , I am glad it isn't as bad as it was but at its worst I was sent to hospital twice being told I needed IV but was sent home which surprised me given the state my skin was also had cellulitis in both legs and feet , the antibiotics (3) different types didn't do anything , I started reading about Metformin being a help with all psoriasis types , I have asked my diabetic nurse and she hadn't even heard of pustular psoriasis infact 2 out 3 doctors I have visited hadn't either , this is a concern that there clearly isn't enough of any knowledge on pustular psoriasis and/or GPP , I get that it is rare but that doesn't mean its any less dangerous!
I don't mean any disrespect but because there is such a lack of knowledge from medical professionals I have had to come on to this forum to find people that have knowledge first hand along the lines of what is the best medication available in UK because nobody in medical profession seems to be able to help or even heard know what GPP is ! 
I'm in my 10th week and still having outbreaks of new pustules daily on various parts of my body and would appreciate any advice you could offer please .

A real-world safety and effectiveness surveillance study of Tremfya (guselkumab) in Japanese patients with psoriasis.

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Guselkumab is a monoclonal antibody that binds to the p19 subunit of interleukin-23 and inhibits its downstream signaling. The safety profile of guselkumab and its superior efficacy over placebo and adalimumab for the treatment of patients with moderate-to-severe psoriasis were reported in phase 3 studies conducted within and outside Japan.

To assess the real-world safety and effectiveness of guselkumab in Japanese patients with psoriasis, we conducted a multicenter, single-arm, prospective, post-marketing surveillance study. Guselkumab was administered by subcutaneous injection at a dose of 100 mg at weeks 0 and 4, then every following 8 weeks.

The patient observation period was 52 weeks after the initial guselkumab dose or until treatment withdrawal. The safety analysis set consisted of 416 patients, including 310 patients with vulgaris (PsV); and the effectiveness analysis set consisted of 251 patients, including 236 patients with PsV or psoriatic arthritis (PsA). There were more men (71.3%, 221/310) than women among the PsV group. The median age among those with PsV was 58 years, the median disease duration was 11.50 years, 50.0% (155/310) had comorbidity, and 41.3% (128/310) had previously been treated with biologic agents.

During the observation period, 8.4% (35/416) of patients experienced 49 adverse drug reactions, 2.9% (12/416) experienced 13 serious adverse drug reactions, and 3.4% (14/416) experienced 16 adverse events leading to treatment discontinuation. In the effectiveness analysis set of 236 patients with PsV or PsA, the Psoriasis Area and Severity Index (PASI) 75, 90, and 100 response rates at week 52 were 69.9%, 54.5%, and 32.5%, respectively. Bio-naïve patients consistently had higher PASI 75 and 90 response rates than bio-experienced patients.

This post-marketing surveillance study demonstrated that guselkumab was well-tolerated and effective in a real-world setting in Japanese patients with psoriasis.

This study asked “If you could improve one thing about your psoriatic arthritis, what would it be?” and “What would an effective treatment change for you?”

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Objective:
The aim was to examine patient-reported treatment goals among individuals with psoriatic arthritis (PsA).

Methods:
Participants in the Psoriatic Arthritis Research Consortium (PARC) completed standardized assessments including patient-reported outcome (PROs) instruments between 2017-2020. Additionally, participants were asked two open-ended questions at enrollment or therapy initiation “If you could improve one thing about your disease, what would it be?” and “What would an effective treatment change for you?” to identify patients’ top improvement priority and their treatment impact goals, respectively. We categorized each response into a theme. The themes were matched to constructs measured by PRO items (i.e., pain, fatigue, skin, etc.). We describe themes and scores from matched PRO items.

Results:
Assessments were completed by 193 participants. Decreasing pain (56%) and improving skin (12%) were the most common improvement priorities. Impact goals were more diverse and included decreasing pain (24%), general improvement in life (18%), the ability to be more active (15%), participate in recreational activities (9%), function at work (11%) and exercise (5%). Of note, responses were often matched to more than one PRO item or instrument. The scores for PRO items that matched the patient's improvement priority, or the impact goal were higher than scores for the remainder of the population (i.e., fatigue item scores were higher among individuals identifying fatigue as their improvement priority).

Conclusions:
The heterogeneity of treatment goals underscores the importance of eliciting patient treatment goals to guide personalized management. Specific items within PROs may be helpful in identifying and following patient-specific treatment goals.

A one year quality of life and sexual health observational study in adult Asian psoriasis patients.

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Genital involvement and sexual dysfunction are common amongst patients with psoriasis. However, the effects of genital psoriasis on quality of life (QOL) and sexual health of psoriasis patients are not well understood.

We performed an observational study on adult Asian psoriasis patients attending psoriasis subspecialty clinics in a tertiary dermatology centre in Singapore over 1 year. Participants underwent clinical examination of the whole-body surface, with particular attention to the genitalia and questionnaires to evaluate QOL and psychosexual health were administered.

A total of 62 patients participated. Most participants were male (82.3%) with a mean age of 41.7 years (SD 12.5). The mean Psoriasis Area and Severity Index (PASI) score was 7.0 (SD 4.3) with a mean Dermatology Life Quality Index (DLQI) score of 9.8 (SD 6.7), indicating moderately impaired QOL. Higher PASI scores were associated with increasing QOL impairment on DLQI (p = 0.021). The commonest site involved was the suprapubic region (61.3%).

Males in whom genital psoriasis prevented sexual intercourse or diminished their libido reported more sexual dysfunction. Females reported a greater severity impact of genital psoriasis in terms of symptoms and embarrassment (p = 0.038) yet were less likely to be on treatment (37.5% vs. 45.0%).

Perceived efficacy of treatment was low, and younger patients fared poorly on the Patient Health Questionnaire-9 depression questionnaire (p = 0.047). Clinicians should proactively evaluate for and treat genital psoriasis, as patients may be reluctant to discuss their genital rashes if not prompted, leading to under-recognition and undertreatment.

How was the study conducted?

Design: Population-based cohort study using linked health administrative data.

Population: Adults age 66+ with psoriasis or psoriatic arthritis using systemic treatments in Ontario, Canada.

Study period: Between April 1, 2002 and December 31, 2020.

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Background:
Systemic treatments for psoriatic disease affect the immune system and may increase infection risk. Older adults are at high risk for infection, and the relative safety of systemic treatments for them is unknown.

Objective:
This study examined the association of systemic treatments for psoriatic disease with rates of serious infection among older adults.

Methods:
We conducted a cohort study used linked population-based health administrative data from 2002 to 2021 in Ontario, Canada.

Results:
Of 11,641 new users of systemic therapy, 53% were female, with a median age of 71. Over 4.8 years of follow-up, there were 1,967 serious infections. Serious infection rates per 100 person-years were 2.7 for methotrexate, 2.5 for other older drugs, 2.2 for anti-TNF biologics, 1.4 for other biologics, and 8.9 for tofacitinib. Methotrexate, older drugs, and anti-TNF biologics were not linked to serious infections, while other biologics had lower rates and tofacitinib had higher rates.

Conclusion:
Biologics targeting IL-12, IL-23, or IL-17 were associated with a lower rate of serious infection among older adults with psoriatic disease. These biologics may have important safety benefits for older adults with higher infection risk.

Patient's perspective on the Impact of psoriasis on their quality of life after 1 year of Ilumya  / Ilumetri (tildrakizumab)

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Background:
Tildrakizumab showed high efficacy and safety for treating moderate-to-severe psoriasis in clinical trials. The development of biologics to treat psoriasis has allowed us to aim for increasingly ambitious objectives. However, patients' and physicians' perspectives on therapeutic goals and satisfaction concerning treatments may sometimes differ.

Objectives:
To analyze the efficacy and safety of tildrakizumab and the impact of the psoriasis improvement regarding the physicians' and patients' point of view, in daily practice, after 1 year of treatment.

Methods:
A prospective multicentric study was conducted in patients who were initiated with tildrakizumab for moderate-to-severe psoriasis. Assessments of psoriasis and its impact on patients' lives were performed at tildrakizumab initiation and after 6 and 12 months of treatment.

Results:
At baseline, psoriasis deeply affected patients' lives, with 42% showing signs of clinical depression and 34.6% experiencing genital involvement with significant impact on their sex life. After 1 year, tildrakizumab was, overall, effective and safe, even in difficult-to-treat areas. Psoriasis Area Severity Index score decreased from 13.6 to 2.3, SF12-mental component score improved from 41 to 48.7 and Dermatology Life Quality Index dropped from 10.4 to 2.5. Despite these improvements, some patients remained dissatisfied, expressing concerns about relapse and persistence of mental impact of the disease over the long term.

Conclusions:
Tildrakizumab confirmed its efficacy and safety for the treatment of moderate-to-severe psoriasis. However, despite good control of their disease, some patients remained dissatisfied, over the long time, raising the issue of the cumulative mental impact of a disease left with no effective treatment for too long before the initiation of an effective treatment. These findings suggest that early treatment of psoriasis with effective therapies is important not only to target tissue-resident memory T cells, as indicated by recent studies, but also to potentially address patients' cicatricial memory of their disease.

This study looked at the effects of different seasons in patients with psoriasis.

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Psoriasis is a chronic inflammatory skin condition driven by immune system dysfunction, genetic predisposition and environmental factors. Patients with psoriasis experience a well-known clinical phenomenon of ‘winter severity and summer relief’, in which seasonal environmental factors play critical roles in the onset and progression of psoriasis.

These factors include temperature, humidity, infection, light exposure and psychological stress. Seasonal changes in temperature and humidity can compromise skin barrier function and exacerbate inflammatory responses, thereby worsening psoriasis symptoms.

Notably, during the winter, decreased light exposure leads to reduced vitamin D (VD) levels, reaching their lowest levels from late winter to early spring. This decline in VD levels is associated with increased disease activity, greater disease severity and more frequent flare-ups in patients with psoriasis.

During the winter, influenza and Streptococcus pneumoniae infections are more prevalent, which can further exacerbate psoriasis symptoms. Moreover, the environmental conditions in winter can trigger or intensify feelings of depression, which may adversely affect psoriasis through the brain–skin axis. In this comprehensive review, we thoroughly examined the influence of seasonal environmental factors on the incidence, recurrence and severity of psoriasis.

By clarifying these complex relationships, we aimed to support the future development of more personalised and effective treatment and management strategies for patients with psoriasis.

Results of a one-year  trial utilising high-resolution peripheral quantitative computed tomography in patients with psoriatic arthritis using Cosentyx (secukinumab).

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Objectives:
This study aimed to ascertain the effect of secukinumab on erosion and enthesiophyte progression in psoriatic arthritis (PsA) by high-resolution peripheral quantitative computed tomography (HR-pQCT).

Methods:
This was a phase 4, double-blind, randomized, placebo-controlled trial. Patients with active PsA and ≥ 1 erosion in the metacarpophalangeal joints (MCPJ) 2-4 were randomised in a 1:1 ratio to subcutaneous secukinumab or placebo. HR-pQCT of the MCPJ 2-4 were performed at baseline, week 24 and week 48 The primary outcome was the changes in the volume of erosions on MCPJ 2-4 measured by HR-pQCT at 24 and 48 weeks.

Results:
Forty patients (age: 51.9±13.4 years, 20 [50%] male, disease duration: 4.7±6.7years) were recruited. Thirty-four patients who completed study treatment were included in the per-protocol analysis. At baseline, week 24 and week 48, the secukinumab group showed a significant reduction in erosion volume, whereas no changes were observed in the placebo group (change in the secukinumab group: -0.1 (-0.5, 0.0) vs: 0.0 (-0.2, 0.4) in the placebo group, p=0.004). A similar trend was observed for enthesiophyte volume changes in the secukinumab group, while no differences were noted in the placebo group (change in the secukinumab group: -0.1 (-0.8, 0.0) vs 0.0 (-0.4, 1.3) in the placebo group, p=0.067). GEE results showed that the odds ratio (OR) for enthesiophyte progression in the secukinumab group was 0.264 (95% CI: 0.080-0.878, p=0.030), while the OR for partial erosion healing in the secukinumab group was 2.882 (95% CI: 1.130 to 7.349, p=0.027).

Conclusions:
Secukinumab demonstrates a potential benefit in facilitating partial erosion repair and preventing enthesiophyte progression in PsA.

This study looked at the safety and effectiveness of Taltz (ixekizumab) in Japanese patients with psoriasis vulgaris, psoriatic arthritis, generalized pustular psoriasis, and erythrodermic psoriasis.

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We report findings from a post-marketing study conducted from November 2016 to September 2022, which evaluated the safety and effectiveness of ixekizumab in Japanese patients with psoriasis under routine clinical practice for up to 52 weeks, and the incidence of serious infections and malignancies for up to 3 years.

Of 804 patients in this analysis (67.9% male; median age, 54 years; mean disease duration, 11.8 years), 72.9%, 37.7%, 7.8%, and 3.7% had psoriasis vulgaris, psoriatic arthritis, pustular psoriasis, and erythrodermic psoriasis, respectively (subtypes not mutually exclusive).

At 52 weeks, adverse events were reported in 203 patients (25.3%). Serious adverse events were reported in 36 patients (4.5%), including serious infections and infestations (n = 13, 1.6%). The incidence of serious infections and benign, malignant, and unspecified neoplasms was 0.8% (n = 5) and 0.6% (n = 4) respectively, at 3 years.

Overall, 137 patients (17.0%) received Q2/Q2 treatment (160 mg starting dose, followed by 80 mg every 2 weeks from week 12); 550 patients (68.4%) received Q2/Q4 treatment (160 mg starting dose, followed by 80 mg every 2 weeks from weeks 2 to 12 and 80 mg every 4 weeks thereafter); and 117 patients (14.6%) discontinued before week 12 or received only one dose after week 12.

A higher proportion of patients in the Q2/Q2 group had psoriatic arthritis (56.9% [n = 78]) compared with the Q2/Q4 group (32.9% [n = 181]). Among patients in the Q2/Q2 versus the Q2/Q4 dose groups, 21 (15.3%) and 141 (25.6%) respectively had adverse events and 2 (1.5%) and 32 (5.8%) respectively had serious adverse events.

The mean Psoriasis Area and Severity Index score and body surface area percentage significantly decreased from baseline to week 52 for all psoriasis subtypes and by Q2/Q2 and Q2/Q4 ixekizumab doses (p < 0.01 or p < 0.001).

Overall, the safety and effectiveness of ixekizumab in real-world settings in Japan were similar to those reported in clinical trials.

This study evaluated treatment response to Skyrizi (risankizumab) and identify potential predictors influencing the treatment response in patients with erythrodermic psoriasis.

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Erythrodermic psoriasis (EP) is a severe and challenging variant of psoriasis that often shows poor drug survival. While risankizumab, an IL-23 inhibitor, has demonstrated efficacy in patients with moderate-to-severe plaque psoriasis, its effectiveness in patients with a history of EP is less explored.

This study aimed to evaluate treatment response to risankizumab and identify potential predictors influencing the treatment response. In this single-center, longitudinal retrospective study, we included 56 patients treated with risankizumab between August 1, 2016, and June 1, 2023, of whom 22 had a history of EP.

Treatment response was assessed using the Psoriasis Area and Severity Index (PASI), and the impact of patient characteristics, including prior biologic exposure and HLA-Cw genotypes, on treatment response was analysed using the Mann–Whitney U test.

Throughout the 100-week follow-up, patients with a history of EP exhibited a poorer treatment response compared to those without such a history. Among patients with a history of EP, those with prior exposure to guselkumab and those treated with more than five biologics demonstrated a decreased response to risankizumab. Additionally, there was a non-significant trend indicating that HLA-Cw1–negative patients responded better to risankizumab.

This case series indicated that risankizumab might be an effective and sustainable treatment option for most patients with a history of EP. However, prior exposure to multiple biologics, particularly those with a similar mode of action targeting IL-23, may reduce its effectiveness. The potential association between HLA-Cw1 genotype and treatment response warrants further investigation.

The study looked at the association between the use of TNF-α inhibitors and an increased risk of fungal infections. 

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TNF-α inhibitors, including infliximab, adalimumab and etanercept, are used to treat various inflammatory diseases, such as arthritis, psoriasis and ankylosing spondylitis. However, these treatments may predispose patients to fungal infections, including histoplasmosis, candidiasis and aspergillosis.

In this study, we systematically reviewed case reports to critically examine the correlations between anti-TNF-α therapies and the occurrence of invasive and superficial fungal infections.

Infliximab was the most commonly used TNF-α inhibitor (50.65%). The highest number of fungal infections during anti-TNF34 α therapy was reported in the USA (84.25%). The conditions treated primarily included rheumatoid arthritis. A total of 517 invasive fungal infections were identified, including histoplasmosis, invasive candidiasis and aspergillosis, with histoplasmosis being the most common.

Most studies were conducted in higher-income countries, highlighting the critical lack of research on the use of immunobiologicals in relation to fungal diseases in African countries, which requires further attention.

Logistic regression analysis revealed significant associations between adalimumab use and increased risks of candidiasis, coccidioidomycosis, onychomycosis and pityriasis versicolor. For etanercept, significant associations were found with aspergillosis, coccidioidomycosis, cryptococcosis, dermatophytosis, invasive candidiasis, pityriasis versicolor and onychomycosis. Infliximab use was significantly associated with coccidioidomycosis, onychomycosis, aspergillosis, cryptococcosis, histoplasmosis and invasive candidiasis.

The data presented in this study clearly demonstrate an association between the use of TNF-α inhibitors and an increased risk of fungal infections. It is imperative that healthcare professionals maintain a high level of vigilance when managing patients on these medications. Regular monitoring and proactive management strategies are essential to mitigate risks and ensure patient safety.

This research suggests there is no link genetic link between psoriasis and diabetes.

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Epidemiological studies proposed a bidirectional link between psoriasis (Ps) and diabetes mellitus (DM); their causal relationship remains inadequately explored.

We obtained summary statistics of genome-wide association analyses for Type 1 diabetes mellitus (T1DM), Type 2 diabetes mellitus (T2DM), and Ps from individuals of European ancestry by accessing the UK Biobank and FinnGen datasets. Inverse-variance weighted (IVW) method was utilized as the primary method.

Additional analyses included debiased IVW (dIVW), constrained maximum likelihood with model averaging, robust adjusted profile score, Mendelian randomization (MR)–Egger, weighted median, and weighted mode. Moreover, sensitivity tests were conducted, including Cochran’s Q, MR pleiotropy residual sum, and outlier analyses.

Eventually, bidirectional MR was conducted to examine the possibility of a causal link between Ps and DM. No significant causal associations were indicated between DM and Ps. Moreover, there was no causal link between Ps and T1DM. Although certain positive correlations were identified between Ps and T2DM, aggregate evidence remains insufficient to establish a causal relationship.

The results demonstrated no evidence of horizontal pleiotropy between genetic variants. Furthermore, a leave-one-out test validated the stability and robustness of this correlation. Our study identifies no genetic causal effect of Ps on DM and of DM on Ps in European ancestry.

Additional research is warranted to verify the presence of an association between Ps and DM in diverse populations.

This study aims to clarify three points [1] Do d-ROM levels correlate with GPP severity? [2] Do d-ROM levels correlate with GPP severity during pregnancy, given that d-ROM levels are known to increase from the middle to late stages of pregnancy? [3] Is 4-HNE involved in the increase in oxidative stress in GPP?

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Reactive oxygen species (ROS) are involved in the pathogenesis of generalised pustular psoriasis (GPP), but this involvement has not been fully elucidated.

We performed the diacron-reactive oxygen metabolite (d-ROM) test and the biological antioxidant potential (BAP) test on sera from nine patients with active GPP who were hospitalised and treated at our hospital, including three patients with pustular psoriasis of pregnancy (PPP).

The serum d-ROM and BAP levels were evaluated before treatment and at 1 month of treatment. We also performed immunostaining of 4-hydroxy-2-nonenal (4-HNE) in skin tissues. In the GPP patients, the average d-ROM levels were significantly reduced at 1 month of treatment (reduced to 343.0 ± 82.1 U.Carr from 423.2 ± 95.0 U.Carr, p = 0.005).

The Generalised Pustular Psoriasis Area and Severity Index (GPPASI) score correlated with d-ROM levels (r = 0.57, p = 0.10), suggesting that those levels reflect the disease severity. In normal pregnancy, d-ROM values are known to increase from mid-term to late-term. The d-ROM values increased when GPP worsened in the case of PPP.

Immunohistochemical staining of 4-HNE was positive for subcorneal pustules, neutrophils, and for the cytoplasm of epidermal keratinocytes, especially in upper epidermal layers. Our findings indicate that 4-HNE may play an important role in GPP and PPP.

Multi-omics studies have revealed altered expression of circadian clock genes and proteins which are associated with an increased risk of Psoriatic Arthritis (PsA)

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Background:
Circadian rhythms have been shown to play a significant role in the etiology and progression of immune-related morbidities, including cancer and autoimmune diseases. As an autoimmune disorder, psoriatic arthritis (PsA) has been underexplored in the context of circadian rhythms. This study aimed to explore the relationship between circadian rhythm and PsA.

Methods:
We conducted a Summary-data–based Mendelian randomization (SMR) analysis, obtaining summary data on gene methylation, expression, and protein abundance levels of circadian clock-related genes (CRGs) from European ancestry individuals, with a total of 1749 genes selected from the GeneCards database using “biological clock” as the search term. The discovery cohort was obtained from the GWAS catalog database, and the replication cohort was obtained from the FinnGen database. Candidate genes related to circadian rhythm and PsA were identified through research, and their pharmacological potential and molecular docking were further validated as drug targets.

Results:
After integrating multi-omics data, we identified 11 methylation sites in three genes (HLA-DQB1, ITPR3, and GABBR1) of CRGs that were causally related to PsA, and the effects produced were not consistent. The three gene expressions of CRGs (IL4, HLA-DQB1, and OPI-AIS5) were related to PsA. At the protein level, we identified three proteins (GCKR, STAT3, and CSNK2B) of CRGs related to PsA. The top 20 drug candidates underwent drug prediction screening, resulting in the identification of 12 compounds that demonstrated effective outcomes with three (HLA-DQB1, STAT3, and IL-4) specific therapeutic targets through molecular docking.

Conclusion:
This study suggests altered expression of circadian clock genes and proteins, including HLA-DQB1, ITPR3, GABBR1, IL4, OIP5-AS1, GCKR, CSNK2B, and STAT3, as factors contributing to the increased risk of PsA.

Efficacy and Safety of oral TYK2 Inhibitor, ICP-488, in patients with moderate to severe plaque psoriasis: A phase II, randomised, double-blinded, placebo-controlled trial.

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The study results demonstrated that ICP-488 is highly effective in treating psoriasis patients at both 6 mg QD and 9 mg QD doses. Moreover, ICP-488 exhibited favorable safety and tolerability profiles, reinforcing its potential as a valuable treatment option for moderate-to-severe psoriasis patients.

A total of 129 psoriasis patients were randomized into three groups to receive once daily oral doses of ICP-488 at 6 mg, 9 mg, or placebo for twelve weeks. The primary endpoint was the percentage of subjects who achieved at least a 75% improvement from baseline in the Psoriasis Area and Severity Index score (PASI 75) at week 12. 

At week 12, the percentage of patients achieving PASI 75 was significantly superior in the ICP-488 6 mg QD group (77.3%) and the 9 mg QD group (78.6%) than that of the placebo group (11.6%) (P<0.0001); the percentages of subjects achieving PASI 90 and sPGA of 0 (clear) or 1 (almost clear) were also significantly higher in the ICP-488 6 mg QD group (36.4%, 70.5%) and 9 mg QD group (50.0%, 71.4%) compared to the placebo group (0%, 9.3%)(P<0.0001). All treatment emergent adverse events (TEAEs) and treatment-related adverse events (TRAEs) and were mild or moderate.