Real-world Safety and Efficacy of Risankizumab in Psoriatic Patients: A Multicenter, Retrospective, and Not-interventional Study.

BACKGROUND AND OBJECTIVE: Risankizumab - a humanized monoclonal antibody that targets the p19 subunit of IL-23 - has been recently approved to treat moderate-to-severe plaque psoriasis. Real-world data based on a representative pool of patients are currently lacking. OBJECTIVE: To assess the mid- and long-term safety and efficacy profile of risankizumab in patients with moderate-to-severe psoriasis in the routine clinical practice. METHODS: This was a retrospective and multicenter study of consecutive psoriatic patients on risankizumab from April 2020 through November 2022. The primary endpoint was the number of patients who achieved a 100% improvement in their Psoriasis Area and Severity Index (PASI) (PASI100) on week 52. RESULTS: A total of 510 patients, 198 (38.8%) women and 312 (61.2%) men were included in the study. The mean age was 51.7±14.4 years. A total of 227 (44.5%) study participants were obese (body mass index [BMI] >30kg/m2). The mean baseline PASI score was 11.4±7.2, and the rate of patients who achieved PASI100 on week 52, 67.0%. Throughout the study follow-up, 21%, 50.0%, 59.0%, and 66% of the patients achieved PASI100 on weeks 4, 16, 24, and 40, respectively. The number of patients who achieved a PASI ≤2 was greater in the group with a BMI ≤30kg/m2 on weeks 4 (P=.04), 16 (P=.001), and 52 (P=.002). A statistically significantly greater number of patients achieved PASI100 in the treatment-naïve group on weeks 16 and 52 (P=.001 each, respectively). On week 16 a significantly lower number of participants achieved PASI100 in the group with psoriatic arthropathy (P=.04). Among the overall study sample, 22 (4.3%) patients reported some type of adverse event and 20 (3.9%) discontinued treatment. CONCLUSIONS: Risankizumab proved to be a safe and effective therapy for patients with moderate-to-severe psoriasis in the routine clinical practice.

Glucagon-Like Peptide-1 Agonists for Treating Obesity in Patients With Immune-Mediated Skin Diseases. / Agonistas del receptor de GLP-1 para el tratamiento de la obesidad en pacientes con dermatosis inmunomediadas.

Psoriasis and hidradenitis suppurativa are often associated with obesity. Because chronic low-grade inflammation underlies these 2 diseases, they can progress to more severe forms in patients with obesity if weight-reduction measures are not taken. This review covers pharmacologic alternatives for treating obesity, with emphasis on the benefits associated with the novel use of glucagon-like peptide-1 (GLP-1) agonists that act on satiety receptors. These drugs have led to greater weight loss in clinical trials and real-world settings than orlistat, which until recently was the only drug approved for treating obesity in the European Union. Although experience with GLP-1 agonists in patients with obesity and inflammatory skin diseases is currently scarce, the promising results reported suggest they may offer a useful tool for managing obesity.

Gluteal Hidradenitis Suppurativa: Analysis of 83 Patients. / [Artículo traducido] Hidradenitis supurativa con afectación glútea: análisis de 83 pacientes.

BACKGROUND: In 2013, Canoui-Poitrine et al. identified three hidradenitis suppurativa (HS) phenotypes by a latent class (LC) analysis, based on anatomical sites of involvement. OBJECTIVE: To improve the classification of the gluteal phenotype (LC3) patients given their diverse lesion types and differences in clinical profile. MATERIAL AND METHODS: We designed a bicentric study gathering all LC3 patients (n=83) from two hospitals. We conducted a two-step cluster analysis among them and also compared their characteristics with the rest of the HS patients (n=661). RESULTS: Compared with global HS series, LC3 patients were more frequently non-obese men, with smoking habit, an associated arthropathy, and a more frequent history of pilonidal sinus. The analysis of LC3 patients yielded two clusters: cluster 1 (38.3%) included elderly female patients, with later diagnosis of the disease and more sinus tracts; cluster 2 (61.7%) encompassed more men with earlier disease onset and more nodules and folliculitis lesions. LIMITATIONS: The study's limitations include its retrospective nature, bicentric design, and small sample size. CONCLUSION: The heterogeneous clinical presentation of HS makes it essential to have a good classification of the patients. Gluteal phenotype could actually be classified into two "subphenotypes" with a different clinical profiles and management.

The effect of genetic defects on pregnancy loss in Swedish dairy cattle.

The effect of carrier status of 10 lethal recessive genetic defects on pregnancy maintenance in Swedish dairy cattle was examined. The genetic defects were Ayrshire Haplotype 1, Ayrshire Haplotype 2, BTA12, BTA23, and Brown Swiss Haplotype 2 in Red Dairy Cattle (RDC), and Holstein Haplotype 1, 3, 4, 6, and 7 (HH1-HH7) in Holstein. Effects of carrier status of BTA12 and HH3 on conception rate (CR), interval from first to last service (FLS), and milk production were also examined. Data were obtained for 1,429 herds in the Swedish milk recording system, while information on carrier status of genetic defects was obtained from the Nordic Cattle Genetic Evaluation. In total, data on 158,795 inseminations in 28,432 RDC and 22,018 Holstein females were available. Data permitted separate analyses of BTA12 and HH3, but carrier frequencies of other defects were too low to enable further analysis. Pregnancy loss was defined as failure to maintain pregnancy, where pregnancy status was confirmed with manual and chemical pregnancy diagnosis, insemination, calving, sales and culling data. Odds ratios (OR) and probabilities of pregnancy loss and CR were estimated using generalized linear mixed models, while pregnancy loss, CR, FLS, milk, protein, and fat yields were analyzed using linear mixed models. Pregnancy losses were reported on average within the first month post-AI. At-risk matings were more prone to suffer pregnancy loss in BTA12 (OR = 1.79) and HH3 carriers (OR = 1.77) than not-at-risk matings. At-risk matings also had lower CR (OR = 0.62 and 0.63 for BTA12 and HH3, respectively) than not-at-risk matings. Carrier females of BTA12 had longer FLS and higher milk production than noncarriers. Conception rate and pregnancy maintenance could be improved by avoiding at-risk matings. This finding could help reduce pregnancy loss due to genetic defects in the breeding program for improved fertility.

[Translated article] Glucagon-Like Peptide-1 Agonists for Treating Obesity in Patients With Immune-Mediated Skin Diseases.

Psoriasis and hidradenitis suppurativa are often associated with obesity. Because chronic low-grade inflammation underlies these 2 diseases, they can progress to more severe forms in patients with obesity if weight-reduction measures are not taken. This review covers pharmacologic alternatives for treating obesity, with emphasis on the benefits associated with the novel use of glucagon-like peptide-1 (GLP-1) agonists that act on satiety receptors. These drugs have led to greater weight loss in clinical trials and real-world settings than orlistat, which until recently was the only drug approved for treating obesity in the European Union. Although experience with GLP-1 agonists in patients with obesity and inflammatory skin diseases is currently scarce, the promising results reported suggest they may offer a useful tool for managing obesity.

Gluteal Hidradenitis Suppurativa: Analysis of 83 Patients.

BACKGROUND: In 2013, Canoui-Poitrine et al. identified three hidradenitis suppurativa (HS) phenotypes by a latent class (LC) analysis, based on anatomical sites of involvement. OBJECTIVE: To improve the classification of the gluteal phenotype (LC3) patients given their diverse lesion types and differences in clinical profile. MATERIAL AND METHODS: We designed a bicentric study gathering all LC3 patients (n=83) from two hospitals. We conducted a two-step cluster analysis among them and also compared their characteristics with the rest of the HS patients (n=661). RESULTS: Compared with global HS series, LC3 patients were more frequently non-obese men, with smoking habit, an associated arthropathy, and a more frequent history of pilonidal sinus. The analysis of LC3 patients yielded two clusters: cluster 1 (38.3%) included elderly female patients, with later diagnosis of the disease and more sinus tracts; cluster 2 (61.7%) encompassed more men with earlier disease onset and more nodules and folliculitis lesions. LIMITATIONS: The study's limitations include its retrospective nature, bicentric design, and small sample size. CONCLUSION: The heterogeneous clinical presentation of HS makes it essential to have a good classification of the patients. Gluteal phenotype could actually be classified into two "subphenotypes" with a different clinical profiles and management.

Approach to the Epidemiology, Disease Management, and Current Challenges in the Management of Generalized Pustular Psoriasis Through a Survey Conducted Among Spanish Dermatologists. / Aproximación a la epidemiología, manejo de la enfermedad y retos actuales en la gestión de la psoriasis pustulosa generalizada en España a través de un cuestionario dirigido a dermatólogos.

BACKGROUND: Generalized pustular psoriasis (GPP) is a rare and severe inflammatory skin disease characterised by recurrent or intermittent flares. Epidemiological and disease management data in Spain are limited. Our goal was to estimate the epidemiology of GPP, explore its management, and reach consensus on the current challenges faced in Spain. METHODS: An electronic survey was submitted to dermatologists from the Spanish Academy of Dermatology and Venereology Psoriasis Working Group. This group is experienced in the management of GPP. It included a Delphi consensus to establish the current challenges. RESULTS: A total of 33 dermatologists responded to the survey. A 5-year prevalence and incidence of 13.05 and 7.01 cases per million inhabitants, respectively, were estimated. According to respondents, the most common GPP symptoms are pustules, erythema, and desquamation, while 45% of patients present > 1 annual flares. A total of 45% of respondents indicated that flares often require a length of stay between 1 and 2 weeks. In the presence of a flare, 67% of respondents often or always prescribe a non-biological systemic treatment as the first-line therapy [cyclosporine (55%); oral retinoid (30%)], and 45% a biological treatment [anti-TNFα (52%); anti-IL-17 (39%)]. The dermatologists agreed that the main challenges are to define and establish specific therapeutic goals to treat the disease including the patients' perspective on the management of the disease. CONCLUSION: Our study describes the current situation on the management of GPP in Spain, increasing the present knowledge on the disease, and highlighting the current challenges faced at the moment.

The Effectiveness of Guselkumab in Patients With Hidradenitis Suppurativa Under Clinical Practice Conditions: A Spanish Multicentre Retrospective Study. / [Artículo traducido] Efectividad de guselkumab en pacientes con hidradenitis supurativa en condiciones de práctica clínica: estudio retrospectivo y multicéntrico en España.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic skin condition causing lesions in which high levels of interleukin (IL)-23 and T-helper17 cells are found. Adalimumab remains the only approved treatment. Guselkumab, an antibody targeting the p19 protein subunit of extracellular IL-23, is approved for the treatment of moderate-severe psoriasis, but evidence on its efficacy in treating HS is limited. OBJECTIVES: To assess the effectiveness and safety of guselkumab in treating moderate-severe HS under clinical practice conditions. METHODS: A multicentre retrospective observational study was carried out in 13 Spanish hospitals including adult HS patients treated with guselkumab within a compassionate use programme (March 2020-March 2022). Data referred to patient demographic and clinical characteristics at treatment initiation (baseline), patient-reported outcomes (Numerical Pain Rating Scale [NPRS] and Dermatology Life Quality Index [DLQI]), physician scores (International Hidradenitis Suppurativa Severity Score System [IHS4], HS Physical Global Score [HS-PGA] and Hidradenitis Suppurativa Clinical Response [HiSCR]) were recorded at baseline and at 16, 24, and 48weeks of treatment. RESULTS: A total of 69 patients were included. Most (84.10%) had severe HS (HurleyIII) and had been diagnosed for over ten years (58.80%). The patients had been subjected to multiple non-biological (mean: 3.56) or biological (mean: 1.78) therapies, and almost 90% of those treated with biologics had received adalimumab. A significant decrease in IHS4, HS-PGA, NPRS, and DLQI scores was observed from baseline to 48weeks of guselkumab treatment (all P<.01). HiSCR was achieved in 58.33% and 56.52% of the patients at 16 and 24weeks, respectively. Overall, 16 patients discontinued treatment, mostly due to inefficacy (n=7) or loss of efficacy (n=3). No serious adverse events were observed. CONCLUSIONS: Our results indicate that guselkumab may be a safe and effective therapeutic alternative for patients with severe HS that fail to respond to other biologics.

The Effectiveness of Guselkumab in Patients With Hidradenitis Suppurativa Under Clinical Practice Conditions: A Spanish Multicentre Retrospective Study.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic skin condition causing lesions in which high levels of interleukin (IL)-23 and T-helper 17 cells are found. Adalimumab remains the only approved treatment. Guselkumab, an antibody targeting the p19 protein subunit of extracellular IL-23, is approved for the treatment of moderate-severe psoriasis, but evidence on its efficacy in treating HS is limited. OBJECTIVES: To assess the effectiveness and safety of guselkumab in treating moderate-severe HS under clinical practice conditions. METHODS: A multicentre retrospective observational study was carried out in 13 Spanish Hospitals including adult HS patients treated with guselkumab within a compassionate use programme (March 2020-March 2022). Data referred to patient demographic and clinical characteristics at treatment initiation (baseline), patient-reported outcomes (Numerical Pain Rating Scale [NPRS] and Dermatology Life Quality Index [DLQI]), physician scores (International Hidradenitis Suppurativa Severity Score System [IHS4], HS Physical Global Score [HS-PGA] and Hidradenitis Suppurativa Clinical Response [HiSCR]) were recorded at baseline and at 16, 24, and 48 weeks of treatment. RESULTS: A total of 69 patients were included. Most (84.10%) had severe HS (Hurley III) and had been diagnosed for over ten years (58.80%). The patients had been subjected to multiple non-biological (mean 3.56) or biological (mean 1.78) therapies, and almost 90% of those treated with biologics had received adalimumab. A significant decrease in IHS4, HS-PGA, NPRS, and DLQI scores was observed from baseline to 48 weeks of guselkumab treatment (all p<0.01). HiSCR was achieved in 58.33% and 56.52% of the patients at 16 and 24 weeks, respectively. Overall, 16 patients discontinued treatment, mostly due to inefficacy (n=7) or loss of efficacy (n=3). No serious adverse events were observed. CONCLUSIONS: Our results indicate that guselkumab may be a safe and effective therapeutic alternative for patients with severe HS that fail to respond to other biologics.

Common Approach to Metabolic-Associated Fatty Liver Disease in Patients With Psoriasis: Consensus-Based Recommendations From a Multidisciplinary Group of Experts. / Abordaje común del paciente con psoriasis y riesgo de esteatosis hepática metabólica: recomendaciones de un grupo de expertos multidisciplinar.

Recent years have seen concerted efforts to understand the relation between psoriasis and metabolic-associated fatty liver disease (MAFLD). Not only is MALFD diagnosed more often in patients with psoriasis, but its clinical course is also more aggressive. A common approach is therefore needed to enable early detection of liver disease coincident with psoriasis. Especially important is an analysis of risks and benefits of potentially hepatotoxic treatments. This consensus paper presents the recommendations of a group of experts in dermatology and hepatology regarding screening for MALFD as well as criteria for monitoring patients and referring them to hepatologists when liver disease is suspected.

Unmet needs in patients with moderate-to-severe plaque psoriasis treated with methotrexate in real world practice: FirST study.

BACKGROUND: Methotrexate (MTX) is frequently used in the treatment of moderate-to-severe psoriasis, however, there is limited data on health-related quality-of-life (HRQoL), psoriasis clinical outcomes and hepatic fibrosis in MTX-treated patients in routine clinical practice. OBJECTIVES: To investigate the impact of moderate-to-severe psoriasis in MTX-treated patients in Spain regarding to HRQoL, psoriasis clinical data and risk of hepatic fibrosis. METHODS: Observational, non-interventional, cross-sectional, retrospective, multicentre study, performed in Spain in moderate-to-severe plaque psoriasis patients treated with MTX > 16 weeks prior to inclusion. RESULTS: Despite ongoing treatment, 17.1% of 457 evaluable patients reported moderate-to-extreme impact on HRQoL (DLQI > 5); 21.4% BSA > 5 and 35.2% moderate-to-severe pruritus (VAS ≥ 4). Persistent severe psoriasis (PASI ≥ 10 and/or DLQI ≥ 10) was observed in 10.7%. Hepatic steatosis was identified in 64.1% of patients (HSI ≥ 36) and 37.2% of the patients were at-risk of advanced fibrosis which was associated to the MTX treatment duration. CONCLUSIONS: The study identified unmet needs in moderate-to-severe plaque psoriasis patients treated with MTX, revealing a significant proportion of sub-optimally controlled patients in terms of HRQoL and different domains of the disease. This study also found patients at-risk of advanced fibrosis, with evidence suggesting a correlation between longer exposures to MTX and higher risk of advanced fibrosis.

The effectiveness and safety of ixekizumab in psoriasis patients under clinical practice conditions: A Spanish multicentre retrospective study.

The objective of the study was to evaluate efficacy and safety of ixekizumab in psoriasis patients under clinical practice conditions. Observational, retrospective, multicentre study that included patients with ixekizumab from March 2017 to March 2019. ≥ 90% reduction in the Psoriasis Area and Severity Index (PASI 90) and absolute PASI <2 were the parameters used to assess treatment response. Adverse events (AEs) were collected. Of the 301 patients included, 111 were women (36.9%), mean age was 48.5 (±13.5) years. Mean baseline PASI score was 13.5 (±7.7). More than half of the patients (68.5%) had received at least one biological drug before. At 3 months, 208 (76.5%) patients achieved PASI <2 and 156 (57.3%) PASI 90. At 12 months, 130 (73.4%) patients achieved absolute PASI <2 and 104 (58.7%) PASI 90. Multivariate analysis revealed that prior use of biologics was influential in achieving PASI <2 at both 3 and 12 months (OR 2.82, P = .006; OR 9.51, P < .001, respectively). Sixty-five patients (21.59%) exhibited at least one AE, injection site reaction was the most common (39; 36.8%). Likewise in trials, ixekizumab displayed an excellent profile of safety and efficacy also in real-life. Effectiveness appears superior in biologic-naive patients.

Real-world effectiveness and safety of apremilast in psoriasis at 52 weeks: a retrospective, observational, multicentre study by the Spanish Psoriasis Group.

BACKGROUND: Little has been published on the real-world effectiveness and safety of apremilast in psoriasis. OBJECTIVES: To evaluate the effectiveness, safety and drug survival of apremilast at 52 weeks in patients with moderate to severe plaque psoriasis or palmoplantar psoriasis in routine clinical practice. METHODS: Retrospective, multicentre study of adult patients with moderate to severe plaque psoriasis or palmoplantar psoriasis treated with apremilast from March 2016 to March 2018. RESULTS: We studied 292 patients with plaque psoriasis and 85 patients with palmoplantar psoriasis. The mean (SD) Psoriasis Area and Severity Index (PASI) score was 10.7 (7.0) at baseline and 3.0 (4.2) at 52 weeks. After 12 months of treatment, 73.6% of patients had a PASI score of 3 or less. In terms of relative improvement by week 52, 49.7% of patients achieved PASI-75 (≥75% reduction in PASI score) and 26.5% achieved PASI-90. The mean physician global assessment score for palmoplantar psoriasis fell from 4.2 (5.2) at baseline to 1.3 (1.3) at week 52. Overall drug survival after 1 year of treatment with apremilast was 54.9 %. The main reasons for treatment discontinuation were loss of efficacy (23.9%) and adverse events (15.9%). Almost half of the patients in our series (47%) experienced at least one adverse event. The most common events were gastrointestinal problems. CONCLUSIONS: Apremilast may be a suitable alternative for the treatment of moderate to severe psoriasis and palmoplantar psoriasis. Although the drug has a good safety profile, adverse gastrointestinal effects are common.

Genetic parameters of endocrine fertility traits based on in-line milk progesterone profiles in Swedish Red and Holstein dairy cows.

Evaluating fertility traits based on endocrine progesterone profiles is becoming a promising option to improve dairy cow fertility. Several studies have been conducted on endocrine fertility traits, mainly in the Holstein breed. In this study, focusing also on the Swedish Red (SR) breed, genetic parameters were estimated for classical and endocrine fertility traits, the latter based on in-line milk progesterone records obtained for 14 Swedish herds using DeLaval Herd Navigator (DeLaval International, Tumba, Sweden). A total of 210,403 observations from 3,437 lactations of 1,107 SR and 1,538 Holstein cows were used. Mixed linear animal models were used for estimation of genetic parameters. Least squares means analysis showed that Holstein cows had a 2.5-d-shorter interval from calving to commencement of luteal activity (C-LA) and longer length of first inter-ovulatory interval (IOI) than SR cows. The highest mean interval for C-LA, IOI, and first luteal phase length (LPL) was observed in the fourth parity. The incidence of short (<18 d), normal, (18-24 d), and long (>24 d) IOI was 29.3, 40.7, and 30%, respectively. Genetic analysis indicated moderate heritability (h2) for C-LA (h2 = 0.24), luteal activity during the first 60 d in milk (LA60, h2 = 0.15), proportion of samples with luteal activity (PLA, h2 = 0.13), and calving to first heat (CFH, h2 = 0.18), and low heritability estimates for LPL (h2 = 0.08) and IOI (h2 = 0.03) in the combined data set for both breeds. Similar heritability estimates were obtained for each breed separately except for IOI and LPL in SR cows, for which heritability was estimated to be zero. Swedish Red cows had 0.01 to 0.06 higher heritability estimates for C-LA, LA60, and PLA than did Holstein cows. Calving interval had moderate heritability among the classical traits for Holstein and the combined data set, but h2 was zero for SR. Commencement of luteal activity had a strong genetic correlation with LA60 (mean ± SE; -0.88 ± 0.06), PLA (-0.72 ± 0.11), and CFH (0.90 ± 0.04). Similarly, CFH had a strong genetic correlation with IOI (0.98 ± 0.20). Number of inseminations per series showed a weak genetic correlation with all endocrine traits except IOI. Overall, endocrine traits had higher heritability estimates than classical traits in both breeds, and may have a better potential to explain the actual reproductive status of dairy cows than classical traits. This might favor inclusion of some endocrine fertility traits-especially those related to commencement of luteal activity-as selection criteria and breeding goal traits if recording becomes more common in herds. Further studies on genetic and genomic evaluations for endocrine fertility traits may help to provide firm conclusions. A prerequisite is that the data from automatic devices be made available to recording and breeding organizations in the future and included in a central database.

Initial results of ixekizumab efficacy and safety in real-world plaque psoriasis patients: a multicentre retrospective study.

BACKGROUND: Ixekizumab (anti-IL17A) is effective as treatment for moderate-to-severe plaque psoriasis, but real-life data on effectiveness and safety are currently very limited. OBJECTIVE: To evaluate the efficacy and safety of ixekizumab in a cohort of real-life plaque psoriasis patients. METHODS: Retrospective chart review of 100 patients with moderate-to-severe plaque psoriasis treated with ixekizumab at seven Spanish dermatological centres. RESULTS: According to the as observed analysis, the percentage of patients achieving a 75% and 90% of reduction from the baseline score of Psoriasis Area and Severity Index (PASI) was 87.5%-50.0% at week 12-16; 88.3%-58.4% at week 24 and 82.9%-58.5% at week 52, respectively. The mean ± standard deviation (SD) score of PASI at baseline was 12.9 ± 9.2, and it declined rapidly after ixekizumab administration to 1.9 ± 4.0 (P < 0.001) at week 12-16 and was maintained at 1.7 ± 4.1 and 1.8 ± 2.9 at week 24 and 52, respectively. Ixekizumab response was not affected by clinical variables like body mass index, disease duration or the presence of psoriatic arthritis. However, the bio-naive group showed significantly higher PASI 75 response rate at week 12-16 compared to patients previously exposed to biologic agents (P = 0.037). Twenty-six (26%) patients experienced adverse events (AEs) during the follow-up period, being most of them of mild-to-moderate intensity. The most common AE was local reaction at the site of injection (14/26; 53.8%). At the end of the observational period, 15 (15%) patients discontinued ixekizumab treatment due to limited clinical improvement (n = 11), adverse events (n = 3) or lost to follow-up (n = 1) within a mean ± SD time of 6.0 ± 3.9 months. CONCLUSION: The present study illustrates the initial experience with ixekizumab in real-world clinical practice confirming its usefulness and safety in the management of plaque psoriasis patients.