Efficacy and safety of apremilast in pediatric patients with moderate-to-severe plaque psoriasis: 16-week results from SPROUT, a randomized controlled trial.

BACKGROUND: Approved systemic treatment options are limited for pediatric patients with moderate to severe plaque psoriasis. OBJECTIVE: To assess the efficacy and safety of apremilast over 16 weeks in pediatric patients with plaque psoriasis. METHODS: SPROUT (NCT03701763) was a phase 3, multicenter, randomized, double-blind, placebo-controlled study of apremilast in patients aged 6-17 years with moderate-to-severe psoriasis (Psoriasis Area and Severity Index [PASI] ≥12, body surface area ≥10%, static Physician Global Assessment [sPGA] ≥3) inadequately controlled by/inappropriate for topical therapy. Patients were stratified by age group and randomized (2:1) to apremilast (20 or 30 mg BID based on weight) or placebo for 16 weeks, followed by apremilast extension to 52 weeks. RESULTS: Of 245 patients randomized (apremilast: 163; placebo: 82), 221 (90%) completed the double-blind phase (apremilast: 149; placebo: 72). Significantly more patients achieved sPGA response and ≥75% reduction in PASI with apremilast than placebo, regardless of baseline age, weight, or disease severity. No new safety signals were observed. LIMITATIONS: Sample size of subgroup analyses. CONCLUSIONS: Improvements in global disease activity and skin involvement were significantly greater in pediatric patients treated with apremilast versus placebo. Adverse events were consistent with the known apremilast safety profile.

Guselkumab effectiveness and survival in patients with psoriasis and psoriatic arthritis: Multicenter analysis in daily clinical practice by the Spanish Psoriasis Group.

Guselkumab is a monoclonal antibody that selectively blocks the p19 subunit of interleukin 23 and has been approved for the treatment of moderate to severe psoriasis and active psoriatic arthritis in adult patients due to its efficacy in different clinical trials. Therefore, itis important to know the performance of guselkumab in this setting of patients in clinical practice given that a high percentage of them are not represented in these clinical trials. Our objective was to evaluate the effectiveness and tolerability of guselkumab in clinical practice in the first patients with psoriasis and psoriatic arthritis treated since the date of its approval for psoriasis in Spain, in joint dermatology-rheumatology clinics. A multicenter retrospective data collection was carried out, in which 14 hospitals participated, including a total of 90 patients with psoriatic arthritis confirmed by a rheumatologist. Data collection was recorded at baseline and at weeks 12, 24, and 52 for both the articular and cutaneous domains. Ninety PsA patients started treatment with guselkumab and therefore were included in this study. The vast majority had already failed to at least to one biologic therapyprior guselkumab prescription. The median age was 55 years, 61% were female and 46% had a BMI ≥ 30 kg/m2 . Sixty-nine percent suffered from peripheral arthritis, and in 34% an axial involvement was also detected; dactylitis or enthesitis was present in 24% and 29% of patients, respectively. Guselkumab was effective in controlling both articular and skin manifestations of PsA patients. Absolute PASI significantly decreased from 10.5 to 4.8, 1.9 and 1.3 at weeks 12, 24, and 52, respectively. In 29 out of 61 (48%) of cases, DAPSA was moderate or high, and patients showed a significant reduction in DAPSA at 12, 24, and 52 weeks of treatment (mean DAPSA values at baseline and follow up were 29, 20, 16, and 14, respectively). Patients with DAPSA in low activity or in remission at the time of initiation of guselkumab maintained response at the end of the study period. No new safety concerns were detected. Seventy-eight out of 90 patients (84.4%) persisted on treatment after 2 years follow-up. Our experience suggests that guselkumab isan effective drug for PsA and PsO patients in clinical practice with good tolerability and no additional safety signals, making it a new therapeutic alternative for the treatment of PsA and PsO patients.

Secukinumab is effective and safe in the long-term treatment of plaque psoriasis in a daily practice setting: Multicenter study in 384 Spanish patients.

The aim of the study was to assess the long-term effectiveness and safety of secukinumab in Spanish patients with moderate-to-severe psoriasis in a daily practice setting. Nationwide multicenter, observational, retrospective, non-interventional, single-cohort study including patients who initiated treatment with secukinumab in daily clinical practice conditions. Subjects were followed for a minimum of 3 months and a maximum of 24 months. Psoriasis Area Severity Index (PASI), Body Surface Area and Physician's Global Assessments were collected at baseline and months 3, 6, 12, 18 and 24 during treatment. Adverse events and reasons for secukinumab withdrawal were collected and classified for analyses. A total of 384 patients were enrolled in the study. Median PASI declined rapidly from 14.3 at baseline to 2.7 at month 3, 2.1 at month 12, and remained low (2.8) at month 24. Within the group of patients with PASI ≥10 at baseline (n = 278), 58.3%, 60.4% and 56.5% achieved a PASI90 response at months 3, 12 and 24, respectively. As for absolute PASI, 86.5%, 69.5%, 42.7% and 37% achieved PASI <5, < 3, < 1 and 0, respectively, at month 3. Secukinumab was more effective in biologic-naïve patients and in those with lower Body Mass Index. Secukinumab presented a good long-term safety profile. Secukinumab was effective and safe in a routine clinical setting, in a large cohort of patients with moderate-to-severe plaque psoriasis, in the short-, medium- and long-term (up to 24 months).

Fast and sustained improvement of patient-reported outcomes in psoriatic patients treated with secukinumab in a daily practice setting.

Psoriasis is a chronic dermatological disease with great impact on patients' quality of life (QoL). The main objective of this study was to assess the impact of secukinumab treatment on different patient-reported outcomes (PROs) during a long-term follow-up in Spanish patients with moderate-to-severe psoriasis under real-world conditions. Retrospective, observational, open-label, nationwide multicenter cohort study that included patients who initiated treatment with secukinumab in daily clinical practice conditions. PROs assessing disease impact and QoL included Dermatology Life Quality Index (DLQI), Patient's Global Psoriasis Assessment, Itch Numerical Rating Scale and EuroQoL Thermometer Visual Analogue Scale. Outcomes, including PROs and Psoriasis Area and Severity Index (PASI), were assessed at months 3, 6, 12, 18, and 24 during treatment. A total of 238 patients were enrolled in the study. Patients had a mean DLQI score of 14.9 at baseline; 78.3%, 73.7%, and 71.7% of them achieved a DLQI 0/1 response at months 6, 12, and 24, respectively. DLQI score was lower in the long term for naïve patients. A sharp decrease in mean DLQI was observed during the first 3 months, reaching a plateau that was maintained until the end of follow-up. Similar findings were observed for the rest of QoL assessments. There was a close association between improvement in QoL and skin clearance (PASI), which progressively increased during follow-up. In this study, secukinumab sustainably improved patient's QoL during a 24-month follow-up, with strongest effects in patients naïve to biological therapies and with a direct correlation with PASI improvement.

Psoriasis of the external auditory canal: prevalence, clinical features and impact on quality of life.

Psoriasis of the external auditory canal (PsEAC) is often under-recognized. The aims of this study were to assess the prevalence of PsEAC, its association with a particular psoriasis subtype and its impact on quality of life (QoL). A prospective study was carried out in two Spanish university hospitals, enrolling consecutive patients who attended a consultation for psoriasis. The clinical features of psoriasis and PsEAC were recorded and the Dermatology Life Quality Index (DLQI) and Itch Numerical Rating Scale (Itch-NRS) were distributed to patients. Overall, 188 of 1000 patients (18.8%) included in the study had PsEAC, which was associated with severity of psoriasis, presence of inverse psoriasis and involvement of the scalp, nails and genitals, but not with obesity or psoriatic arthritis. PsEAC was the main reason for consultation in 27 patients, with itching being the main symptom. In this study, PsEAC had a prevalence of 18.8%. The occurrence of PsEAC was associated with poorer QoL, as measured by DLQI and Itch-NRS.

COVID-19 patients with psoriasis and psoriatic arthritis on biologic immunosuppressant therapy vs apremilast in North Spain.

Immunosuppressive and immunomodulatory treatments are critical for the management of inflammatory and autoimmune conditions such as psoriasis or psoriatic arthritis. Similar to those illnesses, the lung injury and acute respiratory distress shown in coronavirus disease 2019 (COVID-19) patients are the result of a disruption in the balance of pro- and anti-inflammatory cytokines. This hyperinflammatory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), associated with the severity of the coronavirus disease, is called the cytokine storm. There is a growing concern regarding how patients on immunosuppressant biologic therapies might be at higher risk of being infected and whether they need to discontinue their treatment preemptively. Clinical data on COVID-19-infected patients with psoriasis or psoriatic arthritis are still scarce. Here, we presented seven cases of these type of patients. The patient infected with COVID-19 on apremilast and the one on apremilast with infected spouse showed the best safety profile and mildest symptoms. One of the secukinumab patients also presented a relatively good outcome. Infliximab patients and the one with serious comorbidities showed the worst outcome. Even though more clinical data are yet needed to draw strong conclusions, apremilast could be a safer alternative for dermatology and rheumatology patients in case of clinically important active infection.

The Number of Traditional Cardiovascular Risk Factors Is Independently Correlated with Disease Activity in Patients with Psoriatic Arthritis.

Background and objectives: Psoriatic arthritis (PsA) is associated with several comorbidities, including among others an increased risk of cardiovascular (CV) disease, atherosclerosis, metabolic syndrome, hypertension dyslipidemia, and diabetes. The purpose of the present study was to determine how the number of CV risk factors correlates with disease related data such as disease activity. Materials and Methods: Cross-sectional study that encompassed 305 patients who fulfilled the CASPAR criteria for PsA were assessed for lipid profile, disease activity measurements, and the presence of six traditional CV risk factors (diabetes mellitus, dyslipidemia, hypertension, obesity, chronic kidney disease, and smoking status). A multivariable regression analysis, adjusted for age, sex, and disease duration, was performed to evaluate if the number of classic CV risk factors was independently related with specific features of the disease, including disease activity. Results: Disease duration was found to be higher, after adjustment for age and sex, in patients with 1 or 2, and 3 or higher CV factors, compared to those patients without CV risk factors. Similarly, DAPSA (Disease Activity in PSoriatic Arthritis score) was found to be independently upregulated in patients with a higher number of CV risk factors. In this sense, as DAPSA score increases the odds ratio (OR) of having 1 or 2 (OR 1.12 (95% confidence interval (CI) 1.03-1.21), p = 0.010), and 3 or higher (OR 1.15 (95% CI 1.04-1.26), p = 0.004) CV factors was significantly higher compared to no CV risk factors category. This was independently found after adjustment for age, sex, and disease duration. Conclusions: PsA patients with a higher number of CV risk factors exhibit an upregulated disease activity compared to those without them. This is independent of disease duration and other demographics factors.

Papillary Dermal Elastosis.

Papillary dermal elastosis is a rare clinicopathological entity with only 1 case reported. The authors herein report a new case. A 38-year-old woman presented with a 10-month history of slowly progressive appearance of multiple, 1-2 mm, pruritic nonfollicular papules, located on the back. The study of the biopsy with the ordinary staining revealed numerous dermal papillae showing increased elastosis. The Verhoeff elastic stain demonstrated numerous foci of clumped and curled elastic fibers in the papillary dermis. The elastic component of the reticular dermis was normal. This case report confirms this entity and can contribute to a better understanding of the spectrum of the fibroelastolytic entities.

Histopathologic differences between cutaneous vasculitis associated with severe bacterial infection and cutaneous vasculitis secondary to other causes: study of 52 patients.

OBJECTIVES: To determine if cutaneous vasculitis (CV) associated with severe infection has some histopathologic findings that may help us to differentiate patients with this condition from other patients with CV. METHODS: We reviewed the skin biopsy specimens of patients with leukocytoclastic CV associated with a severe bacterial infection. Histopathologic findings of these patients were compared with those observed in leukocytoclastic CV secondary to other causes. Biopsy-proven leukocytoclastic CV were stratified as follows: group a): CV associated with severe underlying bacterial infection; group b): CV without severe bacterial infection but with systemic involvement; group c): CV without systemic involvement. Slides were reviewed by expert pathologists that were blind to the clinical information. The severity of vascular lesions was measured according to a semiquantitative scale (Hodge index). A comparative study between group a) and the other groups was conducted. RESULTS: group a) included 12 patients (2 women/10 men), mean age± SD 56±15 years; group b) 21 patients (10 women/11 men), 52±18 years; and group c) 19 patients (12 women/7 men), 59±24 years. Presence of neutrophilia was significantly increased in biopsies from group a) when compared with the other two groups. Also, a trend to higher frequency of pustular dermatosis was found in patients from group a). Hodge index, degree of inflammatory infiltrate and deep arterioles involvement were similar in all groups. CONCLUSIONS: Neutrophilia is common in skin biopsies of patients with CV associated with severe bacterial infection. No other histopathological findings help us to establish the presence of a severe underlying infection.

Psoriasis vulgaris with or without arthritis and independent of disease severity or duration is a risk factor for hypercholesterolemia.

BACKGROUND: Psoriasis (Ps) has been associated with an increased incidence of cardiovascular disease. Interesting epidemiological evidence suggests associations between Ps and dyslipidemia (DL), a well-established risk factor for cardiovascular disease. OBJECTIVE: This study aimed to investigate the association between Ps and multiple measurements of DL, which include levels of triglycerides (TGs), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and total cholesterol (TCh). We also studied the relationship between DL and disease duration. METHODS: A prospective hospital-based study was conducted. A total of 661 Caucasian patients with chronic plaque Ps and 661 sex- and age-matched controls were enrolled. RESULTS: Multivariate analysis showed that in psoriatic patients the odds ratio (OR) of TCh >200 mg/dl was 1.406 (95% confidence interval 1.115-1.173), the OR of LDL cholesterol >130 mg/dl was 1.375 (95% confidence interval 1.088-1.738), the OR of HDL cholesterol <40 mg/dl was 0.881 (95% confidence interval 0.599-1.297), and the OR of TGs >150 mg/dl was 1.041 (95% confidence interval 0.783-1.385). We did not find a relationship between lipid levels and disease duration. CONCLUSION: Based on our population Ps is associated with alterations in TCh and LDL cholesterol, but not in TGs and HDL cholesterol, when ATP III panel levels are used. These alterations are not related to disease duration.

Revisiting clinical differences between hypersensitivity vasculitis and Henoch-Schönlein purpura in adults from a defined population.

OBJECTIVES: Hypersensitivity vasculitis (HV) and Henoch-Schönlein purpura (HSP) are the most common entities included within the category of cutaneous vasculitis (CV). Palpable purpura and histological changes characterised by the presence of leukocytoclastic vasculitis are common in both conditions. Therefore, considerable overlap between them is often seen. It is especially true when the CV occurs in adults. To further establish clinical differences between these two conditions, in the present study we assessed the main clinical differences between HV and HSP in a wide and unselected series of adults with CV from a defined population. METHODS: We reviewed the clinical records of 297 consecutive adults (age >20 years) seen at a single centre between January 1975 and December 2012 that were classified as having HSP or HV according to the criteria proposed by Michel et al. (J Rheumatol 1992; 19: 721-8). RESULTS: Based on the inclusion criteria, 102 adult patients (71 men/31 women) were classified as HSP and 195 (104 men/91 women) as HV. The mean age was similar in both groups (55.8±16.5 years in HSP and 56.8±18.3 years in HV). Precipitating events, usually an upper respiratory tract infection and/or drug intake, were more frequently observed in HV. Both at the beginning of the disease and when the CV was established clinical manifestations were more frequent in patients with HSP than in those with HV. It was the case for gastrointestinal (57.4% vs. 6.8%; p<0.001), joint (51.5% vs. 36.6%; p=0.01) and renal involvement (86.3% vs. 18.3%; p<0.001). Corticosteroid (56.7% vs. 22%; p<0.001) and cytotoxic drug (19.4% vs. 3.2%; p<0.001) use was also more common in patients with HSP. After a median follow-up of 15.5 (interquartile range- IQR; 3-37) months in HSP and 4 (IQR; 2-12) months in HV, the outcome was better in HV than in HSP. In this regard, complete recovery (72.6% vs. 85.4%; p=0.01) was more commonly observed in HV while residual renal involvement (15.3% vs. 4.2%; p<0.001) was more common in HSP. The disease relapsed in 35.3% of patients with HSP and in 24.4% with HV (p=0.07). CONCLUSIONS: Our results confirm the claim that these two diseases presenting with similar cutaneous involvement are certainly two separate entities with greater systemic involvement and less favourable outcome in HSP.

Clinical and molecular characterization of steatotic liver disease in the setting of immune-mediated inflammatory diseases.

Background & Aims: Growing evidence suggests an increased prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) in the context of immune-mediated inflammatory diseases (IMIDs). We aimed to clinically and mechanistically characterize steatotic liver disease (SLD) in a prospective cohort of patients with IMID compared to controls. Methods: Cross-sectional, case-control study including a subset of patients with IMID. Controls from the general population were age-, sex-, type 2 diabetes-, and BMI-matched at a 1:2 ratio. SLD was established using controlled attenuation parameter. Liver biopsies were obtained when significant liver fibrosis was suspected. Total RNA was extracted from freshly frozen cases and analyzed by RNA-seq. Differential gene expression was performed with 'limma-voom'. Gene set-enrichment analysis was performed using the fgsea R package with a preranked "limma t-statistic" gene list. Results: A total of 1,456 patients with IMID and 2,945 controls were included. Advanced SLD (liver stiffness measurement ≥9.7 kPa) (13.46% vs. 3.79%; p <0.001) and advanced MASLD (12.8% vs. 2.8%; p <0.001) prevalence were significantly higher among patients with IMID than controls. In multivariate analysis, concomitant IMID was an independent, and the strongest, predictor of advanced SLD (adjusted odds ratio 3.318; 95% CI 2.225-4.947; p <0.001). Transcriptomic data was obtained in 109 patients and showed 87 significant genes differentially expressed between IMID-MASLD and control-MASLD. IMID-MASLD cases displayed an enriched expression of genes implicated in pro-tumoral activities or the control of the cell cycle concomitant with a negative expression of genes related to metabolism. Conclusions: The prevalence of advanced SLD and MASLD is disproportionately elevated in IMID cohorts. Our findings suggest that IMIDs may catalyze a distinct MASLD pathway, divergent from classical metabolic routes, highlighting the need for tailored clinical management strategies. Impact and implications: The prevalence of steatotic liver disease with advanced fibrosis is increased in patients with immune-mediated inflammatory diseases, independent of classic metabolic risk factors or high-risk alcohol consumption. Transcriptomic analysis revealed a unique gene expression signature associated with cellular activities that are compatible with a liver condition leading to an accelerated and aggressive form of steatotic liver disease. Our findings underscore the importance of heightened screening for advanced liver disease risk across various medical disciplines overseeing patients with immune-mediated inflammatory diseases.

Dose reduction is a feasible strategy in patients with plaque psoriasis who achieve sustained response with secukinumab: a retrospective, multicenter cohort study in daily practice setting.

BACKGROUND: Biological therapy dose modification is a common practice in the long-term treatment of plaque psoriasis. OBJECTIVE: The objective of the study was to determine prevalence, characteristics of patients, effectiveness, treatment survival of secukinumab dose reduction (SEC-DR) strategy and assess its safety and cost implications. METHODS: A retrospective, observational, multicenter cohort study was conducted in patients with plaque psoriasis treated with secukinumab and up to 2 years of follow-up. RESULTS: In 63/347 patients with an initial standard dose regimen, SEC-DR was tried at any moment in 18.2% of them after sustained response. In 51 patients, the interval between administrations was increased while in 12 patients, monthly dose was reduced to 150 mg. Successful SEC-DR was achieved in 77.8% of the patients, with sustained PASI response to the end of the study. Survival of secukinumab treatment and safety profile were not compromised by DR. The use of DR saved 33% of the cost, including failures in which standard treatment was resumed. LIMITATIONS: The proper of the study designed and the arbitrary definition of "DR success." CONCLUSION: Off-label SEC-DR strategy was used in patients with sustained response to standard dose regimen; this strategy showed long-term efficacy without compromising treatment survival or worsening the safety profile while also being cost saving.