Cardiometabolic Comorbidities in Psoriasis and Psoriatic Arthritis

There is solid epidemiologic evidence linking psoriasis and psoriatic arthritis (PsA) to cardiovascular risk factors and an increased risk of developing cardiovascular disease. Chronic inflammation, with shared pathways and cytokines common to metabolic syndrome, atherosclerosis and psoriasis, might provide the basis for the cardiovascular and metabolic comorbidities of psoriasis and PsA. The purpose of this manuscript is to review recent evidence about the epidemiology and underlying mechanisms of cardiovascular risk factors and cardiovascular disease in patients with psoriasis and/or PsA; the use of analytical determinations, physiologic measures and imaging techniques as surrogate biomarkers of atherosclerosis, endothelial dysfunction and cardiovascular disease in these patients; and the epidemiological and clinical data, including results of clinical trials, supporting a cardioprotective role of anti-inflammatory and disease-modifying treatment in psoriasis and PsA

IL-1 Family Cytokines in Inflammatory Dermatoses : Pathogenetic Role and Potential Therapeutic Implications

The interleukin-1 (IL-1) family is involved in the correct functioning and regulation of the innate immune system, linking innate and adaptative immune responses. This complex family is composed by several cytokines, receptors, and co-receptors, all working in a balanced way to maintain homeostasis. Dysregulation of these processes results in tissue inflammation and is involved in the pathogenesis of common inflammatory dermatoses such as psoriasis, hidradenitis suppurativa, and atopic dermatitis. Therefore, therapeutic targeting of IL-1 pathways has been studied, and several monoclonal antibodies are currently being assessed in clinical trials. So far, promising results have been obtained with anti-IL-36R spesolimab and imsidolimab in pustular psoriasis, and their efficacy is being tested in other conditions

Dual inhibition of IL-17A and IL-17F in psoriatic disease

Psoriasis and psoriatic arthritis are chronic immune-mediated disorders with involvement of interleukin (IL)-17 cytokines in their pathogenesis. IL-17A has been considered to be the most biologically active, but IL-17F is also over-expressed in skin and synovial tissues of patients with these diseases. Many therapeutic advances have been made in the past years, but some needs remain unmet. Dual inhibitor and bispecific antibodies simultaneously targeting IL-17A and IL-17F could provide better disease control. Herein we review current evidence on bimekizumab and sonelokimab. The antigen-binding site of bimekizumab neutralizes both IL-17A and IL-17F; phase I, II, and III studies have demonstrated its efficacy and safety in psoriasis and psoriatic arthritis. Sonelokimab is a trivalent nanobody targeting IL-17A and IL-17F; phase I and II studies with this molecule have yielded promising results in psoriasis

Quantification of Malassezia pachydermatis by real-time PCR in swabs from the external ear canal of dogs

Financial support for this project came from Servei Veterinari de Bacteriologia i Micologia from the Universitat Autònoma de Barcelona.Malassezia pachydermatis is part of the normal microbiota of canine skin and external ear canal, and is also associated with otitis externa in dogs. Laboratory detection of Malassezia otitis relies on the presence of elevated numbers of the yeast on cytologic examination of otic exudate. Although cytology has high specificity, it has low sensitivity, resulting in false-negatives and posing a challenge for clinicians to accurately diagnose Malassezia otitis. We developed a quantitative PCR (qPCR) to detect and quantify M. pachydermatis yeasts and validate the method with swabs from external ear canals of dogs. Our qPCR uses the β-tubulin gene, a single-copy gene, as a target. The limit of quantification was established as 0.18 ng/reaction, equivalent to 2.0 × 10 genome equivalents (gEq). Swabs from healthy dogs yielded quantification values of ≤2.7 × 10 gEq in the qPCR, whereas swabs from dogs with otitis yielded quantification values of ≥2.5 × 10 gEq. Our qPCR assay provides accurate quantification of M. pachydermatis yeasts from swab samples from dogs, is more sensitive than cytology, and could be used to monitor response to treatment. Our assay could also be valuable in a research setting to better understand the pathogenesis of M. pachydermatis

Dermatology Life Quality Index in Patients with Moderate-to-Severe Plaque Psoriasis Treated with Brodalumab or Ustekinumab

Targeted biological therapies for psoriasis have resulted in significant benefits, with therapeutic goals such as clear or almost clear skin accompanied by improvements in health-related quality of life (HRQoL). The objective of this study was to compare the effects of 52 weeks of treatment with brodalumab or ustekinumab on HRQoL in patients with moderate-to-severe plaque psoriasis. Data were pooled from two randomised controlled phase 3 trials (AMAGINE-2 and -3) which included patients with moderate-to-severe plaque psoriasis treated with brodalumab 210 mg or ustekinumab 45 or 90 mg for 52 weeks. HRQoL outcomes were measured using the Dermatology Life Quality Index (DLQI) as well as the DLQI-Relevant (DLQI-R) version which excludes 'not relevant' responses. A total of 929 patients were included, 339 in the brodalumab group and 590 in the ustekinumab group. A significantly greater reduction (improvement) in DLQI score from baseline was observed in the brodalumab group compared with the ustekinumab group at weeks 4 [least-squares (LS) mean difference − 2.9, 95% confidence interval [CI] − 3.6 to − 2.2; p < 0.001), 12 (LS mean difference − 0.85, 95% CI − 1.5 to − 0.2; p = 0.01) and 52 (LS mean difference − 0.94, 95% CI − 1.6 to − 0.2; p = 0.009)]. Significantly greater proportions of patients treated with brodalumab achieved a DLQI score of 0 at weeks 4 (15.0 vs. 5.4%; p < 0.0001), 12 (37.5 vs. 28.0%; p = 0.0140) and 52 (46.3 vs. 30.3%; p < 0.0001), or of ≤ 1 [DLQI (0/1): 33.9 vs. 15.4%, 59.9 vs. 45.6% and 54.9 vs. 39.8%, respectively; all p < 0.0001]. Similar results were observed using the DLQI-R scoring system. Significantly more patients achieved a ≥ 4 or ≥ 5 improvement in DLQI with brodalumab compared to ustekinumab at weeks 4 and 52. Treatment with brodalumab was associated with significantly more patients achieving a DLQI of 0 compared to ustekinumab for all domains after 4 and 52 weeks. Brodalumab was associated with a significantly greater improvement in HRQoL compared to ustekinumab in patients with moderate-to-severe psoriasis

Consistent response to guselkumab treatment between Hispanic and non-Hispanic patients with psoriasis : an analysis from VOYAGE 1 and VOYAGE 2

Altres ajuts: Janssen Research and Development (JRD)Introduction: In VOYAGE 1 (NCT02207231) and VOYAGE 2 (NCT02207244), guselkumab, an interleukin-23 blocker, was safe and effective in patients with moderate-to-severe plaque psoriasis. Methods: Patients who self-identified as Hispanic (n = 117) or non-Hispanic (n = 1686) were randomized to guselkumab, placebo, or adalimumab. Efficacy assessments included Psoriasis Area and Severity Index (PASI), Investigator's Global Assessment (IGA), and Dermatology Life Quality Index (DLQI). Results: At week 16, treatment differences for guselkumab versus placebo in the Hispanic and non-Hispanic populations were 67.4 (95% confidence interval 50.4, 84.4) and 77.2 (73.5, 80.8) percentage points for IGA 0/1 and 59.2 (41.9, 76.4) and 69.2 (65.7, 72.7) percentage points for PASI 90, respectively. Treatment differences for guselkumab versus adalimumab were 25.9 (6.5, 45.3) and 17.5 (12.8, 22.3) percentage points for IGA 0/1 and 21.4 (-0.1, 42.9) and 23.5 (18.2, 28.9) percentage points for PASI 90, respectively. Week 24 results were similar. Adverse event frequency was greater in adalimumab- versus guselkumab-treated patients in the Hispanic population only through weeks 16 and 28. In both populations, DLQI 0/1 responses were greater in guselkumab-treated versus placebo- and adalimumab-treated patients at week 16 and versus adalimumab-treated patients at week 24. Conclusions: Guselkumab safety and efficacy were consistent between Hispanic and non-Hispanic populations

Long-term efficacy and safety of brodalumab in the treatment of psoriasis : 120-week results from the randomized, double-blind, placebo- and active comparator-controlled phase 3 AMAGINE-2 trial

Randomized controlled trials have shown the efficacy and safety of brodalumab in patients with moderate to severe plaque psoriasis. To evaluate the efficacy and safety of brodalumab through 120 weeks of treatment in the AMAGINE-2 trial. Patients received ustekinumab through week 52 followed by brodalumab 210 mg every 2 weeks, continuous brodalumab 210 mg every 2 weeks, or any dose of brodalumab. Efficacy data were reported through 120 weeks by using observed data, last observation carried forward, and nonresponder imputation analyses. Of patients who received brodalumab 210 mg every 2 weeks, 84.4%, 75.6%, and 61.1% achieved 75%, 90%, and 100% improvement from baseline in Psoriasis Area and Severity Index at 120 weeks (observed data analysis), respectively. Patients who received brodalumab 210 mg every 2 weeks after receiving ustekinumab through 52 weeks achieved a similar skin clearance response as patients who received continuous brodalumab 210 mg every 2 weeks. Safety through 120 weeks was comparable to that of the blinded study periods. A large number of discontinuations toward the end of the study (31% in the final 6 months) were due to early termination and led to differences between observed data and nonresponder imputation results. Brodalumab is well tolerated and showed robust efficacy for more than 2 years

New perspectives on the treatment of hidradenitis suppurativa

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by the presence of painful nodules, abscesses, chronically draining fistulas, and scarring in apocrine gland-bearing areas of the body. The exact pathogenesis of HS is not yet well understood, but there is a consensus in considering HS a multifactorial disease with a genetic predisposition, an inflammatory dysregulation, and an influence of environmental modifying factors. Therapeutic approach of HS is challenging due to the wide clinical manifestations of the disease and the complex pathogenesis. This review describes evidence for effectiveness of current and emerging HS therapies. Topical therapy, systemic treatments, biological agents, surgery, and light therapy have been used for HS with variable results. Adalimumab is the only US Food and Drug Administration (FDA) approved biologic agent for moderate-to-severe HS, but new therapeutic options are being studied, targeting different specific cytokines involved in HS pathogenesis. Comparing treatment outcomes between therapies is difficult due to the lack of randomized controlled trials. Treatment strategy should be selected in concordance to disease severity and requires combination of treatments in most cases

Ixekizumab Citrate-Free Formulation : Results from Two Clinical Trials

Introduction: Subcutaneous (SC) injection is a common route of drug administration; however, injection site pain (ISP) might create a negative patient experience. We evaluated ISP, bioequivalence, and overall safety of the citrate-free (CF) formulation of ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A. Methods: Two phase 1, single-blind studies were conducted in healthy participants. The crossover study A (NCT03848403) evaluated pain intensity on injection as measured by visual analog scale of pain (VAS) scores. Subjects (N = 70) were randomized 1:1:1 at the beginning to three possible treatment sequences and received a 1 mL SC injection of the three formulations sequentially in the abdomen on days 1, 8, and 15, respectively. A mixed-effects repeated measures analysis model was used to analyze VAS score by time post-injection. Study B (NCT04259346) evaluated the bioequivalence of a single 80 mg dose of CF formulation compared to the original commercial formulation. Subjects (N = 245) were randomized 1:1 to either commercial or CF formulation and received a single SC injection into the abdomen, arm, or thigh. Results: Primary endpoint was achieved in both studies. In study A, least-squares mean (LSM) difference of VAS scores immediately post injection between commercial (n = 61) and CF formulation (n = 63) was − 21.7 (p < 0.0001), indicating a lower degree of pain associated with CF formulation. In study B, bioequivalence of the CF formulation was established as 90% CIs for the ratio of geometric LSM AUC, AUC, and C between treatments were contained within the prespecified limits of 0.8 and 1.25. Except for less ISP in the CF formulation, overall safety profile was comparable. Conclusion: Ixekizumab CF formulation proved to be bioequivalent, was associated with less ISP, and had no other notable differences in the safety profile compared to the original commercial formulation. Trail Registration: ClinicalTrials.gov identifier NCT03848403, NCT04259346

Improving patient outcomes in psoriasis : strategies to ensure treatment adherence

Psoriasis is a frequent inflammatory disease with a chronic and relapsing course. Therefore, patients with psoriasis are likely to undergo different treatments for long periods of time. Traditionally, therapies used in psoriasis have been associated with poor levels of adherence due to the complexity of the regimens and the poor results obtained with the topical therapies. These poor outcomes are associated with high levels of frustration and anxiety, which decrease adherence and worsen the disease. With the recent introduction of highly efficacious biologic therapies, patients can achieve very good and prolonged responses. However, most patients with psoriasis have mild disease and may be treated with skin-directed therapies. Therefore, it is important to develop strategies to improve adherence in order to achieve better outcomes, and to improve the overall quality of life. Hence, acknowledging the causes of nonadherence is crucial for implementing these strategies. In this summary, we review the causes of nonadherence, and we provide behavioral strategies in order to improve adherence and, ultimately, the outcome of patients with psoriasis