Age affects drug survival rates of interleukin (IL)-17 and IL-23 inhibitors in patients with plaque psoriasis: Results from a retrospective, multicentric, multi-country, cohort study.

BACKGROUND: Scarce data related to the drug survival of biologic agents in psoriasis patients aged ≥65 years is available. OBJECTIVES: To evaluate the drug survival of interleukin (IL)-23 or the IL-17 inhibitors approved for the treatment of moderate-to-severe psoriasis in elderly patients (aged ≥65 years), compared with younger adult patients (aged <65 years), and to identify clinical predictors that can influence the drug survival. METHODS: This retrospective multicentric cohort study included adult patients with moderate-to-severe psoriasis, dissecting two-patient subcohorts based on age: elderly versus younger adults. Kaplan-Meier estimator and proportional hazard Cox regression models were used for drug survival analysis. RESULTS: We included 4178 patients and 4866 treatment courses; 934 were elderly (1072 treatment courses), and 3244 were younger patients (3794 treatment courses). Drug survival, considering all causes of interruption, was higher in patients aged <65 years than in elderly patients overall (log-rank p < 0.006). This difference was significant for treatment courses involving IL-23 inhibitors (p < 0.001) but not for those with IL-17 inhibitors (p = 0.2). According to both uni- and multi-variable models, elder age was associated with an increased risk of treatment discontinuation (univariable analysis: HR: 1.229, 95% CI 1.062-1.422; p < 0.006; multivariable analysis: HR: 1.199, 95% CI 1.010-1.422; p = 0.0377). Anti-IL-23 agents were associated with a reduced likelihood of treatment discontinuation after adjusting for other variables (HR: 0.520, 95% CI 0.368-0.735; p < 0.001). Being previously treated with IL-17 inhibitors increased the probability of discontinuation. CONCLUSIONS: Elderly patients with psoriasis have an increased risk of biologic treatment discontinuation compared with younger adult patients, particularly, if being treated with IL-23 inhibitors. However, in stratified analyses conducted in elderly patients, IL-23 inhibitors showed higher drug survival rates than IL-17 inhibitors.

Successful use of anti-IL-23 molecules in overweight-to-obese psoriatic patients: A multicentric retrospective study.

Advances in treatment with biological agents have changed the course of psoriasis. However observational reports and controlled trials draw attention to the heterogeneity of treatment response and point out that Body Mass index (BMI) may be a key factor for therapy efficacy. Therefore, we investigated the impact of BMI on the efficacy of the most recent biological molecules (anti IL-23 inhibitors) to improve patient care management. A bicentric retrospective study was performed to assess efficacy and safety of guselkumab, risankizumab and tildrakizumab in overweight-to-obese patients with moderate to-severe psoriasis up to 52 weeks of treatment. This study involved 113 patients classified according to BMI as overweight or obese. The clinical response to treatment was assessed by Psoriasis Area and Severity Index (PASI) at week 0, 24 and 52. Across all anti-IL-23 treatments, mean PASI score was ≤2 (1.1) after 6 months of treatment and decreased under 1 after 12 months in all groups. No severe adverse events, death or malignancy cases were recorded. Our results suggest that overweight or obesity does not influence therapeutic response in psoriatic patients treated with anti-IL-23 antagonists. Therefore, therapeutic strategies with this mechanism of action would be more suitable for high BMI patients.

Clinical experience with adalimumab biosimilar imraldi in hidradenitis suppurativa.

Adalimumab is the only biologic therapy approved for the treatment of patients with hidradenitis suppurativa, a chronic and disabling skin condition. To date, there are no studies in the literature about the effectiveness of adalimumab biosimilar SB5 in hidradenitis suppurativa. The aim of this study was to evaluate its efficacy and safety. A retrospective observational study was performed in hidradenitis suppurativa adalimumab naive patients and in patients who were switched from the adalimumab originator. Eleven patients were included in the study. Our results support adalimumab SB5 as an effective and well tolerated drug, with a good interchangeability with its originator also for the treatment of hidradenitis suppurativa.

Clindamycin as unique antibiotic choice in Hidradenitis Suppurativa.

The rifampicin (RF)-clindamycin (CL) combination is recommended as first line therapy in moderate to severe Hidradenitis Suppurativa (HS) by European S1 guidelines. Although prolonged use of RF should be discouraged, there are currently few alternatives to this combination therapy. The aim of the present study was to assess retrospectively the efficacy of oral CL monotherapy in patients diagnosed with HS. In the period January 2017-May 2018, 31 HS patients who received a 300 mg b.i.d. oral dose of CL were studied retrospectively. Efficacy of the treatment was evaluated by comparing the main HS severity scores (Sartorius score modified by Revuz, Hidradenitis Suppurativa Physician Global Assessment [HS-PGA] and International Hidradenitis Suppurativa Severity Score System [IHS4]) before (W0) and after (W12) CL oral therapy. CL efficacy was demonstrated by the extreme and significant reduction of all three disease severity parameters during the 12-week period (p ≤ .01). There was also a statistically significant change in the mean visual analogue scale for pain. The present study demonstrates the efficacy of oral CL monotherapy as RF-sparing regimen alternative to RF-CL combination in a selected group of patients.

Epidermal barrier reaction to an in vitro psoriatic microenvironment.

Keratinocytes (KCs) and Langerhans cells (LCs) contribute to create the epidermal barrier. To form a functional epidermis, KCs express filaggrin and Toll-like Receptors (TLRs). LCs are the first line of epidermal defence and can be activated by interleukin (IL)-17 and Tumor Necrosis Factor (TNF)-alpha. In psoriasis, an alteration of TLR expression, a defective expression of filaggrin, and LC activation occur. In organotypic cultures of human skin we investigated the interplay between IL-17 and TNF-alpha on i) expression of filaggrin, TLR2, 7 and 9, and Nuclear Factor (NF)-kB localization by immunofluorescence and ii) LC ultrastructural features by transmission electron microscopy. Normal human skin was obtained after aesthetic surgery (n=7), overnight incubated in a Transwell system, and exposed to TNF-alpha and/or IL-17 for 24 (T24), 48 (T48), and 72 (T72) hours. Cytokines always influenced the expression of filaggrin. TNF-alpha alone activated LCs only starting from T48. TLR2 and TLR7 expressions were affected at T24 by IL-17 and the combination of cytokines, but not by TNF-alpha. TLR9-positive cells were detectable in the granular layer after cytokine exposure. A nuclear localization of NF-kB was always observed after cytokine incubation. In conclusion, each cytokine possess an intrinsic activity on the different components of the epidermal barrier.

Safety and efficacy of HCV eradication during etanercept treatment for severe psoriasis.

Treatment of severe psoriasis in HCV positive patients is challenging, because several psoriasis medications have a toxic effect on the liver, and interferon alpha, used to treat hepatitis, can induce worsening of psoriatic lesions. TNF-alpha inhibitors seem to be a safe and effective option in HCV positive psoriatic patients, but there are concerns about long-term safety, impact on liver fibrosis progression and risk of immune-mediated liver injury. With regard to HCV treatment, new direct-acting antiviral therapies (DAA) seem to be extremely effective, with minimal side effects, but little is known about possible interactions with other medications, particularly with biologics. We report the case of a psoriatic patient, in treatment with Etanercept, who needed to undergo HCV eradication with Daclastavir and Sofosbuvir because of worsening liver fibrosis due to chronic hepatitis C. The present treatment produced excellent results in terms of HCV eradication and control of psoriatic lesions, without side effects.

Treatment of psoriasis with topical agents: Recommendations from a Tuscany Consensus.

Psoriasis is a chronic and relapsing inflammatory skin disease, clinically characterized by erythematous and scaly plaques. Treatment approach is mainly driven by disease severity, though several factors should be considered in order to identify the optimal therapeutic choice. Mild psoriasis may be treated with a wide array of topical agents including corticosteroids, vitamin D analogs, keratolytics, and calcipotriol/betamethasone propionate compound. Because guidelines may not provide practical indications regarding the therapeutic approach, the use of topical agents in psoriasis is more individually tailored. In order to homogenize the standard of care, at least in a local setting, we collected the real-life-based recommendations for the use of topical therapies from an expert panel, the Tuscany Consensus Group on Psoriasis, representing all leading centers for psoriasis established in Tuscany. With this document, this consensus group sought to define principles guiding the selection of therapeutic agents with straightforward recommendations derived from a real-life setting.

A Pediatric Case of Sclerodermatous Graft-Versus-Host Disease Responsive to Ultraviolet A1 Phototherapy.

Graft-versus-host disease (GVHD) is one of the major complications after hematopoietic stem cell transplantation and is responsible for post-therapeutic morbidity, mortality, and poor quality of life of recipients. Sclerodermatous graft-versus-host disease (sGVHD) is a rare variant of chronic GVHD characterized by deposition of collagen in the skin and other soft tissues and resulting in loss of range of motion and functional capabilities. Treatment of sGVHD is challenging and largely limited by systemic side effects. Ultraviolet A1 phototherapy has been reported to be effective in connective tissue disorders, including sGVHD. We report a case of sGVHD in a 15-year-old girl that was resistant to traditional therapy but showed improvement in cutaneous symptoms with ultraviolet A1 phototherapy three times a week for 6 weeks (10 J/cm(2) single dose, 180 J/cm(2) cumulative dose).

Tuberculosis reactivation risk in dermatology.

The treatment of some dermatological diseases, especially psoriasis, has been revolutionized by the advent of biologic therapies that target various immune cells or cytokines. However, biologic therapies may affect the risk of active tuberculosis (TB). We review the published safety data about TB risk reactivation for biologic agents used in dermatology. According to recent findings, psoriasis itself could represent an independent risk factor for TB; a high prevalence of TB was found in patients with psoriasis (18.0%), even after adjusting for age, work, and other characteristics. Latent TB infection was more common in patients with psoriasis (50%) than in those with inflammatory bowel disease (24.2%). Risk of TB reactivation was also influenced by the type of agent used. Several structural and functional differences among biologic drugs could account for differences in risk of granulomatous infection. Different kinetics of currently available tumor necrosis factor (TNF) antagonists, leading to different TNF bioavailability in granulomatous tissue, may explain differences in TB reactivation among patients treated with biologics. One could argue that etanercept should be the first choice of anti-TNF agent in populations at high risk of TB. Risk of TB reactivation during treatment with other biologics is not yet well defined.

Etanercept restores a differentiated keratinocyte phenotype in psoriatic human skin: a morphological study.

Tumor Necrosis Factor-α (TNF-α) plays a pivotal role in psoriasis, an immuno-mediated and genetic skin disease. Anti-TNF-α inhibitors, such as etanercept, are widely used in clinical practice. By immunofluorescence, we investigated the expression of junctional transmembrane proteins in desmosomes (desmocollin-1, Dsc1; desmoglein-1, Dsg1), adherens junctions (E-cadherin), tight junctions (occludin), biomarkers of keratinocyte differentiation (keratin-10, K10; keratin-14, K14; keratin-16, K16; involucrin), epithelial proliferation and apoptosis in psoriatic skin before/after etanercept treatment (n = 5) and in control skin samples (n = 5). Occludin, K14, K16 and involucrin expressions were altered in psoriatic epidermis, while Dsc1, Dsg1, E-cadherin and K10 localisations were comparable to controls. Etanercept promoted the restoration of the physiological condition as suggested by a more differentiated keratinocyte phenotype and a reduced epidermal proliferation rate.

Induction of apoptosis by fractional CO2 laser treatment.

INTRODUCTION: Fractional CO2-laser is considered a preferential method for skin resurfacing, but little is known about the molecular mechanisms underlying this surgical tool. In the present study, we investigated the possible role of apoptosis by the sequential analysis of lesional skin after laser treatment, with special attention to power. Moreover, we have analyzed if there is a correlation with clinical improvement. MATERIALS AND METHODS: We evaluated the effects of fractional CO2-laser in twelve patients with photodamage skin Fitzpatrick types I to III. Apoptosis markers were assessed by an immunohistochemical study on skin samples of foream at 24 h, 72 h and 7 days after the irradiation with 15 W or 20 W. Moreover, clinical improvement was assessed by iconography. RESULTS: Fractional CO2-laser induced an inflammatory repair process mediated by activation of apoptotic pathway that was completed in 7 days. The expression of proapototic markers, as annexin-VII and Caspases-9 was increased 24-72 hours after irradiation and decreased after 7 days. While the expression of the anti-apototic marker Bcl-2 increased progressively during 7 days after treatment. CONCLUSION: Our study suggests that the skin's appearance may be enhanced by creating skin changes through apoptosis. Apoptosis, one of the major mechanisms of cell death, might play a key role in initiating the paracrine cascades that lead to cell proliferation.

Therapy of PsO in Special Subsets of Patients.

Psoriasis is a chronic, inflammatory skin disease that may occur at any age, with a bimodal peak of incidence around the age of 16-20 years of age (early onset) and 57-60 years (late-onset). It is estimated that roughly 70% of patients develop the disease before the age of 40, which coincides with the reproductive years. Moreover, psoriasis is a chronic disease, meaning that, with increased life-duration expectancy, the number of patients affected with psoriasis aged over 65 years is going to increase and represent a big therapeutic challenge. Actually, no specific drug recommendation is available, based only on the age of the patients, while therapeutic prescription should take into account that elderly patients have more comorbidities than younger patients, with polypharmacy and an increased risk of drug interactions. Women with psoriasis are more likely to report a worse influence of the disease on their quality of life, and they are more susceptible to the development of depression. Furthermore, pregnancy and lactation represent a major contraindication to several systemic agents, and only a few studies exist providing the safety of certain drugs during these periods of life of a woman, such as certolizumab pegol. In this paper, we discuss systemic therapeutic strategies, including conventional and biological therapies, in a special subset of patients affected with moderate-to-severe psoriasis focusing on elderly patients and on female patients in fertile age, pregnancy, and lactation.

Long-term safety and efficacy of anti-tumor necrosis factor-alpha biosimilar agents in the treatment of psoriasis: a single center study.

Biosimilar anti-tumor necrosis factor (TNF)-alpha drugs are widely used in the treatment of psoriasis, but only few studies reported the long-term experience of the various biosimilar agents in the real world practice. A monocentric retrospective observational study was performed to assess the long-term efficacy, tolerability, and safety of biosimilars adalimumab (bADA), biosimilar etanercept (bETN), and biosimilar infliximab (bIFX) in psoriasis patients. A total of 73 patients (19 patients treated with bADA, 37 with bETN and 17 with bIFX) were enrolled and observed up to 48 months of follow-up. Regarding the efficacy, across all biosimilar treatments combined, the mean PASI score was ≤2 (1.2) after 12 months of treatments. Notably, the mean PASI score remained relatively stable during all 48 months of follow-up. With regard to tolerability and safety in the present study, 34 (28%) patients experienced adverse events during all biosimilar therapy, and three (4.3%) discontinued treatment. No severe adverse events, death, or malignancy cases were recorded during the study period. Our results support that biosimilar anti-TNF-alpha drugs are effective and well tolerated drugs for the long-term treatment of psoriasis.

Hidradenitis Suppurativa: The Influence of Gender, the Importance of Trigger Factors and the Implications for Patient Habits.

Hidradenitis suppurativa (HS) is a debilitating, chronic, inflammatory skin disease primarily affecting apocrine gland-rich areas of the body. On the one hand, the presence of triggering factors-some identified, others only hypothesized-may initiate or perpetuate the pathogenic process of HS. In addition to cigarette smoking and diet, other trigger factors, including choice of clothing, are frequently observed in clinical practice. On the other hand, the presence of disease may influence habits of HS patients. Indeed, high incidences of sexual and sleep impairment have been reported in these patients. Consequently, alcohol and substance abuse may be a coping strategy for the emotional and psychological disease burden. Furthermore, a greater awareness of gender differences in HS may be important for dermatologists in their own clinical practice (i.e., pregnancy and breastfeeding). Consequently, in this loop interaction, comprehensive knowledge of all factors involved is crucial for the management of HS patients. Thus, the objective of this review is to (i) discuss the influence of gender on HS, (ii) summarize the most frequent triggering factors of HS and (iii) analyze the impact of HS on patient habits.

Efficacy and safety of dimethylfumarate in elderly psoriasis patients: a multicentric Italian study.

The number of psoriatic elderly patients is steadily increasing in the Western world, nevertheless they are frequently excluded from clinical trials and described as a high-risk group for adverse events.We conducted a retrospective multicentric study of DMF use in elderly (>65 years) psoriatic patients. DMF efficacy was evaluated up to 24 weeks by Psoriasis Area and Severity Index (PASI) score. We also evaluated drug maintenance and safety.Our study population included 81 elderly psoriatic patients treated with DMF up to 24 weeks. The PASI score at the baseline (week 0) ranged from 3,7-24 (mean ± SD, 9,8 ± 4,1), which changed after DMF administration to 4,3 ± 3,2 at week 16 and 2,7 ± 3,2 at week 24. Among 81 elderly psoriatic patients 59 (72,8%) adverse events were reported during the observation period. The most common were gastrointestinal complaints (n = 24, 29,6%) and flushes (n = 10, 12,3%). Lymphocytopenia (n = 10, 12,35%) was frequently observed.In daily practice, DMF seems to be efficacy and well tolerated in elderly psoriatic patients. DMF may be a first-line systemic treatment option to manage elderly psoriasis, provided that also the long-term safety data are closely monitored, in particular lymphocytopenia.

Tuscany consensus for the treatment of moderate-severe psoriasis: update and focus on practical guidelines for place in therapy of anti-IL-17 and anti-IL-23 biologics.

Psoriasis is a common chronic skin disease characterized by a worldwide distribution and a natural tendency towards progression. According to the many clinical forms, the extension of the disease and the many comorbidities, almost the 20% of the patients require a systemic treatment. Biologics have greatly changed the ongoing of psoriasis and the quality of life of psoriasis patients. After the anti-TNF-alpha, which were the first biologics in use for psoriasis, the improvement in knowledge of the pathogenetic mechanisms underlying the disease has led to the development of a series of more specific therapies for psoriasis. This "second generation" of biologics includes the interleukin (IL)-12/23 inhibitor ustekinumab, IL-17 inhibitors (secukinumab and ixekizumab), the IL-17 receptor A (IL-17RA) antagonist brodalumab, and the IL-23 inhibitors guselkumab, risankizumab and tildrakizumab. This study represents an update of the Tuscany consensus focused on the use of new drugs, such as anti-IL-17 and anti-IL-23 in moderate-to-severe psoriasis and their correct place in therapy according to specific clinical requests and in full respect of the current financial restrictions.