Injection site reactions resulting from the use of biological therapy in the treatment of moderate-to-severe plaque psoriasis.

INTRODUCTION: Biological medications have significantly improved the prognosis of psoriasis patients. All biological drugs (except infliximab) for psoriasis require subcutaneous (SC) administration. Adverse events of biologic drug treatment include injection site reactions. ISRs are a local phenomenon characterized by swelling, erythema, pruritus, and pain around the injection site. AREAS COVERED: We conducted a review to analyze the differences between the ISRs of various biologics approved for psoriasis. Specifically, the review focused on anti-TNF-α, anti-IL12/23, anti-IL-17, and anti-IL-23 drugs. EXPERT OPINION: Etanercept and adalimumab have reported ISR rates of 37% and 20%, respectively, with erythema, pruritus, pain, and irritation being the most common. Citrate free (CF) solution and thinner needles have reduced ISR associated with adalimumab. Ustekinumab showed a low risk of ISR. Regarding secukinumab and ixekizumab, pain was found to be the most common ISR. The introduction of CF ixekizumab formulation has shown promise in reducing ISRs associated with ixekizumab. The risk of ISR appears insignificant with bimekizumab, brodalumab, and anti-IL23 drugs, with ISR rates ranging from less than 1% to 7.1%. The choice of biologic agent should consider ISR risk. Education on injection techniques and the use of single-dose autoinjectors/pens can mitigate ISR risk.

The role of bDMARDs in the prevention and treatment of inflammatory-related comorbidities in Psoriatic Arthritis.

INTRODUCTION: Psoriatic arthritis (PsA) is an immune-inflammatory disease that affects both joints and entheses, and with diverse extra-articular manifestations (psoriasis, inflammatory bowel disease (IBD), and uveitis). A wide range of comorbid conditions, including cardiovascular diseases, obesity, metabolic syndrome (MetS), nonalcoholic fatty liver disease (NAFLD), mental health disorders (depression/anxiety), and osteoporosis are highly prevalent in course of PsA.Biological DMARDs (bDMARD), including TNF-inhibitors (TNFi), Interleukin (IL-17i) and IL-23i represent the cornerstone of the management of active disease. The use of these therapies obviously requires considering comorbidities presence, safety aspects and contraindications. AREAS COVERED: The aim of this review is to describe the inflammatory mechanisms behind PsA comorbidities, and the role of bDMARDs in the prevention and treatment of these conditions in course of PsA. EXPERT OPINION: Tailoring therapeutic strategies to the individual characteristics of each PsA patient can be an effective approach to manage comorbidities, maximizing the efficacy of bDMARDs, and reducing the incidence of AEs. Identifying targets within disease pathways can guide research into therapeutics that address both PsA and comorbidities simultaneously, but more studies are advocated for clarifying the potential prevention and management of bDMARDs used for PsA.

Secukinumab for Severe Hidradenitis Suppurativa in a Patient on Haemodialysis: Efficacy and Safety on 300 mg Every 2 Weeks Administration - A Case Report.

This case study outlines the management of a 24-year-old male with a history of juvenile nephronophthisis who underwent renal transplantation at age 12 and later required dialysis at 18 due to chronic rejection and hypertension. Subsequently, the patient developed severe Hidradenitis Suppurativa (HS) affecting the axillary, groin, and gluteal regions. Despite undergoing various systemic and intravenous antibiotic therapies, as well as Adalimumab treatment, the HS remained refractory. Adalimumab was discontinued due to a detected ejection fraction of 45% during cardiologic follow-up, likely due to COVID-19 related myocarditis. Following this, the patient was initiated on secukinumab therapy, initially undergoing an induction phase followed by maintenance dosing. Significant improvements were observed in quality of life, pain scores, and HS activity after 5 weeks of secukinumab therapy, with sustained benefits at the 6-month follow-up. Secukinumab was well tolerated, with no reported adverse events. This case underscores the effectiveness and safety of secukinumab as a therapeutic option for refractory HS, particularly in patients with comorbidities such as renal transplant recipients.

Management of Psoriasis Patients with Serious Infectious Diseases.

The management of patients affected by moderate-to-severe psoriasis may be challenging, in particular in patients with serious infectious diseases [tuberculosis (TB), hepatitis B and C, HIV, COVID-19]. Indeed, these infections should be ruled out before starting and during systemic treatment for psoriasis. Currently, four conventional systemic drugs (methotrexate, dimethyl fumarate, acitretin, cyclosporine), four classes of biologics (anti-tumour necrosis factor alpha, anti-interleukin (IL)12/23, anti-IL-17s, and anti-IL-23], and two oral small molecules (apremilast, deucravacitinib) have been licensed for the treatment of moderate-to-severe psoriasis. Each of these drugs is characterized by a unique safety profile which should be considered before starting therapy. Indeed, some comorbidities or risk factors may limit their use. In this context, the aim of this manuscript was to evaluate the management of patients affected by moderate-to-severe psoriasis with serious infectious diseases.

Efficacy and safety of deucravacitinib for the management of psoriasis: a drug safety evaluation.

INTRODUCTION: Nowadays, despite the wide availability of biological drugs and apremilast for psoriasis management, there is always a need for new therapies to customize the therapeutic approach on the basis of the patient's clinical features and comorbidities, especially in order to achieve a prolonged therapeutic response. Thus, new treatment strategies are required to offer patients a personalized approach. In this scenario, major knowledge on psoriasis pathogenesis led to the development of deucravacitinib, an orally administered selective TYK2 inhibitor. AREAS COVERED: The aim of this manuscript is to review the current literature on the effectiveness and safety of deucravacitinib in psoriasis to offer readers a wide perspective. The current English literature was analyzed using the PubMed, Google Scholar, Embase, Cochrane Skin, and clinicaltrials.gov databases, selecting the most relevant manuscripts. EXPERT OPINION: Deucravacitinib appears to be an innovative weapon for the management of moderate to severe psoriasis. Despite its efficacy and safety profiles have been revealed by RCTs, real-life data are still scant. Certainly, deucravacitinib broadens the range of therapeutic alternatives for psoriasis patients, thus enhancing the holistic and personalized approaches required for the treatment of this disease.

Long-Term Efficacy and Safety of Guselkumab in Psoriasis Patients Who Failed Anti-IL17: A Two-Year Real-Life Study.

Guselkumab is the first approved human IgG1λ monoclonal antibody selectively targeting the p19 subunit of interleukin (IL)-23. Despite its effectiveness and safety, which have been widely reported by clinical trials and real-life experiences, data regarding its use on patients who previously failed anti-IL17 are limited or characterized by a reduced follow-up period. These data are essential to guide clinicians in biologic switching, considering that anti-IL23 and anti-IL17 partially share their therapeutic targets, as well as some patients who may have to interrupt treatment with anti-IL17 for loss of efficacy over time or the development of adverse events (AEs). In this context, we performed a retrospective study with the aim of evaluating the long-term use (2 years) of guselkumab in psoriasis patients who previously failed at least one anti-IL17 in a real-life setting, also focusing attention on psoriasis located in difficult-to-treat areas (the scalp, palms or soles, fingernails, genitals). A total of 61 patients (35 male, 57.4%; mean age 57.6 ± 8.8 years) were enrolled. Of these, 30 (49.2%) patients failed secukinumab, 21 (34.4%) failed ixekizumab, 7 (11.5%) failed brodalumab, and 3 (4.9%) failed both secukinumab and ixekizumab. At the baseline, the mean PASI and BSA were 12.8 ± 8.4 and 24.5 ± 26.6, respectively. During week 16, PASI90 and PASI100 responses were achieved by 60.7% and 37.7% of patients, respectively, which continued to improve up to week 104 (PASI90: 73.8%, PASI100: 59.0%). Clinical improvement in difficult-to-treat areas was detected as well. In particular, a slower improvement for fingernails and the palmoplantar region was reported compared to scalp and genital psoriasis at week 16. However, no differences were found following 28 weeks of therapy. Primary and secondary inefficacy were reported by 1 (1.6%) and 5 (8.2%) patients. As regards safety, no severe AEs were collected.

Effectiveness and Safety of Tildrakizumab in Psoriasis Patients Who Failed Anti-IL17 Treatment: A 28-Week Real-Life Study.

Tildrakizumab is a humanised IgG1/k-type monoclonal antibody that targets the p19 protein subunit of IL23. Despite its effectiveness and safety have been widely reported by clinical trials and real-life experiences, data regarding its use on patients who previously failed anti-IL17 (brodalumab, ixekizumab, bimekizumab and/or secukinumab) are scant. Therefore, further studies on this topic would be beneficial for clinicians in guiding the selection of biologic shifting, considering that anti-IL23, -12/23, and -IL17 partially share their therapeutic targets. In this context, we performed a 28-week, single-center, real-life, retrospective study, with the aim of assessing the efficacy and safety of tildrakizumab in patients who previously failed anti-IL17, also focusing the attention on psoriasis located in difficult-to-treat areas (scalp, palms or soles, fingernails, genitals). A total of 23 patients (12 male, 52.2%; mean age 52.8 ± 12.4 years) were enrolled. Of these, 11 (47.8%) failed secukinumab, 7 (30.4%) ixekizumab, 3 (13.0%) brodalumab, 1 (4.3%) both secukinumab and ixekizumab and 1 (4.3%) bimekizumab. At baseline, mean PASI and BSA were 12.8 ± 5.9 and 18.7 ± 9.6, respectively. At W16 PASI75 and PASI90 response were achieved by 15 (65.2%), and 9 (39.1%) patients, respectively, whereas 19 (82.6%) and 13 (56.6%) subjects reached these scores at W28. One (4.3%) case of primary inefficacy and 1 (4.3%) case of secondary inefficacy were assessed. Finally, no severe adverse events were collected. Tildrakizumab seems to be a valuable option in selected patients with psoriasis unresponsive to anti-IL17, suggesting that prior exposure to biological therapies seem not directly affect its effectiveness.

Efficacy and Safety of bimekizumab in psoriasis management in real-life: bio-naïve vs bio-experienced.

Bimekizumab is the latest monoclonal antibody approved for the management of moderate-to-severe plaque psoriasis. Currently, data investigating its use in real-life setting are limited. Therefore, we performed a short term [(16 weeks (W)] real-life, monocentric, prospective study aiming to assess the efficacy and safety of bimekizumab, also comparing bio-naïve vs bio-experienced patients. Globally, 56 patients were included. At baseline, mean PASI and DLQI were 16.9±7.8 and 22.6±5.9, respectively. PASI75/90/100 were reached by 76.8%/50.0%/42.9% of patients at W4 and by 92.9%/82.1%/69.6% of subjects at W16. In our cohort, 29 (51.8%) patients were bio-naïve whereas 27 (48.2%) bio-experienced. At baseline, both PASI and DLQI were significantly higher in bio-naïve cohort as compared with bio-experienced group (PASI: 19.4±7.7 vs 14.2±7.0, p<0.05; DLQI: 25.3±4.5 vs 19.7±6.0, p<0.001). Despite not significant, a higher percentage of patients in bio-naïve cohort as compared with bio-experienced group reached PASI75 (79.3% vs 63.0%, p=0.176), PASI90 (62.1% vs 44.4%, p=0.186) and PASI100 (48.3% vs 37.0%, p=0.396) at W4. However, the percentage of PASI75/90/100 response were similar between the two cohorts at W16. Regarding safety, 3 candidiasis (5.4%) and 1 (1.8%) eczematous reaction were reported, without differences between the two groups. Finally, 2 (3.6%) bimekizumab discontinuation for treatment failure and 3 (5.4%) for AEs were collected.

The Past, the Present and the Future of Teledermatology: A Narrative Review.

Teledermatology may be defined as the application of telemedicine to dermatology. According to published data, teledermatology is more widespread in Europe and North America, probably where resources for health care are greater than in other areas of the world. Indeed, teledermatology requires advanced technology to be efficient, as high image quality is necessary to allow the dermatologist to make correct diagnoses. Thanks to the recent advances in this field, teledermatology is become routinary in daily clinical practice. However, its use has been improved over time, overcoming several challenges. The aim of this narrative review is to retrace the almost 30-year history of teledermatology, to address the new challenges posed by advancing technologies such as artificial intelligence and the implications it may have on healthcare.

Pityriasis Rosea and Pityriasis Rosea-Like Eruption Following COVID-19 Vaccination: A Narrative Review.

COVID-19 pandemic completely changed every aspect of human life. Several measures were adopted to limit the spreading of the infection. Among these, vaccination was the main one. Globally, vaccination campaign was a success, showing to be efficient in controlling and preventing the SARS-Cov2 infection, reducing the risk of disease progression, hospitalization, and mortality. However, with the increasing number of vaccines administered, several cutaneous reactions were described, making dermatologists key players in their recognition and treatment. Among these, also viral reactivations have been described. In particular, cases of Pityriasis Rosea (PR) and PR-like reactivations have been collected. An early diagnosis is mandatory to avoid mistreatments. In this context, we conducted a review of the current literature investigating cases of PR following COVID-19 vaccination with the aim of understanding the possible pathogenetic mechanisms and causal correlation as well as to investigate the risk of this cutaneous eruption, to offer clinicians a wide perspective on the linkage between PR and COVID-19 vaccines.

Dupilumab-associated inflammatory arthritis: a literature review.

Dupilumab is a fully human monoclonal antibody that acts by inhibiting the interleukin (IL)-4 receptor subunit α, and hence the IL-4 and IL-13 signalling pathway. Dupilumab treatment has been linked to the onset of T helper 17-driven inflammatory diseases, including cases of seronegative arthritis and enthesitis. To date, dupilumab-associated inflammatory arthritis (DAIA) represents a relatively unknown adverse event, initially reported in single cases or case series reports. Indeed, the onset of DAIA may not be promptly recognized, and is probably underestimated. Here we have reviewed the available English literature regarding arthritis and enthesitis onset during dupilumab treatment for atopic dermatitis, aiming to improve rapid recognition and thus prompt treatment of these diseases.

A Case of Erythrodermic Psoriasis Successfully Treated with Risankizumab.

Psoriasis is a chronic inflammatory cutaneous disease, affecting up to 3% of the worldwide population. Several clinical phenotypes can be distinguished. Among these, erythrodermic psoriasis (EP) is a rare and severe variant (less than 3% of cases), characterized by severe generalized erythema and scaling affecting at least 90% of the body surface area. EP is often a life-threatening condition, since several systemic symptoms (tachycardia, fever, fatigue, lymphadenopathy, dehydration, serum electrolyte disturbances) can be associated. Thus, a prompt and appropriate treatment is mandatory. Unfortunately, EP treatment is challenging. Indeed, the reduced prevalence of EP makes clinical trials feasibility difficult, leading to the absence of established guidelines. So, the treatment of EP is often derived from moderate-to-severe psoriasis management which relies on the use of conventional systemic drugs (cyclosporine, dimethyl fumarate, methotrexate, retinoids) and biologic agents. However, conventional systemic drugs are often contraindicated for patients' comorbidities, or their use is characterized by reduced efficacy and various adverse events (AEs). The recent development of biologic drugs, which showed excellent results in terms of effectiveness and safety in plaque psoriasis, made these drugs an ideal weapon in EP management, despite their use in EP is still off-label. Among these, risankizumab, a humanized immunoglobulin G1 monoclonal antibody targeting the p19 subunit of the IL23, is one of the latest biologics approved for the management of moderate-to-severe psoriasis. Herein, we reported the first case of a caucasian patient affected by EP successfully treated with risankizumab, reaching PASI100 response after 16 weeks of treatment, without experiencing AEs.

JAK Inhibitors in Psoriatic Disease.

Psoriasis is now considered to be the cutaneous phenotype of a systemic inflammatory condition, recognized under the term Psoriatic Disease (PsD). PsD has several extracutaneous manifestations, such as inflammatory articular and entheseal involvement, leading to psoriatic arthritis (PsA), and the less frequent intestinal and ocular manifestations with colitis/inflammatory bowel disease and uveitis, respectively. There have also been several reports of an increased frequency of comorbidities such as hypertension, diabetes, dyslipidemia, obesity, metabolic syndrome and cardiovascular manifestations during the course of PsD. The link between psoriasis and related comorbidities is considered a long-term disease sequela, often characterized by an unhealthy lifestyle and a consequence of systemic inflammation; hence, psoriasis requires adequate and prompt treatment, with the aim of controlling not only cutaneous manifestations but also extracutaneous manifestations and systemic inflammation. Pharmacological strategies for PsD have significantly increased over recent years. Recently, the targeted synthetic DMARDs, Janus kinase (JAK) inhibitors, tofacitinib and upadacitinib, were added to the therapeutic armamentarium for treating PsA, and deucravacitinib for psoriasis. These oral agents act directly on inflammatory mechanisms underlining the disease, as antagonists of the intracellular JAK signal pathway and, by STAT phosphorylation, inhibit gene proinflammatory cytokine transcription. JAK inhibitors represent a recent additional treatment strategy for PsD management and, among these, tofacitinib and upadacitinib have recently been approved for PsA, and deucravacitinib for psoriasis. In this review we describe ongoing and recent phase II and III randomized controlled trials (RCTs) evaluating the efficacy and safety of investigational JAK inhibitors in psoriasis and PsA.

Management Strategies for Pediatric Moderate-to-Severe Plaque Psoriasis: Spotlight on Biologics.

Although psoriasis onset has been reported at any ages, in up to one-third of cases, it begins during childhood, with an estimated prevalence of about 2% in pediatric population. The management of moderate-to-severe forms of childhood psoriasis may represent a challenge for dermatologists, especially for parents' concerns about the need of systemic treatments. However, a prompt safe and effective treatment is mandatory in these patients, due to the significative impact that psoriasis may have on their quality of life, with well-known consequences on psychological health of both patients and caregivers. Due to the relatively frequent parents' refusal of systemic treatments, probably due to the fear of eventual adverse events, difficulties of oral or injective route, the management of moderate-to-severe forms still represents a challenge. Herein, we report a narrative review, aiming to resume the systemic treatments for pediatric psoriasis, focusing on the use of biologics and small molecules in the pediatric ages. The most widely used therapeutic strategies today for the pediatric population with moderate-severe psoriasis are traditional systemic therapies, while more innovative drugs such as biologics and small molecules now represent a somewhat unexplored but certainly promising field for unresponsive patients.

Effectiveness of Brodalumab in Patients with Moderate-to-Severe Plaque Psoriasis Located in Difficult-to-Treat Areas.

Background: Recent knowledge of psoriasis pathogenesis has led to the development of selective drugs. Among these, brodalumab is a monoclonal antibody targeting the interleukin (IL)-17A receptor approved for the treatment of moderate-to-severe plaque psoriasis. Biologics may be considered in patients with milder diseases in case of active psoriatic arthritis, severe impact on patient's quality of life, and involvement of sensitive and difficult-to-treat areas. These skin locations commonly require systemic drugs. Recently, psoriasis severity monitoring has also changed. Indeed, the clinical evaluation by means of specific efficacy scores was combined with serological evaluation by means of the assay of specific inflammatory biomarkers. Methods: An observational study enrolled patients affected by moderate-to-severe plaque psoriasis involving difficult-to-treat areas, undergoing treatment with brodalumab to evaluate the effectiveness and safety of brodalumab in patients with psoriasis affecting difficult-to-treat areas (scalp and palmoplantar regions). Secondary outcomes were the assessment of the development of serum markers of inflammation during the treatment period as well as the evaluation of the dermoscopic features of the affected sites to quantify disease activity and response to treatment. Results: Twenty-five patients were included in the study. A statistically significant reduction from baseline in PASI, PSSI, ppPASI and DLQI values as early as week 24 was observed, with further improvement up to week 52. Plasma levels of MMP-3, VEGF-A, and hs-PCR decreased during treatment from week 0 to week 52. Conclusion: Our real-life experience suggests brodalumab as a valuable option for the management of psoriasis located in difficult-to-treat areas. Moreover, our study highlights that the use of brodalumab reduces the plasmatic levels of inflammatory biomarkers (MMP-3, VEGF-A and hs-PCR), showing how the drug modulates the skin inflammatory response by reducing systemic inflammation.

Guselkumab, Risankizumab, and Tildrakizumab in the Management of Hidradenitis Suppurativa: A Review of Existing Trials and Real-Life Data.

The treatment of hidradenitis suppurativa (HS) has always been a real challenge for dermatologists; to date, the only biologic drugs approved for HS are adalimumab, an anti-tumor necrosis factor (TNF)-α drug, authorized in 2015, and secukinumab, recently licensed. The management of this condition is challenging as the available treatments show variable results, and the course of the condition is often chronic-recurrent; therefore, it will be necessary for the future to identify new therapeutic targets for HS. In recent years, studies have focused on the development towards new therapeutic targets. The purpose of our review was to perform a comprehensive literature review of real-life data on anti-IL23 (guselkumab, tildrakizumab, and risankizumab) in HS to summarize the existing evidence on the efficacy and safety of these drugs. We selected 64 articles, among which 32 had the characteristics that we were looking for in our review. To date, the positive data expressed in real-life experiences contrast with the three existing Phase 2 studies conducted so far, where it seems that these drugs may be useful only for a subgroup of patients with HS whose features need to be elucidated. Data from Phase 3 studies and other real-life experiences, perhaps more detailed and with higher numbers, will certainly be needed to fully understand the efficacy and safety of this class of drugs.

Efficacy and safety of spesolimab for the management of generalized pustular psoriasis: a drug safety evaluation.

INTRODUCTION: Generalized pustular psoriasis (GPP) is a rare form of psoriasis (less of 1% of cases). Currently, GPP is recognized as a clinical entity, distinguished from plaque psoriasis. However, there are not guidelines for GPP management and treatments are often derived from plaque psoriasis. Therefore, conventional systemic drugs are usually used as first-line treatment options, and biologics are still used off label. Recently, spesolimab, an anti-IL36 receptor humanized IgG1 monoclonal antibody, has been specifically approved for GPP disease, revolutionizing treatment scenario. AREAS COVERED: The aim of this review is to investigate current literature on the use of spesolimab for GPP management to underline its potential role in GPP and offer a current clinical perspective. Literature research using the Google Scholar, Pubmed, Embase, Cochrane Skin, and clinicaltrials.gov databases was performed, selecting the most relevant manuscripts. EXPERT OPINION: Spesolimab is efficacious and has a consistent and favorable safety profile in patients presenting with a GPP flare. However, despite excellent results in terms of safety and efficacy have been reported by both clinical trials and very limited real-life experiences, long-term data, especially in flare-up prevention, are scant. Thus, while the available data are encouraging, further research is warranted to understand the efficacy, safety, and long-term outcomes associated with spesolimab treatment in GPP.