Photodynamic Therapy for the Treatment of Basal Cell Carcinoma: A Comprehensive Review of Randomized Controlled Trials.

INTRODUCTION: Basal cell carcinoma (BCC) is the most common skin cancer worldwide and has been reported to have a rising incidence in the last years. Multiple therapeutic modalities are approved for the treatment of BCC, making it difficult for physicians to choose the most suitable option for every patient. Photodynamic therapy (PDT) using either 5-aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) as photosensitizing agents is an established treatment option for low-risk BCC. OBJECTIVES: This review aims to summarize the available evidence from randomized clinical trials (RCTs) that utilize either ALA or MAL PDT and compare it with other treatment modalities. The main outcomes related to the effectiveness, adverse events, cosmetic outcomes and pain sensation, along with data from long-term follow-ups will be presented and discussed. METHODS: Thorough literature searches were conducted through the electronic databases ClinicalTrials. gov and Pubmed/MEDLINE from inception up to 28 March 2023. Only studies in English were included. All relevant data were extracted accordingly from the eligible studies. RESULTS: Eight RCTs included superficial BCC (sBCC) alone, 7 included nodular BCC (nBCC), 2 included both sBCC and nBCC and 1 included BCC of unspecified subtype. Follow-up duration ranged from 3 months to 5 years. Both ALA-PDT and MAL-PDT demonstrated acceptable efficacy, adverse events, cosmetic outcomes and pain sensation while no major differences were observed between them. PDT was less effective than surgery but with better reported cosmetic outcomes. CONCLUSIONS: PDT is a safe and efficacious treatment option for sBCC and to a lesser extent nBCC.

Bimekizumab in psoriasis: a monocentric study evaluating short- and mid-term effectiveness and safety profile in a real-world setting.

INTRODUCTION: Bimekizumab is a humanized monoclonal IgG1 antibody with a unique mechanism of action, as it inhibits both IL17A and IL17F molecules. This dual inhibition is thought to be responsible for its high efficacy in treating chronic plaque psoriasis with rapid onset of action in Randomized Controlled Trials (RCTs). Concerning safety, oral candidiasis was one of the most common drug-related adverse events, commonly mild-to-moderate in severity. Although data from RCTs supporting this efficacy and safety profile of bimekizumab is numerous, results from the real-world setting concerning short- and mid-term treatment effectiveness and safety profile are limited. MATERIALS AND METHODS: An observational, retrospective, monocentric study was conducted at the Psoriasis Outpatient Unit of "A. Sygros" Hospital for Skin and Venereal Diseases, in Athens, Greece, which included 61 adult patients with moderate-to-severe skin psoriasis, who received at least one dosage of bimekizumab. RESULTS: At week 4, 65.7% achieved PASI75, 45.7% PASI90, and 32.4% PASI100. After 16 weeks of treatment, 92.3/76.9/66.7% of the patients achieved PASI75/90/100, respectively. Increased BMI, previous treatment with another IL-17 inhibitor, or previous exposure to another biologic did not seem to influence the possibility of achieving PASI90 and PASI100 at week 16 of bimekizumab treatment in this cohort. Six (9.8%) cases of possibly drug-related AEs were reported, from which four incidences of oral candidiasis. CONCLUSION: Our results confirm that this IL17A/F inhibitor is highly effective, with a tolerability profile similar to the one expected from RCTs.

Treatment of Psoriasis Patients with Latent Tuberculosis Using IL-17 and IL-23 Inhibitors: A Retrospective, Multinational, Multicentre Study.

BACKGROUND: Tuberculosis has a major global impact. Immunocompetent hosts usually control this disease, resulting in an asymptomatic latent tuberculosis infection (LTBI). Because TNF inhibitors increase the risk of tuberculosis reactivation, current guidelines recommend tuberculosis screening before starting any biologic drug, and chemoprophylaxis if LTBI is diagnosed. Available evidence from clinical trials and real-world studies suggests that IL-17 and IL-23 inhibitors do not increase the risk of tuberculosis reactivation. OBJECTIVE: To evaluate psoriasis patients with treated or untreated newly diagnosed LTBI who received IL-17 and IL-23 inhibitors and the tolerability/safety of tuberculosis chemoprophylaxis. METHODS: This is a retrospective, observational, multinational study from a series of 14 dermatology centres based in Portugal, Spain, Italy, Greece and Brazil, which included adult patients with moderate-to-severe chronic plaque psoriasis and newly diagnosed LTBI who were treated with IL-23 or IL-17 inhibitors between January 2015 and March 2022. LTBI was diagnosed in the case of tuberculin skin test and/or interferon gamma release assay positivity, according to local guideline, prior to initiating IL-23 or IL-17 inhibitor. Patients with prior diagnosis of LTBI (treated or untreated) or treated active infection were excluded. RESULTS: A total of 405 patients were included; complete/incomplete/no chemoprophylaxis was administered in 62.2, 10.1 and 27.7% of patients, respectively. The main reason for not receiving or interrupting chemoprophylaxis was perceived heightened risk of liver toxicity and hepatotoxicity, respectively. The mean duration of biological treatment was 32.87 ± 20.95 months, and only one case of active tuberculosis infection (ATBI) was observed, after 14 months of treatment with ixekizumab. The proportion of ATBI associated with ixekizumab was 1.64% [95% confidence interval (CI): 0-5.43%] and 0% for all other agents and 0.46% (95% CI 0-1.06%) and 0% for IL-17 and IL-23 inhibitors, respectively (not statistically significant). CONCLUSIONS: The risk of tuberculosis reactivation in patients with psoriasis and LTBI does not seem to increase with IL-17 or IL-23 inhibitors. IL-17 or IL-23 inhibitors should be preferred over TNF antagonists when concerns regarding tuberculosis reactivation exists. In patients with LTBI considered at high risk for developing complications related to chemoprophylaxis, this preventive strategy may be waived before initiating treatment with IL-17 inhibitors and especially IL-23 inhibitors.

The Impact of Treatment with IL-17/IL-23 Inhibitors on Subclinical Atherosclerosis in Patients with Plaque Psoriasis and/or Psoriatic Arthritis: A Systematic Review.

Accumulating evidence considers psoriasis a systemic inflammatory disorder that is associated with comorbidities such as psoriatic arthritis, cardiovascular disease, and metabolic syndrome. Although the precise pathogenetic links between psoriasis and atherosclerosis warrants further investigation, it is believed that chronic systemic inflammation along with the T helper (Th)-1 and Th17 polarization are associated with endothelial dysfunction and subsequent acceleration of atherosclerosis. Considering the above, several studies have evaluated if optimal control of the inflammation in psoriasis by inhibiting interleukins targeting the Interleukin (IL)-23/Th17 axis could subsequently reduce the atherosclerotic process during anti-psoriatic treatment by using a variety of surrogate markers of subclinical atherosclerosis. This systematic review summarizes current knowledge on the pathogenetic mechanisms and diagnostic evaluation of atherosclerosis in the context of psoriasis and provides a systematic review of the literature on the impact of treatment with biologics targeting the IL-23/Th17 axis on subclinical atherosclerosis in patients with plaque psoriasis and/or psoriatic arthritis.

Brodalumab in plaque psoriasis: Real-world data on effectiveness, safety and clinical predictive factors of initial response and drug survival over a period of 104 weeks.

BACKGROUND: Brodalumab, a fully human IgG2k antibody blocking the receptor of IL17, is characterized by a rapid onset of action with high skin clearance rates in clinical trials. Since setting PASI90/100 or absolute PASI ≤ 3 as treatment goals have become attainable, evaluating the effectiveness and safety profile of biologic agents, such as brodalumab, in a real-world setting is essential. OBJECTIVE: The aim of this study was to evaluate the effectiveness and safety profile of brodalumab over a period of 104 weeks in everyday practice. Clinical predictive factors of initial (week 12/16) response to treatment and long-term drug survival were also investigated. METHODS: In this monocentric, retrospective study, PASI90/100 and absolute PASI ≤ 1/3 were assessed in 91 patients with moderate-to-severe skin psoriasis under brodalumab at weeks 12/16, 24, 52 and 104 of treatment. At week 12/16, patients with an absolute PASI ≤ 3 were defined as 'initial responders' and ≤1 as 'super-responders'. Clinical parameters, such as age, gender, BMI, comorbidities and previous systemic treatment, were assessed in order to predict 'super-responders'. Drug survival and its prognostic factors were also evaluated. RESULTS: PASI90/100 has reached 81.1/66.0% in week 12/16. This response rate increased at week 104, where 87.1/80.7% had PASI90/100 and 84.9% had absolute PASI ≤ 1. The presence of >3 comorbidities, prior treatment with >2 systemic agents and obesity tended to be negative predictive factors of 'super-response'. Previous exposure to IL17 inhibitors had no impact on both PASI < 1 and PASI < 3 initial response. One- and two-year drug survival probability was 87.6% and 77.32%, respectively. 'Initial responders' and anti-IL17 drug-naïve patients had better drug survival. Drug discontinuation occurred in 24.2%, mostly due to secondary failure, and arthralgia was the most common adverse event that led to discontinuation. CONCLUSIONS: Our study confirms the high effectiveness and good safety profile of brodalumab in the real-world setting.

Drug Survival of Interleukin (IL)­17 and IL­23 Inhibitors for the Treatment of Psoriasis: A Retrospective Multi­country, Multicentric Cohort Study.

BACKGROUND: Drug survival, defined as the length of time from initiation to discontinuation of a given therapy, allows comparisons between drugs, helps to predict patient's likelihood of remaining on a specific treatment, and achieving the best decision for each patient in daily clinical practice. OBJECTIVE: The aim of this study was to provide data on drug survival of secukinumab, ixekizumab, brodalumab, guselkumab, tildrakizumab, and risankizumab in a large international cohort, and to identify clinical predictors that might have an impact on the drug survival of these drugs. METHODS: This was a retrospective, multicentric, multi-country study that provides data of adult patients with moderate to severe psoriasis who started treatment with an interleukin (IL)-17 or IL-23 inhibitor between 1 February 2015 and 31 October 2021. Data were collected from 19 distinct hospital and non-hospital-based dermatology centers from Canada, Czech Republic, Italy, Greece, Portugal, Spain, and Switzerland. Kaplan-Meier estimator and proportional hazard Cox regression models were used for drug survival analysis. RESULTS: A total of 4866 treatment courses (4178 patients)-overall time of exposure of 9500 patient-years-were included in this study, with 3164 corresponding to an IL-17 inhibitor (secukinumab, ixekizumab, brodalumab) and 1702 corresponding to an IL-23 inhibitor (guselkumab, risankizumab, tildrakizumab). IL-23 inhibitors had the highest drug survival rates during the entire study period. After 24 months of treatment, the cumulative probabilities of drug survival were 0.92 (95% confidence interval [CI] 0.89-0.95) for risankizumab, 0.90 (95% CI 0.88-0.92) for guselkumab, 0.80 (95% CI 0.76-0.84) for brodalumab, 0.79 (95% CI 0.76-0.82) for ixekizumab, and 0.75 (95% CI 0.73-0.77) for secukinumab. At 36 months, only guselkumab [0.88 (95% CI 0.85-0.91)], ixekizumab [0.73 (95% CI 0.70-0.76)], and secukinumab [0.67 (95% CI 0.65-0.70)] had more than 40 patients at risk of drug discontinuation. Only two drugs had more than 40 patients at risk of drug discontinuation at 48 months, with ixekizumab demonstrating to have a higher cumulative probability of drug survival [0.71 (95% CI 0.68-0.75)] when compared with secukinumab [0.63 (95% CI 0.60-0.66)]. Secondary failure was the main cause for drug discontinuation. According to the final multivariable model, patients receiving risankizumab, guselkumab, and ixekizumab were significantly less likely to discontinue treatment than those receiving secukinumab. Previous exposure to biologic agents, absent family history of psoriasis, higher baseline body mass index (BMI), and higher baseline Psoriasis Area and Severity Index (PASI) were identified as predictors of drug discontinuation. CONCLUSION: The cumulative probability of drug survival of both IL-17 and IL-23 inhibitors was higher than 75% at 24 months, with risankizumab and guselkumab demonstrating to have overall cumulative probabilities ≥ 90%. Biological agent chosen, prior exposure to biologic agents, higher baseline BMI and PASI values, and absence of family history of psoriasis were identified as predictors for drug discontinuation. Risankizumab, guselkumab, and ixekizumab were less likely to be discontinued than secukinumab.

Psychopathology and Alexithymia in Patients with Moderate-to-Severe Psoriasis: Development of a Novel Index with Prognostic Value.

BACKGROUND: Psoriasis is a chronic, relapsing, inflammatory disease with a high risk of developing mental health difficulties. OBJECTIVE: The purposes of the study were to evaluate in moderate-to-severe psoriasis (a) the prevalence of depression and psychopathology, (b) the relationship between depression, psychopathology symptoms, and alexithymia, including its three dimensions, difficulty in identifying feelings (DIF), difficulty in describing feelings (DDF), and externally oriented thinking (EOT), and (c) to establish a novel index for the development of depression according to patients' psychopathological profile. METHODS: In 104 patients, alexithymia was evaluated with the Toronto Alexithymia Scale (TAS-20), depression with the Beck Depression Inventory (BDI), and psychopathology with the Brief Symptom Inventory SCL-90 (SCL90). A psychopathology index that combines information from the BDI and SCL90 scales was constructed and the performance of the index with alexithymia was examined. RESULTS: Female patients and active smokers score higher on BDI and SCL90 scales. Overweight patients tend to score arithmetically higher. The psychopathology index developed correlates significantly with age, DIF, DDF, and TAS-20. DIF, DDF, and TAS-20 are significant predictors of the psychopathology index. Patients with alexithymia/possible alexithymia are six times as likely to score higher in one of the psychopathology scales. CONCLUSIONS: Alexithymia is a significant factor in the development of psychopathology in psoriasis patients. The use of the proposed novel psychopathology index could be essential in order to identify patients with moderate-to-severe psoriasis who are more likely to experience depression and psychopathology. This could have an impact on the decision-making of psoriasis treatment and monitoring of the patient.

Management of Nail Psoriasis.

Nail psoriasis is a chronic nail disorder that requires personalized treatment. General prophylactic measures are suggested for all patients. Topical treatment is considered when treating a few-nail disease, with involvement of 3 or fewer nails, without joint involvement and without (or with mild) skin psoriasis. The ideal formulation should be ointment, solution, or foam. When moderate to severe skin psoriasis or psoriatic arthritis coexists, systemic treatment is suggested. This also should be considered when more than 3 nails are affected or significant impairment of quality of life is present. Conventional systemic agents, biologics, and small molecules are highly efficacious.

Real world data from the use of secukinumab in the treatment of moderate-to-severe psoriasis, including scalp and palmoplantar psoriasis: A 104-week clinical study.

Several clinical studies demonstrated the safety and efficacy of the interleukin-17 inhibitor secukinumab in the systemic treatment of moderate-to-severe psoriasis, as well as psoriatic arthritis (PsA) in adults, whereas real-world data is limited. A single-center clinical study was performed to evaluate in real-world practice the efficacy of secukinumab up to Week 104 of treatment in moderate-to-severe chronic plaque psoriasis, including scalp and palmoplantar involvement, according to Physician Global Assessment (PGA), PASI75/90/100 and scalp, and palmoplantar PGA. Drug survival, the safety profile of secukinumab, and patient's quality of life were also assessed during a 2-year observation period. Out of 83 patients included, 56.3% were biologic-naïve, and 94% had scalp, 25.3% palmoplantar, and 43.9% joint involvement. At Week 16, PASI75/PASI90/PASI100 were observed in 83.8/70.0/46.3%, respectively. Scalp and palmoplantar PGA were rapidly improved, with 98.7 and 95.5%, respectively, reaching clear/almost clear skin at Week 16. After 104 weeks, drug survival was 74.5%. A significant improvement of the quality of life was observed. Biologic-naïve patients without coexisting PsA benefited the most. Real-world data demonstrated secukinumab efficacious in chronic plaque psoriasis, including specific locations such as scalp and palmoplantar psoriasis with a safety profile similar to that in clinical trials.

Recommendations for the definition, evaluation, and treatment of nail psoriasis in adult patients with no or mild skin psoriasis: A dermatologist and nail expert group consensus.

Nail involvement in psoriasis is common, and the severity of it does not always parallel the intensity of cutaneous disease. We created a consensus group, of which the aim was to provide practical recommendations for the treatment of nail psoriasis in patients without skin psoriasis or with mild skin lesions with no indication for a systemic treatment. This collaborative process was conducted by an international panel of dermatologists with special expertise in nail disorders, using formal consensus methods. During this process, the panel strived to establish an agreement regarding the definition of nail psoriasis, the severity of nail psoriasis, and treatment response. Treatment recommendations are provided regarding nail psoriasis severity and matrix or bed involvement. Few-nail disease was considered as nail psoriasis affecting ≤3 nails. In the case of matrix involvement only, intralesional steroid injections were considered the treatment of choice. Topical steroids alone or in combination with topical vitamin D analogues were suggested for nail psoriasis limited to the nail bed. For the systemic treatment of nail psoriasis acitretin, methotrexate, cyclosporine, small molecules, and biologics may be employed.

Lymphopenia and CD4+/CD8+ Cell Reduction under Fumaric Acid Esters.

BACKGROUND: Fumaric acid esters (FAEs) are a broadly used therapy option for patients suffering from moderate-to-severe plaque psoriasis. Various studies in psoriasis have already shown peripheral blood lymphopenia during oral FAE therapy. Smaller studies also documented a reduction of CD4+ and CD8+ cell counts. Up to now, there are few case reports on opportunistic infections under FAE therapy - all of them associated with lymphopenia. OBJECTIVE: To examine the influence of FAEs on white blood cells with special regard to leukocytes, lymphocytes, and CD4+ and CD8+ cells during psoriasis therapy. PATIENTS AND METHODS: A cohort of 105 patients with diagnosed moderate-to-severe chronic plaque psoriasis was enrolled in this single-centre observational trial. For a cohort of 36 patients, T-cell subset analyses were performed. RESULTS: Of the total, 65 patients were male (61.9%) and 40 (38.1%) female; the mean age was 43.3 years (range 16-73 years). The median lymphocyte count was significantly reduced by about 35.8% after the first 6 months of therapy. When assessing the lymphocyte count nadir over the whole period observed, 46.7% of the patients developed lymphopenia. Severe lymphopenia (<500/µL) was documented in 11.4% of the patients. The CD4+ and CD8+ cell counts were significantly reduced by about 30.2 and 45.3%, respectively. CONCLUSION: To the best of our knowledge this is the largest clinical investigation analysing prospectively CD4+ and CD8+ cell counts in psoriasis patients receiving FAEs. We suggest periodic monitoring of absolute lymphocyte counts as well as the establishment of the determination of T-cell subsets prior to and during therapy.

Corticosteroids augment BRAF inhibitor vemurafenib induced lymphopenia and risk of infection.

We have previously demonstrated an impact of the BRAF inhibitor vemurafenib on patient lymphocyte counts. In the current study, the extent to which concomitant use of corticosteroids in BRAF inhibitor treated patients affects lymphocyte counts and predisposes to infection was investigated. A cohort of 102 patients receiving either the selective BRAF inhibitor vemurafenib or dabrafenib was analyzed. The amount of patients receiving either medication with or without systemic corticosteroids (dexamethasone) was determined and lymphocyte counts before and under therapy assessed. Additionally, the number and severity of infections occurring in these groups was analyzed. Vemurafenib treatment led to a considerable decrease in lymphocyte cell counts, with 62.3% of patients having lymphopenia. Dabrafenib treated patients only rarely demonstrated lymphopenia (12.5%). Dexamethasone co-administration further diminished lymphocyte counts. Lymphopenias were observed in 84.6% of patients receiving vemurafenib and dexamethasone. In our cohort, infections were noted in 9 patients, 4 of these were severe and 2 eventually fatal. All 9 cases with infections demonstrated lymphopenia, 8 of these had received dexamethasone and 7 of these a therapy with vemurafenib. Our findings demonstrate a significant lymphopenia in patients treated with the BRAF inhibitor vemurafenib, which is further augmented by dexamethasone and predisposes to infection. If validated in other studies, risk of infection should be considered when applying corticosteroids in combination with BRAF inhibitors, in particular vemurafenib.