Long-Term Drug Survival and Effectiveness of Secukinumab in Patients with Moderate to Severe Chronic Plaque Psoriasis: 42-Month Results from the SUPREME 2.0 Study.

Purpose: SUPREME, a phase IIIb study conducted in Italy, demonstrated safety and high efficacy of secukinumab for up to 72 weeks in patients with moderate-to-severe plaque-type psoriasis. SUPREME 2.0 study aimed to provide real-world data on the long-term drug survival and effectiveness of secukinumab beyond 72 weeks. Patients and Methods: SUPREME 2.0 is a retrospective observational chart review study conducted in patients previously enrolled in SUPREME study. After the end of the SUPREME study, eligible patients continued treatment as per clinical practice, and their effectiveness and drug survival data were retrieved from medical charts. Results: Of the 415 patients enrolled in the SUPREME study, 297 were included in SUPREME 2.0; of which, 210 (70.7%) continued secukinumab treatment throughout the 42-month observation period. Patients in the biologic-naïve cohort had higher drug survival than those in the biologic-experienced cohort (74.9% vs 61.7%), while HLA-Cw6-positive and HLA-Cw6-negative patients showed similar drug survival (69.3% and 71.9%). After 42 months, Psoriasis Area and Severity Index (PASI) 90 was achieved by 79.6% of patients overall; with a similar proportion of biologic-naïve and biologic-experienced patients achieving PASI90 (79.8% and 79.1%). The mean absolute PASI score reduced from 21.94 to 1.38 in the overall population, 21.90 to 1.24 in biologic-naïve and 22.03 to 1.77 in biologic-experienced patients after 42 months. The decrease in the absolute PASI score was comparable between HLA-Cw6-positive and HLA-Cw6-negative patients. The baseline Dermatology Life Quality Index scores also decreased in the overall patients (10.5 to 2.32) and across all study sub-groups after 42 months. Safety was consistent with the known profile of secukinumab, with no new findings. Conclusion: In this real-world cohort study, secukinumab showed consistently high long-term drug survival and effectiveness with a favourable safety profile.

A Multidisciplinary Approach to Patients with Psoriasis and a History of Malignancies or On-Treatment for Solid Tumors: A Narrative Literature Review.

Psoriasis is a chronic immune-mediated disease that is linked to an increased risk of cancer. Although numerous studies have explored whether neoplasms are concurrent conditions or are induced by psoriasis, a definitive definition remains elusive. In this study, we conducted a comprehensive narrative literature review to offer practical guidance to oncologists and dermatologists regarding the initiation and discontinuation of biologics for psoriasis. The findings indicate that a customized approach is recommended for each patient, and that a history of malignancies does not constitute an absolute contraindication for biologics. Growing evidence supports the treatment of selected patients, emphasizing a nuanced assessment of benefits and risks. There is a lack of data specifying a safe timeframe to initiate biologics following a neoplasm diagnosis due to influences from cancer-related and patient-specific characteristics impacting prognosis. Some patients may continue anti-psoriasis therapy during cancer treatments. Enhanced comprehension of the biological mechanisms in cancer progression and the immune microenvironment of psoriasis holds promise for refining therapeutic strategies. In conclusion, a personalized treatment approach necessitates collaboration between oncologists and dermatologists, considering factors such as cancer prognosis, psoriasis clinical manifestations, patient characteristics, and preferences when making treatment decisions.

Efficacy and Safety of Secukinumab in Elderly Patients with Moderate to Severe Plaque-Type Psoriasis: Post-Hoc Analysis of the SUPREME Study.

Purpose: Secukinumab is a fully human monoclonal antibody that inhibits interleukin (IL)-17A approved for the treatment of moderate to severe plaque psoriasis in adults and children. We compared the efficacy and safety of secukinumab in patients aged < 65 years (adult patients) versus patients aged ≥ 65 years (elderly patients) in a post-hoc analysis of the SUPREME study. Patients and Methods: Patients with moderate to severe plaque psoriasis received subcutaneous secukinumab 300 mg per week for the first 5 weeks, then 300 mg per month. We compared the following outcomes in patients aged ≥ 65 years vs < 65 years: baseline characteristics; PASI50/75/90/100 response rates (improvements ≥ 50%/75%/90%/100% in Psoriasis Area and Severity Index (PASI) from baseline); changes in Dermatology Life Quality Index (DLQI); Hospital Anxiety and Depression Scale (HAD-A, HAD-D) score changes; treatment-emergent adverse events (TEAEs). Results: Secukinumab was slightly less effective in elderly patients than in adult patients (response rates at week 16: PASI90, 69.4% vs 80.9%, p = 0.4528; PASI100, 44.4% vs 56.7%, p = 0.8973). Elderly and adult patients showed a similar time course of changes in absolute PASI scores. Patients aged ≥ 65 years had a statistically significantly lower improvement in quality of life (mean DLQI reduction) than patients aged < 65 years at week 16 [-5.4 (±4.3) vs -8.8 (±6.9), p = 0.0065] and at week 24 [-5.3 (±4.4) vs -9.2 (±7.1), p = 0.0038]. Secukinumab treatment resulted in comparable mean reductions in anxiety and depression scores in both cohorts at 24 weeks [HAD-A, -1.3 (±3.3) vs -2.1 (±3.8), p = 0.9004; HAD-D, -1.0 (±3.3) vs -1.5 (±3.1), p = 0.4598]. The frequency of TEAEs in the two cohorts was similar (16.7% vs 14.6%, p = 0.7391). Conclusion: Secukinumab is a valid option for the management of moderate to severe psoriasis in elderly patients.

Single-Centre Real-Life Experience of Guselkumab in Patients with Moderate-to-Severe Plaque Psoriasis.

The efficacy of guselkumab has been demonstrated in randomized controlled trials, but real-life data are still missing. This study presents a single-center real-life experience in treating moderate-to-severe plaque psoriasis with guselkumab, underlying the efficacy and safety of this biological agent. Primary efficacy endpoint was the percentage of patients reaching psoriasis area and severity index (PASI) 90 response at week 28. The cohort included 79 patients of mean age 51 ± 15 years. Mean duration of guselkumab treatment was 16,5 ± 7.5 months. All 79 patients completed at least 28 weeks of treatment. At week 28, 73 (92%) patients reached PASI 50 or higher, 65 (82%) achieved PASI 75 or higher, 54 (68%) achieved PASI 90 or higher, and 35 (44%) reached PASI 100. Very similar percentages were found at week 44 and at the end of the study period. No significant adverse effects were reported. This study confirms that guselkumab is an effective and safe biologic agent capable of maintaining long-lasting clinical response efficacy in real-world clinical practice, although at slightly lower levels than in clinical trials. J Drugs Dermatol. 2022;21(8):864-866. doi:10.36849/JDD.6962.

Three cases of symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) induced by proton-pump inhibitors.

Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), previously termed drug-related baboon syndrome, is an uncommon drug eruption. It is characterized by symmetrical erythema involving the gluteal and/or inguinal area in association with one other intertriginous area in the absence of systemic involvement. It typically develops a few hours to days after drug exposure. The diagnosis is based on clinical presentation and drug history. The treatment consists mainly of withdrawal of the causative agent; corticosteroids (topical or systemic) are prescribed to accelerate the resolution. We present three cases that appeared after proton-pump inhibitors (PPIs) intake.

Treat-to-Target Approach for the Management of Patients with Moderate-to-Severe Plaque Psoriasis: Consensus Recommendations.

INTRODUCTION: Treat-to-target strategies are used in several chronic diseases to improve outcomes. Treatment goals have also been suggested for psoriasis, but there is currently no consensus on targets, and guidance is needed to implement this strategy in clinical practice. The project 'Treat to Target Italia' was launched by a scientific board (SB) of 10 psoriasis experts to generate expert consensus recommendations. METHODS: On the basis of the published literature, their clinical experience, and the results of a survey among Italian dermatologists, the SB identified four relevant topics: (1) clinical remission; (2) quality of life; (3) abrogation of systemic inflammation; (4) safety. They drafted 20 statements addressing these four topics and submitted them to a panel of 28 dermatologists, in a Delphi process, to achieve consensus (greater than 80% agreement). RESULTS: Consensus was reached on all statements. Treatment goals defining clinical remission should include a 90% improvement from baseline in the Psoriasis Area and Severity Index (PASI90 response) or an absolute PASI score of less than or equal to 3. Patient's quality of life and satisfaction are important targets. If PASI targets are achieved, there should be no or very low impact of psoriasis on quality of life [Dermatology Life Quality Index (DLQI) score less than or equal to 3]. If PASI or DLQI goals are not achieved within 3-4 months, treatment should be changed. Abrogation of systemic inflammation may be crucial for preventing or delaying inflammatory comorbidities. Safety is an equally important target as efficacy. CONCLUSION: These 20 consensus statements define the parameters of a treat-to-target strategy for psoriasis in Italy. It is hoped that use of these in the management of patients with psoriasis will improve treatment outcomes and patient health-related quality of life.

Predicting Secukinumab Fast-Responder Profile in Psoriatic Patients: Advanced Application of Artificial-Neural-Networks (ANNs).

BACKGROUND: Drug resistance to biologics in psoriasis therapy can occur – it may be acquired during a treatment or else present itself from the beginning. To date, no biomarkers are known that may reliably guide clinicians in predicting responsiveness to biologics. Biologics may pose a substantial economic burden. Secukinumab efficiently targets IL-17 in the treatment of psoriasis. OBJECTIVE: To assess the “fast responder” patient profile, predicting it from the preliminary complete blood count (CBC) and clinical examination. MATERIALS AND METHODS: From November 2016 to May 2017 we performed a multicenter prospective open label pilot study in three Italian reference centers enrolling bio-naive plaque psoriasis patients, undergoing the initiation phase secukinumab treatment (300mg subcutaneous at week 0,1,2,3,4). We define fast responders as patients having achieved at least PASI 75 at the end of secukinumab induction phase. Clinical and CBC data at week 0 and at week 4 were analyzed with linear statistics, principal component analysis, and artificial neural networks (ANNs), also known as deep learning. Two different ANNs were employed: Auto Contractive Map (Auto-CM), an unsupervised ANNs, to study how this variables cluster and a supervised ANNs, Training with Input Selection and Testing (TWIST), to build the predictive model. RESULTS: We enrolled 23 plaque psoriasis patients: 19 patients were responders and 4 were non-responders. 30 attributes were examined by Auto-CM, creating a semantic map for three main profiles: responders, non-responders and an intermediate profile. The algorithm yielded 5 of the 30 attributes to describe the 3 profiles. This allowed us to set up the predictive model. It displayed after training testing protocol an overall accuracy of 91.88% (90% for responders and 93,75% for non-responders). CONCLUSIONS: The present study is possibly the first approach employing ANNs to predict drug efficacy in dermatology; a wider use of ANNs may be conducive to useful both theoretical and clinical insight. J Drugs Dermatol. 2020;19(12) doi:10.36849/JDD.2020.5006.

PACE study: real-life Psoriasis Area and Severity Index (PASI) 100 response with biological agents in moderate-severe psoriasis.

BACKGROUND: Few studies have compared the use of different biologics in a real-life setting in plaque psoriasis patients. OBJECTIVE: To compare the efficacy of biologics in psoriasis/psoriatic arthritis patients. METHODS: Patients treated with adalimumab, etanercept and ustekinumab for at least 16 weeks were included. Achievement of Psoriasis Area Severity Index (PASI), PASI 90/100 response and time taken to achieve PASI 90/100 response were measured. Logistic regression was used to evaluate the effect of psoriasis localization on achievement of PASI 100 response. RESULTS: Two hundred and fifty five patients were included. No difference was observed in PASI 90 response between etanercept and ustekinumab (65.5 vs. 55.4%), while adalimumab-treated patients had a higher response versusustekinumab (71.6 vs. 55.4%, p = .02). More patients achieved complete remission (PASI 100 response) with adalimumab versus etanercept (65.7 vs. 23%, p < .001) or ustekinumab (65.7 vs. 44.6%, p = .003). Adalimumab-treated patients achieving PASI 90 responded more quickly (by three and six months) versus ustekinumab or etanercept. PASI100 response was achieved in ∼43% of adalimumab and ustekinumab treated-patients by three months versus etanercept (14.3%), increasing to 92.5, 85.4 and 35.7%, respectively by six months. PASI100 response was associated with psoriasis nail involvement or genital psoriasis. CONCLUSION: In the real-life setting, adalimumab was the most effective biological agent for the treatment of plaque psoriasis.

The EPIPSOFIRE project: a preliminary report.

Psoriatic arthritis (PsA) is a musculoskeletal condition complicating psoriasis that can lead to joint deformity and disability; however, psoriatic patients may suffer from other kind of arthropathies that could be confused with PsA by nonrheumatologists. Our aim was to determine the prevalence of PsA and to determine the prevalence of other musculoskeletal conditions in a cohort of psoriatic patients. In this cohort, musculoskeletal discomfort was frequently reported, while inflammatory disorders were detected in <4% of subjects. The cohort lacked subjects with very long-standing psoriasis duration (>20 years) or severe cutaneous disease. Because musculoskeletal discomfort symptoms affected about 62% of patients, other disorders, particularly morphologic conditions, need careful evaluation in psoriasis subjects.

Not simply a matter of psoriatic arthritis: epidemiology of rheumatic diseases in psoriatic patients.

This study investigated the occurrence of rheumatic conditions (RCs) in a psoriasis (PSO)-dedicated dermatological clinic. PSO subjects with musculo-skeletal discomfort, and/or carrying signs (articular/systemic, even asymptomatic) of RCs; and/or suffering flares of previously established psoriatic arthritis (PsA) were referred to rheumatologist for evaluation. Laboratory tests/imaging were performed as needed. Categorization adhered to RCs classification endorsed by the Italian Society of Rheumatology. Of the 1,200 psoriatic subjects, 277 (23.1 %) were enrolled (146 females). The mean age was 55.7 years (range 21-81), PSO duration was 13.5 years (range 0-62). Thirty-seven patients (13.4 %) were asymptomatic. On an average, 92 (7.6 %) patients/year were evaluated, of whom 79.4 % näive to rheumatological consultations (NRC). Osteoarthritis (OA) and PsA (isolated or combined) showed the highest prevalence, with 156 (56.3 %) and 110 cases (39.7 %), respectively. Among NRC subjects, the mean PsA annual incidence was 29.5 % (standard error of the mean ±5.4 %). Other RCs, isolated or associated with PsA/OA, were diagnosed in 31 cases (11.2 %). Thirty-two subjects (11.5 %) had arthralgias, 20 of whom due to congenital/mechanical disorders, the remaining were unclassifiable. In conclusion, the largest part (88.5 %) of PSO subjects referred to rheumatologist showed some RCs. On annual basis, 29.5 % of näive enrolled patients were diagnosed as PsA.

Tomesa balneophototherapy in mild to severe psoriasis: a retrospective clinical trial in 174 patients.

Psoriasis is a chronic inflammatory skin disease with a high social and psychological impact on the quality of life of patients. Tomesa balneophototherapy is based on bathing in a magnesium-rich salt solution combined with exposure to narrowband ultraviolet B phototherapy. We conducted a retrospective clinical trial on 174 patients affected by mild to severe psoriasis undergoing Tomesa balneophototherapy. The basal course consisted of three to five sessions per week for a total of 30 sessions. Subsequently, patients could continue with a maintenance course of one session per week for a total of 30 sessions. We recorded a significant reduction of the mean Psoriasis Area and Severity Index (PASI) index with an achievement of at least PASI 75 in 52.1% of the 119 patients who completed the basal course and an improvement of the 'quality of life' of patients. The good efficacy obtained by this treatment, and the psychological impact on the quality of life of patients, demonstrated that Tomesa balneophototherapy could be a good option for the treatment of a chronic disease associated with psychological distress, like psoriasis.