Treatment of psoriasis with different classes of biologics reduces the likelihood of peripheral and axial psoriatic arthritis development.

OBJECTIVE: To assess the potential role of biological treatment for psoriasis (PsO) in reducing the likelihood of psoriatic arthritis (PsA), through a detailed analysis that considered the different historical phases in the PsA management, the different biologics classes, and the different patterns of articular involvement. METHODS: A monocentric cohort of 1023 PsO patients underwent a rheumatologic assessment in which clinical and therapeutic data were recorded. Chi-squared test and multivariate logistic regression analysis (adjusted for the main PsA risk factors) were performed to compare the likelihood of PsA development in different treatment groups. RESULTS: The PsA prevalence in PsO patients treated at least once with biologics was significantly lower than in patients never treated with biologics (8.9% vs 26.1%, p< 0.001). In multivariate analysis, a significantly (p< 0.01) lower likelihood of PsA development in biologic-treated patients was confirmed in the whole cohort (adjOR 0.228), as well as in the subgroups of patients with PsO onset after 2005 (adjOR 0.264) and after 2014 (adjOR 0.179). Separately analysing the different biologics classes, both the TNF (adjOR 0.206), IL-17 (adjOR 0.051) and IL-23 or 12/23 (adjOR 0.167) inhibitors were significantly (p< 0.01) associated with a lower likelihood of PsA development. Finally, patients treated with biologics had a significantly (p< 0.04) lower prevalence of both pure peripheral PsA (adjOR 0.182) and peripheral PsA with axial involvement (adjOR 0.115). CONCLUSIONS: This study provides meaningful and concordant evidence supporting the significant role of different classes of biologics in reducing the likelihood of peripheral and axial PsA development.

The Challenging Differentiation of Psoriatic Arthritis from Other Arthropathies and Nonspecific Arthralgias in Patients with Psoriasis: Results of a Cross-Sectional Rheumatologic Assessment of a Large Dermatologic Cohort.

Aiming to identify the potential challenges in the classification of musculoskeletal manifestations in patients with psoriasis (PsO), this study analyzed the outcomes of a cross-sectional rheumatologic assessment of 1057 PsO patients. In total, 209 had a previous diagnosis of psoriatic arthritis (PsA). Out of the remaining 848 subjects, 293 (35%) were classified as suspected PsA cases according to the rheumatologist's judgment and/or Early PsA Screening Questionnaire score (EARP) ≥ 3. However, only 14% received a PsA diagnosis, 49% had a PsA-alternative diagnosis, and the remaining 37% had nonspecific arthralgias. Most of the newly diagnosed PsA patients had a symptoms duration ≥1 year (72%) and moderate disease activity (55%) with active oligoarthritis (85%), dactylitis, or enthesitis (35%) as the most frequent clinical pattern. The most frequent PsA-alternative diagnoses were osteoarthritis and fibromyalgia (44% and 41%). The only factors with significant (p < 0.05) utility in discriminating PsA from other diseases and nonspecific arthralgias were young age and EARP score with a history of morning stiffness, swollen joints, or dactylitis. These results demonstrated a high prevalence of suspected musculoskeletal symptoms in PsO patients, with, however, only a small proportion due to PsA. Close collaboration between the dermatologist and rheumatologist plays a crucial role in the differential diagnosis of PsA, as well as in monitoring nonspecific arthralgias for the potential transition to overt PsA.

Secukinumab in Patients with Psoriasis and a Personal History of Malignancy: A Multicenter Real-Life Observational Study.

INTRODUCTION: There is limited evidence to guide clinicians on the treatment of psoriasis with biologics in patients with a history of malignancy who are often excluded from clinical trials investigating biologics. The aim of this work is to report a multicenter real-life experience of secukinumab treatment in patients with psoriasis and a personal history of cancer. METHODS: This retrospective observational study included adult patients with moderate-to-severe plaque psoriasis treated with secukinumab for at least 24 weeks and a previous diagnosis of cancer at 15 Italian referral centers. The primary endpoint of the study was tumor recurrence or progression and new cancer diagnosis during treatment. Secondary outcome assessment of secukinumab effectiveness (reduction of Psoriasis Area and Severity Index [PASI] score, improvement of Dermatology Life Quality Index [DLQI], itch and pain). RESULTS: Forty-two patients (27 male) were included. Malignancy was diagnosed in the previous 5 years in 21 (56.8%) and in the previous 10 years in 37 (88.1%). The mean interval between cancer diagnosis and the start of secukinumab treatment was 3.5 ± 3.3 years. No tumor recurrence nor progression occurred over a mean of 56 ± 31.7 weeks of treatment. Three patients developed a new malignancy not related to the previous cancer. At week 48, PASI 90 was reached by 64.7% of patients and PASI 100 by 38.2%. Mean DLQI, itch, and pain VAS scores significantly improved during treatment. CONCLUSIONS: Our multicenter real-life experience is the largest reported to date focusing on a specific biologic and adds evidence to the safety of secukinumab in psoriatic patients with a personal history of cancer.

Efficacy and Safety of Dimethyl Fumarate in Patients with Moderate-to-Severe Plaque Psoriasis: DIMESKIN-2, a Multicentre Single-Arm Phase IIIb Study.

This open-label multicentre trial evaluated the efficacy and safety of oral dimethyl fumarate (DMF) in patients with moderate-to-severe plaque psoriasis in real-life clinical practice over 52 weeks. Disease severity and improvement were assessed using the psoriasis area severity index (PASI), body surface area (BSA) affected, and Physician Global Assessment (PGA). Quality of life (QoL) was assessed using the Dermatology Life Quality Index (DLQI) questionnaire. The visual analogue scale (VAS) was used to quantify pruritus and measure treatment satisfaction. A total of 141 patients were included, being 66.7% male, aged 49.1 ± 14.7 years and with disease duration of 16 ± 12.1 years. After 52 weeks, mean PASI decreased from 15.9 ± 6.8 to 1.5 ± 2 and 87.7%, 56.9% and 24.6% of patients achieved PASI 75/90/100 response, respectively. BSA decreased from 26.5 ± 14.8% to 2.7 ± 3.5% at 52 weeks, and 81.5% of patients had a PGA 0-1. DLQI scores decreased from 9.4 ± 6.4 to 2.1 ± 3.3, and VAS of pruritus decreased from 53 ± 28.4 to 19.1 ± 26.2 at Week 52. VAS for treatment satisfaction was 79.4 ± 29.4 at Week 52. A total of 34.2% of patients had an AE leading to permanent discontinuation. These findings show that DMF can significantly improve indices of disease severity, pruritus and QoL, with high levels of patient satisfaction and similar safety profile to other fumarates.

Real-world outcomes in patients with moderate-to-severe plaque psoriasis treated with guselkumab for up to 1 year.

BACKGROUND: Real-world data on guselkumab, especially at times >6 months, are limited. RESEARCH DESIGN AND METHODS: We performed a longitudinal, retrospective analysis on 307 patients with moderate-severe chronic plaque psoriasis (Psoriasis Area Severity Index [PASI] >10) treated with guselkumab for up to 12 months. MAIN OUTCOME MEASURES: PASI 75, PASI 90, and PASI 100 were assessed at baseline and at 4, 12, 20, 28, 36, 44, and 52 weeks. RESULTS: At 12 weeks, PASI 75, PASI 90, and PASI 100 were achieved in 56.4%, 33.6%, and 24.1% of patients, respectively. At 52 weeks, PASI 75, PASI 90, and PASI 100 were achieved in 82.7%, 68.7%, and 51.1% of patients, respectively. Patients without comorbidities and those naïve to previous biological therapy had better responses. The mean Dermatology Life Quality Index score decreased from 14.0 at baseline to 3.1 at 12 weeks and 1.6 at 6 months, which was maintained at later times. Similar improvements were seen in pruritus visual analog scale. CONCLUSIONS: Guselkumab maintains its efficacy for up to 12 months among responders in a real-world cohort of patients with moderate-severe plaque psoriasis, confirming data from prior real-world studies with smaller cohorts and shorter duration of follow-up.

Secukinumab for the treatment of palmoplantar psoriasis: a 2-year, multicenter, real-life observational study.

BACKGROUND: Palmoplantar psoriasis is difficult to treat and often recalcitrant to conventional therapies. Clinical trials have demonstrated the efficacy and safety of secukinumab for this debilitating psoriasis form, but real-life evidence is currently limited. Therefore, here we described the outcomes of patients treated with secukinumab in clinical practice. RESEARCH DESIGN AND METHODS: This was a real-life, retrospective, observational study involving patients with palmoplantar psoriasis treated with secukinumab (300 mg, subcutaneously) at seven dermatologic clinics in Italy. Treatment effectiveness was evaluated based on the changes of the Psoriasis Area and Severity Index (PASI) and palmoplantar (pp) PASI during treatment and by recording safety and tolerability issues over 104 weeks. RESULTS: Forty-three patients initiated treatment with secukinumab. Previous treatments included topical and systemic therapies; half of patients had already tried one or more biologics. Secukinumab improved mean PASI rapidly and substantially with a 78.2% decrease at 16 weeks. Mean ppPASI also improved substantially, but more gradually, with reductions of 55.0% and 79.3% at 16 and 104 weeks, respectively. Approximately half of patients achieved complete skin clearance at 40 weeks. Secukinumab was well tolerated and no relevant treatment-related adverse events were reported. CONCLUSIONS: Secukinumab appears to be effective for the treatment of palmoplantar psoriasis also in the real-life setting.

Secukinumab Exhibits Sustained and Stable Response in Patients with Moderate-to-Severe Psoriasis: Results from the SUPREME Study.

Secukinumab, a fully human monoclonal antibody, neutralizes interleukin-17A, a cornerstone cytokine driving the multiple manifestations of psoriasis. This post-hoc analysis of the SUPREME study was performed to determine the sustainability of response to secukinumab in terms of Psoriasis Area and Severity Index (PASI) 90 in patients with moderate-to-severe plaque psoriasis. Based on PASI 90 response at week 16, patients were stratified as PASI 90 responders (PASI90R, n = 337) or non-responders (PASI90NR, n = 72). At week 20, 94.2% (n = 295/313) achieved PASI 90/100 response in PASI90R, with response maintained through week 48 (89.6%, n = 189/211). An increased proportion of patients achieved PASI 90/100 response in PASI90NR (week 20: 29.9%, n = 20/67; week 48: 57.1%, n = 20/35). Overall, 64.4% patients achieved absolute PASI score = 0 at week 24 with response sustained to week 48 (66.9%). Secukinumab showed sustained and stable efficacy in maintaining PASI 90 response in patients with moderate-to-severe plaque psoriasis up to week 48.

Secukinumab Improves Patient Perception of Anxiety and Depression in Patients with Moderate to Severe Psoriasis: A Post hoc Analysis of the SUPREME Study.

This study evaluated whether secukinumab treatment for patients with moderate to severe plaque psoriasis correlates with improvements in symptoms of anxiety and depression. SUPREME was a 24-week, phase IIIb, multicentre, prospective study conducted across 50 centres in Italy with an extension period of up to 72 weeks. Assessments used were: Psoriasis Area Sever-ity Index (PASI), Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A), and HADS - Depression (HADS-D) scores and Dermatology Quality Life Index (DLQI). Compared with baseline, a significantly greater proportion of patients who reported moderate to severe clinical symptoms of anxiety or depression (HADS-A or HADS-D ≥ 11) were free of moderate to severe symptoms at weeks 16 and 48. The PASI and DLQI scores reduced over time with secukinumab treatment. Psoriasis treatment with secukinumab for 48 weeks resulted in significantly improved skin clearance and a parallel improvement in symptoms of anxiety and depression, assessed by HADS.

Patients' demographic and socioeconomic characteristics influence the therapeutic decision-making process in psoriasis.

BACKGROUND: Knowledge regarding differences in care for psoriatic patients is limited. The aim of this study was to investigate factors influencing prescription of systemic treatments for patients with psoriasis with a special focus on socioeconomic factors. METHODS AND FINDINGS: This was a non-interventional, cross-sectional study, conducted in 18 Italian University and/or hospital centers with psoriasis-specialized units. Questionnaires evaluating demographic and socioeconomic characteristics were administered to participants. Overall, 1880 consecutive patients affected by mild-to-severe psoriasis were recruited. Univariate and multivariable logistic regression analyses of systemic therapy prescription, with a special focus on biologics, accounting for the above mentioned characteristics were performed. Our analysis showed that all analyzed patients' characteristics were significantly associated with biological therapy compared to non-biological systemic one. Particularly, women were less likely to receive biologics than men (OR = 0.66; 95% CI, 0.57-0.77). Elderly patients (≥65 years) and subjects with a BMI ≥30 had lower odds to receive biologics respect to adults (≥35-64 years) (OR = 0.33; 95% CI, 0.25-0.40), and subjects with BMI≥25<30 (OR = 0.64; 95% CI, 0.53-0.77), respectively. Northern and Southern patients were both less likely to receive biologics than Central patients (OR = 0.75; 95% CI, 0.63-0.89, and OR = 0.56; 95% CI,0.47-0.68, respectively). Lower economic profile and never reading books were both associated with decreased odds of receiving biological therapy. CONCLUSIONS: This study shows that sex, age, comorbidities, and socioeconomic characteristics influence the prescription of systemic treatments in psoriasis, highlighting that there are still unmet needs influencing the therapeutic decision-making process that have to be addressed.

Clinical efficacy, speed of improvement and safety of apremilast for the treatment of adult Psoriasis during COVID-19 pandemic.

Time to improvement is a crucial characteristic for effective treatments of chronic inflammatory conditions, such as psoriasis. Apremilast is a recently approved drug, belonging to the small molecule phosphodiesterase 4 inhibitors, whose optimal safety and efficacy profile is somewhat affected by slow activity rate in clinical trials. Real world case series are suggesting a more consistent improvement, and with this additional personal investigation on 48 patients, we signal that 58% of patients achieved Psoriasis Area and Severity Index (PASI) 50, and 19% PASI 75 improvement in the first 8 weeks of treatment. Results at 16-week are remarkable, with overall 55% of patients achieving PASI 75, 21% PASI 90 and 14% PASI 100. Only 8 patients (18, 6%) had slightly improved, although satisfied with the regimen, and determined to continue. Noteworthy, our population was rather problematic in terms of comorbidities (86%), and resistance to other treatments, with only 28% naïve to systemics, including biologics. Moreover, the observation period includes the Italian outbreak of COVID-19 epidemic, and further information on apremilast safety are provided, no one of the patients having stopped treatment. In such a critical period, the apremilast satisfactory speed of therapeutic response in a real-world setting has further strengthens patient's compliance to remain safely at home, which is the best strategy to limit contagion.

Successful guselkumab treatment in a psoriatic patient affected with Cornelia de Lange syndrome, and prosecution during the COVID-19 pandemic.

Psychomotor delay and intellectual disability are potential limitations in psoriasis management, due to low compliance, and strict dependence from caregivers intervention. We report our successful experience with a 58-year-old woman, who was genetically affected by Cornelia De Lange syndrome, which causes intellectual disability and psychomotor disorders. The patient had been already treated with topical and traditional therapies, without any clinical benefits. Eventually, she adhered to guselkumab treatment. The compliance was excellent, significant improvements were observed after only 3 months of treatment, without adverse effects. During follow-up, the COVID-19 pandemic address concern on the possible increased risk of infection due to immunosuppression. In agreement with current Italian recommendations, risk and benefits profile was discussed with the patient's legal tutor and the decision to continue the treatment was taken. Psoriasis complete clarification was maintained during the most difficult period of the Italian outbreak, allowing the patient to remain safely at home.

Erythrodermic psoriasis in a dialyzed patient successfully treated with Secukinumab.

Erythrodermic psoriasis is a severe, life-threatening condition with additional complications, when occurring in hemodialyzed patients, as the majority of treatments are contraindicated. A 44-years-old man, of Philippine origins, with a 15-years-history of psoriasis treated with cyclosporine developed progressive hypertension and renal insufficiency. Despite drug dismission, renal function worsen to end-stage, and hemodialysis was necessary three times a week. Phototherapy was not able to control the skin condition, progressing to erythroderma, and after nephrology consultation, the patient consent to the off-label secukinumab treatment, at the standard regimen (300 mg subcutaneously once weekly at weeks 0-4 followed by 300 mg every 4 weeks). Seven days after the first injection, a rapid improvement was noted, with the psoriasis area severity index (PASI) score passing from 31.5 to 17.6. At the 52-week-follow-up visit, the patient was completely clarified, without any side effects. The case supports secukinumab effectiveness and safety in difficult patients, including erythrodermic psoriasis with end-stage renal failure, as drug plasma levels seem not to be affected by hemodialysis. Results are rapidly achieved, and long term maintained, with the additional advantage of a very comfortable monthly administration.

Biologics exposure during pregnancy and breastfeeding in a psoriasis patient.

Biologic agents have revolutionized the treatment of psoriasis, and the increasing use of these agents in women of childbearing age raises questions regarding pregnancy safety. We report a case of a woman affected with severe psoriasis, who underwent three pregnancies while exposed to biologic agents. Although immediately dismissed at first pregnancy awareness, first-trimester exposure occurred, and the course of the pregnancies was carefully monitored. The patient was under adalimumab treatment during her first pregnancy and ustekinumab at her second and third gestation. She had a premature birth at 35 weeks during the first two pregnancies and at 36 weeks during her last pregnancy. All babies were born healthy without congenital anomalies. Furthermore, due to the rapid worsening of her psoriasis, biologics treatment was reintroduced immediately after breastfeeding in the first two occasions, but immediately after delivery in the last pregnancy, with the explicit consent of the patients. There are few data available on biologics treatment safety during pregnancy and breastfeeding, especially regarding ustekinumab. We report our positive experience with the aim of increasing case notifications, facilitate meta-analysis, and eventual consensus recommendations regarding the use of biologics in special population.

Efficacy and safety of adalimumab after failure of other anti-TNFα agents for plaque-type psoriasis: clinician behavior in real life clinical practice.

Introduction: During treatment with biologic agents for psoriasis (Pso) in a number of patients a failure may occur and discontinuation with transitioning to another drug or an optimization strategy, consisting in a dose-adjustment or a co-medication with a traditional systemic agent, represent two possible alternatives. Objective: The SAFARI study objective was a retrospective observation of adalimumab efficacy and safety profile after switching from other anti-TNFα agents related to clinician behavior after the failure of the first-line agent. Results: The retrospective multicenter observation demonstrated that after a first-line anti-TNFα failure adalimumab efficacy was consistent at week-12 and 24 with a further significant improvement at week-48 with a proportion of patients achieving PASI75/PASI90/PASI100 of 83.3, 71.6, and 56.9.%, respectively. Clinician strategies to extend drug-survival after first-line anti-TNFα failure, such as co-medication or dose-adjustment, were irrelevant to future drug effectiveness. Conclusions: Adalimumab profile was excellent in this 5-year retrospective observation, showing the clinical validity of interclass transitioning among anti-TNFα options.