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Abstract Background Psoriatic arthritis (PsA) is a chronic, immune-mediated, spondyloarthropathy characterised by musculoskeletal signs and symptoms with associated joint pain and tenderness. The average worldwide PsA prevalence is 133/100,000, while in the Italian population is 90–420/100,000. Traditionally, nonsteroidal anti-inflammatory drugs, glucocorticoid, and disease-modifying antirheumatic drugs have been used in the treatment of PsA. However, for those patients who are not adequately controlled with conventional therapies, the new biologics compounds represent a valid option. Biologic therapies have been shown to be more effective but also more expensive than conventional systemic treatments. Based on the CHRONOS study, the economic analyses presented in this paper aim to assess the annualised direct costs and the cost-per-responder of biologics in a real-world context assuming the Italian National Health System perspective. Methods The economic assessments were carried out on the overall cohort of patients, and on the tumour necrosis factor alpha inhibitors (TNFi) and the secukinumab subgroup, the most prescribed biologic therapies within the CHRONOS study. Results The annual economic impact of PsA in the overall group was €12,622, €11,725 in the secukinumab subgroup, and €12,791 in the TNFi subgroup. Biologics absorbed the main expenditure costs in the treatment of PsA accounting for about the 93% of total costs. At 6 months, secukinumab performed better in all the considered outcomes: cost-per-responder according to EULAR DAS28 and ACR50 response criteria were €12,661- €28,975, respectively, while they were €13,356 - €33,368 in the overall cohort and €13,138 - €35,166 in the TNFi subgroup. At 12 months secukinumab remained the subgroup with the lowest cost-per-responder ratio in EULAR DAS28 and ACR50 response criteria, while TNFi subgroup was the lowest one considered the ACR20. Conclusion Despite some potential methodological limitations, our cost-per-response analysis provides physicians and payers additional insights which can complement the traditional risk-benefit profile assessment and drive treatment decisions.

Abstract Background Biologics have demonstrated efficacy in PsA in randomized clinical trials. More evidence is needed on their effectiveness under real clinical practice conditions. The aim of the present work is to provide real-world evidence of the effectiveness of biologics for PsA in the daily clinical practice. Methods CHRONOS was a multicenter, non-interventional, cohort study conducted in 20 Italian hospital rheumatology clinics. Results 399 patients were eligible (56.9% females, mean (SD) age: 52.4 (11.6) years). The mean (SD) duration of PsA and psoriasis was 7.2 (6.9) and 15.3 (12.2) years, respectively. The mean (SD) duration of the biologic treatment under analysis was 18.6 (6.5) months. The most frequently prescribed biologic was secukinumab (40.4%), followed by adalimumab (17.8%) and etanercept (16.5%). The proportion of overall responders according to EULAR DAS28 criteria was 71.8% (95% CI: 66.7–76.8%) out of 308 patients at 6 months and 68.0% (95% CI: 62.7–73.3%) out of 297 patients at 1 year. Overall, ACR20/50/70 responses at 6 months were 41.2% (80/194), 29.4% (57/194), 17.1% (34/199) and at 1-year were 34.9% (66/189), 26.7% (51/191), 18.4% (36/196), respectively. Secondary outcome measures improved rapidly already at 6 months: mean (SD) PASI, available for 87 patients, decreased from 3.2 (5.1) to 0.6 (1.3), the proportion of patients with dactylitis from 23.6% (35/148) to 3.5% (5/142) and those with enthesitis from 33.3% (49/147) to 9.0% (12/133). Conclusions The CHRONOS study provides real-world evidence of the effectiveness of biologics in PsA in the Italian rheumatological practice, confirming the efficacy reported in RCTs across various outcome measures.

Background: In psoriasis, several studies have indicated sex differences in clinical characteristics, type of treatment, and outcomes. A higher impact of psoriasis on quality of life (QoL) and a lower treatment satisfaction have been reported in women by different authors. Objectives: This article reports the results of a post hoc gender analysis of CANOVA study, aimed at assessing 16/24/52-week effectiveness of biologics in patients with moderate-severe plaque psoriasis. Materials and Methods: CANOVA was a real-world, multicenter, noninterventional, retro-prospective study conducted in 17 Italian hospital dermatology clinics. Results: Of the 669 eligible patients, 63.8% were men. Demographic and baseline characteristics and duration of disease were rather homogeneous between sexes. Slightly more women had been treated with biologics (50.4% vs. 46.5%) and had received ?2 biologic treatment lines (17.2% vs. 12.4%) before study treatment. The most frequently used biologics were secukinumab, ustekinumab, adalimumab, and ixekizumab in both sexes. At 6 months, Psoriasis Area Severity Index (PASI) 75/90/100 responders were 90.8%/72.3%/45.3% of men and 89.2%/76.6%/48.2% of women. Sustained PASI responders were 79.5% of men and 75.9% of women. Treatment satisfaction was significantly lower in women at enrolment for all subscales, and was still lower at 6 months, no longer significantly. Gender distribution in Dermatology Life Quality Index total score classes showed a significantly greater effect of psoriasis on QoL in women, both at enrolment and at the 6-month follow-up. Conclusions: In conclusion, this gender analysis confirms in both genders the efficacy of biologics in psoriasis. However, women reported a greater impact of the disease on QoL and lower treatment satisfaction.

Background: Phenotypic features and outcome differences between sexes have been reported in psoriatic arthritis (PsA). However, little is known about sex differences in effectiveness of biologics in clinical practice. Methods: Post hoc gender analysis of the CHRONOS, a multicenter, noninterventional, retroprospective Italian real-world study assessing 6-month and 1-year effectiveness of biologics for PsA. Results: Eligible patients were 399, 43.1% men. Sociodemographic characteristics, type of arthritis, baseline Disease Activity Score 28 joints (DAS28), and duration of biologic treatment were rather homogeneous. More men were overweight/obese and naive to biologics. The most frequently used biologics were TNF-inhibitors and secukinumab in both sexes. DAS28 responders were 72.7% (women) and 70.5% (men) at 6 months, and 68.0% in both sexes at 1 year. American College of Rheumatology (ACR) response showed a trend for men versus women to achieve more frequently ACR50 (32.6% vs. 26.5% at 6 months; 34.9% vs. 20.0% at 1 year) and ACR70 (22.3% vs. 12.4% at 6 months and 25.0% vs. 13.0% at 1 year). Global satisfaction with treatment at enrollment and after 6 months was slightly higher among men [mean (standard deviation) Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) score: 68.6 (18.6) and 69.9 (18.2), respectively] than women [65.3 (18.2), 66.2 (18.5)]. Conclusions: Overall response to biologics for PsA was rather favorable. With similar baseline disease severity, men appear to have a somewhat earlier and better response with higher treatment satisfaction.

Abstract Background Psoriasis is a chronic immune-mediated inflammatory skin disease which can also involve joints. It is often associated with burdensome comorbidities which negatively impact prognosis and quality of life (QoL). Biologic agents have been shown to be effective in controlling disease progression, but their use is associated with higher costs compared with traditional systemic treatments. The economic analysis of the CANOVA (EffeCtiveness of biologic treAtmeNts for plaque psOriasis in Italy: an obserVAtional longitudinal study of real-life clinical practice) study aims to assess the costs and cost-effectiveness of biologics in a real-world context in Italy. Methods The annualised overall direct costs of moderate-to-severe plaque psoriasis management, the annualised cost of biologic drugs and the cost per responder in the Italian National Health System perspective were assessed. More specifically, the cost per response and cost per sustained response of the most prescribed biologic therapies for the treatment of moderate-to-severe plaque psoriasis within the CANOVA study were assessed using the Psoriasis Area Severity Index (PASI) at several score levels (75, 90 and 100%). Results The most frequently used biologic therapies for plaque psoriasis were secukinumab, ustekinumab, adalimumab originator, and ixekizumab. Cost of biologics was the driver of expenditure, accounting for about 98% of total costs. Adalimumab originator was the biologic with the lowest cost per responder ratio (range: €7848 - €31,378), followed by secukinumab (range: €9015 - €33,419). Ustekinumab (range: €11,689 – €39,280) and ixekizumab (range: €11,092 – €34,289) ranked respectively third and fourth, in terms of cost-effectiveness ratio. As concerns the cost per sustained response analysis, secukinumab showed the lowest value observed (€21,375) over the other options, because of its high response rate (86% vs. 60–80%), which was achieved early in time. Conclusion Biologic therapy is a valuable asset for the treatment of moderate-to-severe plaque psoriasis. Concomitant assessment of treatment costs against the expected therapeutic response over time can provide physicians and payers additional insights which can complement the traditional risk-benefit profile assessment and drive treatment decisions.

HTLV-1 orf-I is linked to immune evasion, viral replication and persistence. Examining the orf-I sequence of 160 HTLV-1-infected individuals; we found polymorphism of orf-I that alters the relative amounts of p12 and its cleavage product p8. Three groups were identified on the basis of p12 and p8 expression: predominantly p12, predominantly p8 and balanced expression of p12 and p8. We found a significant association between balanced expression of p12 and p8 with high viral DNA loads, a correlate of disease development. To determine the individual roles of p12 and p8 in viral persistence, we constructed infectious molecular clones expressing p12 and p8 (D26), predominantly p12 (G29S) or predominantly p8 (N26). As we previously showed, cells expressing N26 had a higher level of virus transmission in vitro. However, when inoculated into Rhesus macaques, cells producing N26 virus caused only a partial seroconversion in 3 of 4 animals and only 1 of those animals was HTLV-1 DNA positive by PCR. None of the animals exposed to G29S virus seroconverted or had detectable viral DNA. In contrast, 3 of 4 animals exposed to D26 virus seroconverted and were HTLV-1 positive by PCR. In vitro studies in THP-1 cells suggested that expression of p8 was sufficient for productive infection of monocytes. Since orf-I plays a role in T-cell activation and recognition; we compared the CTL response elicited by CD4+ T-cells infected with the different HTLV-1 clones. Although supernatant p19 levels and viral DNA loads for all four infected lines were similar, a significant difference in Tax-specific HLA.A2-restricted killing was observed. Cells infected with Orf-I-knockout virus (12KO), G29S or N26 were killed by CTLs, whereas cells infected with D26 virus were resistant to CTL killing. These results indicate that efficient viral persistence and spread require the combined functions of p12 and p8.