Clinical characteristics and response to biological therapies for inverse psoriasis: a real-life comparison between the therapeutic effects of anti-IL-23 and anti-IL-17 agents.

BACKGROUND: Inverse psoriasis (IP) is a variant of plaque psoriasis involving flexor surfaces. A clear definition of IP is still lacking. Therapy is based on topical and systemic treatments, including classic systemic drugs and biologic agents, but a well-defined therapeutic strategy is absent. MATERIALS AND METHODS: This retrospective study investigated the general characteristics of patients with IP or vulgar psoriasis and compared the effectiveness of anti-interleukin-17 or anti-interleukin-23 agents in the same groups. Second, treatment effectiveness and the demographic characteristics of IP patients treated with IL-23 and IL-17 inhibitors were also compared. IP patients were included if they had specific psoriatic involvement of the axillary, inguinal, or submammary lines, breast folds, antecubital and popliteal pits, intergluteal fold, and perianal area. Patients with vulgar plaque psoriasis and concomitant intertriginous involvement were included in the vulgar psoriasis cohort. RESULTS: Patients with IP were prevalently female and treated with IL-17 inhibitors compared to those with vulgar psoriasis. They also had a greater risk of drug discontinuation and subsequent therapeutical switch (32.1% vs. 18.1%, P = 0.002). At later time points, those with IP showed progressively slower achievement of PASI100 and 90 compared to the cohort with vulgar psoriasis. In the IP cohort, there was greater joint involvement in patients treated with an anti-IL-17 agent (P = 0.011), who also had a lower median age of onset (P = 0.011) compared to patients treated with an anti-IL-23 agent. Patients with IP treated with an anti-IL-23 agent initiated with a lower mean PASI and showed a slower response than patients on an anti-IL-17 agent. At later time points, progressively greater effectiveness of IL-23 inhibitors was observed compared to IL-17 inhibitors. CONCLUSIONS: Patients with IP responded less to biologic agents than those with vulgar psoriasis. In the IP cohort, IL-17 inhibitors had a faster onset than IL-23 inhibitors, but long-term anti-IL-23 agents seem to be associated with better outcomes.

Drug survival, effectiveness, and safety of brodalumab for moderate-to-severe psoriasis up to 3 years.

BACKGROUND: Brodalumab is a monoclonal antibody and IL-17 RA inhibitor that is approved for the treatment of moderate-to-severe psoriasis. The present study aims to estimate the drug survival (DS), effectiveness, and safety of brodalumab over a period of 156 weeks. METHODS: The primary objectives were: (i) to determine the treatment response rate at Weeks 16, 28, 52, 78, 104, and 156 as defined by PASI100, PASI90, and an absolute PASI ≤ 3 and (ii) long-term DS. Secondary objectives included the evaluation of possible predictive factors associated with the achievement of response outcomes, and possible predictive factors associated with lower DS. RESULTS: The treatment response was rapid, with 80.3% of patients achieving PASI ≤ 3, 66% PASI90, and 54.3% the complete clearance of disease at Week 16. The response improved at Week 28, when a plateau was achieved with mild loss of response at later time points, in particular for PASI100 and PASI90 in 55.2 and 65.5% of patients, respectively, at Week 156. After 156 weeks of treatment, 66.22% of patients were still on therapy, and the previous use of IL-17 inhibitors appeared to be associated with an increased risk of treatment discontinuation (HR: 2.51, CI: 1.06-5.98, P = 0.037), and achievement of PASI ≤ 3 until Week 16 with less risk (HR: 0.27 CI: 0.14-0.51, P < 0.001). Bio-naïve status was favorably associated with treatment response, while high BMI negatively affected the achievement of outcomes. CONCLUSION: Our study confirms the good effectiveness and favorable safety profile of brodalumab in a real-world setting for up to 3 years of treatment.

Drug survival and clinical effectiveness of secukinumab, ixekizumab, brodalumab, guselkumab, risankizumab, tildrakizumab for psoriasis treatment.

BACKGROUND: Biologics targeting IL-23 and IL-17 show efficacy and safety in the treatment of moderate-to-severe psoriasis. OBJECTIVE: To investigate drug survival in patients with psoriasis treated with biologics. PATIENTS AND METHODS: We performed a comparative evaluation of the achievement of PASI 90 and PASI ≤ 3 at 16, 28, and 52 weeks along with a DS (drug survival) analysis with IL-17 and IL-23 inhibitors brodalumab, ixekizumab, secukinumab, risankizumab, tildrakizumab, and guselkumab on 1,057 patients. RESULTS: IL-17 inhibitors showed a faster achievement of PASI 90 and PASI ≤ 3 with significant superiority over IL-23 inhibitors at week 16 (p < 0.001; 56% vs. 42% and 70% vs. 59%, respectively). A difference was shown in favor of IL-23 inhibitors regarding DS (p < 0.001), which was 88% at 24 months vs. 75% for IL-17 inhibitors. In multivariate analysis, IL-23 inhibitors (HR 0.54 CI 0.37-0.78, p = 0.001), and male sex (HR 0.57 CI 0.42-0.76, p < 0.001) were all associated with a lower probability of drug interruption. Risankizumab (HR 0.42 CI 0.26-0.69, p = 0.001), guselkumab (HR 0.49 CI 0.24-0.99, p = 0.046), and male sex (HR 0.57 CI 0.43-0.77, p < 0.001) were associated with a lower probability of drug interruption than secukinumab. CONCLUSIONS: IL-23 inhibitors showed the best performance on DS. Overall, the most effective class was IL-17 inhibitors considering the short-term effectiveness, but long-term effectiveness is in favor of anti-IL-23.

Interclass Switch between IL17 and IL23 Inhibitors in Psoriasis: A Real-Life, Long-Term, Single-Center Experience.

BACKGROUND: Interleukin 23 (IL-23) inhibitors, such as guselkumab, risankziumab, and tildrakizumab, have proved to be highly effective and safe for psoriasis treatment either in bio-naïve or bio-experienced patients. A substantial proportion of patients show a primary or secondary inefficacy to IL-17 inhibitors and can benefit from an alternative line of treatment, like IL-23 inhibitors. To date, no sufficient data are available on the effectiveness of IL-23 inhibitors after an anti-IL-17 agent. METHODS: Our study includes 48 patients with moderate to severe psoriasis undergoing a switch from IL-17 to IL-23 inhibitors. This trial is registered with SS_DERMO_20. RESULTS: The mean PASI (Psoriasis Area Severity Index) decreases from 11.6 to 3.3 at week 16, with responses maintained at weeks 28 and 52 (2 and 1.4, respectively), and a PASI100 achievement in more than 24% of patients at 16 weeks and 61.9 at 48 weeks, with no occurrence of serious adverse events. However, almost one in six patients interrupted the IL-23 inhibitors mainly due to primary ineffectivenss. CONCLUSIONS: Our data support the evidence that an interclass switch among IL-17 inhibitors is a safe and effective therapeutic option for these patients.

Clinical effectiveness of IL-17 and IL-23 inhibitors on difficult-to-treat psoriasis areas (scalp, genital, and palmoplantar sites): a retrospective, observational, single-center, real-life study.

INTRODUCTION: Psoriasis affecting the genital, palmoplantar, and scalp regions is recognized as difficult-to-treat, and data on the efficacy of biologics in these areas remains limited. RESEARCH DESIGN AND METHODS: This single-center study evaluated the effectiveness of anti-IL-17 and anti-IL-23 agents on scalp, genital, and palmoplantar psoriasis. We retrospectively analyzed data from all patients with psoriasis being treated with IL inhibitors at our clinic. Effectiveness was evaluated at 16, 28, and 52 weeks, according to the achievement of relative and mean PSSI, PGA-G, and ppPASI. RESULTS: In all, 308 patients showed involvement of the scalp, 136 in the genital area, and 94 in the palmoplantar regions. On scalp psoriasis, anti-IL-17 agents demonstrated superiority in disease control compared to anti-IL-23 agents. PSSI100 at week 16 was reached by 59% of patients on an anti-IL17 vs 39.8% on an anti-IL-23 (p < 0.003). At genital sites, no significant differences between anti-IL-17 and anti-IL-23 agents were observed, and all classes achieved PGA-G 0/1. No significant differences between anti-IL-17 and anti-IL-23 agents were observed in palmoplantar areas. CONCLUSIONS: The present data support the utility of both anti-IL-17 and anti-IL-23 agents for the treatment of difficult-to-treat areas in patients with psoriasis. Anti-IL-17 agents achieved better control of scalp psoriasis.

Seven Years of Culture Collection of Neisseria gonorrhoeae: Antimicrobial Resistance and Molecular Epidemiology.

The emergence of Neisseria gonorrhoeae isolates displaying resistance to antimicrobials, in particular to ceftriaxone monotherapy or ceftriaxone plus azithromycin, represents a global public health concern. This study aimed to analyze the trend of antimicrobial resistance in a 7-year isolate collection retrospective analysis in Italy. Molecular typing on a subsample of gonococci was also included. A total of 1,810 culture-positive gonorrhea cases, collected from 2013 to 2019, were investigated by antimicrobial susceptibility, using gradient diffusion method, and by the N. gonorrhoeae multiantigen sequence typing (NG-MAST). The majority of infections occurred among men with urogenital infections and 57.9% of male patients were men who have sex with men. Overall, the cefixime resistance remained stable during the time. An increase of azithromycin resistance was observed until 2018 (26.5%) with a slight decrease in the last year. In 2019, gonococci showing azithromycin minimum inhibitory concentration above the EUCAST epidemiological cutoff value (ECOFF) accounted for 9.9%. Ciprofloxacin resistance and penicillinase-producing N. gonorrhoeae (PPNG) percentages increased reaching 79.1% and 18.7% in 2019, respectively. The most common sequence types identified were 5,441, 1,407, 6,360, and 5,624. The predominant genogroup (G) was the 1,407; moreover, a new genogroup G13070 was also detected. A variation in the antimicrobial resistance rates and high genetic variability were observed in this study. The main phenotypic and genotypic characteristics of N. gonorrhoeae isolates were described to monitor the spread of drug-resistant gonorrhea.

Understanding Barriers Impacting upon Patient Wellbeing: A Nationwide Italian Survey and Expert Opinion of Dermatologists Treating Patients with Moderate-to-Severe Psoriasis.

A nationwide cross-sectional online survey was administered to dermatologists managing patients with moderate-to-severe plaque psoriasis across Italy to obtain real-world dermatologists' perspectives on the impact of psoriasis and its treatment on patients' daily lives and quality of life (QoL). A total of 91 dermatologists (aged 39.1 ± 11.2 years) completed a 31-question survey and workshop sessions were undertaken in order to identify the best management approach to achieve patient wellbeing. Social (4.2 ± 0.1), physical (4.26 ± 0.2) and mental components (4.1 ± 0.3) were rated by dermatologists as contributing to patient wellbeing to similar extents. While a high proportion (85.4%; rating of 4.3 out of 5) of dermatologists felt that they considered the QoL of patients, a lower proportion (69.6%; rating of 3.7 out of 5) felt that patients were satisfied in this regard. The psoriasis area and severity index and body surface area were the instruments most frequently used to assess the physical domain, while interviews/questions and the dermatology life quality index were used to assess social and mental domains, with only 60% of dermatologists following up on these aspects. The importance of investigating the presence of comorbidities was recognized but not always carried out by many dermatologists, (>70%), particularly for obesity and anxiety/depression. This survey identified key components contributing to barriers impacting on the QoL of patients with moderate-to-severe psoriasis from the perspective of the dermatologist.

Sharing Patient and Clinician Experiences of Moderate-to-Severe Psoriasis: A Nationwide Italian Survey and Expert Opinion to Explore Barriers Impacting upon Patient Wellbeing.

A nationwide survey was conducted in adult patients with psoriasis (PsO) across Italy to obtain their real-world perspective of the impact of PsO on their wellbeing. Patients completed a 26-question survey (based on the patient benefit index; PBI, The Dermatology Life Quality Index; DLQI and the World Health Organization-five; WHO-5 wellbeing index) and workshop discussion sessions were undertaken by dermatologists to interpret results from the survey. 392 patients with PsO completed the survey. Analysis of results was restricted to patients who had moderate-to-severe plaque psoriasis (assessed by patients; n = 252; 64.3%). Dermatologists (n = 32) completed one question from the survey related to wellbeing and rated social, physical and mental domains as contributing to a similar extent, with comparable scores also observed by patients. For treatment, biologics yielded higher scores on average, whereas little difference was observed between topical and conventional systemic treatments. Only 23.8% of patients felt that their dermatologist was taking into consideration their wellbeing and 32.6% of the patients considered their therapy as inadequate in improving signs and symptoms of the disease. This survey identified key factors contributing to barriers impacting on patient wellbeing. Simple, but comprehensive questionnaires can provide important insight to patients' needs that may significantly increase clinician awareness during visits leading to tailored treatment.

Efficacy, safety, and drug survival of IL-23, IL-17, and TNF-alpha inhibitors for psoriasis treatment: a retrospective study.

BACKGROUND: Real-life studies in psoriasis are lacking. Many monoclonal antibodies targeting tumor-necrosis factor (TNF)-alpha, interleukin 17, and 23 are approved drugs for psoriasis treatment. OBJECTIVES: To compare the short and long-term efficacy, safety, and drug survival of anti TNF-alpha, anti-IL-17, and anti-IL-23 in a large case series. METHODS: Psoriasis area severity index (PASI) and retention rates for adalimumab, secukinumab, guselkumab, ixekizumab, and brodalumab were analised. RESULTS: A total of 263 patients were randomly selected among the five drugs register of the patients attending the Psoriasis Unit at the Turin University Hospital. The mean PASI at baseline was 14.3. Ixekizumab showed a significantly higher efficacy profile compared to other drugs in terms of PASI90 and PASI100 at week 12, 24, and week 48 even when adjusted for other confounding factors. This superiority was not followed by an expected higher drug survival. On the contrary, secukinumab was the only drug that showed a higher drug survival among bio-naïve patients.

Management of psoriatic arthritis in rheumatology and dermatology settings: sub-analysis of the Italian population from the international LOOP study.

Psoriatic arthritis (PsA) patients are often treated by dermatology and rheumatology specialities and may receive different treatments. To evaluate the impact of dermatology/rheumatology specialist settings on diagnosis and therapeutic approach in PsA patients. This cross-sectional multicounty study in Italy involved twenty-eight rheumatology or dermatology clinics. Patients with suspected or confirmed PsA were examined by both a dermatologist and a rheumatologist. A total of 413 patients were enrolled and 347 (84%) were diagnosed with PsA. The majority of patients were enrolled from a rheumatology setting (N = 224, 64.6%). Patients with PsA in the dermatology settings had significantly higher disease activity, including skin involvement and musculoskeletal symptoms. Time from PsA onset to diagnosis was 22.3 ± 53.8 vs. 39.4 ± 77.5 months (p = 0.63) in rheumatology and dermatology settings; time from diagnosis to initiation of csDMARD was 7.3 ± 27.5 vs. 19.5 ± 50.6 months, respectively (p < 0.001). In contrast, time from diagnosis to bDMARD use was shorter in dermatology settings (54.9 ± 69 vs. 44.2 ± 65.6 months, p = 0.09, rheumatology vs. dermatology), similar to the time taken from first csDMARDs and bDMARDs (48.7 ± 67.9 vs. 35.3 ± 51.9 months, p = 0.34). The choice to visit a rheumatologist over a dermatologist was positively associated with female gender and swollen joints and negatively associated with delay in time from musculoskeletal symptom onset to PsA diagnosis. This study highlights a diagnostic delay emerging from both settings with significantly different therapeutic approaches. Our data reinforce the importance of implementing efficient strategies to improve early identification of PsA that can benefit from the integrated management of PsA patients. Key Points • A diagnostic delay was observed from both dermatology and rheumatology settings with significantly different therapeutic approaches. • Shared dermatology and rheumatology clinics offer the combined expertise to improve in the early identification and management of PsA.

Recurrent herpes labialis and Herpes simplex virus-1 genitalis: what is the link?

BACKGROUND: Recently, Herpes simplex virus (HSV)-1 seroprevalence declined among adolescents, rendering young people lacking HSV-1 antibodies more susceptible to genital HSV-1 acquisition, if sexually exposed. The aim of the present study was to identify the possible risk factors for the development of HSV-1 related Herpes genitalis (HG). METHODS: From January 2012 to December 2015, patients with HG attending three Sexually Transmitted Infections Units in Northern Italy were recruited. A genital swab on the lesions for the search of HSV-1/2 DNA through real time polymerase chain reaction (PCR) and a serum sample for HSV-1/2 specific serology were performed. Moreover, patients were asked whether they had personal history of herpes labialis (HL). Patients with PCR proved HSV-1 HG were included as cases; asymptomatic subjects attending STI Units for a blood check were recruited as controls and were checked for HSV-1/2 serology. RESULTS: The study included 141 cases and 70 controls. Specific HSV-1 antibodies were found in 34.7% of the cases and 67% of the controls. History of recurrent herpes labialis (RHL) was found in 4% of the cases and 31% of the controls. The occurrence of RHL in HSV-1 seropositive patients resulted lower in the case group compared to the control group. CONCLUSIONS: We can speculate about a protective role for RHL against the clinical appearance of HSV-1 HG. The clinical usefulness of our study involved especially the counselling in serodiscordant couples. The presence of HSV-1 antibodies in asymptomatic sexual partners does appear protective for HG manifestation only in presence of RHL history.

Time trend analysis (2009-2016) of antimicrobial susceptibility in Neisseria gonorrhoeae isolated in Italy following the introduction of the combined antimicrobial therapy.

INTRODUCTION: Neisseria gonorrhoeae (NG) antimicrobial susceptibility trends to azithromycin, cefixime and ceftriaxone were analyzed, from 2009 to 2016, to monitor changing antimicrobial susceptibility concomitant with the change in prescribing practice in 2012 from cefixime, or ceftriaxone, to ceftriaxone plus azithromycin. Patient characteristics predictive to be infected by antibiotic resistant N. gonorrhoeae were estimated. Finally, the protocol for the treatment of gonorrhoea, in comparison with the international guidelines, was also evaluated. MATERIALS AND METHODS: Data on NG antimicrobial resistance were obtained from a network of sexually transmitted diseases clinics and other laboratories in 12 cities in Italy. We tested the 1,433 gonococci for antimicrobial susceptibility to azithromycin, cefixime and ceftriaxone using a gradient diffusion method. Logistic-regression methods with cluster robust standard errors were used to investigate the association of resistance categories with demographic and clinical patient characteristics and to assess changes in prescribing practices. To minimize bias due to missing data, all statistical models were fitted to data with forty rounds of multiple imputation, using chained equations. RESULTS: The percentage of isolates resistant to cefixime was 17.10% in 2009 and declined up to 1.39% in 2016; at the same time, those resistant to azithromycin was 23.68% in 2009 and 3.00% in 2012. Starting from 2013, azithromycin resistant gonococci tended to increase up to 7.44% in 2016. No ceftriaxone resistant isolates were observed. By multivariate analysis, the men who have sex with women (MSW) and women had a proportional adjusted OR of resistance of 1.25 (95%CI: 0.90; 1.73) and 1.67 (95%CI: 1.16; 2.40), respectively, in comparison with men who have sex with men (MSM). An aOR of resistance of 0.48 (95%CI: 0.21; 1.12) among NG isolated in the pharynx, compared with those isolated in genital sites, was calculated. The proportional aOR of resistance was 0.58 (95%CI: 0.38; 0.89) for presence vs absence of co-infection and 2.00 (95%CI: 1.36; 2.96) for past history vs no history of gonorrhoea.Finally, at least for the period 2013-2016, the older, subjects with anorectal or pharyngeal gonorrhoea infection, subjects with a co-infection, subjects with a previous gonorrhoea infection were not always correctly treated. CONCLUSIONS: Overall, our findings suggest the shifts in N. gonorrhoeae susceptibility to cefixime and azithromycin in the time frame period. First of all, the increasing rate of azithromycin resistance in 2015-2016 in NG isolated in the country need to be monitor in the future. Finally, extensive information on treatment regimens may be useful to asses treatment adherence particularly for the older subjects, subjects with an anorectal or pharyngeal infection, subjects with a co-infection and subjects with a previous history of gonorrhoea. Gonorrhoea treatment strategy should be based on the evidence obtained by the local antimicrobial surveillance system and data about treatment failures.

Skin cancers and other cutaneous diseases in renal transplant recipients: a single Italian center observational study.

Kidney transplant recipients frequently suffer from skin infections and malignancies, due to the effects of long-term immunosuppressive therapy. Herein, a dermatological screening was performed to evaluate the relationship between risk factors, cutaneous tumours and other skin diseases in a group of 282 kidney transplant patients. Infectious diseases (16.7%) were the most frequent dermatological disorders, whereas cutaneous inflammatory and autoimmune diseases were relatively rare, probably due to an indirect therapeutic role of immunosuppressive regimens. Thirty patients experienced cutaneous side effects from immunosuppressants, mainly when receiving corticosteroids (p = 0.0372). We identified 99 patients (35.1%) who developed cutaneous tumours after transplantation. Cumulative tumour incidence was observed during long-term immunosuppressive therapy; no relationships were identified between skin cancer risk and single class of drug or combination regimens. When we evaluated the eventual relevance of other risk factors for skin cancers, we demonstrated a statistical significance in univariate analysis for male gender, more advanced age at transplantation, long duration of immunosuppressive regimens, no sunscreen usage, outdoor job, absence of cherry angiomas and presence of actinic keratoses (AKs). Age at transplantation (p = 0.0174), presence of AKs (p = 0.0005) and duration of immunosuppression (p = 0.0011) also confirmed their significance in multivariate analysis.