Effectiveness of guselkumab in patients with facial and/or genital psoriasis: Interim analysis results at Week 12 from the GULLIVER study.

BACKGROUND: Facial (FP) and genital psoriasis (GP) significantly affect patients' quality of life. Despite the advances in treatments, limited data on efficacy and safety are available on these difficult-to-treat areas. Guselkumab is an interleukin (IL)-23 inhibitor which has been proven effective in treating patients with moderate-to-severe plaque psoriasis. OBJECTIVES: The aim of this interim analysis was to report the efficacy and safety of guselkumab in the treatment of patients with FP and/or GP. MATERIALS AND METHODS: GULLIVER is a 52-week Italian observational study to evaluate the effectiveness and safety of guselkumab in a real-life setting in patients with FP and/or GP. Adult patients with facial and/or genital moderate-to-severe psoriasis (sPGA score ≥ 3) were included. The primary endpoint of this analysis was the percentage of patients achieving a facial or genital sPGA score of 0 (clear) or 1 (almost clear), at Week 12. The change in the score of the facial or genital sPGA components in patients with a score ≥3 for each sPGA component was assessed. PASI score in patients with a baseline PASI above or below 10 was evaluated. RESULTS: Overall, 351 patients were included in the study; 83.3% of FP and 76.5% of GP patients achieved the primary endpoint. Similar response rates were observed for the facial or genital sPGA components in patients with a baseline facial or genital sPGA score ≥3 in each component. Among patients with a baseline PASI score >10, mean PASI score improved from 19.0 (SD 8.3) to 2.2 (SD 4.8). Forty-four AEs were observed in 32 patients; two mild and transient AEs (fatigue and nausea) were considered treatment related. No SAEs were observed. CONCLUSIONS: Guselkumab, showing to be effective and safe in treating FP and GP, may be a valid therapeutic option for patients with psoriasis localized in these difficult-to-treat areas.

Drug survival, effectiveness and safety of ixekizumab for moderate-to-severe psoriasis up to 5 years.

INTRODUCTION: Ixekizumab proved to be effective and safe for psoriasis treatment in several randomized clinical trials and real-life studies. Nevertheless, long-term real-world experiences are still lacking, with little data up to 4 years of treatment. OBJECTIVES: To analyse survival, effectiveness and safety of ixekizumab in a real-life cohort of patients affected by moderate-to-severe psoriasis or psoriatic arthritis up to 260 weeks (5 years). METHODS: We included all patients treated with ixekizumab from December 2017 to March 2021. Drug survival (DS) was analysed in patients at risk for up to 5 years. Cox analysis was adopted to evaluate possible predictive factors of discontinuation. Psoriasis Area Severity Index (meanPASI and PASI100, 90, and ≤3) was used as outcomes of effectiveness on observed patients at 16, 52, 104, 156, 208 and 260 weeks. Logistic regression was performed to identify possible predictive factors of response. RESULTS: DS was 65.5% at 260 weeks, with being a super-responder patient (achievement of PASI100 at 16 weeks and maintained at 28 weeks) correlated with less risk of discontinuation. PASI100, 90 and ≤3 was achieved by 54.1%, 60.5% and 73% of observed patients, respectively, at 16 weeks, and by 59.1%, 81.8% and 95.5%, respectively, at 260 weeks. High mean BMI was the only factor strongly associated with less achievement of the outcomes at the earlier time points: PASI100 at 16 weeks (OR 0.93, CI 0.87-0.98, p = 0.014) and at 104 weeks (OR 0.91, CI 0.84-0.98, p = 0.019), PASI90 achievement at 16 weeks (OR 0.94, CI 0.88-0.99, p = 0.028) and 104 weeks (OR 0.91, CI 0.83-0.99, p = 0.027), and PASI ≤3 (OR 0.86, CI 0.76-0.97, p = 0.018) at 104 weeks. No severe adverse events were observed. CONCLUSIONS: Ixekizumab showed high effectiveness and safety for up to 5 years, with survival of 2/3 of treated patients. Rapid response to treatment is predictive of long-term response.

Efficacy of anti-IL-23 and anti-IL-17 after adalimumab failure in psoriatic patients.

BACKGROUND: Many national guidelines at the European level recommend first-line therapy based on the anti-TNF-alpha adalimumab for treatment of psoriasis and psoriatic arthritis, mainly for economic reasons. Consequently, patients being treated with newer IL-17 and IL-23 inhibitors underwent previous unsuccessful first-line adalimumab-based therapy. OBJECTIVES: Evaluate the efficacy and safety of IL-17 and IL-23 inhibitors after treatment with adalimumab compared to adalimumab-naive psoriatic patients. METHODS: We retrospectively analysed 1053 psoriatic patients treated with anti-IL17 and anti-IL23 agents, which included 68 and 24 adalimumab-experienced and 399 and 260 bio-naive patients. Efficacy was assessed with mean PASI, PASI90, PASI100, and <3. RESULTS: Concerning the achieving of PASI100, PASI90 and PASI < 3 in patients treated with anti-IL17 agents, no significant differences were observed between adalimumab-experienced and bio-naive patients. In patients treated with an anti-IL-23 agent, a faster response was observed in bio-naive patients, with PASI < 3 significantly higher than ADA-experienced patients at 16 weeks (77% vs. 58% p = 0.048). In a sub-analysis that evaluated the performance of anti-IL17 and anti-IL23 agents in adalimumab-experienced patients with a history of secondary failure, no significant differences were found. In multivariate analysis of PASI100, only anti-IL-17 therapy appeared to have a negative impact at 52 weeks (OR: 0.54 p = 0.04) independently of previous treatment. For PASI90, type of treatment and bio-naïve status did not seem to have an impact at any time point. CONCLUSIONS: Anti-IL 23 and anti-IL 17 agents are not significantly different in terms of efficacy in bio-naive patients or as second-line therapy after failure with a biosimilar or originator adalimumab.

Real-life experience with ixekizumab in plaque psoriasis: a multi-center, retrospective, 3-year study.

BACKGROUND: Confirmatory data on the long-term effectiveness and safety of ixekizumab in psoriatic patients from real-world studies are needed. OBJECTIVES: The primary aim was to evaluate the 3-year drug survival of ixekizumab in the treatment of patients with moderate-to-severe plaque psoriasis, in a multicenter real-world setting. The secondary aim was to assess the influence of predictive factors on the drug survival of ixekizumab. METHODS: A retrospective analysis was performed on a cohort of patients with chronic plaque psoriasis, who received at least one dose of ixekizumab before December 2018. The drug survival analysis was performed and descriptively analyzed using Kaplan-Meier survival curves. Multivariable Cox regression analyses were carried out including variables considered to be of clinical importance. RESULTS: A total of 306 patients were enrolled. The overall drug survival at 12, 24, and 36 months of treatment with ixekizumab was 92.11%, 83.85%, and 80.19%, respectively. A higher probability (HR 2.34) of drug withdrawal was found among patients who had already received an anti-IL-17 agent compared with bio-naive patients (p 0.017). CONCLUSIONS: We found that ixekizumab is a biological agent characterized by long-term effectiveness, not influenced by several clinical factors and associated with a good safety profile.

Brodalumab for the treatment of moderate-to-severe plaque-type psoriasis: a real-life, retrospective 24-week experience.

BACKGROUND: Brodalumab was efficacious and safe in moderate-to-severe plaque-type psoriasis in the AMAGINE trials; published reports under real-life conditions are limited. OBJECTIVES: To evaluate the effectiveness and safety of brodalumab in patients with moderate-to-severe plaque-type psoriasis in a real-world setting. METHODS: This observational, retrospective study enrolled adult patients (≥18 years) with moderate-to-severe plaque-type psoriasis who underwent 24 weeks of treatment with brodalumab at 17 Italian dermatological centres. Baseline data included demographics, comorbidities, age of onset and duration of psoriasis and previous treatments. Psoriasis Area and Severity Index (PASI), Physician Global Assessment (PGA), static PGA of Genitalia, Dermatology Life Quality Index and patient satisfaction were assessed at weeks 0, 4, 12 and 24; adverse events were recorded. RESULTS: Seventy-eight patients (mean age 47.9 years, 71.8% male, average disease duration 16.8 years) were enrolled. A rapid and significant reduction in mean PASI score was observed after 4 weeks of treatment, decreasing further at weeks 12 and 24 (all P < 0.0001 vs. baseline). A higher number of cardiometabolic comorbidities and previous therapies were negatively associated with the achievement of PASI 90 at all assessments. Brodalumab was effective in bio-experienced patients, including those who had failed on anti-interleukin (IL)-17 therapies. Quality of life and patient satisfaction increased significantly during treatment (P < 0.0001 and P < 0.01 vs. baseline, respectively). Treatment was interrupted in 9 (11.5%) patients due to adverse events (n = 4), lack of efficacy (n = 3), lost to follow-up (n = 1) and surgical procedure (n = 1). CONCLUSIONS: Brodalumab is effective and safe in the treatment of moderate-to-severe psoriasis in a real-world setting, including in patients with failure to anti-IL17 therapies.

Evidence for a 'window of opportunity' in hidradenitis suppurativa treated with adalimumab: a retrospective, real-life multicentre cohort study.

BACKGROUND: The anti-tumour necrosis factor (TNF)-α adalimumab is the only licenced biologic for moderate-to-severe hidradenitis suppurativa (HS). No predictors of response have been identified so far. OBJECTIVES: To identify clinical parameters predicting response to adalimumab and confirm its efficacy/safety. METHODS: The data of 389 patients with HS treated with adalimumab in 21 Italian centres were reviewed. Sex, age at onset/diagnosis/baseline, body mass index, smoking, phenotype, previous treatments, concomitant antibiotics and 'therapeutic delay', defined as the time from HS onset to adalimumab initiation, were assessed. Response to adalimumab and its impact on quality of life (QoL) were evaluated using the Hidradenitis Suppurativa Clinical Response (HiSCR) and the Dermatology Life Quality Index (DLQI) or the Visual Analogue Scale for pain (VAS pain), respectively. Logistic regression analysis was performed. RESULTS: The therapeutic delay correlated to lack of response to adalimumab at week 16 [odds ratio (OR) 1·92 for therapeutic delay > 10 years; 95% confidence interval (CI) 1·28-2·89; P = 0·0016). HiSCR was achieved in 43·7% and 53·9% patients at week 16 and 52, respectively. Significant reductions in both DLQI and VAS pain were found between week 16 vs. baseline (P < 0·0001 for both) and week 52 vs. baseline (P < 0·0001 for both). Previous immunosuppressants inversely correlated to HiSCR at week 52 (OR = 1·74, 95% CI 1·04-2·91, P = 0·0342). CONCLUSIONS: Inverse correlation between therapeutic delay and clinical response was found, supporting early adalimumab use and providing evidence for a 'window of opportunity' in HS treatment. Adalimumab efficacy and safety were confirmed, along with patients' QoL improvement. Immunosuppressants could negatively influence the response to adalimumab inducing a switch to non-TNF-α-driven pathways.

Creation of a severity index for hidradenitis suppurativa that includes a validated quality-of-life measure: the HIDRAscore.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, debilitating disease with a considerable effect on patient quality of life. Its clinical severity can be measured using different scoring systems; however, few of them include patient-centred parameters. OBJECTIVE: To create a new scoring system for HS that includes a quality-of-life instrument, the HIDRAdisk. METHODS: This post hoc analysis was carried out within the framework of a multicentre, longitudinal, epidemiologic study conducted over 9 months on quality-of-life aspects of HS. The new severity score was created using as reference a question from the Subject Satisfaction Questionnaire (SSQ) concerning the severity of HS as evaluated by the patient. Associated variables were selected using univariable and multivariable logistic regression models. The discriminant capabilities of the final model and of the final score were evaluated by the area under the receiver operating characteristic curve and the Hosmer-Lemeshow test. RESULTS: The study population included 308 patients with HS of any severity grade. According to the results of the regression models, the variables associated with the reference SSQ measure were number of inflammatory nodules, abscesses and draining fistulas; the HIDRAdisk score; and the number of subumbilical lesions. The HIDRAscore is obtained by the sum of the scores associated with the number of these parameters. Possible scores range from 0 to 10. CONCLUSION: The HIDRAscore is a new scoring system for HS severity which, in addition to the clinical evaluation by the physician, includes a validated patient-reported outcome measure, the HIDRAdisk.