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.

Guselkumab shows high efficacy and maintenance in the improvement of response until week 48, a real-life study.

Guselkumab is an IL-23 inhibitor that has been demonstrated to be effective and safe for the treatment of moderate-to-severe plaque psoriasis in clinical trials. The data pool relating to the use of guselkumab in a real-life setting is still lacking. To evaluate the efficacy and safety of guselkumab in a real-life setting, focusing on predictors of early clinical response, a single-center prospective study was conducted enrolling patients with moderate-to-severe psoriasis. The clinical data relating to the efficacy and safety of the drug were acquired at initiation of treatment and at all subsequent clinical follow-ups: the primary endpoint was PASI90 and PASI100 response at week 12, 24, and 48. Out of the total cohort of 74 patients, 62 (83.8) reached a 48-week follow-up 64 (87.8%) reached a 24-week follow-up, while 72 (97.3%) a 12-week follow-up. Treatment with guselkumab reduced the mean PASI from the initial 11 ± 6.3 to 2.5 ± 3.1 at 12 weeks, to 1.2 ± 1.8 at 24 weeks, and to 0.8 ± 1.6 at 48 weeks. At week 12, a PASI 90 and PASI 100 response was achieved by 44.4% and 23.6% of patients, respectively. After 24 weeks, 63% of patients reported a PASI 90 while 46.1% achieved PASI 100. Previous treatment with one or more other biologics did not impact significantly on the achievement of the PASI 90 and 100 at any endpoints analyzed. We reported no difference between bio-naïve and non-naïve patients in the response to guselkumab, high safety, and efficacy was showed in both populations.

Risankizumab shows high efficacy and maintenance in improvement of response until week 52.

Risankizumab has been recently approved for moderate-to-severe plaque psoriasis; however, real-life studies are scarce. Analysis of possible predictor factors of treatment response are limited to body mass index (BMI) and previous biologic experience. Our objectives were to evaluate the effectiveness and safety of Risankizumab and to investigate on possible predictor factors response. We retrospectively analyzed 166 patients from two centers in Italy who undergone Risankizumab for psoriasis. The proportion of patients achieving a 100%, 90%, 75% of improvement in Psoriasis Area Severity Index (PASI) and PASI <3 were collected at weeks 16, 28, 40, and 52. Study population was analyzed in subgroups to investigate possible predictors of response to Risankizumab since week 40. At the time of analysis 165, 103, 30, and 11 patients had completed 16, 28, 40, and 52 weeks of treatment, respectively. The mean PASI score decreased from 12.5 ± 5.1 at baseline to 1.9 ± 2.4 at week 16. Similar reductions were observed when considering PASI <3, PASI 75, PASI 90, and PASI 100. Previous biologics failure, different smoking habits, obesity, and joint involvement resulted in a lower response to risankizumab. In particular, significant differences in mean PASI at any time-points was observed between psoriatic arthritis (PSA) and non-PSA patients: 2.7 versus 1.7 (p = 0.036), 1.9 versus 0.4 (p = 0.006), and 4.1 versus 0.5 (p = 0.016) at 16, 28, and 40 weeks, respectively. No difference in response to risankizumab occurred in the case of involvement of difficult-to-treat areas. In this population, Risankizumab was effective and safe. Smoking habits, joint involvement, obese status, and previous biologic experience may negatively affect treatment response, while difficult body sites involvement have minor impact.

Dupilumab in HIV-positive patients with atopic dermatitis: a long-term follow-up patient and a literature review.

Dupilumab is an IgG4 human monoclonal antibody licensed for the treatment of moderate-to-severe atopic dermatitis. Despite evidence suggesting that T helper type two cytokines can modulate HIV-1 replication and anti-HIV-specific immune responses, impacting on viral reservoirs, HIV-positive patients under immunomodulating therapy have been excluded from clinical trials. We report a 47-year-old HIV-positive man with late-onset severe atopic dermatitis, treated with dupilumab and followed up for 27 months. Improvements in skin lesions and quality of life were observed after four months. Blood tests showed normalization of IgE levels, with the clinical condition remaining stable at a 27- month follow-up. We gathered 16 other cases reported in the literature of HIV-positive patients treated with dupilumab, with no, or few adverse reactions, for which it is unclear if dupilumab should be held accountable. With our case and literature review, we aim to shed light on dupilumab efficacy, safety, and tolerability among HIV-positive patients suffering from atopic dermatitis. In this regard, future research should focus on the effective role, underlying mechanisms, and efficacy of dupilumab in HIV-positive patients and HIV-positivity could be questioned as a valid exclusion criterion for clinical trials.

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.

Misuse, consequences and phototoxic skin-related effects of Rutaceae.

Ruta is a common plant growing in Italy and in the Mediterranean area. It has been used in popular tradition with different aims, ranging from therapeutic to esoteric purposes. However, the plant is still used as a common remedy in some of present-day rural and urban communities and it can be found in gardens all over Europe. Ruta's photosensitizing effect has been described in the literature and seems to be mediated by furanocoumarins. We collected data from the 18 case-reports for a total of 32 patients that we included in our analysis, assessing demographic variables, clinical findings, diagnosis, time of onset of lesions, time of resolution and therapy. The main aim of this work was to outline the clinical presentation, therapeutic management and demography of phytophototoxic reactions from contact with Ruta in order to suggest the correct diagnostic approach and disease recognition, as well as its possible prevention.

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.