Dupilumab-associated inflammatory arthritis: a literature review.

Dupilumab is a fully human monoclonal antibody that acts by inhibiting the interleukin (IL)-4 receptor subunit α, and hence the IL-4 and IL-13 signalling pathway. Dupilumab treatment has been linked to the onset of T helper 17-driven inflammatory diseases, including cases of seronegative arthritis and enthesitis. To date, dupilumab-associated inflammatory arthritis (DAIA) represents a relatively unknown adverse event, initially reported in single cases or case series reports. Indeed, the onset of DAIA may not be promptly recognized, and is probably underestimated. Here we have reviewed the available English literature regarding arthritis and enthesitis onset during dupilumab treatment for atopic dermatitis, aiming to improve rapid recognition and thus prompt treatment of these diseases.

Efficacy and Safety of bimekizumab in psoriasis management in real-life: bio-naïve vs bio-experienced.

Bimekizumab is the latest monoclonal antibody approved for the management of moderate-to-severe plaque psoriasis. Currently, data investigating its use in real-life setting are limited. Therefore, we performed a short term [(16 weeks (W)] real-life, monocentric, prospective study aiming to assess the efficacy and safety of bimekizumab, also comparing bio-naïve vs bio-experienced patients. Globally, 56 patients were included. At baseline, mean PASI and DLQI were 16.9±7.8 and 22.6±5.9, respectively. PASI75/90/100 were reached by 76.8%/50.0%/42.9% of patients at W4 and by 92.9%/82.1%/69.6% of subjects at W16. In our cohort, 29 (51.8%) patients were bio-naïve whereas 27 (48.2%) bio-experienced. At baseline, both PASI and DLQI were significantly higher in bio-naïve cohort as compared with bio-experienced group (PASI: 19.4±7.7 vs 14.2±7.0, p<0.05; DLQI: 25.3±4.5 vs 19.7±6.0, p<0.001). Despite not significant, a higher percentage of patients in bio-naïve cohort as compared with bio-experienced group reached PASI75 (79.3% vs 63.0%, p=0.176), PASI90 (62.1% vs 44.4%, p=0.186) and PASI100 (48.3% vs 37.0%, p=0.396) at W4. However, the percentage of PASI75/90/100 response were similar between the two cohorts at W16. Regarding safety, 3 candidiasis (5.4%) and 1 (1.8%) eczematous reaction were reported, without differences between the two groups. Finally, 2 (3.6%) bimekizumab discontinuation for treatment failure and 3 (5.4%) for AEs were collected.

Hidradenitis Suppurativa and JAK Inhibitors: A Review of the Published Literature.

Background: Hidradenitis suppurativa (HS), also known as acne inversa or Verneuil's disease, is a chronic, inflammatory, recurrent, and debilitating skin disease of the hair follicles characterized by inflammatory, painful, deep-rooted lesions in the areas of the body characterized by the presence of the apocrine glands. Unfortunately, huge unmet needs still remain for its treatment. Objective: The purpose of our review was collecting all cases, case series, trials, and ongoing studies available in the literature on the use of this class of drugs for HS. Materials and Methods: The investigated manuscripts included trials, reviews, letters to the editor, real-life studies, case series, and reports. Manuscripts were identified, screened, and extracted for the relevant data following the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. Results: We selected 56 articles of which 25 met the selection criteria for our review. Among the JAK inhibitors to date, there is only one published clinical trial in the literature (Janus kinase 1 inhibitor INCB054707), a real-life study with 15 patients up to week 24 in which upadacitinib was used and a case series where tofacitinib was successfully used. Conversely, there are several ongoing clinical trials. Conclusions: Results to date in the literature show promising levels of efficacy and the safety of JAK inhibitors in HS. Several clinical trials are underway from which it will be very important to compare the available data. There are still too few studies conducted with a low sample size, so it remains critical to investigate this issue further in the future with a real-life study involving a large sample of patients in order to provide safe and viable therapeutic alternatives for HS.

Real world practice indirect comparison between guselkumab and risankizumab: Results from an Italian retrospective study.

IL-23-inhibitors, such as guselkumab and risankizumab, represent the newest class of biologics approved for psoriasis. Phase III trials have shown their efficacy and safety. However, real life data are still scant. to indirectly compare the effectiveness, safety and tolerability of guselkumab and risankizumab in real world practice. An Italian single-center retrospective cohort study enrolling moderate-to-severe psoriasis patients from September 1, 2018 and December 31, 2020 was performed to indirectly compare guselkumab and risankizumab efficacy and safety. Sixty eight patients were included (36 received guselkumab and 32 risankizumab). The groups were comparable for all analyzed characteristics, except for mean psoriasis duration (p < 0.01) which was higher for guselkumab. In guselkumab group, mean PASI reduced from 16.1 ± 6.4 (baseline) 2.1 ± 0.9 (week-28) (p < 0.001) up to 0.9 ± 0.8 (week-44) (p < 0.001). In risankizumab group mean PASI decreased from 13.5 ± 4.9 (baseline) 1.9 ± 0.8 (p < 0.001), (week-28) (p < 0.001) up to 0.9 ± 0.4 (week-40) (p < 0.001). No significant difference in mean PASI and BSA were observed between the treatments. No cases of serious AEs, injection site reaction, candida, malignancy, cardiovascular events were reported in both groups. Guselkumab and risankizumab showed favorable efficacy and safety profile, being comparable in terms of PASI90 and PASI100 responses as well as in AEs frequency and discontinuation rates.

Risankizumab treatment in psoriasis patients who failed anti-IL17: A 52-week real-life study.

Recent knowledge on the key role of interleukin (IL) 23/17 axis in psoriasis pathogenesis, led to development of new biologic drugs. Risankizumab is a humanized immunoglobulin G1 monoclonal antibody specifically targeting IL23. Its efficacy and safety were showed by both clinical trials and real-life experiences. However, real-life data on effectiveness and safety of risankizumab in patients who previously failed anti-IL17 are scant. To assess the efficacy and safety of risankizumab in patients who previously failed anti-IL17. A 52-week real-life retrospective study was performed to assess the long-term efficacy and safety of risankizumab in patients who previously failed anti-IL17. A total of 39 patients (26 male, 66.7%; mean age 50.5 ± 13.7 years) were enrolled. A statistically significant reduction of psoriasis area severity index (PASI) and body surface area (BSA) was assessed at each follow-up (PASI at baseline vs. week 52: 13.7 ± 5.8 vs. 0.9 ± 0.8, p < 0.0001; BSA 21.9 ± 14.6 vs. 1.9 ± 1.7, p < 0.0001). Nail psoriasis severity index improved as well, being statistically significative only at week 16 and thereafter [9.3 ± 4.7 at baseline, 4.1 ± 2.4 (p < 0.01) at week 16, 1.4 ± 0.8 (p < 0.0001) at week 52]. Treatment was discontinued for primary and secondary inefficacy in 1(2.6%) and 3(7.7%) patients, respectively. No cases of serious adverse events were assessed. Our real-life study confirmed the efficacy and safety of risankizumab, suggesting it as a valuable therapeutic weapon among the armamentarium of biologics, also in psoriasis patients who previously failed anti-IL17 treatments.

Ixekizumab and brodalumab indirect comparison in the treatment of moderate to severe psoriasis: Results from an Italian single-center retrospective study in a real-life setting.

Eleven biologic drugs are currently approved for psoriasis management. Real-life studies are needed to guide clinicians in choosing a tailored-tail therapy. The aim of our retrospective study is to indirectly compare the efficacy and safety of ixekizumab and brodalumab in psoriasis patients. A single-centre real-life retrospective study was performed enrolling moderate-to-severe psoriatic patients under biologic treatment with ixekizumab or brodalumab. For each patient, clinical and demographic data were collected and the effectiveness and safety of brodalumab and ixekizumab treatment were evaluated at weeks 4, 12, and 24. Psoriasis Area Severity Index (PASI) and Body Surface Area (BSA) were used for psoriasis severity. A total of 139 patients were included in the study: 98(70.5%) and 41(29.5%) patients received ixekizumab and brodalumab, respectively. Mean PASI and BSA significantly reduced at each follow up for both ixekizumab and brodalumab groups. Even if ixekizumab reached higher rates of PASI90 and PASI100 than brodalumab (PASI90: 43.8% vs. 39.0% PASI100: 20.4% vs. 17.1% at week4 and PASI90: 83.6% vs. 75.6% PASI100: 71.5% vs. 60.9% at week24), these results were not statistically significant. Adverse events, mainly mild, were registered in 25.5% of ixekizumab and 26.8% of brodalumab group, respectively. Discontinuation rate was higher for brodalumab (17.1% vs. 9.1%), without statistical significance. Our study showed comparable efficacy and safety for ixekizumab and brodalumab.

Eczematous drug eruption in patients with psoriasis under anti-interleukin-17A: does interleukin-22 play a key role?

BACKGROUND: Eczematous drug eruption (EDE) is a spongiotic skin reaction in response to systemic medications. To date, EDE has been described in patients treated with anti-interleukin (IL)-17A monoclonal antibodies with a prevalence of 2.2%-12.1%. AIM: To describe the clinical and histological features and the skin cytokine milieu in patients with EDE induced by anti-IL-17A biologics. METHODS: This was a prospective study, enrolling patients with psoriasis who developed EDE during treatment with two anti-IL-17 biologics, ixekizumab and secukinumab, from June 2019 to April 2021. Skin biopsies were taken from all patients: a 5-mm lesional biopsy (LB) and a 3-mm nonlesional biopsy (NLB). The LB sample was split into two parts, one for histological examination and the other for cytokine profile evaluation. RESULTS: During the study period, treatment with an anti-IL-17A drug was given to 289 patients of whom 8 (2.8%) developed EDE during the treatment. Histopathological evaluation suggested a diagnosis of spongiotic dermatitis in all eight patients. Cytokine gene expression showed a predominance of T helper (Th)2/Th22 cytokines in EDE lesions with a large increase in IL-4, IL-22 and S100A7 levels in both LB and NLB samples compared with healthy skin. IL-4, IL-22 and S100A7 were significantly higher in LB compared with NLB samples. IL-26 levels were also significantly increased in both LB and NLB compared with healthy skin, whereas low levels of IL-23A were found in both LB and NLB. CONCLUSION: Eczematous drug eruption skin lesions have mainly Th2/Th22 features, with IL-22 playing a major role in their pathogenesis. EDE seems to be the result of an imbalance towards a Th2/Th22 response, secondary to the blockade of IL-17A activity.

Efficacy and safety of guselkumab in psoriasis patients who failed ustekinumab and/or anti-interleukin-17 treatment: A real-life 52-week retrospective study.

Recent major research advancements have significantly expanded our understanding of psoriasis pathophysiology, resulting in the development of highly effective, targeted therapies. Guselkumab is the first interleukin (IL)-23 inhibitor approved for the treatment of moderate-to-severe-psoriasis, providing a new therapeutical option for psoriasis. The aim of our study was to evaluate the efficacy of guselkumab in psoriatic patients who previously failed anti-IL-12/23 and/or anti-IL-17 treatment. A 52-week single-center retrospective study was performed enrolling moderate-to-severe patients attending our Psoriasis Care Center from October 2018 to May 2020. Study population included 13 patients; 46.1% have been previously treated with ustekinumab, while 69.2% have previously failed an anti-IL-17 treatment (38.5% secukinumab, 30.8% ixekizumab, and 38.5% both). At baseline, mean Psoriasis Area and Severity Index was 13.2 ± 6.8, reducing up to 0.5 ± 0.7 at week 52 (P < .001). Body surface area reduced from 22.3 ± 10.5 (baseline) to 0.8 ± 1.1 at week 52 (P < .001). No statistically significant differences have been found between patients previously treated with anti-IL-12/23 compared to anti-IL-17 or both. Only one patient discontinued guselkumab at week 36 due to secondary inefficacy. This is a single institution study with a relatively small sample size. Our real-life data confirm trial results, showing guselkumab as a safe and effective option in patients with moderate-to-severe psoriasis even in those who previously failed ustekinumab and/or anti-IL-17 treatment.

New emergent therapies for atopic dermatitis: A review of safety profile with respect to female fertility, pregnancy, and breastfeeding.

Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease. Systemic treatment is usually mandatory in moderate-to-severe AD of the adult; these patients need to be informed about safe and effective management of AD also regarding the reproduction. Treating a pregnant woman with AD with systemic drugs may affect the unborn child. While effects of traditional systemic treatments for AD on female fertility, pregnancy, and breastfeeding are largely known, data about new emergent therapies for AD are still poor. Treating pregnant or lactating women with AD can be a challenge since no large clinical studies on its possible effects and side-effects on conception, pregnancy, the unborn child and lactation are currently available for new AD treatments.

Community Knowledge About the Use, Reuse, Disinfection and Disposal of Masks and Filtering Facepiece Respirators: Results of a Study Conducted in a Dermatology Clinic at the University of Naples in Italy.

In Italy, as well as in almost all countries, the use of masks in public with several other measures has been an important health measure during the ongoing COVID-19 pandemic. The correct use of masks is essential, as a wrong use and disposal may increase the rate of contagious. Herein, we report a descriptive study evaluating the knowledge and use, reuse and disposal of masks in community settings. An anonymous questionnaire called MaSK (Mask uSe and Knowledge) questionnaire was developed and offered to patients referring at our dermatologic outpatient clinic. A total of 2562 full complete patients' questionnaires were considered for the study. Our results showed that awareness and information campaigns aimed at the general population are urgently needed in order to implement a correct use of masks and limit as much as possible the infection rate.

Low dose oral corticosteroids, microneedling, and topical 5-fluorouracil: A novel treatment for recalcitrant pediatric vitiligo.

A 10-year-old boy was referred to our outpatient clinic with a 2-year history of vitiligo minimally responsive to topical corticosteroids and phototherapy. Low dose oral corticosteroids were prescribed in combination with sessions of microneedling and 5-fluourouracil 5% cream applied immediately after needling on a monthly basis. Repigmentation was initially noted after the first cycle at week 4. After 3 sessions of treatment (week 16), the patient showed a complete repigmentation of the knees.

Efficacy and safety of risankizumab in psoriasis patients who failed anti-IL-17, anti-12/23 and/or anti IL-23: Preliminary data of a real-life 16-week retrospective study.

Up until now, real-life experiences on the efficacy of risankizumab in patients who had previously failed anti-IL17, anti-IL12/23 or anti-IL23 inhibitor are not reported. We carried out a single-center, retrospective study, to evaluate the efficacy, safety and tolerability of patients under risankizumab who previously failed anti-IL17, anti-IL12/23, or anti-IL23 inhibitors in a real-life setting. A total of eight patients were enrolled (four men and four women, mean age 45.8 ± 14.3 years). Five of them (62.5%) had received ustekinumab, seven (87.5%) at least one anti-IL17, and only one (12.5%) patient guselkumab. Secukinumab had been used in five (62.5%) cases, and ixekizumab in four (50.0%). Baseline mean PASI and BSA were 11.9 ± 5.5, and 22.9 ± 13.1, respectively, and 3.3 ± 1.7 and 7.5 ± 5 (P < .001 and P < .01) at week 16. Mean baseline NAPSI (18.0 ± 8.5) reduced to 7 ± 1.4 at week 16. Palmo-plantar and scalp area showed a reduction of 67.5% and 99.9% at week 16, respectively. No AEs was reported. Real-life preliminary data show risankizumab as a promising therapeutic option in patients who failed anti-IL-17, anti-IL12/23 and even the other anti-IL-23 counterpart, guselkumab.

A case of erythrodermic psoriasis successfully treated with guselkumab.

Erythrodermic psoriasis (EP) is the most severe form of psoriasis, resulting in significant morbidity and mortality. EP treatment with biologics is not well ruled by international guidelines, so most biological drugs are used basing on case reports or small case series. Guselkumab, a fully human anti-interleukin (IL)-23 monoclonal antibody, is approved for moderate to severe plaque psoriasis while its use in EP is off label. To date, no case reports on Caucasian patients have been described in the literature. We report the case of 38-year-old Caucasian male with EP successfully treated with guselkumab, reaching PASI 100 after 20 weeks of therapy and still maintaining this response at Week 48. Our case report suggests guselkumab as an efficacious and well-tolerated treatment in EP, presenting a long-term efficacy in the prevention of recurrences. Further studies are warrant to confirm our data, with controlled trials specifically dedicated to EP being strictly needed in order to verify the role and efficacy of anti-IL23 in EP.