Assessing Prevalence and Characteristics of Oro-bulbar Involvement in Children and Adults with SMA Type 2 and 3 Using a Multimodal Approach.

Bulbar and jaw muscles are impaired in patients with Spinal Muscular Atrophy (SMA) but the assessment of their severity and progression are limited by the lack of age-appropriate and disease-specific measures. We investigated mastication and swallowing in children and adults with SMA, sitters and walkers. In a 2-year multicentre cross-sectional prospective study, lip and tongue strength (Iowa Oral Performance Instrument), chewing and swallowing (Test of Masticating and Swallowing Solids), active mouth opening (aMMO) were compared to age-appropriate normative data. The perceived burden of oro-bulbar involvement (SMA-Health Index) was recorded. 78 patients were included, 45 children (median age 7.4 years),22 adults (median age 26.8 years) on nusinersen and 11 untreated (median age 32.7 years). Forty-three percent children had reduced mouth opening, 50% had prolonged total time to eat. These issues were more prominent in sitters than in walkers (p = 0.019, p = 0.014). Sixty-six percent needed increased swallows for bolus clearance. Nusinersen treated adults had median aMMO, tongue strength and total time at TOMASS values within normal range (z score: -1.40, -1.22, -1.32, respectively) whereas untreated adults had reduced aMMO (z score: -2.68) and tongue strength (z score: -2.20). Only a minority of children (2/17) and treated adults (5/21) reported burden in swallowing or mastication compared to all untreated adults (5/5). After 16 months, mastication and swallowing were stable in treated children and adults, whether sitters or walkers. The reported multimodal approach to assess oro-bulbar functions demonstrate that swallowing and mastication are impaired in SMA despite patients' perception. These results suggest a trend towards stabilization of oro-bulbar function in patients on long-term treatment with nusinersen.

Secukinumab in the Treatment of Psoriasis: A Narrative Review on Early Treatment and Real-World Evidence.

Psoriasis is a chronic, immune-mediated, inflammatory skin disease, associated with multiple comorbidities and psychological and psychiatric disorders. The quality of life of patients with this disease is severely compromised, especially in moderate-to-severe plaque psoriasis. Secukinumab, a fully humanized monoclonal antibody, was the first anti-interleukin (IL)-17 biologic approved for treating psoriasis. Secukinumab demonstrated long-lasting efficacy and a good safety profile in individuals with plaque psoriasis, and it is associated with an improvement in health-related quality of life. While there is evidence that early treatment with systemic therapy can affect disease progression and improve long-term outcomes in other autoimmune diseases, evidence is limited in psoriasis, especially in real-world settings. This review provides an overview of studies describing the effectiveness of secukinumab in the treatment of psoriasis summarizing the literature and focusing on real-world evidence and early intervention.

Effectiveness and Safety After a Switch to Tildrakizumab: A Real World Multicenter Italian Study in Psoriasis.

INTRODUCTION: Tildrakizumab is a humanized IgG1κ monoclonal antibody targeting the p19 subunit of interleukin (IL)-23, approved in 2018 for the treatment of patients with moderate-to-severe chronic plaque psoriasis. OBJECTIVES: This study aimed to evaluate the effectiveness, safety and survival of tildrakizumab in the medium term (48 weeks) in psoriatic patients failure to previous biologic treatment in a real world setting. METHODS: This was a retrospective, multicenter observational study that included adult patients with moderate-to-severe plaque psoriasis, failure to previous biologic therapy, consecutively treated with tildrakizumab. Psoriasis Area Severity Index (PASI) and Body Surface Area (BSA) values were recorded at baseline, at 12 and 48 weeks of treatment. Safety and tolerability of tildrakizumab were investigated by examining the presence of any adverse events. RESULTS: Overall 51 patients were enrolled. Baseline disease severity was moderate to severe with a mean PASI score of 19.2 ± 8.5, mean BSA of 16 ± 10.4, and mean Dermatology Life Quality Index (DLQI) of 18.2 ± 6.8. A significant reduction in the mean PASI score was detected at 12 weeks of tildrakizumab therapy (3.5 ± 2.7, P < 0.001), with a further improvement at week 48 (0.6 ± 1.5, P < 0.001). At week 12, there was a great improvement in BSA score for all groups (P <0.001) with further increase at week 48. The effectiveness was confirmed also by DLQI assessment, with a significant decrease at week 12 and even more at week 48 (P <0.001). CONCLUSIONS: This study confirms the effectiveness of tildrakizumab in daily clinical practice in patients with moderate-to-severe plaque psoriasis.

Long-term efficacy and safety of secukinumab in real life: a 240 weeks multicenter study from Southern Italy.

BACKGROUND: Long-term real-life data on secukinumab use in psoriasis are limited. OBJECTIVES: Determine the long-term effectiveness of secukinumab in moderate-to-severe psoriasis in real-life. METHODS: Multicenter retrospective study analyzing data from adult patients treated with secukinumab for at least 192 weeks and up to 240 weeks in Southern Italy, between 2016 and 2021. Clinical data, including concurrent comorbidities and prior treatments were collected. Effectiveness was assessed by Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA), Dermatology Life Quality Index (DLQI) scores at the initiation of secukinumab and at weeks 4, 12, 24, 48, 96, 144, 192, and 240. RESULTS: Two hundred and seventy-five patients (174 males), mean age 50.80 ± 14.78 years, were included; 29.8% had an uncommon localization, 24.4% psoriatic arthritis, 71.6% comorbidities. PASI, BSA, and DLQI improved significantly from week 4 and continued to improve over time. Between weeks 24 and 240, PASI score was mild (≤10) in 97-100% of patients, 83-93% had mild affected BSA (BSA ≤ 3), and 62-90% reported no effect of psoriasis on their quality of life (DLQI 0-1). Only 2.6% of patients reported adverse events and no patient discontinued the treatment during the study period. CONCLUSIONS: Secukinumab effectiveness in the long-term treatment of psoriasis is confirmed in real-world.

Long-term Effectiveness and Safety of Upadacitinib for Atopic Dermatitis in a Real-world Setting: An Interim Analysis Through 48 Weeks of Observation.

BACKGROUND: Janus kinase (JAK) inhibitors, including upadacitinib, have been recently approved for the treatment of moderate-severe atopic dermatitis (AD) and real-world data on upadacitinib effectiveness and safety are limited. This interim analysis aimed to assess effectiveness and safety of upadacitinib throughout 48 weeks of observation in a real-world adult AD population. METHODS: This prospective study collected data on adult patients affected by moderate-to-severe AD and treated with upadacitinib at the dosage of either 15 mg or 30 mg daily based on the physician decision. Upadacitinib was prescribed in the context of a national compassionate use programme. In this interim analysis, within patient comparisons of continuous scores of different scales (namely Eczema Area and Severity Index [EASI], body surface area [BSA], Dermatology Life Quality Index [DLQI], Patient Oriented Eczema Measure [POEM], Numeric Rating Scale [NRS] subtests) were performed. The percentage of patients achieving EASI 75, EASI 90 and EASI 100 at Week 16, 32 and 48 was also evaluated. RESULTS: One hundred and forty-six patients were included in the analysis. Upadacitinib 15 mg or 30 mg daily was prescribed as monotherapy in most cases (127/146, 87.0%). Upadacitinib was initially prescribed at the dosage of 30 mg daily in 118 of 146 (80.8%) patients and 15 mg daily in 28/146 (19.2%) patients. A significant improvement in the clinical signs and symptoms of AD was detected by Week 16 and throughout the study period. EASI 75, EASI 90 and EASI 100 responses were achieved by 87.6%, 69.1% and 44.3% at Week 48, associated with a sustained reduction in the mean values of all physician-reported (EASI and BSA) and patient-reported (Itch- Sleep- and Pain-NRS, DLQI, and POEM) disease severity outcomes, up to 48 weeks of treatment. Treatment response observed in 15 mg upadacitinib-treated patients was comparable with that detected in 30 mg upadacitinib-treated patients, revealing no statistical difference between the two patient sub-cohorts. Through the observation period, dose reduction or escalation was observed in 38/146 (26%) of treated cases. Overall, 26 of 146 (17.8%) patients experienced at least one adverse event (AE) during the treatment period. In total, 29 AEs were recorded and most of them were evaluated as mild to moderate, while in 4 cases the occurrence of AE led to drug discontinuation, for a total of 7/146 (4.8%) dropouts. CONCLUSION: This study provides strong evidence of a sustained response obtained by upadacitinib in AD patients, who had failed to respond to conventional or biological systemic agents, through 48 weeks of observation. Upadacitinib was also demonstrated to be advantageous in terms of flexibility in dose reduction or escalation as upadacitinib dose was shaped on clinical needs that, in a real-world setting, might frequently change.

Effectiveness and Safety of Upadacitinib in the Treatment of Moderate-Severe Atopic Dermatitis: A Multicentric, Prospective, Real-World, Cohort Study.

BACKGROUND: The efficacy and safety of upadacitinib in atopic dermatitis (AD) have been defined in clinical trials, but no real-world data are currently available. We aimed to assess the safety and effectiveness of upadacitinib in a real-world AD patient cohort that mostly included patients who failed the available systemic therapies, including dupilumab. METHODS: Prospective cohort study collecting data on upadacitinib-treated AD adult patients completing at least 16 weeks of therapy. RESULTS: Forty-three patients showed rapid and marked response to upadacitinib with significant reduction of all disease severity scores since the first follow-up visit. At week 16, Eczema Area and Severity Index (EASI) 75, EASI 90, and EASI 100 response was observed in 97.5%, 82.1%, and 69.2% of patients, respectively. EASI 90 response reflected the achievement of a clear or almost clear condition (POEM 0-2), self-evaluated by 79.5% of patients. Patients' quality of life improved as suggested by the achievement of DLQI 0/1 by 38.5% of patients at week 4, and by 76.9% at week 16. CONCLUSION: Elevated effectiveness and favorable safety of upadacitinib were confirmed in patients unresponsive to dupilumab, who were not included in upadacitinib trials.

National Information Campaign Revealed Disease Characteristic and Burden in Adult Patients Suffering from Atopic Dermatitis.

Atopic dermatitis (AD) is a common inflammatory skin disease often associated with a significant impairment in the quality of life of affected patients. The Italian Society of Dermatology and Venereology (SIDeMaST) planned a national information campaign, providing direct access to 27 dermatologic centers dedicated to the management of AD. The aim of this study aimed was to outline critical aspects related to AD in the general population. Overall, 643 adult subjects were included in this study, and in 44.2% (284/643) of cases, a diagnosis of AD was confirmed, whereas about 55% of subjects were affected by other pruritic cutaneous diseases. Higher intensity of pruritus and sleep disturbance, as well as an increased interference in sport, work, and social confidence was reported in the AD group compared to the non-AD group. In the AD subgroup, the mean duration of disease was of 15.3 years, with a mean eczema area and severity index (EASI) score of 11.2, and investigator global assessment (IGA) score of 1.9 and an itch numeric rating scale (NRS) of 6.9. Almost 32% of patients were untreated, either with topical or systemic agents, whereas 44.3% used routine topical compounds (topical corticosteroids and calcineurin inhibitors), and only 7.0% of patients were systemically treated. Only 2.8% of patients reported complete satisfaction with the treatment received for AD to date. This study reveals a profound unmet need in AD, showing a poorly managed and undertreated patient population despite a high reported burden of disease. This suggests the usefulness of information campaigns with the goal of improving patient awareness regarding AD and facilitating early diagnosis and access to dedicated healthcare institutions.

Resolution of post-adalimumab vitiligo with secukinumab in a patient with psoriasis vulgaris.

Plaque psoriasis is a chronic debilitating condition, and biologic agents that inhibit tumor necrosis factor-α (TNF-α) are widely employed in management of the condition. Notwithstanding, several paradoxical adverse reactions have been reported with TNF-α inhibitors, including vasculitis, vitiligo, alopecia areata, sarcoidosis and other granulomatous diseases. Herein, we report the case of a 63-year-old man who developed vitiligo while on therapy with adalimumab following failure of conventional agents for plaque psoriasis. After discontinuation of adalimumab and initiation of secukinumab, vitiligo and other psoriatic symptoms gradually resolved. After 1 year of treatment, only small plaque areas were present in the flexor site with complete remission in the extensor area along with near complete resolution of depigmented areas. In this case of possible adalimumab-induced vitiligo in a patient with plaque psoriasis, secukinumab resolved both the symptoms of psoriasis and the likely adalimumab-related vitiligo.

Posterior Urethral Polyp Treated With Endoscopic Transurethral Resection: The Second Pediatric Case Managed With Holmium Laser.

Fibroepithelial urethral polyp is a rare benign tumor more common in children than adult that can cause bladder outlet obstruction. We describe a 3-year-old boy who presented with intermittent acute urinary retention affected by a fibroepithelial urethral polyp managed with endoscopic transurethral resection by HOLMIUM laser; no complications neither recurrence were observed. To our knowledge this is the second pediatric case of fibroepithelial urethral polyp treated by HOLMIUM laser.