Spesolimab decreases generalized pustular psoriasis (GPP) body surface area (BSA) over time: Results from the EFFISAYIL® 2 trial

Toxic epidermal necrolysis syndrome is an uncommon, acute, life-threatening, medication-induced disorder with a reported mortality rate of 20 to 60 percent. Different variables have been identified as risk factors. The extent to which these variables, when combined, affect the mortality and outcome in toxic epidermal necrolysis syndrome patients has not yet been reliably defined. Because of the high mortality rate, the logistic analysis of studied variables was performed to see whether a prognostic algorithm could be developed to aid the management of these patients. Thus, a retrospective review of 56 consecutive toxic epidermal necrolysis syndrome patients treated over a period of 13 years was undertaken in the authors' burn center. The demographics included age, sex, race, and total body surface area involved. The other variables studied were comorbidities, sepsis, steroid administration, and the interval between onset of rash and burn center admission. Data were subjected to Fisher's exact test and logistic analysis. Thirty-six patients (64.3 percent) were alive and 20 (35.7 percent) died. Univariate analysis indicated that the male/female ratio was 12:24 for survivors and 9:11 for nonsurvivors (p = 0.4). The white/nonwhite ratio was 80 percent for survivors and 54 percent for nonsurvivors (p = 0.58). The median age was 48.4 +/- 22.8 years (survivors, 41.7 +/- 22.0; nonsurvivors, 60.5 +/- 19.5; p = 0.002). Total body surface area involvement for survivors was 56.9 +/- 32 and 77.7 +/- 21 for nonsurvivors (p = 0.005). The presence of one or more comorbidities between the two groups differed (53 percent survivors and 90 percent nonsurvivors, p = 0.007), indicating eight times higher odds of dying in their presence. The average time between the onset of symptoms and admission to the burn unit was 5.25 +/- 3.4 days for survivors and 7.15 +/- 4.5 days for nonsurvivors (p = 0.08). The presence of sepsis (19.4 percent survivors, 95 percent nonsurvivors, p < 0.001) decreased odds for survival by a factor of 79. Steroids given as a single dose or multiple doses before the patient's transfer to the burn unit were not significantly associated with death (44 percent survivors, 65 percent nonsurvivors, p = 0.14). A multivariate logistic regression model yielded odds ratios of 1.11 (95 percent confidence interval, 1.03 to 1.19) for age in years, 304 (95 percent confidence interval, 8.83 to 10,400) for the presence of sepsis, and 1.03 (95 percent confidence interval, 0.99 to 1.08) for body surface area in percent. All those entering the burn unit with sepsis died. Equivalently, no survivors had sepsis before admission to the burn unit, whereas 55 percent of nonsurvivors had sepsis before admission and 40 percent developed sepsis after admission. When investigating the effect of age and sepsis, no patients over age 60 ever having sepsis survived, whereas all those who were under 60 and without sepsis survived. Likewise, all patients whose age was over 60 and whose total body surface area involved was over 60 percent died. The main factors contributing to the mortality from toxic epidermal necrolysis syndrome, when considering covariates separately, are the presence of sepsis at any time (odds ratio, 79), the presence of comorbidities (odds ratio, 8.05), age, and total body surface area, whereas multivariate models suggested age (odds ratio per year of additional age, 1.11), total body surface area (odds ratio per additional percent of body surface area, 1.03), and the presence of sepsis (odds ratio, 304). By using the actual coefficients in the logistic model, the log odds that the patient will die as the result of his or her condition can be summarized in the following formula: -11.5 + (10 percent of the patient's age + 3 percent of total body surface area + 5.75 if sepsis is present). The awareness of the importance of these covariates, and their early recognition as risk factors, should offer a focused approach to the patients' management and improve their outcome.

Introduction &amp; Objectives: Generalized pustular psoriasis (GPP) is a chronic, rare and potentially life-threatening skin disease, characterized by flares of sterile pustules. Spesolimab, an anti-interleukin-36 receptor monoclonal antibody, is an effective and approved treatment for GPP flares in adults. Effisayil 2 (NCT04399837) was a pivotal, randomized controlled trial that evaluated the efficacy and safety of subcutaneous spesolimab in preventing GPP flares. Here, we report the effect of high-dose spesolimab versus placebo on GPP lesions.&#x0D; Materials &amp; Methods: Eligible patients with a history of GPP were randomized (1:1:1:1) to receive one of three subcutaneous spesolimab regimens or placebo for 48 weeks. High-dose spesolimab regimen was loading dose 600 mg, followed by maintenance dose 300 mg every 4 weeks. GPP Physician Global Assessment (GPPGA) subscores for erythema, pustules and scaling/crusting, and total score were compared between high-dose spesolimab and placebo groups at baseline and over the treatment period (scale: 0, clear to 4, severe).&#x0D; Results: Proportion of patients with baseline score of 0 for each GPPGA subscore and total score was generally similar between treatment groups, except erythema; (high-dose spesolimab [n=30] vs placebo [n=31]: erythema, 13.3% vs 22.6%; pustules, 66.7% vs 67.7%; scaling/crusting, 23.3% vs 22.6%; total score, 10.0% vs 12.9%). By Week 4, proportion of patients with scores of 0 increased with high-dose spesolimab versus placebo, (erythema, 33.3% vs 19.4%; pustules, 80.0% vs 41.9%; scaling/crusting, 30.0% vs 19.4%; total score, 26.7% vs 16.1%), and high-dose spesolimab group had fewer flares (10.0% vs 35.5%). This trend was maintained at Week 24 (erythema, 36.7% vs 22.6%; pustules, 63.3% vs 45.2%; scaling/crusting, 36.7% vs 19.4%; total score, 33.3% vs 19.4%) and Week 48 (erythema, 36.7% vs 22.6%; pustules, 66.7% vs 45.2%; scaling/crusting, 43.3% vs 25.8%; total score, 36.7% vs 22.6%). There were no new flares after Week 4 in high-dose spesolimab group; however, flares increased with placebo (45.2% at Week 24; 51.6% at Week 48).&#x0D; Conclusion: Versus placebo, high-dose subcutaneous spesolimab resulted in a greater proportion of patients maintaining GPPGA scores of 0, a lower proportion having flares at Week 4, and no new flares after Week 4. This was sustained at Weeks 24 and 48.

ABSTRACTIntroduction: Generalized pustular psoriasis (GPP) is characterized by widespread erythema and edema, superficial sterile coalescing pustules, and lakes of pus. Although the impact of GPP is thought to be substantial, emerging literature on its clinical, humanistic, and economic burden has not previously been described in a structured way.Areas covered: A structured search focused on the identification of studies in GPP using specific search terms in PubMed and EMBASE® from 2005 onwards, with additional back-referencing and pragmatic searches. Outcomes of interest included clinical, humanistic, and economic burden.Expert opinion: Despite its significant clinical, humanistic, and economic burden, GPP is poorly classified and inadequately studied. A recent European (ERASPEN) consensus classifies GPP into relapsing and persistent disease and classifies patients on the presence or absence of psoriasis vulgaris. Classification of GPP lesions involving >30% body surface area or use of hospitalization as a surrogate may be a way to identify significant flares. Given the frequency of flares, the impaired quality of life during the post-flare period, and safety/tolerability issues, it is clear that current treatment options are not sufficient. Long-term studies utilizing the European consensus statement with subclassifiers are required to supplement our current understanding of the burden of GPP.

Background: Generalized pustular psoriasis (GPP) rarely occurs under 10 years of age. GPP is typically characterized by an eruption of generalized pustules accompanied by systemic symptoms such as fever for several days, malaise, and anorexia. Pustules are sterile, with a size of 2-3 mm, and spread over the trunk and extremities. This disease can be life-threatening; therefore, optimal therapy is required. Purpose: to report a rare case of GPP in childhood. Case: A 4-year-old girl with complaints of widespread red patches that spread to her neck, back, and hands, with red patches turning into streaks that are partially pus-filled and itchy. In almost all parts of the body, skin abnormalities were seen in the form of generalized erythematous plaques, well-defined borders, multiple pustules on the edges, and some plaques covered by thick scales and crusts. In the calculation of body surface area (BSA), the result is 44%, and in the calculation of generalized pustular psoriasis area and severity index (GPPASI), the result is 21.30. The patient was treated with combination topical therapy of 3% salicylic acid, desoximethasone cream 0.25%, momethasone cream 0.1% vaseline albume as emollients, and coal tar. Significant improvement was seen after 1 month of therapy. Discussion: GPP in children is a rare case. GPP is idiopathic and can be life-threatening. Until now, there has been no standard therapy that is considered the most effective and safe for children. Topical therapy may be an option.

Introduction: Generalized pustular psoriasis (GPP) is a heterogeneous, systemic, neutrophilic, inflammatory disease associated with chronic symptoms and periods of flaring. Spesolimab is an anti-interleukin-36 receptor monoclonal antibody approved for the treatment of flares in adult patients with GPP in Argentina (17 Aug 2023).1 Here, we present safety data from a real-world expanded access program (EAP: 22 Feb 2023–10 Jan 2024) in Argentina which provided early access to spesolimab intravenous (IV) for GPP patients presenting with a flare with no other treatment options. Methods: Patients (18–75 years old) diagnosed with GPP received a 900mg dose of spesolimab IV for flare treatment, with an optional second dose after 1 week for persistent flare symptoms. Adverse events (AEs), serious AEs (SAEs), and AEs of special interest (AESIs) were recorded for up to 16 weeks after the last spesolimab infusion.Results: Six female patients were treated with spesolimab IV (1 dose, n=2; 2 doses, n=4).Mean (standard deviation [SD]) age: 49.3 (11.5) years (range: 30–60 years), mean (SD) body mass index: 28.1 (5.8) kg/m2, and mean (SD) follow-up: 3.85 (0.11) months. At baseline, GPP had been diagnosed within ≤1 year (n=2), &gt;1–≤5 years (n=1), and &gt;10 years (n=3). Reported flare triggers were stress (n=2), treatment withdrawal (n=1), heat (n=1), lack of current treatment efficacy (n=1), and unknown (n=1). At baseline, 4 patients had ≥1 comorbidity, including hypertension (n=2), tachycardia, hypothyroidism, chronic gastritis, arthritis, and epilepsy (each n=1). Five patients reported use of ≥1 concomitant medication (including immunosuppressants and corticosteroids) during the EAP; 1 patient had discontinued ustekinumab (biologic). Three patients had signs of plaque psoriasis within the past year and had received treatment for plaque psoriasis; 1 patient had ongoing plaque psoriasis. In total, 4 patients had any AEs (all 4 patients had mild AEs [influenza, catarrh, pruritis, rash, pain] and 1 of these patients also had a moderate AE [headache]). Two drug-related AEs (pruritus and rash) were reported in 1 patient. The hypersensitivity event (rash) was non-serious. There were no reports of SAEs, AESIs, or AEs that led to discontinuation/death. Conclusion: Spesolimab showed a favorable safety profile in patients with GPP, including patients with comorbidities and those taking concomitant medication. Findings were comparable with a Phase 2a randomized controlled trial in patients with GPP flares (EFFISAYIL 1).

Hospital management and clinical factors associated with ophthalmic involvement in Toxic Epidermal Necrolysis

The dying declaration remains important evidence in trials of burned victims in India. However, its evidentiary value is often negated because facial involvement or larger body area involved due to burns may make victims incapable of speaking properly. Hence, this study aimed to study the effect of burn on speech in relation to parameters like age, gender, and total body surface area affected (TBSA). The study included eighty patients having burn injuries over the head, neck, face, and upper chest. They were evaluated longitudinally from the time of infliction of burns at six hourly intervals, at 6 hours, 12 hours, 18 hours, and 24 hours. The speech was assessed using a scale having components of orientation, content, coherence, and articulation. The speech was well preserved in maximally affected age groups (21-40 years); speech was found to be preserved in varying involvement of body surface area. While considering gender and speech, it is observed that speech is relatively unaffected in females; in fact, females can tolerate burns better than males and have well-preserved speech. The above findings were constant at all-time intervals, i.e., at 6 hours, 12 hours, 18 hours, and 24 hours. Overall, the study disproves the notion that burn victims having facial involvement and greater total body surface area (TBSA) involvement cannot give a valid dying declaration.

Final Results of the BP22333 Study Demonstrate Non-Inferior Pharmacokinetics (PK) and Safety of Subcutaneous (SC) Administration of Rituximab Compared with Intravenous (IV) Administration As Maintenance Therapy in Patients with Follicular Lymphoma (FL)

The CARI guidelines. Evidence for peritonitis treatment and prophylaxis: treatment of peritoneal dialysis-associated peritonitis in adults.

Clinical pharmacokinetics of phenobarbital in neonates

Health disparities in narrowband UVB phototherapy for mycosis fungoides: A multi-institutional cohort study across Fitzpatrick skin types.

34617 Imsidolimab in the treatment of adult subjects with generalized pustular psoriasis: Design of a pivotal phase 3 clinical trial and a long-term extension study

Introduction: Generalized pustular psoriasis (GPP) and bullous pemphigoid (BP) are two distinct but occasionally coexisting inflammatory skin disorders. Their simultaneous presence presents diagnostic and therapeutic challenges. Spesolimab and dupilumab are novel biologics targeting the IL-36 and IL-4/IL-13 pathways, respectively. However, their sequential use in treating GPP with BP has not been previously reported. Case Presentation: We report a 58-year-old man with a 10-year history of psoriasis who developed acute GPP followed by BP. Initial acitretin therapy resolved pustules but not bullae. A single dose of intravenous spesolimab led to rapid improvement of systemic symptoms and pustular lesions. Persistent bullae were subsequently treated with dupilumab (600 mg loading dose, then 300 mg biweekly), resulting in complete resolution within 2 months. The patient remained relapse-free for 6 months, with no adverse events. Conclusion: This case highlights the potential of sequential spesolimab and dupilumab therapy as an effective and safe approach for managing GPP coexisting with BP. Targeting distinct inflammatory pathways may provide a new treatment option for complex dermatological comorbidities.

Multicenter epidemiological investigation of hospitalized children with severe burn

After burn injury, patients can struggle psychologically in addition to issues with physical function and cosmesis. Posttraumatic stress disorder (PTSD) is a known sequela of burn injury, with a suggested frequency of 18-33%. However objective measures of injury have not been reliably linked to the development of symptoms, making routine identification a challenge. The objective of this study to identify patient characteristics associated with a positive PTSD screening exam in the outpatient setting. The Primary Care Posttraumatic Stress Disorder screening questionnaire (PC-PTSD-4) was administered to patients at their initial outpatient clinic visit at a large regional Burn Center over a four month period of May-October 2018. Patients excluded included those with dermatologic disorders, known history of PTSD and repeat questionnaires. Patient demographics, injury mechanism, total body surface area (TBSA) involvement and questionnaire results were recorded. Patients were considered screen positive if they responded affirmatively to at least three of the four questions. Chi-square and student’s t-tests were used to compare patients with positive and negative screens. Further evaluation assessed the sub-population that answered affirmatively to all four screening questions. 188 surveys were answered in total, with 182 remaining for analysis after exclusions. Patients had a mean age of 41.8±15.5 years, mean TBSA of 4.5±7.5%, with equal gender distribution. 6.6% of questionnaires were completed in Spanish. The most common injury etiologies included scald (24.2%), flame (24.2%) and grease burns (20.3%). Positive screens were noted in 48 patients (26.4%), with 30 of these patients responding affirmatively to all four questions, and 83 with negative responses to all questions. The only significant predictor for a positive screen was increased total TBSA% (4.0±5.6 vs 6.0±11.2, p = 0.004). A similar finding was noted when examining patients with four affirmative responses (p < 0.001). Although all patients are susceptible to PTSD after burn injury, positive screening correlates with larger initial injury. Future directions of this project will evaluate additional factors including concurrent traumatic injuries, prior psychiatric history and the presence of assault. Early identification of at-risk individuals enables expedited efforts to provide education and support.