Spesolimab for the Treatment of Generalized Pustular Psoriasis.

Generalized pustular psoriasis (GPP) is a rare but severe skin inflammatory disorder characterized by the eruption of widespread sterile neutrophilic pustules, often accompanied by systemic inflammation. Given its life-threatening potential, GPP requires prompt accurate diagnosis and effective treatment, but its rarity and relapsing-remitting nature pose challenges in performing large-scale randomized controlled clinical trials. Established international guidelines are currently lacking and management guidance often follows that for plaque psoriasis. However, while it can co-exist with plaque psoriasis and has traditionally been classified as a most severe form of psoriasis, GPP is now recognized as a distinct entity, with its own clinicopathological, autoinflammatory, immunologic and genetic features. Research conducted over the past decade revealed that an imbalance of interleukin (IL)-36 signaling favoring the proinflammatory activity is the central driver of the pathogenesis of GPP, thereby laying the groundwork for the development of targeted therapies for the disease. This article reviews the evidence thus far on spesolimab, a selective humanized antibody against the IL-36 receptor that was recently licensed in Europe and the United States for the treatment of GPP flares in adults. In phase II, randomized controlled clinical trials, spesolimab led to rapid and effective skin clearance in patients experiencing a GPP flare and demonstrated superiority to placebo in preventing flares for up to 48 weeks with maintenance treatment, with reassuring safety and tolerability profiles. Spesolimab is considered to be a first-in-class medication establishing itself as the standard of care for the treatment of GPP flares, thus changing the paradigm of the management of GPP to a new era of scientifically- and evidence-based targeted therapy for this distinctive disease.

Lebrikizumab for the Treatment of Moderate-to-Severe Atopic Dermatitis.

Atopic dermatitis (AD) is a common, heterogeneous, inflammatory skin disorder characterized by chronic or relapsing eczematous lesions with intense pruritus and discomfort. Affected patients often experience significant impairment in their quality of life, and the treatment of moderate-to-severe AD forms remains challenging. In the past few decades, increasing knowledge on the AD pathogenesis has driven the development of novel targeted therapies. Interleukin (IL)-13 plays a central and pleiotropic role in AD pathogenesis, contributing directly or indirectly to epidermal barrier disfunction, type-2 inflammation, dysbiosis, fibrosis, and itch response. For this reason, agents selectively targeting IL-13, such as lebrikizumab, emerged as a potential therapy for AD. This article reviews the current evidence about lebrikizumab in the management of AD. The phase II and phase III trials seem to corroborate efficacy of lebrikizumab in the treatment of moderate-to-severe AD, as shown by significant improvement of Eczema Area and Severity Index, body surface area, and pruritus scores. Also, lebrikizumab demonstrated favorable safety and tolerability profiles, with the majority of patients experiencing no significant adverse events. Lebrikizumab seems to be a promising emerging targeted biological agent for patients with moderate-to-severe AD. More data on the long-term efficacy and safety, head-to-head comparisons with other agents, and real-world evidence will help to clarify its place in therapy in AD.

Effectiveness of a structured exercise intervention in gestational weight gain in pregnant women with overweight and obesity: A systematic review with meta-analysis.

OBJECTIVES: To assess the effectiveness of exercise interventions during pregnancy in managing gestational weight gain (GWG), excessive GWG, gestational diabetes (GD), hypertensive disorders, 2-h post-oral glucose tolerance test (OGTT), and birth weight in pregnant women with overweight/obesity (OW/OB). METHODS: The search strategy was conducted in five electronic databases, restricting to articles published within the past 10 years. Randomized controlled trials comparing exercise intervention with usual prenatal care in pregnant women with OW/OB were considered. Two reviewers extracted data and assessed the risk of bias using version 2 of the Cochrane risk-of-bias tool for randomized trials and the quality of studies using Grading of Recommendations Assessment, Development and Evaluation classification. Continuous data were calculated as mean differences (MDs) and dichotomous data as risk ratios (RRs). RESULTS: Seven trials comprising 1648 pregnant women were included. Exercise interventions were associated with lower GWG (MD, -1.19 kg [95% confidence interval, CI, -1.79 to -0.60]) and lower incidence of GD (RR, 0.56 [95% CI, 0.40-0.78]). When analyzing excessive GWG, 2-h post-OGTT, birth weight, and hypertensive disorders, there was no statistically significant difference between the exercise and usual care groups. The strength of evidence was considered moderate. CONCLUSION: Exercise interventions during pregnancy in women with OW/OB were shown to influence GWG and the incidence of GD.

Comparison of the Portuguese Version of the Pregnancy Physical Activity Questionnaire (PPAQ) with Accelerometry for Classifying Physical Activity among Pregnant Women with Obesity.

In recent years, the number of pregnant women with obesity has increased exponentially; thus, it is important to evaluate and characterize the physical activity levels of this specific group. The aim of this study is to evaluate the reliability and validity of the Portuguese version of the Physical Activity and Pregnancy Questionnaire and Pregnancy Questionnaire in pregnant women with obesity and to classify physical activity using the Physical Activity and Pregnancy Questionnaire and accelerometry. An analytical observational study was carried out between May and August of 2019 at the University Hospital Center of São João, with a sample of 31 pregnant women with obesity (30.9 ± 4.6 years 36.5 ± 4.6 kg/m2 of BMI and 21.5 ± 9 gestational weeks). The physical activity of participants was evaluated using an accelerometer and Physical Activity and Pregnancy Questionnaire at two time points (the first visit at the moment of consultation and the second seven days after, with accelerometer retest), the interclass correlation coefficient was used to test reliability between the Physical Activity and Pregnancy Questionnaire filled out at visit1 and the Physical Activity and Pregnancy Questionnaire filled out at visit2, and Pearson's correlation was used to determine validity between the Physical Activity and Pregnancy Questionnaire and accelerometry. The interclass correlation coefficient values for total activity were 0.95, 0.97 for moderate and 0.58 for vigorous intensities. It ranged from 0.74 for sports/exercise to 0.96 for domestic activities. The Pearson's correlations showed that the Physical Activity and Pregnancy Questionnaire is moderately valid for moderate intensity (r = 0.435). A total of 67.7% of the pregnant women complied with international physical activity recommendations.