Risankizumab, a therapeutic alternative for psoriasis in people living with HIV.

The management of psoriasis in individuals with human immunodeficiency virus (HIV) presents a unique challenge, marked by a more severe progression and limited efficacy of first- and second-line treatments. Although conventional systemic therapies might be considered, these agents are immunosuppressants, making their use challenging in people living with HIV (PLHIV). Biologic agents are frequently used in individuals with moderate-to-severe psoriasis, but their efficacy and safety data in PLHIV are very limited, as this patient group tends to be excluded from clinical trials. Risankizumab is a selective interleukin-23 (IL-23) inhibitor that has demonstrated a favourable safety profile and high efficacy in long-term studies and clinical practice. This current case report presents two clinical cases of PLHIV with plaque psoriasis who were effectively treated with the biologic agent risankizumab, with no reported safety issues. Although there are limited data on the use of biologics in PLHIV, this case series suggests that IL-23 inhibitors, namely risankizumab, might be a valuable therapeutic option for this population. Additional research and larger studies are needed to gain a more comprehensive understanding of the long-term safety and efficacy of IL-23 inhibitors in individuals affected by HIV.

Difamilast for the treatment of atopic dermatitis.

Atopic dermatitis (AD) is a common chronic relapsing inflammatory skin disease. The pathogenesis of AD is complex and still not fully understood. Despite recent therapeutic developments, the current therapeutic arsenal of AD remains limited and is associated with long-term efficacy and safety issues. Therefore, new topical therapies with different mechanisms of action are required to overcome the limitations of existing treatments. Difamilast is a phosphodiesterase 4 inhibitor currently in phase 3 studies. Difamilast shows antipruritic and anti-inflammatory properties and a rapid onset of action, with significant differences in some parameters from the vehicle within 1 week of treatment. Phase 2 and 3 clinical trials have shown that difamilast ointments are effective and well tolerated in adult and pediatric patients with AD, and are expected to be used for long-term AD treatment. In 2021, difamilast was the first phosphodiesterase 4inhibitor to acquire manufacturing and marketing approval in Japan for the treatment of adult and pediatric patients (2 years of age and older) with AD. This article is a narrative review of the current literature on difamilast in the management of AD.

New molecules for atopic dermatitis treatment beyond biological therapy.

PURPOSE OF REVIEW: This review aims to provide a summary of current knowledge on new topical and oral non-biological therapies recently approved for Atopic Dermatitis (AD) treatment. RECENT FINDINGS: The immense research carried out in the last decade has focused on understanding the molecular basis underlying AD and has allowed the development of new targeted drugs. Despite several biologic therapies are approved or in development, other non-biologic targeted therapies (small molecules) have emerged, such as the Janus kinase (JAK) inhibitors baricitinib, upadacitinib and abrocitinib, expanding the range of therapeutic options. Based on recent available data from head-to-head comparisons and meta-analysis studies, JAK inhibitors showed a faster onset of action and slightly higher efficacy at 16 weeks compared with biologic agents. Concerning topical treatment, presently, corticosteroids and calcineurin inhibitors are the main therapeutic options, but are not recommended for long-term management due to potential safety issues. Currently, two topical JAK inhibitors (ruxolitinib and delgocitinib) and one phosphodiesterase 4 (PDE4) inhibitor (difamilast) are approved and have shown good efficacy results and a favorable safety profile. SUMMARY: These new drugs (systemic and topical) are needed to increase the success of AD treatment, particularly for patients who do not or no longer respond to treatment.

Efficacy and safety of baricitinib in patients with alopecia areata: evidence to date.

Alopecia areata (AA) is a chronic, tissue-specific autoimmune disorder, characterized by non-scaring hair loss, with a global prevalence of approximately 2%. Typically, it affects a young population, with initial onset frequently occurring before the age of 30 years. Even though the exact pathogenesis of AA remains unclear, the predominant hypothesis is the breakdown of immune privilege of the hair follicle, resulting in increased self-antigen and major histocompatibility complex expression in the follicular epithelium. The relapsing nature of the disease negatively impacts patients' quality of life and makes them more susceptible to developing psychiatric comorbidities. Although many treatment modalities have been proposed, there are no currently available treatments able to induce and sustain disease remission. Traditional treatment modalities, despite being widely used, present limited results and a high risk of adverse effects. Hence, there exists an unfulfilled requirement for treatments that are both more efficient and safer. The latest understanding of the pathophysiology of AA and its connection to the JAK-STAT pathway has prompted the advancement of JAK inhibitors. These small-molecule agents function by obstructing the JAK-STAT intracellular signalling pathway. Baricitinib an orally administered, selective JAK1 and JAK2 inhibitor is a promising alternative to the available treatments, and is already approved for the treatment of AA.

Baricitinib for the Treatment of Alopecia Areata.

Alopecia areata (AA) is a relapsing, chronic, immune-mediated disease characterized by nonscarring, inflammatory hair loss that can affect any hair-bearing site. AA clinical presentation is heterogeneous. Its pathogenesis involves immune and genetic factors and several pro-inflammatory cytokines involved in AA pathogenesis, including interleukin-15 and interferon-γ, as well as Th2 cytokines, such as IL-4/IL-13, that signal through Janus kinase (JAK) pathway. AA treatment aims to stop its progression and reverse hair loss, and JAK inhibition has been shown to stop hair loss and reverse alopecia and has exhibited promising results in treating AA in clinical trials. Baricitinib, an oral, reversible, selective JAK1/JAK2 inhibitor, was shown to be superior to placebo on hair growth after 36 weeks of treatment in adults with severe AA in a phase 2 trial and recently in two phase 3 trials (BRAVE-AA1 and BRAVE-AA2). In both studies, the most common adverse events were upper respiratory tract infections, urinary tract infection, acne, headache, and elevated creatine kinase levels. On the basis of these trial results, baricitinib was recently approved by the European Medicines Agency (EMA) and US Food and Drug Administration (FDA) for the treatment of adults with severe AA. Nevertheless, longer trials are needed to determine the long-term efficacy and safety of baricitinib in AA. Current trials are ongoing and are planned to remain randomized and blinded for up to 200 weeks.

Orthostatic hypotension as an unusual presentation of spinal calcium pyrophosphate deposition disease: case report and review of literature.

Calcium pyrophosphate crystal deposition disease (CPPD), also known as pseudogout, with spinal involvement, is associated with clinical manifestations of acute nerve compression or chronic spinal stenosis. Precipitation of crystals of calcium pyrophosphate dihydrate in connective tissues can lead to acute inflammatory arthritis, degenerative chronic arthropathies, and radiographic evidence of cartilage calcification. We present a case of an 87-year-old woman, with unstudied chronic polyarthralgia and symptomatic orthostatic hypotension. It were documented acute calcium pyrophosphate deposition wrist arthritis, and cervical CT and MRI was suggestive of spinal involvement of CPPD. Workup excluded other causes of OH. Surgical approach could be indicated to minimize the symptoms, but it was contra-indicated due to the patient's performance status, so histological diagnosis was not possible. Muscle atrophy played an important part in the rapid progression of this insidious chronic disease. Conservative and symptomatic treatment achieve scarce short-term clinical improvement. Spinal involvement of CPPD was thought to be rare but recent studies show a higher prevalence than expected. We call for attention to the extent of structural changes that may occur when not early diagnosed nor treated. High clinical suspicion is required and this is, to our knowledge, the first report of orthostatic hypotension as a presentation of CPPD.

New Topical Therapies in Development for Atopic Dermatitis.

Atopic dermatitis (AD) is a common chronic pruritic inflammatory cutaneous disease. AD is characterized by intense pruritus and enormous clinical heterogeneity. Treatment goals are to improve skin lesions and minimize exacerbations and symptom burden. Currently, topical corticosteroids (TCS) and topical calcineurin inhibitors (TCI) are still considered the main topical therapies in disease treatment. However, despite being very effective, TCS and TCI are not recommended for continuous long-term use, due to potential safety issues. Although research in AD has focused primarily on systemic drugs, more than 20 new topical compounds are under development to treat the disease. This review aims to provide a synthesized summary of the current knowledge about AD topical treatment, echoing existing gaps and coming research trends. The available data seems promising, with some drugs already approved (ruxolitinib being the most recent), and several are in an advanced stage of development and will soon be available for treatment of mild to moderate disease, namely tapinarof, difamilast, and roflumilast. However, longer and larger prospective studies are needed to assess the long-term efficacy and safety of these new compounds and evaluate their benefits over current treatments.

Bimekizumab for psoriasis.

Psoriasis is a chronic, immune-mediated, inflammatory skin disease, affecting 1% to 3% of the population in Western countries. Due to advances in the understanding of psoriasis pathogenesis, in particular, the role of the interleukin-23 (IL-23)/T-helper 17 (Th17) immune axis, highly effective, targeted biologic therapies have been developed, shifting the psoriasis treatment paradigm. However, some patients do not respond or lose response to these novel therapies. Bimekizumab is a first-in-class humanized monoclonal immunoglobulin G1 (IgG1) antibody that potently and selectively inhibits both IL-17A and IL-17F, functioning as a dual inhibitor. All bimekizumab studies have shown high efficacy in psoriasis patients. Its onset of response was rapid and sustained for periods up to 60 weeks. In active-comparator trials to date, bimekizumab was superior to adalimumab (BE SURE), ustekinumab (BE VIVID) and secukinumab (BE RADIANT). It has demonstrated a consistent safety profile and high tolerability. The most common adverse events were largely restricted to mucosal candidiasis. Dual inhibition of IL-17A and IL-17F with bimekizumab showed to be a highly effective treatment for psoriasis, and the product is already approved for treatment of moderate to severe plaque psoriasis in Europe, Canada and Japan.

Bimekizumab: the new drug in the biologics armamentarium for psoriasis.

Bimekizumab, a humanized monoclonal IgG1 antibody being currently evaluated for multiple immune-mediated diseases, is mentioned in the recent report by Clarivate, Drugs to Watch in 2021, as one of the drugs to be observed in 2021. Due to its novel mechanism of action (dual inhibition of IL-17A and IL-17F), bimekizumab is considered a new therapeutic approach for the treatment of moderate-to-severe psoriasis. Bimekizumab has demonstrated superiority in all direct comparative clinical trials conducted, whether against ustekinumab (IL-12/23 inhibitor), adalimumab (TNF inhibitor) or secukinumab (IL-17A inhibitor), and has shown very encouraging results for the treatment of psoriatic arthritis. Since September 2020, the drug is being reviewed by the EMA and FDA for the treatment of psoriasis. Herein, the current status of bimekizumab is discussed.

Tralokinumab for the Treatment of Atopic Dermatitis.

Atopic dermatitis (AD) is a relapsing or chronic heterogeneous inflammatory skin disorder with a substantial economic and social impact. AD is a multifactorial disease regulated by a diverse set of environmental and genetic determinants. The main factors involved in the pathogenesis of AD are epidermal barrier dysfunction, immune dysregulation, and dysbiosis. Current data have valued interleukin (IL)-13 as conceivably the crucial cytokine in the underlying inflammation of AD. Advances in understanding AD pathophysiology have driven the progress of targeted immunomodulatory treatments for the treatment of AD, including tralokinumab, a selective IL-13 inhibitor. A phase IIb clinical trial showed that a dosing regimen of 150 or 300 mg every 2 weeks effectively treated moderate-to-severe AD in adults with an acceptable tolerability profile. Phase III clinical trials demonstrated that results with tralokinumab in monotherapy were superior to those with placebo at 16 weeks of treatment. It was also well tolerated up to 52 weeks in the vast majority of patients. In addition, in association with topical corticosteroids, tralokinumab was well tolerated and effective and had a favorable risk-benefit profile. These data provide additional evidence that IL-13 is central to AD pathogenesis, suggesting that tralokinumab may be seen as an innovative option for the treatment of moderate-to-severe AD.

Bimekizumab for the Treatment of Psoriasis.

Psoriasis is a chronic, systemic, immune-mediated disease, with prominent skin and joint manifestations, associated with several comorbidities. In the past few decades, advances in the knowledge of psoriasis pathogenesis have driven the development of highly effective targeted biologic therapies, transforming the treatment landscape of psoriasis. Bimekizumab is a humanized antibody that selectively binds and neutralizes the biologic functions of interleukin (IL)-17A and IL-17F. This article reviews the current knowledge about bimekizumab in psoriasis treatment. The results obtained in the phase 3 studies (BE VIVID, BE READY, BE RADIANT, BE SURE) corroborate the high levels of efficacy of bimekizumab seen in previous studies, and show superior efficacy over adalimumab, ustekinumab, and secukinumab in direct comparative studies. In all phase 3 trials, bimekizumab was also well tolerated, with a safety profile similar to the other biologic drugs tested, except for a higher frequency of oral candidiasis. Dual inhibition of IL-17A and IL-17F is a highly effective therapeutic option for the treatment of psoriasis, both for naïve patients and for those resistant to previous biologic treatments.

Selective IL-13 inhibitors for the treatment of atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases worldwide. AD pathogenesis is multifactorial, involving environmental and genetic factors. IL-13 stands out as one of the main cytokines in the pathophysiology of AD. Currently, dupilumab, which targets both IL-4 and IL-13 signalling, is the only biologic agent approved for the treatment of moderate-to-severe AD. New targeted biologic therapies are being developed, such as lebrikizumab and tralokinumab, two selective IL-13 inhibitors. This article reviews the role of IL-13 in AD and the most recent data on lebrikizumab and tralokinumab. METHODS: A narrative review of the literature was written after retrieving relevant articles in the PubMed database (up until December 2020) using the following keywords present in the title, abstract or body: atopic dermatitis; interleukin 13; IL-13; tralokinumab; lebrikizumab, biologic therapy. DISCUSSION: A phase IIb trial showed that all three dosing regimens evaluated (lebrikizumab 125 mg every 4 weeks (Q4W), 250 mg Q4W or 250 mg every 2 weeks) achieved rapid and dose-dependent efficacy concerning the signs and symptoms of AD, with a statistically significant improvement, at week 16. Tralokinumab was studied in three phase III clinical trials and reached its primary endpoints at week 16 (ECZTRA 1 and 2 in monotherapy and ECZTRA 3 with concomitant topical corticosteroids), with response maintained over time. Both lebrikizumab and tralokinumab exhibited good safety profiles in AD trials, with adverse effects usually being comparable between the control and treatment groups. CONCLUSION: The evidence supports the hypothesis that selective antagonism of IL-13 is sufficient to control AD, providing an improvement in the patient's quality of life. Therefore, the development of lebrikizumab and tralokinumab represents a new and exciting phase in the management of AD.

Diagnosis, Screening and Treatment of Patients with Palmoplantar Pustulosis (PPP): A Review of Current Practices and Recommendations.

Palmoplantar pustulosis (PPP) is a rare, chronic, recurrent inflammatory disease that affects the palms and/or the soles with sterile, erupting pustules, which are debilitating and usually resistant to treatment. It has genetic, histopathologic and clinical features that are not present in psoriasis; thus, it can be classified as a variant of psoriasis or as a separate entity. Smoking and upper respiratory infections have been suggested as main triggers of PPP. PPP is a challenging disease to manage, and the treatment approach involves both topical and systemic therapies, as well as phototherapy and targeted molecules. No gold standard therapy has yet been identified, and none of the treatments are curative. In patients with mild disease, control may be achieved with on-demand occlusion of topical agents. In patients with moderate-to-severe PPP, phototherapy or a classical systemic agent (acitretin being the best treatment option, especially in combination with PUVA) may be effective. Refractory patients or those with contraindications to use these therapies may be good candidates for apremilast or biologic therapy, particularly anti-IL-17A and anti-IL-23 agents. Recent PPP trials are focusing on blockage of IL-36 or IL-1 pathways, which play an important role in innate immunity. Indeed, IL-36 isoforms have been strongly implicated in the pathogenesis of psoriasis. Therefore, blockage of the IL-36 pathway has become a new treatment target in PPP, and three studies are currently evaluating the use of monoclonal antibodies that block the IL-36 receptor in PPP: ANB019 and spesolimab (BI 655130). In this review, we explore the diagnosis, screening and treatment of patients with PPP.