Analyzing the Benefits and Costs of the Safe Step Act on Patients, Physicians, and Insurers.

Pharmaceutical expenditures in the United States, particularly in dermatology, have grown rapidly, driven by expensive topical and biologic treatments. Insurers are employing cost-containing strategies such as step therapy, which mandates the use of lower-cost treatments before more expensive medications. The bipartisan Safe Step Act aims to enhance step therapy policies by introducing a transparent process for requesting exceptions and reasonable timelines for the process. However, there is limited analysis on how the Safe Step Act would affect the healthcare environment. We examine the policies of the Safe Step Act and existing literature on prior authorizations and discuss how the bill could affect patients, physicians, and insurers. While the act could expedite access to necessary medications and prevent irreversible harm to patients from delaying efficacious treatment, it falls short in relieving the administrative burdens on dermatology clinics. Although there is no ideal solution for managing healthcare costs, measures like step therapy encourage cost-effective treatments and optimizing care for the population. Curtailing step therapy with the exemptions process of the Safe Step Act might streamline patient access to treatments but could impede cost-containment strategies, weaken the bargaining power of insurers, and result in higher insurance premiums.

The Influence of Psoriasis on Type 2 Diabetes Mellitus Patient Profiles: A National Inpatient Sample Study.

Background: Psoriasis is believed to be a common comorbidity of type 2 diabetes mellitus (T2DM). Little is known on the impact psoriasis has on T2DM patients' disease profiles. Objective: To assess the impact psoriasis has on T2DM patients' demographics, comorbidities, and health care outcomes. Methods: We retrospectively analyzed the 2017 U.S. National Inpatient Sample (NIS) database. We utilized ICD-10 codes to determine T2DM and psoriasis patients along with associated comorbidities. Continuous variables were compared by independent-sample t-tests and categorical variables were compared via Pearson chi-square. All analysis were conducted in IBM SPSS 25. Results: Among 7,705,988 T2DM admissions, 0.67% of them had comorbid psoriasis. T2DM psoriasis patients (64.38; SD: 12.403) were, on average, younger (64.38 vs 66.73; P < .001) and white (78.7% vs 63.1%; P < .001) and had increased foot ulcers (4.2% vs 3.8%; P < .001), hyperglycemia (22.4% vs 21.0%; P < .001), retinopathy (22.4% vs 21.0%; P < .001), hypercoagulopathy (8.5% vs 6.9%; P < .001), and hypertension (72.5% vs 70.4%; P < .001) than T2DM patients without psoriasis. T2DM psoriasis patients spent more days in the hospital (5.49 vs 5.37; P < .001), had more concurrent diagnoses (19.05 vs 16.5; P < .001), less total charges ($60,596.71 vs $61,534.66; P = 0.010) and had less in-hospital deaths (2.0% vs 2.7%; P < .001) than T2DM patients without psoriasis. Conclusions: The presence of comorbid psoriasis significantly impacts T2DM patients' demographics, comorbidities, and health care outcomes. These findings underscore the importance of early disease monitoring, cross-specialty collaboration, and medication monitoring in order to guide individualized management strategies and optimize patient care.

Biologics and Small Molecule Targeted Therapies for Pediatric Alopecia Areata, Psoriasis, Atopic Dermatitis, and Hidradenitis Suppurativa in the US: A Narrative Review.

BACKGROUND: The management of pediatric dermatological conditions such as alopecia areata (AA), psoriasis, atopic dermatitis (AD), and hidradenitis suppurativa (HS) has significantly evolved with the introduction of biologics and small molecule targeted therapies. The advancement in understanding the immunopathogenesis of these chronic skin conditions has led to the development and approval of novel biologics and small molecule therapies. Initially approved by the United States Food and Drug Administration (FDA) for adults, most of these therapies are now being evaluated in clinical trials for safety and efficacy in adolescents and children, expanding new treatment options for pediatric patients. The role of the FDA in drug approval is multifaceted from drug inception, ensuring that research, data, and evidence show that the proposed drug is effective and safe for the intended use. OBJECTIVE: The goal of this review article is to provide an overview of the recently FDA-approved and potential biologic and oral small molecule therapies in clinical trials for AA, psoriasis, AD, and HS in pediatric patients. METHODS: The search for this review included keywords in ClinicalTrials.gov, PubMed, and Google Scholar for the latest research and clinical trials relevant to these conditions and treatments without the PRISMA methodology. RESULTS: For pediatric AA, ritlecitinib is FDA-approved, while baricitinib and updacitinib are in phase 3 clinical trials for pediatric approval. The FDA-approved drugs for pediatric psoriasis include secukinumab, ustekinumab, ixekizumab, etanercept, and apremilast. Other phase 3 clinical trials for pediatric psoriasis include risankizumab, guselkumab, tildrakizumab, brodalumab, and deucravacitinib. For pediatric AD, the FDA-approved drugs are dupilumab, tralokinumab, abrocitinib, and upadacitinib, with many other drugs in phase 3 trials. Adalimumab is an FDA-approved biologic for pediatric HS, with various clinical trials ongoing for adults. The approved biologics and small molecule therapies had higher efficacy and improved safety profiles compared to traditional medications. CONCLUSIONS: With numerous ongoing trials, the success of these clinical trials could lead to their inclusion in treatment guidelines for these chronic skin conditions. Biologics and small molecule therapies offer new avenues for effective disease management, enabling personalized therapeutic interventions and improving pediatric health outcomes.

The role of nemolizumab in the treatment of atopic dermatitis for the adult population.

Atopic dermatitis (AD) often requires long-term treatment that may be associated with adverse effects. This review aims to characterize nemolizumab as a treatment for AD in adults. A literature search was performed to assess nemolizumab's role in moderate-to-severe AD in adults. Currently, clinical trials are being conducted to evaluate the clinical efficacy, safety profile and optimal dosing of nemolizumab for adults with moderate-to-severe AD. The most common adverse effects include nasopharyngitis, AD exacerbation and increased blood creatinine phosphokinase. Recent data from clinical trials suggest nemolizumab may be an acceptable treatment in adults with moderate-to-severe AD.

Atopic dermatitis, also known as eczema, is a long-lasting skin condition that is difficult to treat. Symptoms include itching, redness, dryness and pain. Various eczema treatments are available to help patients based on how severe their symptoms are. Nemolizumab is a treatment that blocks immune system pathways involving itching and inflammation. This review describes nemolizumab as a treatment option for moderate-to-severe eczema in adults. We completed a literature search to understand nemolizumab's role in eczema treatment. Nemolizumab has decreased itchiness in adults with moderate-to-severe eczema in clinical trials. The most common side effects of nemolizumab treatment were the common cold, worsening of eczema and an increased muscle marker (creatinine phosphokinase). Nemolizumab appears to be an effective treatment for moderate-to-severe eczema in adults with bearable side effects.

CD22-directed CAR T-cell therapy for large B-cell lymphomas progressing after CD19-directed CAR T-cell therapy: a dose-finding phase 1 study.

BACKGROUND: Outcomes are poor for patients with large B-cell lymphoma who relapse after CD19-directed chimeric antigen receptor (CAR) T-cell therapy (CAR19). CD22 is a nearly universally expressed B-cell surface antigen and the efficacy of a CD22-directed CAR T-cell therapy (CAR22) in large B-cell lymphoma is unknown, which was what we aimed to examine in this study. METHODS: In this single centre, open-label, dose-escalation phase 1 trial, we intravenously administered CAR22 at two dose levels (1 million and 3 million CAR22-positive T cells per kg of bodyweight) to adult patients (aged ≥18 years) who relapsed after CAR19 or had CD19-negative large B-cell lymphoma. The primary endpoints were manufacturing feasibility, safety measured by the incidence and severity of adverse events and dose-limiting toxicities, and identification of the maximum tolerated dose (ie, the recommended phase 2 dose). This study is registered with ClinicalTrials.gov (NCT04088890) and is active, but closed for enrolment. FINDINGS: From Oct 17, 2019, to Oct 19, 2022, a total of 41 patients were assessed for eligibility; however, one patient withdrew. 40 patients underwent leukapheresis and 38 (95%) had CAR T-cell products manufactured successfully. The median age was 65 years (range 25-84), 17 (45%) were women, 32 (84%) had elevated pretreatment lactate dehydrogenase, 11 (29%) had refractory disease to all previous therapies, and patients had received a median of four lines of previous therapy (range 3-8). Of the 38 patients treated, 37 (97%) had relapsed after previous CAR19. The identified maximum tolerated dose was 1 million CAR T cells per kg. Of 29 patients who received the maximum tolerated dose, no patients developed a dose-limiting toxicity or grade 3 or higher cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or immune effector cell-associated haemophagocytic lymphohistiocytosis-like syndrome. INTERPRETATION: This trial identifies CD22 as an immunotherapeutic target in large B-cell lymphoma and demonstrates the durable clinical activity of CAR22 in patients with disease progression after CAR19 therapy. Although these findings are promising, it is essential to recognise that this is a phase 1 dose-finding study. Further investigations are warranted to establish the long-term efficacy and to delineate the patient subgroups that will derive the most benefit from this therapeutic approach. FUNDING: National Cancer Institute, National Institutes of Health, Stanford Cancer Institute, Leukemia & Lymphoma Society, Parker Institute for Cancer Immunotherapy, Lymph & Co, and the European Hematology Association.

Dapsone Use in Dermatology.

Dapsone, initially synthesized for textile dyeing, gained recognition in the 1930s for its antibacterial properties, leading to its utilization in dermatology for leprosy and dermatitis herpetiformis. Despite US Food and Drug Administration (FDA) approval for these conditions, dapsone's off-label uses have expanded, making it a valuable option in various dermatologic conditions. This review seeks to highlight the common uses of dapsone in its FDA indications and off-label indications. Diseases in which dapsone is considered first-line therapy or adjunctive therapy are reviewed, with highlights from the resources included. An overview of dapsone's pharmacokinetics, pharmacodynamics, indications, dosages, and safety profile are also reviewed. Dapsone's versatility and safety profile make it a cost-effective treatment option in dermatology, particularly for patients with limited access to specialized medications. Ongoing clinical trials are also described exploring dapsone's efficacy in novel dermatologic uses. Dapsone has been a valuable adjunctive therapy across various dermatologic conditions for years and evidence for its use continues to expand.

A Phase 1 Clinical Trial of NKTR-255 with CD19-22 CAR-T Cell Therapy for Refractory B-cell Acute Lymphoblastic Leukemia.

While chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of B-cell malignancies, many patients relapse and therefore strategies to improve antitumor immunity are needed. We previously designed a novel autologous bispecific CAR targeting CD19 and CD22 (CAR19-22), which was well tolerated and associated with high response rates but relapse was common. Interleukin-15 (IL15) induces proliferation of diverse immune cells and can augment lymphocyte trafficking. Here, we report the results of a phase 1 clinical trial of the first combination of a novel recombinant polymer-conjugated IL15 receptor agonist (NKTR-255), with CAR19-22, in adults with relapsed / refractory B-cell acute lymphoblastic leukemia. Eleven patients were enrolled, nine of whom successfully received CAR19-22 followed by NKTR-255. There were no dose limiting toxicities, with transient fever and myelosuppression as the most common possibly related toxicities. We observed favorable efficacy with eight out of nine patients (89%) achieving measurable residual disease negative remission. At 12 months, progression-free survival for NKTR-255 was double that of historical controls (67% vs 38%). We performed correlative analyses to investigate the effects of IL15 receptor agonism. Cytokine profiling showed significant increases in IL15 and the chemokines CXCL9 and CXCL10. The increase in chemokines was associated with decreases in absolute lymphocyte counts and CD8+ CAR T-cells in blood and ten-fold increases in CSF CAR-T cells, suggesting lymphocyte trafficking to tissue. Combining NKTR-255 with CAR19-22 was safe, feasible and associated with high rates of durable responses (NCT03233854).

How can physicians improve medication adherence and outcomes in dermatological conditions?

INTRODUCTION: Medication non-adherence is a major contributor to suboptimal disease treatment across medical specialties and is a particular hurdle with topicals. While adherence is a patient behavior affected by many socioeconomic and health system factors, physicians can play an important role in encouraging good adherence. AREAS COVERED: We discuss methods for measuring adherence, including ethics of such research, provide select examples of dermatology-specific adherence studies, and conclude with physician-focused practices to improve patients' adherence. Articles were selected from a PubMed search spanning 2003 to 10 December 2023, using the following terms: 'dermatology,' 'medication,' 'treatment,' 'adherence,' 'compliance,' and 'intervention.' EXPERT OPINION: Poor adherence to treatment is a major cause of poor treatment outcomes. As the goal of medical care is to achieve successful treatment outcomes, encouraging good adherence may be as much a foundation of care as making the right diagnosis and prescribing the right treatment. Taking a doctor-centric perspective on reasons for non-adherence may be more productive than simply finding fault with the patient. Establishing trust and accountability is a foundation for good adherence; after establishing the provider-patient relationship, physicians can improve adherence by incorporating behavioral and counseling strategies, communicating through technology, and advocating for distribution of validated educational information.

Evaluation of ruxolitinib cream 1.5% as an at-home therapy for repigmentation in non-segmental vitiligo.

INTRODUCTION: Vitiligo is a chronic, autoimmune condition characterized by skin depigmentation caused by inflammatory-mediated melanocyte degradation. Treatment of vitiligo is challenging due to the chronic nature of the condition. Ruxolitinib cream 1.5% was recently approved by the Food and Drug Administration (FDA) as a Janus kinase 1 and 2 inhibitor for use in nonsegmental vitiligo for those 12 years and older. AREAS COVERED: The purpose of this review is to describe the role of ruxolitinib in treating nonsegmental vitiligo.We searched PubMed using search terms nonsegmental vitiligo, jak inhibitor, and ruxolitinib. Clinicaltrials.gov was used to identify clinical trial data including efficacy, pharmacodynamics, pharmacokinetics, safety, and tolerability. EXPERT OPINION: In both phase II and phase III (TRuE-V1 and TRuE-V2) trials, ruxolitinib cream 1.5% improved repigmentation with minimal adverse effects. Topical ruxolitinib is a much needed new vitiligo treatment option.  Real life efficacy may not match that seen in clinical trials if the hurdle of poor adherence to topical treatment is not surmounted.

Cytokine-Mediated Molecular Pathophysiology of Hidradenitis Suppurativa: A Narrative Review.

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory condition of the skin that mainly affects the apocrine gland-rich intertriginous areas. The disease manifests as painful nodules, abscesses, and pus-filled tunnels, which can severely impact patient's quality of life. While diagnosis is clinical, successful treatment options for this condition are limited. There has been an increase in research and clinical trials focusing on biomarkers and cytokines for clinical use. Understanding the potential biomarkers and cytokines implicated in HS pathogenesis may allow efficacious and safe treatment options. Summary: A literature review was conducted on nine biomarkers and cytokines. IL-1, IL-10, IL-17, IL-23, TNF-α, YKL-40, G-CSF, NOD2, and the complement system were identified due to their potential clinical utilization and pathophysiological involvement in HS. Key Messages: With further research expanding our understanding of the pathophysiology of HS and the roles these cytokines and biomarkers play, there is potential for utilization as diagnostic markers or development of antagonists against these specific agents for HS management.