Bimekizumab efficacy and safety in patients with moderate to severe plaque psoriasis: two-year interim results from the open-label extension of the randomized BE RADIANT phase 3b trial.

BACKGROUND: Bimekizumab is a monoclonal IgG1 antibody that inhibits interleukin (IL)-17A/F. Bimekizumab is more efficacious than secukinumab over one year in the treatment of psoriasis. OBJECTIVE: Evaluate safety and efficacy of bimekizumab through two years in patients with moderate to severe plaque psoriasis. METHODS: The BE RADIANT phase 3b randomized controlled trial consisted of a 48-week double-blinded period, where patients received bimekizumab (320mg every 4 or 8 weeks) or secukinumab (300mg weekly to Week 4, then every 4 weeks), and an open-label extension (OLE). From Week 48, all patients received bimekizumab in the OLE. RESULTS: At Week 48, more patients achieved complete skin clearance (PASI100; modified non-responder imputation) with bimekizumab than secukinumab (74.8% vs 52.8%). PASI100 responses were maintained to Week 96 in continuous bimekizumab patients (70.8%); patients who switched from secukinumab to bimekizumab had increased rates at Week 96 (76.6%). The most common adverse events were: nasopharyngitis, oral candidiasis, urinary tract infection. Safety data were consistent with the known safety profile of bimekizumab. LIMITATIONS: Limited racial diversity; overlap with COVID-19 pandemic. CONCLUSIONS: High PASI100 responses achieved with bimekizumab over 48 weeks were sustained through Week 96; secukinumab patients who switched to bimekizumab achieved similar response by Week 96.

Brodalumab: 4-Year US Pharmacovigilance Report.

Brodalumab is an interleukin-17 receptor A antagonist approved for the treatment of moderate-to-severe psoriasis in adults without response or with loss of response to other systemic therapies. Brodalumab carries a boxed warning in the United States regarding suicidal ideation and behavior, though no causal relationship has been established. Here, we summarize 4 years of pharmacovigilance data, from August 15, 2017, through August 14, 2021, reported to Ortho Dermatologics by US patients and healthcare providers. The most common AEs listed in the brodalumab package insert (incidence ≥1%) and AEs of special interest are described. Brodalumab exposure estimates were calculated using the time between the first prescription-dispensing authorization date and last prescription-dispensing authorization date. Data were collected from 4019 patients with an estimated brodalumab exposure of 4563 patient-years. The most common AE was arthralgia (115 events; 2.52 events per 100 patient-years). No completed suicides and no new suicidal attempts were reported. There were 102 cases with serious infections; however, no serious fungal infections (including no new cases of oral candidiasis) were reported. There were 26 COVID-19 cases, and 3 of the cases with comorbid conditions were fatal. There were no new cases of Crohn’s disease. Of 37 reported malignancies among 32 cases, none were deemed related to brodalumab. Four-year pharmacovigilance data are consistent with the established safety profile reported in long-term clinical trials and 3-year pharmacovigilance data. J Drugs Dermatol. 2023;22(4) doi:10.36849/JDD.7344 Citation: Lebwohl M, Koo J, Leonardi C, et al. Brodalumab: 4-Year US pharmacovigilance report. J Drugs Dermatol. 2023;22(4):419-422. doi:10.36849/JDD.7344.

COVID-19 Vaccine-Induced Lichenoid Eruptions—Clinical and Histopathologic Spectrum in a Case Series of Fifteen Patients with Review of the Literature

Lichen planus is a distinctive mucocutaneous disease with well-established clinical and histopathologic criteria. Lichenoid eruptions closely resemble lichen planus and may sometimes be indistinguishable from it. Systemic agents previously associated have included medications, viral infections and vaccines. Sporadic case reports of lichen planus and lichenoid reactions associated with COVID-19 vaccines have recently emerged. Herein, we review the world literature (31 patients) and expand it with a case series of 15 patients who presented with vaccine-induced lichenoid eruption (V-ILE). The spectrum of clinical and histopathologic findings is discussed with emphasis on the subset whose lesions manifested in embryologic fusion lines termed lines of Blaschko. This rare Blaschkoid distribution appeared in seven of the 46 patients studied. Of interest, all seven were linked to the mRNA COVID-19 vaccines. We believe that all lichenoid eruptions should be approached with a heightened index of suspicion and patients should be specifically questioned with regards to their vaccination history. When diagnosed early in its course, V-ILE is easily treated and resolves quickly in almost all patients with or without hyperpigmentation. Additional investigative studies regarding its immunopathology and inflammatory signaling pathways may offer insight into other Th1-driven autoimmune phenomena related to COVID-19 vaccination.

COVID-19 Vaccine-Induced Lichenoid Eruptions-Clinical and Histopathologic Spectrum in a Case Series of Fifteen Patients with Review of the Literature.

Lichen planus is a distinctive mucocutaneous disease with well-established clinical and histopathologic criteria. Lichenoid eruptions closely resemble lichen planus and may sometimes be indistinguishable from it. Systemic agents previously associated have included medications, viral infections and vaccines. Sporadic case reports of lichen planus and lichenoid reactions associated with COVID-19 vaccines have recently emerged. Herein, we review the world literature (31 patients) and expand it with a case series of 15 patients who presented with vaccine-induced lichenoid eruption (V-ILE). The spectrum of clinical and histopathologic findings is discussed with emphasis on the subset whose lesions manifested in embryologic fusion lines termed lines of Blaschko. This rare Blaschkoid distribution appeared in seven of the 46 patients studied. Of interest, all seven were linked to the mRNA COVID-19 vaccines. We believe that all lichenoid eruptions should be approached with a heightened index of suspicion and patients should be specifically questioned with regards to their vaccination history. When diagnosed early in its course, V-ILE is easily treated and resolves quickly in almost all patients with or without hyperpigmentation. Additional investigative studies regarding its immunopathology and inflammatory signaling pathways may offer insight into other Th1-driven autoimmune phenomena related to COVID-19 vaccination.

Perspectives on nonmedical switching and the COVID-19 pandemic: a narrative review.

OBJECTIVES: Nonmedical switching (NMS) is a change in a patient's treatment regimen for reasons other than lack of efficacy, intolerance, adverse effects, or poor adherence. We describe the impact of NMS on patients, health care workers, and health systems, focusing on NMS to in-class biologic alternatives in US patients with chronic, immune-mediated rheumatic and dermatologic conditions. Additionally, we evaluate the ways in which the COVID-19 pandemic may exacerbate the physical, psychological, and economic impacts of NMS. STUDY DESIGN: Narrative review. METHODS: We performed a search of MEDLINE's PubMed database from October 2015 to October 2020, with a repeat search in October 2021. Search terms included relevant keywords pertaining to NMS, biologics, and disease areas. Results were supplemented by a search of key congress abstracts from 2015 to 2021 and a targeted internet search. RESULTS: NMS increases medication abandonment, errors, and adverse effects, and it can lead to longer patient visits, increased follow-up visits, additional laboratory tests and procedures, and greater overall health care resource utilization (HCRU). The increased HCRU associated with NMS increases patients' financial burden due to additional co-pays and out-of-pocket costs. CONCLUSIONS: The decision to switch treatments should result from shared decision-making between health care providers (HCPs) and patients to achieve the best clinical outcomes and optimal HCRU. The issues related to NMS may be compounded by the financial and psychosocial stress on HCPs and patients created by the COVID-19 pandemic. HCPs should advocate for continuous patient treatment and be familiar with continuity of care legislation, appeals processes, and manufacturer assistance programs.

Perspectives on Nonmedical Switching and the COVID-19 Pandemic: A Narrative Review

Objectives: Nonmedical switching (NMS) is a change in a patient's treatment regimen for reasons other than lack of efficacy, intolerance, adverse effects, or poor adherence. We describe the impact of NMS on patients, health care workers, and health systems, focusing on NMS to in-class biologic alternatives in US patients with chronic, immune-mediated rheumatic and dermatologic conditions. Additionally, we evaluate the ways in which the COVID-19 pandemic may exacerbate the physical, psychological, and economic impacts of NMS. Study Design: Narrative review. Methods: We performed a search of MEDLINE's PubMed database from October 2015 to October 2020, with a repeat search in October 2021. Search terms included relevant keywords pertaining to NMS, biologics, and disease areas. Results were supplemented by a search of key congress s from 2015 to 2021 and a targeted internet search. Results: NMS increases medication abandonment, errors, and adverse effects, and it can lead to longer patient visits, increased follow-up visits, additional laboratory tests and procedures, and greater overall health care resource utilization (HCRU). The increased HCRU associated with NMS increases patients' financial burden due to additional co-pays and out-of-pocket costs. Conclusions: The decision to switch treatments should result from shared decision-making between health care providers (HCPs) and patients to achieve the best clinical outcomes and optimal HCRU. The issues related to NMS may be compounded by the financial and psychosocial stress on HCPs and patients created by the COVID-19 pandemic. HCPs should advocate for continuous patient treatment and be familiar with continuity of care legislation, appeals processes, and manufacturer assistance programs.

Evolution of Patient Perceptions of Psoriatic Disease: Results from the Understanding Psoriatic Disease Leveraging Insights for Treatment (UPLIFT) Survey.

INTRODUCTION: Since the 2012 Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) survey, several systemic treatments for psoriasis (PsO) and/or psoriatic arthritis (PsA) have been approved. The population-based UPLIFT survey was conducted to understand how perceptions of treatment-related outcomes have evolved, particularly for patients with mild to moderate PsO and/or PsA and their dermatologists. METHODS: This population- and web-based survey was conducted from 2 March to 3 June 2020, in North America, Europe, and Japan. Adults with self-reported healthcare practitioner (HCP)-diagnosed PsO and/or PsA and dermatologists who spent > 50% of time treating patients and treated ≥ 20 patients with PsO, including plaque PsO, per month were included. Patient participants were recruited at random from online panels; dermatologists were recruited randomly from representative physician panels. RESULTS: Of 264,054 patient responses, 3806 who self-reported an HCP diagnosis of PsO and/or PsA were included in the final sample; 67% had PsO alone, 28% had PsO and PsA, and 5% had PsA alone. The estimated population prevalence of psoriatic disease was 7% (PsO only: 4%; PsO and PsA: 2%; PsA only: 1%). Most patients (78%) reported PsO-involved body surface area (BSA) ≤ 3 palms, and ~ 90% or more reported itching, redness, flaking, and scales. Many PsO patients without diagnosed PsA reported musculoskeletal symptoms suggestive of PsA (63%). Across BSA categories, approximately one in four patients was not currently receiving treatment and > 50% had Dermatology Life Quality Index score > 5. Patients and dermatologists had different perceptions of PsO severity, office visit discussions, treatment goals, and treatment satisfaction. The survey was conducted during the coronavirus disease 2019 (COVID-19) pandemic, which could have affected assessments of patient-reported outcomes and ability to have in-person HCP visits. CONCLUSIONS: Patients with PsO and PsA in UPLIFT reported high disease burden, including patients with limited skin involvement. An opportunity exists to align patient and dermatologist perceptions to optimize management of PsO and PsA. INFOGRAPHIC: DIGITAL FEATURE: This article is published with digital features, including an infographic, to facilitate understanding of the article. To view digital features for this article go to https://doi.org/10.6084/m9.figshare.17104586 .

In recent years, several new treatments for psoriasis and psoriatic arthritis have become available. The UPLIFT survey was conducted to understand how viewpoints on psoriatic disease outcomes have changed, especially for patients whose disease is mild or moderate. UPLIFT was a large, online, population-based survey conducted in North America, Europe, and Japan. Adults with psoriasis and/or psoriatic arthritis and dermatologists who treated at least 20 patients with psoriasis per month were included. There were 3806 patients who participated; of these, most had psoriasis and few had psoriatic arthritis. Most patients (78%) with mild to moderate psoriasis had a limited area of skin affected by psoriasis. Psoriasis symptoms were common and included itching, redness, flaking, and scales. Many patients without a diagnosis of psoriatic arthritis reported symptoms that could be related to this disease (such as joint discomfort). Although many patients had psoriasis symptoms, approximately one in four was not currently receiving treatment and more than half reported psoriasis impacted their quality of life. Patients and dermatologists had different perceptions of psoriasis severity, office visit discussions, treatment goals, and treatment satisfaction. There is an opportunity to improve treatment of psoriasis and psoriatic arthritis and to better align patient and physician perceptions of psoriasis. This survey was conducted during the COVID-19 pandemic, which could have partially affected some assessments and the ability to have in-person doctor visits.

COVID-19 Symptoms Are Attenuated in Moderate-to-Severe Atopic Dermatitis Patients Treated with Dupilumab.

BACKGROUND: In the SARS-CoV-2/COVID-19 pandemic, we need to understand the impact of immunomodulatory medications on COVID-19 symptom severity in patients with inflammatory diseases, including the type 2/Th2 polarized skin disease, atopic dermatitis (AD). OBJECTIVE: Because it is believed that type 1/Th1 immunity controls viral infections and that there is a Th1/Th2 counter-regulation, we hypothesized that Th2 targeting with the IL-4Rα-antagonist, dupilumab, in patients with moderate-to-severe AD would rebalance the Th1/Th2 axis, potentially leading to attenuated COVID-19 symptoms. METHODS: A total of 1237 patients with moderate-to-severe AD in the Icahn School of Medicine at Mount Sinai Department of Dermatology were enrolled in a registry. Patients were screened for COVID-19-related symptoms and assigned a severity score (asymptomatic [0]-fatal [5]). Scores were compared among 3 treatment groups: dupilumab (n = 632), other systemic treatments (n = 107), and limited/no treatment (n = 498). Demographic and comorbid covariates were adjusted by multivariate generalized logistic regression models. RESULTS: The dupilumab-treated group showed reduced incidence and severity of COVID-19 symptoms versus other treatment groups. Dupilumab-treated patients were less likely to experience moderate-to-severe symptoms versus patients on other systemics (P = .01) and on limited/no treatment (P = .04), and less likely to experience any symptoms versus patients on other systemics (P = .01). This effect was seen in our entire cohort and in the subgroup of patients with verified COVID-19 or high-risk exposure. CONCLUSIONS: Patients on dupilumab experienced less severe COVID-19 manifestations and lesser symptoms compared with patients on other systemics and on limited/no treatment. These results suggest that Th2 modulation with dupilumab may have a protective effect on anti-viral immune response in patients with AD.

National Psoriasis Foundation COVID-19 Task Force guidance for management of psoriatic disease during the pandemic: Version 2-Advances in psoriatic disease management, COVID-19 vaccines, and COVID-19 treatments.

OBJECTIVE: To update guidance regarding the management of psoriatic disease during the COVID-19 pandemic. STUDY DESIGN: The task force (TF) includes 18 physician voting members with expertise in dermatology, rheumatology, epidemiology, infectious diseases, and critical care. The TF was supplemented by nonvoting members, which included fellows and National Psoriasis Foundation staff. Clinical questions relevant to the psoriatic disease community were informed by inquiries received by the National Psoriasis Foundation. A Delphi process was conducted. RESULTS: The TF updated evidence for the original 22 statements and added 5 new recommendations. The average of the votes was within the category of agreement for all statements, 13 with high consensus and 14 with moderate consensus. LIMITATIONS: The evidence behind many guidance statements is variable in quality and/or quantity. CONCLUSIONS: These statements provide guidance for the treatment of patients with psoriatic disease on topics including how the disease and its treatments affect COVID-19 risk, how medical care can be optimized during the pandemic, what patients should do to lower their risk of getting infected with severe acute respiratory syndrome coronavirus 2 (including novel vaccination), and what they should do if they develop COVID-19. The guidance is a living document that is continuously updated by the TF as data emerge.

National Psoriasis Foundation COVID-19 Task Force Guidance for Management of Psoriatic Disease During the Pandemic: Version 1.

OBJECTIVE: To provide guidance about management of psoriatic disease during the coronavirus disease 2019 (COVID-19) pandemic. STUDY DESIGN: A task force (TF) of 18 physician voting members with expertise in dermatology, rheumatology, epidemiology, infectious diseases, and critical care was convened. The TF was supplemented by nonvoting members, which included fellows and National Psoriasis Foundation (NPF) staff. Clinical questions relevant to the psoriatic disease community were informed by questions received by the NPF. A Delphi process was conducted. RESULTS: The TF approved 22 guidance statements. The average of the votes was within the category of agreement for all statements. All guidance statements proposed were recommended, 9 with high consensus and 13 with moderate consensus. LIMITATIONS: The evidence behind many guidance statements is limited in quality. CONCLUSION: These statements provide guidance for the management of patients with psoriatic disease on topics ranging from how the disease and its treatments impact COVID-19 risk and outcome, how medical care can be optimized during the pandemic, what patients should do to lower their risk of getting infected with severe acute respiratory syndrome coronavirus 2 and what they should do if they develop COVID-19. The guidance is intended to be a living document that will be updated by the TF as data emerge.