The emergence of data from clinical trials of biologics, the approval of new biologics, and our improved understanding of psoriasis pathogenesis have increased the therapeutic possibilities for the treatment of moderate-to-severe psoriasis. Biologics currently approved for the treatment of psoriasis include tumor necrosis factor inhibitors, interleukin (IL)-17 inhibitors, ustekinumab (an IL-12/23 inhibitor), and IL-23 inhibitors. Data from clinical trials and studies of the safety and efficacy of biologics provide essential information for the personalization of patient care. We discuss the benefits and disadvantages of biologics as a first-line treatment choice, update treatment recommendations according to current evidence, and propose psoriasis treatment algorithms. Our discussion includes the following comorbid conditions: psoriatic arthritis, multiple sclerosis, congestive heart failure, inflammatory bowel disease, hepatitis B, nonmelanoma skin cancer, lymphoma, and latent tuberculosis. We make evidence-based treatment recommendations for special populations, including pediatric patients, patients with coronavirus 2019 (COVID-19), and pregnant and breastfeeding patients with psoriasis. Ultimately, individualized recommendations that consider patient preferences, disease severity, comorbid conditions, and additional risk factors should be offered to patients and updated as new trial data emerges.
To describe the profile of patients with psoriasis who were treated with secukinumab, a newly approved biologic, in the U.S. and to examine secukinumab dosage use in real world practice. Retrospective data from the Symphony Health Solutions Lx commercial claims database between July 1, 2013 and July 31, 2015 (study period) were included in the study. Adult patients (≥18 years) with at least one secukinumab claim during the study period and with ≥1 pharmacy or medical claim in the 12 months before (baseline period) their first secukinumab claim (index date) were selected. Patient demographics, insurance type and secukinumab dosage (estimated based on the days of supply and quantity) were examined as of the index date. Comorbidities and prior systemic therapies were identified during the baseline period. A total of 1,947 secukinumab patients were included, with a mean age of 49.8 years (standard deviation (SD): 12.6). 47.9% of the patients were female, 40.8% from the south, and 89.3% had commercial insurance. The mean modified Charlson Comorbidity Index (excluding psoriasis-related comorbidities) was 0.14 (SD: 0.5); the most prevalent comorbidities included hypertension (19.1%), hyperlipidemia (16.7%), and psoriatic arthritis (15.0%). Most patients (72.9%) received systemic treatments in the baseline period: 58.6% of patients used a biologic, with the most common being ustekinumab (27.3%) and adalimumab (21.7%); 34.0% of patients used a non-biologic, mostly methotrexate (19.9%); and 2.7% used phototherapy. The majority of patients (99.8%) initiated secukinumab on the 300mg dose. The most prevalent comorbidities among secukinumab patients included hypertension, hyperlipidemia and psoriatic arthritis. Many patients received previous treatment, with more than half using a biologic prior to secukinumab. Almost all patients used the 300mg dose.
Herrinton, Lisa J. PhD∗; Ray, G. Thomas MBA∗; Wu, Jashin J. MD†; Fireman, Bruce MA∗; Liu, Liyan MD, MSc∗; Goldfien, Robert MD‡; Curtis, Jeffrey R. MD, MPH§ Author Information
Despite the recent approvals of biosimilars in the United States, the current landscape is still an evolving process. The overall impetus for the passage of the Biologics Price and Competition Act of 2009 and the abbreviated pathway for the development of biosimilars are to decrease the economic burden of biologics and increase access to qualified patients. The regulatory agenda for biosimilars involves an analytical approach through methods embodying a “totality of evidence” to demonstrate that a biosimilar has no clinically meaningful differences compared to the reference product. The establishment of extrapolation and interchangeability in a developmental program for biologics has no precedence for implementation. Because of these unique parameters associated with biosimilars, further mitigation is necessary to address concerns among health-care professionals. The acceptance and utilization of biosimilars in the United States may gain traction similar to generic drugs if reduced costs, increased access, and alleviation of concerns from clinicians are attained.
To the Editor: Patients with and dermatologists treating psoriasis usually strive for complete skin clearance, yet some patients prefer being off treatment. However, the prognosis after treatment discontinuation following remission is not well characterized. We investigated epidemiological characteristics and disease markers during the first 2 years following cessation of biologics due to remission. DERMBIO contains detailed information on all Danish psoriasis patients treated with biologics including cause of discontinuation.1Egeberg A. Iversen L. Gniadecki R. et al.Characteristics of patients receiving ustekinumab compared with secukinumab for treatment of moderate-to-severe plaque psoriasis – nationwide results from the DERMBIO registry.J Eur Acad Dermatol Venereol. 2017; 31: 1183-1187Crossref PubMed Scopus (22) Google Scholar Data on comorbidity and concurrent treatment (eg, topical therapy) were obtained through individual-level linkage across nationwide registries.2Pottegård A. Schmidt S.A.J. Wallach-Kildemoes H. Sorensen H.T. Hallas J. Schmidt M. Data resource profile: the Danish National Prescription Registry.Int J Epidemiol. 2017; 46 (798-798f)PubMed Google Scholar,3Schmidt M. Schmidt S.A.J. Sandegaard J.L. Ehrenstein V. Pedersen L. Sorensen H.T. The Danish National Patient Registry: a review of content, data quality, and research potential.Clin Epidemiol. 2015; 7: 449-490Crossref PubMed Scopus (2641) Google ScholarAdults treated with biologics between January 1, 2007, and December 31, 2016, were included and followed for 24 months. In DERMBIO, physicians state the reason for discontinuation through predefined options (eg, “Lack of efficacy”, “Side effects”, or “Remission”). The choice of “remission” is made by the dermatologist and may thus be chosen even with residual plaques. We defined remission as discontinuation with “remission” stated as reason and a Psoriasis Area and Severity Index (PASI) <3 at time of cessation. Characteristics were reported as frequencies and percentages or medians and interquartile ranges (IQRs). The proportions of patients to restart biologics or initiate nonbiologic systemics (including phototherapy) were reported and visualized with 95% confidence intervals. Kaplan–Meier curves displayed time from remission to initiation of a new treatment (Supplementary Material, available via Mendeley at https://data.mendeley.com/datasets/9trkp6r3n4/1). We used SAS v9.4 (SAS Institute Inc) and Python 3.7.4. In total, 40 (1%) of 3844 treatment series were discontinued due to remission and were compared to the rest of the 3804 (99%) treatment series. Upon treatment discontinuation, PASI = 0 was achieved in 24 (60.0%) treatment series. The median Dermatology Life Quality Index at remission was 0 for both overall and patients with PASI = 0, while it was 1 for patients with PASI >0. Most patients were men (53 %) and bio-naïve (60%). The median (IQR) age at diagnosis and prescription of treatment was 29.0 years (15.0, 44.0) and 43.0 years (30.8, 58.3), respectively. Seven (18%) patients were diagnosed with psoriatic arthritis and 5 (13%) patients had concomitant diabetes (Table I).Table IPatient characteristicsDiscontinued due to remissionDiscontinued due to remission (PASI = 0)Discontinued due to remission (PASI >0)Not discontinued due to remissionTreatment series, n4024163804Men, n (%)21 (53)12 (50)9 (56)2305 (61)Treatment duration in d, median (IQR)681 (336-1419)681 (336-1419)646 (345-1500)812 (259, 1791)Age at diagnosis, median (IQR), y29.0 (15.0-44.0)32.5 (18.5-44.0)17.0 (13.0-43.0)21.0 (14.0, 34.0)Age at prescription, median (IQR), y43.0 (30.8-58.3)48.5 (38.0-62.3)34.0 (23.8-46.5)46.0 (36.0-56.0)Number of previous biologics, median (IQR)0.0 (0.0-1.0)0.0 (0.0-1.0)0.0 (0.0-1.0)0.0 (0.0-1.0)Baseline PASI, median (IQR)5.3 (2.0-14.3)4.3 (1.8-10.0)10.0 (3.0-15.0)8.6 (3.7-13.4)Baseline DLQI, median (IQR)10.0 (2.0-14.0)5.0 (0.0-10.5)14.0 (5.0-18.0)10.0 (400-16.0)Last PASI, median (IQR)0.0 (0.0-1.2)0.0 (0.0-0.0)1.5 (0.90-2.0)2.0 (0.0-6.6)Last DLQI, median (IQR)0.0 (0.0-2.5)0.0 (0.0-0.0)1.0 (0.0-4.0)2.0 (0.0-7.0)Weight [kg], median (IQR)80.0 (70.5-87.8)75.0 (67.5-79.0)86.0 (80.0-102.0)90.0 (75.0-103.0)BMI [kg/m2], median (IQR)25.8 (25.0-31.6)25.7 (25.0-30.3)26.9 (25.1-35.9)28.2 (24.6-33.2)PsA, n (%)7 (18)≤6 (≤25)<3 (<13)1002 (26)Diabetes, n (%)5 (13)≤5 (≤21)<3 (<13)225 (6)0 previously failed biologic treatments, n (%)24 (60)14 (58)10 (63)2011 (53)1 previously failed biologic treatment, n (%)9 (23)6 (25)3 (19)957 (25)2+ previously failed biologic treatments, n (%)7 (18)4 (17)3 (19)836 (22)Drug (cytokine target), n (%) TNF-alpha inhibitor28 (70)18 (75)10 (63)2349 (62) IL-12/23 inhibitor12 (30)6 (25)6 (38)1131 (30) IL-17 inhibitor0 (0)0 (0)0 (0)251 (6.6) Other0 (0)0 (0)0 (0)73 (1.9)Time with PASI = 0 prior to discontinuation, n (%) Only last visitNA10 (42)NANA <6 moNA5 (21)NANA 6-12 moNA3 (13)NANA >12 moNA6 (25)NANABMI, Body mass index; DLQI, Dermatology Life Quality Index; IL, interleukin; IQR, interquartile range; NA, not applicable; PASI, Psoriasis Area and Severity Index; PsA, psoriatic arthritis; TNF-alpha, tumor necrosis factor alpha. Open table in a new tab BMI, Body mass index; DLQI, Dermatology Life Quality Index; IL, interleukin; IQR, interquartile range; NA, not applicable; PASI, Psoriasis Area and Severity Index; PsA, psoriatic arthritis; TNF-alpha, tumor necrosis factor alpha. Two years after discontinuation, 17 (43%) remained in remission or initiated treatment with topical therapy only. Among the patients achieving PASI = 0 at discontinuation, 12 (50%) were in remission or managed their symptoms with topical therapy for a minimum of 2 years. Among patients achieving remission with PASI >0, 5 (31%) remained in remission or were treated with topical therapy after 2 years (Table II).Table IIProportion (95% CI) of patients that have restarted treatment (any treatment, topicals only, or systemic treatment including biologics) at different time points, after biologics were stopped due to remissionAnyTopicalsSystemicsOverall Within 6 mo65.0% (49.5%-77.9%)35.0% (22.1%-50.5%)30.0% (18.1%-45.4%) Within 12 mo82.5% (68.1%-91.3%)32.5% (20.1%-48.0%)50.0% (35.2%-64.8%) Within 18 mo85.0% (70.9%-92.9%)27.5% (16.1%-42.8%)57.5% (42.2%-71.5%) Within 24 mo85.0% (70.9%-92.9%)27.5% (16.1%-42.8%)57.5% (42.2%-71.5%)PASI = 0 at discontinuation Within 6 mo62.5% (42.7%-78.8%)37.5% (21.2%-57.3%)25.0% (12.0%-44.9%) Within 12 mo79.2% (59.5%-90.8%)33.3% (18.0%-53.3%)45.8% (27.9%-64.9%) Within 18 mo83.3% (64.1%-93.3%)33.3% (18.0%-53.3%)50.0% (31.4%-68.6%) Within 24 mo83.3% (64.1%-93.3%)33.3% (18.0%-53.3%)50.0% (31.4%-68.6%)PASI >0 at discontinuation Within 6 mo68.8% (44.4%-85.8%)31.3% (14.2%-55.6%)37.5% (18.5%-61.4%) Within 12 mo87.5% (64.0%-96.5%)31.3% (14.2%-55.6%)56.3% (33.2%-76.9%) Within 18 mo87.5% (64.0%-96.5%)18.8% (7.0%-43.0%)68.8% (44.4%-85.8%) Within 24 mo87.5% (64.0%-96.5%)18.8% (7.0%-43.0%)68.8% (44.4%-85.8%)PASI, Psoriasis Area and Severity Index. Open table in a new tab PASI, Psoriasis Area and Severity Index. Patients were most likely to initiate topical treatment compared to systemics/biologics. Of the 18 patients restarting biologics, 13 initiated the same drug as they had previously discontinued. The median (IQR) duration of treatment in the patients who reinitiated the same drug was 768 (265-1200) days, suggesting that patients who stop biologic treatment because of a remission have a low risk of loss of effect on reinitiating that treatment. Only a small fraction of patients discontinued their treatment due to remission, which limits this study. More data and further investigations into this topic are relevant to fully illuminate and understand the prognosis after remission. In conclusion, these results suggest the tantalizing possibility that some patients, especially those who achieved complete skin clearance, can discontinue their biologic treatment and still maintain long-term control of their disease. Dr Thein has received funding from Ebba Celinders Legat and Else og Mogens Wedell-Wedellsborgs Fond. With no relation to the present manuscript Dr Rasmussen has been a speaker or has served on advisory boards for AbbVie, LEO Pharma, Novartis, UCB Pharma, and Janssen Pharmaceuticals; and has been an investigator for UCB Pharma and Novartis. With no relation to the present manuscript Dr Bertelsen has received research funding from Novartis, the Danish National Psoriasis Foundation, The A.P Moller foundation, and the Kgl Hofbundtmager Aage Bang Foundation, and received educational grants from Pfizer and Abbvie, and has been a paid speaker for Eli Lilly and Leo Pharma. Dr Skov has been a paid speaker for AbbVie, Eli Lilly, Pfizer, Novartis, Janssen and LEO Pharma, and has been a consultant or has served on Advisory Boards with AbbVie, Janssen Pharmaceuticals, Novartis, Eli Lilly, Boehringer Ingelheim, LEO Pharma, Almirall, Bristol-Myers Squibb, UCB and Sanofi. She has served as an investigator for AbbVie, Sanofi, Janssen Pharmaceuticals, Boehringer Ingelheim, Galderma, Eli Lilly, Novartis, Regeneron, and LEO Pharma, and has received research founding from Novartis, Sanofi, Bristol-Myers Squibb, Janssen Pharmaceuticals, LEO Pharma and Leo Foundation. Dr Bryld has received an educational grant from Janssen Pharmaceuticals. Dr Wu is or has been an investigator, consultant, or speaker for AbbVie, Almirall, Amgen, Arcutis, Aristea Therapeutics, Bausch Health, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, DermTech, Dr Reddy's Laboratories, Eli Lilly, EPI Health, Galderma, Janssen, LEO Pharma, Mindera, Novartis, Pfizer, Regeneron, Samsung Bioepis, Sanofi Genzyme, Solius, Sun Pharmaceutical, UCB, and Zerigo Health. With no relation to the present manuscript Dr Thomsen has been a speaker or has served on advisory boards for Sanofi, AbbVie, LEO Pharma, Pfizer, Eli Lilly and Company, Novartis, UCB Pharma, Union Therapeutics, Almirall, and Janssen Pharmaceuticals; has received research support from Sanofi, AbbVie, LEO Pharma, Novartis, UCB Pharma, and Janssen Pharmaceuticals; and has been an investigator for Sanofi, Regeneron, AbbVie, CSL, AstraZeneca, LEO Pharma, Boehringer Ingelheim, Janssen Pharmaceuticals, Novartis and Pfizer. With no relation to the present manuscript Dr Thyssen is an advisor for AbbVie, Almirall, Arena Pharmaceuticals, Coloplast, OM Pharma, Aslan Pharmaceuticals, Union Therapeutics, Eli Lilly & Co, LEO Pharma, Pfizer, Regeneron, and Sanofi-Genzyme; a speaker for AbbVie, Almirall, Eli Lilly & Co, LEO Pharma, Pfizer, Regeneron, and Sanofi-Genzyme; and received research grants from Pfizer, Regeneron, and Sanofi-Genzyme. With no relation to the present manuscript Dr Egeberg has received research funding from Pfizer, Eli Lilly, Novartis, Bristol-Myers Squibb, Boehringer Ingelheim, AbbVie, Janssen Pharmaceuticals, the Danish National Psoriasis Foundation, the Simon Spies Foundation, and the Kgl Hofbundtmager Aage Bang Foundation; and honoraria as consultant and/or speaker from AbbVie, Almirall, Leo Pharma, Zuellig Pharma Ltd, Galápagos NV, Sun Pharmaceuticals, Samsung Bioepis Co, Ltd, Pfizer, Eli Lilly and Company, Novartis, Galderma, Dermavant, UCB, Mylan, Bristol-Myers Squibb, McNeil Consumer Healthcare, Horizon Therapeutics, Boehringer Ingelheim, and Janssen Pharmaceuticals. Ms Nielsen, Dr Dam, and Dr Ajgeiy have no conflicts of interest to disclose. We acknowledge the substantial contribution of the academic hospitals and private clinics and their physicians that report data to DERMBIO.
Prolonged systemic antibiotic treatment is often a part of management of hidradenitis suppurativa (HS). Although biologic therapies are now available, the patient's treatment journey leading to biologic therapy is unclear.To examine treatment patterns and duration of systemic treatment use in patients with HS preceding biologic therapy.We identified all patients with HS receiving treatment with biologics in the Danish National Patient Registry from 2010 to 2018 and extracted their entire prescription history of specific systemic treatments from the Danish National Prescription Registry since its inception in 1995. The patients' treatment journeys are graphically displayed through Sankey diagrams and box plots generated to show temporal distributions. Descriptive patient characteristics were presented as frequencies with percentages for categorical variables and as means with SDs or medians with interquartile ranges (IQRs) for continuous variables.A total of 225 patients with HS were included. Patients had most frequently been treated with penicillin (n = 214; 95·1%), dicloxacillin (n = 194; 86·2%), tetracycline (n = 145; 64·4%) and rifampicin/clindamycin (n = 111; 49·3%), as well as the retinoids isotretinoin and acitretin, and dapsone. Prior to biologic therapy, patients received a mean of 4·0 (SD 1·3) different systemic therapies, across a mean of 16·9 (SD 11·3) different treatment series. The mean time from first systemic therapy until biologic therapy was initiated was 15·3 (SD 5·1) years [8·2 (SD 5·9) years when excluding penicillin and dicloxacillin].Patients with HS who receive biologic therapy have long preceding treatment histories with multiple drug classes and treatment series, many of which are supported by relatively weak evidence in HS. Delay in the initiation of biologic therapy may represent a missed opportunity to prevent disease progression. What is already known about this topic? The treatment journey leading to biologic therapy in patients with HS has not previously been investigated. What does this study add? Our data from 225 patients with HS illustrate that patients who receive biologic therapy have long preceding treatment histories with multiple drug classes and treatment series, many of which are supported by relatively weak evidence in HS.
This study aimed to assess the accuracy of GPT-4 in generating appropriate differential diagnoses and arriving at the correct diagnoses for common skin lesions. Additionally, we investigated any differences in its diagnostic accuracy between darker and lighter skin tones. GPT-4 exhibited better performance in providing the correct diagnosis for lighter skin tones (44%, n = 11 of 25) compared with darker skin tones (12%, n = 3 of 25), and this was statistically significant (P < 0.05). Furthermore, with each unit increase in the Fitzpatrick scale, GPT-4’s performance decreased by 11.4% in accurately providing a differential diagnosis and by 7.1% in accurately providing the correct diagnosis.
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