Atopic dermatitis is a highly prevalent, chronic, relapsing disease in both adults and children. On the severity spectrum, lower-end patients benefit from small amounts of topical anti-inflammatory ...treatments (TAT), whereas higher-end patients need systemic immunosuppressants; in-between patients are treated with TAT and phototherapy. The major therapeutic challenge in this population is the long-term control of disease activity, and the current TAT-based pro-active strategy does not meet all their needs. Immunosuppressants are used as long-term control add-on treatments, but they are restricted to the most severely affected patients because of safety concerns. In addition, neither immunosuppressants nor other strategies have been properly evaluated in the long term despite long-term control having been acknowledged as one of the most important core outcome domains to be targeted in atopic dermatitis trials. Safe add-on therapies, rigorously evaluated for long-term control of the disease, are therefore needed. Phototherapy and vitamin D supplementation are both good candidates.
This is a multicenter, national, randomized, superiority, crossover trial testing add-on phototherapy (one winter under spaced sessions of phototherapy and one winter under observation) among subjects receiving standard care (i.e., TAT). On the same population, we will test the long-term control provided by oral supplementation of vitamin D versus placebo in a randomized, superiority, double-blind, parallel-group trial. The primary outcomes are (1) repeat measures of the PO-SCORAD severity score over 1 year and (2) cumulate consumption of TAT (number of tubes) during the winter. They will be tested following a hierarchical testing procedure. The secondary outcomes will be measures repeated over 2 years of investigator-based severity scores, patient-reported severity and quality of life scores, serum vitamin D levels, weeks during which the disease is well-controlled, inter-visit cumulate consumption of TAT, and synthetic patient-reported satisfaction at the end of each winter.
This study includes two separate 2-year pragmatic trials designed to evaluate the efficacy of vitamin D supplementation and pro-active phototherapy for primary care atopic dermatitis patients receiving TAT on long-term control of disease activity. The experimental design enables the study of both interventions and exploration of the interaction between vitamin D and phototherapy. A pragmatic trial is particularly suited to the assessment of long-term control. This study explores the possibility of new and safe therapeutic strategies for the control of long-term atopic dermatitis, and is an example of efficacy research that is unlikely to be sponsored by industrialists. A potentially effective low-cost therapeutic strategy for long-term control is essential for patients and public health.
ClinicalTrials.gov Identifier: NCT02537509 , first received: 1 September 2015.
The treatment of moderate-to-severe plaque psoriasis has seen significant improvements in recent years with the advent of biologic drugs. The aim of this study was to assess the cost-effectiveness of ...anti-IL17 drugs and other biologic therapies used to treat moderate-to-severe plaque psoriasis in France and Germany over a one-year time horizon.
We developed a cost per responder model for biologic drugs used in psoriasis treatment. The model included anti-IL17s (brodalumab, secukinumab, ixekizumab and bimekizumab), anti-TNFs (adalimumab, etanercept, certolizumab and infliximab), an anti-IL12/23 (ustekinumab), and anti-IL23s (risankizumab, guselkumab and tildrakizumab). Efficacy estimates were collected through a systematic literature review of network meta-analyses on long-term Psoriasis Area and Severity Index (PASI) measures. Dose recommendations and country-specific prices were used to calculate drug costs. Biosimilar drug prices were used when available as a substitute for the originator drugs.
After one year, brodalumab had the lowest cost per PASI100-responder in both France (€20,220) and Germany (€26,807) across all available biologic treatments. Among the anti-IL17s, brodalumab had a 23% lower cost per PASI100-responder vs. the nearest comparator in France (bimekizumab, €26,369), and 30% lower vs. nearest comparator in Germany (ixekizumab, €38,027). Brodalumab also had the lowest cost per PASI75- and PASI90-responder among the anti-IL17s in both France and Germany after one year. Adalimumab had the lowest cost per PASI100-responder among the anti-TNFs in both France (€23,418) and Germany (€38,264). Among the anti-IL-23s, risankizumab had the lowest cost per PASI100-responder in both France (€20,969) and Germany (€26,994).
Driven by its lower costs and high response rates, brodalumab was the most cost-effective treatment option for moderate-to-severe plaque psoriasis over a one-year time-horizon within the anti-IL17 class and when compared to all other biologics in France and Germany.
Prurigo pigmentosa following booster dose of COVID‐19 vaccine Skowron, François; Carbonnelle‐Puscian, Amélie
Journal of the European Academy of Dermatology and Venereology,
March 2023, 2023-03-00, 20230301, Letnik:
37, Številka:
3
Journal Article
Immune checkpoint inhibitors (ICI) significantly improve overall survival (OS) in patients with advanced melanoma, but immune-related colitis may occur and warrant anti-tumor necrosis factor α (TNFα) ...treatment in severe forms. A nationwide, multicenter retrospective survey was conducted to assess both, the real-life incidence of grade 3/4 ICI-induced colitis treated with anti-TNFα, in patients with advanced melanoma, and the consequence of this therapeutic strategy on disease outcome. All patients with advanced melanoma treated with anti-TNFα agents for severe ICI-related colitis in the participating centers were included. Relative incidence was calculated according to the total number of patients treated with ICI in network centers during the period of inclusion. The possible impact of anti-TNFα treatment on disease outcome was evaluated through comparison of objective response rate, progression-free survival, and OS with pivotal literature data. Twenty-seven patients from 13 tertiary referral centers were included. Overall, severe ICI-related colitis treated with anti-TNFα occurred in 1% of patients with advanced melanoma, mostly with ipilimumab. Infliximab was successfully used in all patients but 1, mostly after 1 infusion. OS and progression-free survival of 12 and 3 months, respectively, were observed in these patients, along with an objective response rate of 41% at 12 months. This survey shows a low real-life incidence of severe colitis requiring anti-TNFα. Response rates to immunotherapy and survival data do not appear to significantly differ from those observed in pivotal studies. Severe ICI-induced colitis requiring anti-TNFα treatment appears to be a rare event in advanced melanoma, and infliximab does not seem to adversely affect disease outcome.
VEXAS syndrome following COVID‐19 mRNA vaccination Skowron, François; Klepfisch, Lucas; Guillaume, Laurent ...
Journal of the European Academy of Dermatology and Venereology,
August 2023, Letnik:
37, Številka:
8
Journal Article
Pigmented genital lesions: A prospective cross‐sectional study David‐Ferreira, Chloé; Ravni, Estelle; Bourgea, Céline ...
JEADV. Journal of the European Academy of Dermatology and Venereology/Journal of the European Academy of Dermatology and Venereology,
April 2023, 2023-04-00, 20230401, Letnik:
37, Številka:
4
Journal Article
OBJECTIVE:To describe the spectrum, treatment, and outcome of cranial nerve disorders associated with immune checkpoint inhibitors (Cn-ICI).
METHODS:This nationwide retrospective cohort study on ...Cn-ICI (2015-2019) was conducted using the database of the French Refence Center. In addition, a systematic review of the literature (MEDLINE, Scopus, and Web of Science) for records published between 2010-2019 was performed following the PRISMA guidelines, using the search terms “cranial nerve” or “neuropathy” or “palsy” and “immune checkpoint inhibitors”.
RESULTS:Among 67 cases with ICI-related neurological toxicities diagnosed in our Reference Center, 9 patients with Cn-ICI were identified (7 men, 78%; median age 62 years range26-82). Patients were receiving a combination of anti-CTLA-4 and anti-PD-1/PD-L1 (n=5, 56%), or anti-PD-1 antibodies alone (n=4, 44%). Cn-ICI involved optic (n=3), vestibulocochlear (n=3), abducens (n=2), facial (n=2), and oculomotor nerve (n=1). Two patients had involvement of 2 different cranial nerves. Treatment comprised corticosteroids (n=8, 89%), ICI permanent discontinuation (n=7, 78%), plasma-exchange (n=2, 22%), and IVIG (n=1, 11%). Median follow-up was 11 months (range1-41). In 3 cases (33%) neurological deficit persisted/worsened despite treatment2 optic and 1 vestibulocochlear. Among cases from the literature and the present series combined (n=39), the most commonly affected cranial nerves were facial (n=13, 33%), vestibulocochlear (n=8, 21%), optic (n=7, 18%), and abducens (n=4, 10%). Trigeminal, oculomotor, and glossopharyngeal nerves were less frequently affected (total n=7).
CONCLUSION:Cranial nerve disorders can complicate treatment with ICIs. Approximately one third of the patients had persisting deficits, most frequently involving hearing and vision loss.
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