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Fyziologicky tvoří kožní bariéra, kožní mikrobiom, složky nespecifické a specifické imunity funkční celek. Léčebné a preventivní ovlivnění atopického ekzému cestou obnovení správného kožního mikrobiomu je potenciální cestou k doplnění stávajících léčebných možností. Má ale svá úskalí, neboť kožní mikrobiom je individuálně specifický a v čase proměnlivý. V praxi jsou tomuto záměru zatím nejblíže postbiotika ve speciálních emolienciích.

Skin barrier, skin microbiome, components of non-specific and specific skin immunity build physiologically a functional complex. Therapeutic and preventive management of atopic eczema by restoring proper skin microbiome is a potential way for adjunction to existing therapeutic options. However, it has its pitfalls as the skin microbiome is individually specific and variable over time. In practice, postbiotics in special emollients are the closest to this aim, so far.

MeSH
alergie imunologie MeSH
atopická dermatitida * etiologie farmakoterapie imunologie patofyziologie MeSH
emoliencia terapeutické užití MeSH
lidé MeSH
mikrobiota * imunologie MeSH
Check Tag
lidé MeSH
Publikační typ
přehledy MeSH

Článek

Liečba atopickej dermatitídy
[Treatment of atopic dermatitis]

Takáčová, Gabriela, 1987-
Autor Autorita ORCID Klinika dermatovenerológie, UPJŠ LF a UNLP, Košice

Dermatologie pro praxi. 2024 ; 18 (3) : 151-153. [pub] 20241007

ISSN 1802-2960
Medvik
Zdroj

Atopická dermatitída je chronické zápalové ochorenie kože s multifaktoriálnou etiológiou. U väčšiny pacientov začína v detskom veku, u časti pacientov pretrváva do dospelosti. Cieľom terapie je predĺžiť remisiu. Terapia atopickej dermatitídy je komplexná. K dispozícii máme v súčasnosti široké spektrum možností topickej, fyzikálnej a sytémovej liečby. Výber terapie zohľadňuje fázu ochorenia, závažnosť atopickej dermatitídy a individuálnu preferenciu pacienta.

Atopic dermatitis is a chronic inflammatory skin disease with a multifactorial etiology. In most patients, it begins in childhood, in some patients it persists into adulthood. The goal of therapy is to prolong remission. The therapy of atopic dermatitis is complex. We currently have a wide range of topical, physical and systemic treatment options available. The choice of therapy takes into account the stage of the disease, the severity of atopic dermatitis and the individual preference of the patient.

MeSH
atopická dermatitida * diagnóza farmakoterapie patologie terapie MeSH
dermatologické látky klasifikace terapeutické užití MeSH
lidé MeSH
Check Tag
lidé MeSH
Publikační typ
přehledy MeSH

Článek

Cendakimab in Patients With Moderate to Severe Atopic Dermatitis: A Randomized Clinical Trial

JAMA dermatology. 2024 ; 160 (8) : 856-864. [pub] 20240801

JAMA Dermatol
ISSN 2168-6084
Medvik
Zdroj

IMPORTANCE: Cendakimab selectively targets interleukin (IL)-13, a type 2 cytokine implicated in atopic dermatitis (AD) pathogenesis, by inhibiting binding to its receptors (IL13R-α1 and IL13R-α2). Proof-of-concept work in AD supports using cendakimab for type 2 inflammatory diseases. OBJECTIVE: To evaluate the efficacy and safety of cendakimab compared with placebo in patients with moderate to severe AD. DESIGN, SETTING, AND PARTICIPANTS: This phase 2, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging clinical trial was conducted from May 2021 to November 2022. Adult patients with moderate to severe AD and inadequate response to topical medications were enrolled at 69 sites in 5 countries (US [n = 26], Japan [n = 17], Canada [n = 9], Poland [n = 9], and Czech Republic [n = 8]). Data were analyzed between April 25, 2023, and October 16, 2023. INTERVENTIONS: Patients were randomized (1:1:1:1) to receive subcutaneous cendakimab, 360 mg, every 2 weeks; 720 mg, every 2 weeks; 720 mg, once weekly; or placebo. MAIN OUTCOME AND MEASURE: Mean percentage change in Eczema Area and Severity Index scores from baseline to week 16. Hierarchical testing with multiplicity adjustment was performed for 720 mg, once weekly vs placebo, then 720 mg, every 2 weeks vs placebo, and then 360 mg, every 2 weeks vs placebo. RESULTS: Overall, 221 patients were randomized, and 220 received study drug (95 women [43%]; mean [SD] age, 37.7 [13.9] years; 720 mg, once weekly [54 (24%)]; 720 mg, every 2 weeks [55 (25%)]; 360 mg, every 2 weeks [55 (25%)]; placebo [56 (26%)]). The primary efficacy end point was met for cendakimab, 720 mg, once weekly vs placebo (-84.4 vs -62.7; P = .003) but missed statistical significance for 720 mg, every 2 weeks (-76.0 vs -62.7; P = .06). The treatment effect for 360 mg, every 2 weeks (-16.3; nominal P = .03 vs placebo) was comparable with 720 mg, once weekly (-21.8); however, significance was not claimed because the hierarchical testing sequence was interrupted. Of patients with treatment-emergent adverse events leading to discontinuation, 4 (7.4%) received 720 mg, once weekly; 2 (3.6%) 720 mg, every 2 weeks; 1 (1.8%) 360 mg, every 2 weeks; and 2 (3.6%) placebo. CONCLUSIONS AND RELEVANCE: The results of this randomized clinical trial indicated that cendakimab was effective, generally safe, and well-tolerated in patients with moderate to severe AD. The primary end point was met with a significant reduction in Eczema Area and Severity Index scores with 720 mg, once weekly at week 16. Cendakimab demonstrated progressive AD improvement at all doses during 16 weeks of treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04800315.

Článek

Nemolizumab with concomitant topical therapy in adolescents and adults with moderate-to-severe atopic dermatitis (ARCADIA 1 and ARCADIA 2): results from two replicate, double-blind, randomised controlled phase 3 trials

Lancet (London, England). 2024 ; 404 (10451) : 445-460. [pub] 20240724

Lancet
ISSN 1474-547X
Medvik
Zdroj

BACKGROUND: Nemolizumab, an interleukin (IL)-31 receptor subunit α antagonist, inhibits the IL-31 pathway of itch and skin inflammation in atopic dermatitis. Two international phase 3 studies were done to assess the efficacy and safety of nemolizumab in atopic dermatitis. In this Article we report results for the 16-week initial treatment period of both trials. METHODS: ARCADIA 1 and ARCADIA 2 were identical 48-week randomised, double-blind, placebo-controlled phase 3 trials in adult and adolescent participants (aged ≥12 years) with moderate-to-severe atopic dermatitis, associated pruritus, and inadequate response to topical steroids. Participants were enrolled from 281 clinics, hospitals, and academic centres in 22 countries across both trials, and were randomly assigned (2:1) to receive nemolizumab 30 mg subcutaneously (baseline loading dose 60 mg) or matching placebo once every 4 weeks with background topical corticosteroids (TCS) with or without topical calcineurin inhibitors (TCI; ie, TCS-TCI background treatment). Randomisation was done via interactive response technology and stratified by baseline disease and pruritus severity. Study staff and participants were masked throughout the study, with outcome assessors masked until database lock. Coprimary endpoints at week 16 post-baseline were Investigator's Global Assessment (IGA) success (score of 0 [clear skin] or 1 [almost clear skin] with a ≥2-point improvement from baseline) and at least 75% improvement in Eczema Area and Severity Index score from baseline (EASI-75 response). Outcome rates were compared between groups with the Cochran-Mantel-Haenszel test adjusting for randomisation strata. The key secondary endpoints were the proportion of participants with Peak Pruritus Numerical Rating Scale (PP-NRS) score improvement of at least 4 points at weeks 1, 2, 4, and 16; PP-NRS score below 2 at weeks 4 and 16; Sleep Disturbance Numerical Rating Scale score improvement of at least 4 points at week 16; EASI-75 response plus PP-NRS score improvement of at least 4 points at week 16; and IGA success plus PP-NRS score improvement of at least 4 points at week 16. Efficacy analyses were done on an intention-to-treat basis; safety analyses included all participants who received one dose of nemolizumab or placebo. Both studies are completed (ClinicalTrials.gov: ARCADIA 1, NCT03985943 and ARCADIA 2, NCT03989349). FINDINGS: Between Aug 9, 2019, and Nov 2, 2022, 1728 participants were enrolled across both trials: 1142 were allocated to nemolizumab plus TCS-TCI (620 in ARCADIA 1 and 522 in ARCADIA 2) and 586 to placebo plus TCS-TCI (321 in ARCADIA 1 and 265 in ARCADIA 2). ARCADIA 1 included 500 (53%) male participants and 441 (47%) female participants, and ARCADIA 2 included 381 (48%) male participants and 406 (52%) female participants. Mean age ranged from 33·3 (SD 15·6) years to 35·2 (17·0) years across the treatment groups. Both trials met the coprimary endpoints; at week 16, a greater proportion of participants receiving nemolizumab plus TCS-TCI versus placebo plus TCS-TCI had IGA success (ARCADIA 1: 221 [36%] of 620 vs 79 [25%] of 321, adjusted percentage difference 11·5% [97·5% CI 4·7-18·3], p=0·0003; ARCADIA 2: 197 [38%] of 522 vs 69 [26%] of 265, adjusted difference 12·2% [4·6-19·8], p=0·0006) and an EASI-75 response (ARCADIA 1: 270 [44%] vs 93 [29%], adjusted difference 14·9% [7·8-22·0], p<0·0001; ARCADIA 2: 220 [42%] vs 80 [30%], adjusted difference 12·5% [4·6-20·3], p=0·0006). Significant benefits were observed with nemolizumab for all key secondary endpoints including improvement in itch, as early as week 1, and sleep improvement by week 16. The safety profile was similar between nemolizumab plus TCS-TCI and placebo plus TCS-TCI. In the safety sets, 306 (50%) of 616 participants (ARCADIA 1) and 215 (41%) of 519 participants (ARCADIA 2) who received nemolizumab plus TCS-TCI had at least one treatment-emergent adverse event (serious treatment-emergent adverse events in six [1%] and 13 [3%], respectively); and 146 (45%) of 321 (ARCADIA 1) and 117 (44%) of 263 (ARCADIA 2) who received placebo plus TCS-TCI had at least one treatment-emergent adverse event (serious treatment-emergent adverse events in four [1%] and three [1%], respectively). Ten serious treatment-emergent adverse events possibly related to nemolizumab were reported in five (1%) participants in ARCADIA 2. No deaths occurred. INTERPRETATION: Nemolizumab plus TCS-TCI was efficacious and showed statistically and clinically significant improvements in inflammation and itch in adults and adolescents with moderate-to-severe atopic dermatitis. Nemolizumab might offer a valuable extension of current therapies if approved. FUNDING: Galderma.

Článek

Odvykací stav od kortikoidů a syndrom závislosti
[Topical steroid withdrawal and the dependence syndrome]

Praktický lékař. 2024 ; 104 (2) : 93-96.

ISSN 0032-6739
Medvik
Zdroj

Odvykací stav od kortikoidů a syndrom závislosti (red skin syndrome, topical steroid withdrawal a addiction) je potenciální komplikací dlouhodobé anebo nadměrné terapie kortikoidovými externy. Syndrom z odnětí zahrnuje zvláště fyzické projevy plynoucí z tachyfylaxe, rebound fenoménu a potlačení HPA osy (erytrodermie, pálení kůže, pruritus, exsudace a xeróza, otoky, poruchy termoregulace, zhoršení visu, zvýšené riziko ohrožujících infekcí zvláště bakteriálních nebo virových, ale i mykotických nebo parazitárních, dále často alopecie a u žen amenorea). Jedná se ale i o projevy psychické (poruchy spánku, zvýšená únava, deprese, úzkosti, sebevražedné myšlenky až dokonaná suicidia). V případě prolongované terapie kortikoidy se mohou objevit naopak pocity euforie nebo emoční labilita. Léčba je symptomatická, s režimovými opatřeními, čítá měsíce až léta. V některých případech se využívá chemoterapeutik, biologické léčby nebo inhibitorů Janusových kináz. Může být na místě najít si podporujícího lékaře, popřípadě zvážit přínos psychiatra a psychoterapeuta. V rámci anamnézy je třeba zjišťovat od pacienta i informaci o používání těchto léčiv, z nichž některá jsou volně prodejná nebo mohla být pacientovi darována laikem. V rámci prevence, která je velmi důležitá, je třeba pacienta v případě indikace léčby o správné aplikaci a době používání náležitě, třebaže opakovaně edukovat.

The topical steroid withdrawal and addiction (red skin syndrome, topical steroid withdrawal and addiction) is a potential complication of long-term or excessive topical steroid therapy. The withdrawal syndrome includes especially physical manifestations resulting from tachyphylaxis, rebound phenomenon and suppression of the HPA axis (erythroderma, burning skin, pruritus, exudation and xerosis, swelling, thermoregulation disorders, worsening of the vision, increased risk of threatening infections, especially bacterial or viral, but also fungal or parasitic, also often alopecia and, in women, amenorrhea). But there are also psychological manifestations (sleep disorders, increased fatigue, depression, anxiety, suicidal thoughts, and even committed suicide). In the case of prolonged topical steroid therapy, on the contrary, feelings of euphoria or emotional lability may appear. The treatment is symptomatic, with regimen measures, lasting months to years. In some cases, chemotherapy, biological treatments or Janus kinase inhibitors are used. It may be appropriate to find a supportive doctor, or consider the contribution of a psychiatrist and psychotherapist. As part of the anamnesis, the information about the use of these drugs, some of which are over-the-counter or may have been given to the patient by a layman, must also be obtained from the patient. As a part of prevention, which is very important, if the treatment is indicated, the patient needs to be properly educated, even if repeatedly, about the correct application and duration of use.

Klíčová slova
red skin syndrome,
MeSH
atopická dermatitida * farmakoterapie komplikace MeSH
exfoliativní dermatitida chemicky indukované terapie MeSH
hormony kůry nadledvin * škodlivé účinky terapeutické užití MeSH
lidé MeSH
nežádoucí účinky léčiv MeSH
Check Tag
lidé MeSH
Publikační typ
kazuistiky MeSH

Článek

Registr biologické/cílené léčby BIOREP - Souhrnná zpráva za rok 2023
[Registry of biological/Targeted therapy BIOREP - Summary report 2023]

Česko-slovenská dermatologie. 2024 ; 99 (2) : 62-86.

ISSN 0009-0514
Medvik
Zdroj

Cíl práce: Hodnocení pacientů zařazených do registru biologické/cílené léčby BIOREP v České republice za rok 2023. Metody: Bylo provedeno retrospektivní hodnocení pacientů k datu 31. 12. 2023 zařazených do registru BIOREP s diagnózou psoriázy, hidradenitis suppurativa a atopické dermatitidy léčených biologickou/cílenou léčbou v daném období. V případě kategoriálních proměnných byly výsledky vyjádřeny pomocí počtu a procenta. Spojité proměnné byly popsány pomocí počtu, průměru, směrodatné odchylky, mediánu, minima a maxima. Výsledky: K 31. 12. 2023 bylo v registru BIOREP evidováno celkem 6 676 pacientů. S psoriázou bylo sledováno 4 763 pacientů (71,3 %), s hidradenitidou 538 pacientů (8,1 %), 1 346 pacientů (20,2 %) s atopickou dermatitidou a zbývajících 29 pacientů (0,4 %) s použitím „off-label“ léčby. Ve skupině léčených pro psoriázu bylo 62,5 % mužů, průměrný věk pacientů ke konci roku 2023 byl 52,3 let, průměrný věk v době diagnózy byl 25,6 let a při nasazení první biologické/cílené léčby 46,4 let. Průměrná doba od diagnózy do zahájení první cílené léčby byla 20,8 let. Ke konci roku 2023 byli pacienti léčeni cílenou léčbou v průměru 5,2 let. Přidružená onemocnění mělo 70,6 % pacientů, nejčastější byla metabolická/endokrinní onemocnění (39,2 %) a kardiovaskulární onemocnění (37,8 %). Ze sledovaných komorbidit byla nejčetnější hypertenze (35,2 %), dyslipidemie (26,5 %) a diabetes mellitus (12,5 %). Celkem 76,1 % pacientů trpělo nadváhou či obezitou a v registru bylo 33 % kuřáků. Souběžnou psoriatickou artritidu mělo 30,8 % pacientů. Při zahájení léčby a při poslední návštěvě bylo průměrné PASI 18,6, resp. 1,8, BSA bylo v průměru 29 %, resp. 2,5 %, a průměrné DLQI 16,1, resp. 1,6. Po 12 měsících léčby dosáhlo PASI50 celkem 91,8 % pacientů, PASI75 82,6 % pacientů, PASI90 64,7 % pacientů a PASI100 40,8 % pacientů. V roce 2023 nově zahájilo léčbu celkem 645 pacientů, na konci sledovaného roku 2023 bylo aktivně léčeno celkem 4 120 pacientů a nejčastěji používaným preparáty byly Skyrizi (15,7 %), Humira (12,1 %) a Cosentyx (12,0 %). S diagnózou hidradenitis suppurativa bylo v registru na konci sledovaného období celkem 538 pacientů, z toho 55,4 % mužů, průměrný věk byl 44,5 let. V době diagnózy bylo pacientům v průměru 32,7 let a v době nasazení léčby v průměru 41,7 let. Průměrná doba od diagnózy do zahájení první biologické léčby byla 9 let a pacienti byli léčeni v průměru 2,7 let. V roce 2023 svou první biologickou léčbu zahájilo celkem 85 pacientů. Na konci sledovaného roku bylo léčeno celkem 422 pacientů, průměrná délka léčby jedním léčivým přípravkem byla 2,4 let a nejčastěji použitým preparátem byla Humira (67,8 %). S atopickou dermatitidou bylo v registru BIOREP sledováno k 31. 12. 2023 celkem 1 346 pacientů, z toho 51 % mužů. V roce 2023 byl průměrný věk pacientů 36,2 let. V době diagnózy onemocnění byl průměrný věk pacientů 5,2 let a při nasazení první cílené léčby 34,9 let. Průměrná doba od diagnózy do zahájení první cílené léčby byla 29,8 let. Ke konci roku 2023 byli pacienti léčeni v průměru 1,7 let. Souběžnou alergickou rýmu mělo 60,1 % pacientů, potravinovou alergii 54,8 % a alergické astma 42,1 %. Oční postižení se vyskytlo u 23,6 % pacientů, nejčastější byla atopická konjunktivitida (12,2 %). Průměrné EASI při zahájení léčby a na poslední návštěvě bylo 30,8, resp. 4,1, BSA bylo v průměru 56 %, resp. 8 %, a průměrné DLQI 18,2, resp. 3,7. V roce 2023 zahájilo cílenou léčbu celkem 496 pacientů. Na konci sledovaného roku bylo léčeno celkem 1 239 pacientů, nejvíce pacientů bylo léčeno přípravkem Dupixent (81 %) a průměrná délka léčby jedním léčivým přípravkem byla 1,6 let. Závěr: Analýza potvrzuje vysokou aktivitu sledovaných onemocnění dle objektivního hodnocení a značné negativní ovlivnění kvality života pacientů při zahájení cílené léčby s poklesem hodnocených parametrů při léčbě. Současně prokazuje významnou prevalenci souběžných onemocnění a rizikových faktorů a dlouhé období nedostatečné léčby před nasazením cílené léčby.

Background and objectives: Evaluation of patients included in the registry of biological/targeted therapy BIOREP in the Czech Republic. Methods: A retrospective evaluation of patients to date 31 December 2023 enrolled in the BIOREP registry was performed. The aim of our study was to evaluate patients on biological/targeted treatment in the given period in individual categories and to analyze the population of patients with psoriasis, hidradenitis suppurativa and atopic dermatitis. In the case of categorical variables, the results were expressed using number and percentage. Continuous variables were described using count, mean, standard deviation, median, minimum, and maximum Results: As of 31 December 2023, a total of 6,676 patients were registered in the BIOREP registry: 4,763 (71.3%) patients with psoriasis, 538 (8.1%) with hidradenitis, 1,346 (20.2%) with atopic dermatitis and 29 (0.4%) were treated off label with targeted treatment. Of the psoriasis group, 62.5% of patients were men. The average patient age at the end of 2023 was 52.3 years, the mean age at the time of diagnosis was 25.6 years, and the age at first biological/targeted treatment was 46.4 years. In 2023, the average time from diagnosis to the introduction of targeted treatment was 20.8 years, the average duration of biological/targeted treatment was 5.2 years. The comorbidities occurred in 70.6% of patients. The most common disorder were metabolic/endocrine diseases (39.2%) and cardiovascular diseases (37.8%). From the individual comorbidities, hypertension (35.2%), dyslipidemia (26.5%) and diabetes mellitus (12.5%) were the most common. A total of 76.1% of patients were overweight or obese and 33% of patients were smokers. Psoriatic arthritis was observed in 30.8% of patients. At the start of treatment and at the last visit, the mean PASI was 18.6 and 1.8, respectively, the mean BSA 29% and 2.5%, respectively and DLQI 16.1 and 1.6, respectively. After 12 months of treatment, a total of 91.8%; 82.6%; 64.7% and 40.8% of patients achieved PASI50, PASI75, PASI90 and PASI100, respectively. In 2023, a total of 645 patients newly started treatment and at the end of year 2023, a total of 4.120 patients were treated, the most patients used Skyrizi (15.7%), Humira (12.1%) and Cosentyx (12%). As of 31 December 2023, there were a total of 538 patients with hidradenitis suppurativa in the registry of mean age 44.5 years and 55.4% were men. The mean age at the time of diagnosis was 32.7 years and the age at first biological treatment was 41,7 years. The average time from diagnosis to the start of the biological treatment was 9 years and patients were treated for an average of 2.7 years. In 2023, a total of 85 patients started the biological treatment. At the end of 2023, a total of 422 patients were treated and the average duration of treatment was 2.4 years, the most common medication was Humira (67.8%). At the end of 2023, there were a total of 1,346 patients with atopic dermatitis in the registry of mean age 36.2 years, 51% were men. The mean age at the time of diagnosis was 5.2 years and the age at first targeted treatment was 34.9 years. The average time from diagnosis to the start of the targeted treatment was 29.8 years and patients were treated for an average of 1.7 years. A total of 60.1% of patients had concomitant allergic rhinitis, 54.8% food allergy and 42.1% allergic asthma. Ocular comorbidities occurred in 23.6% of patients, the most common were atopic conjunctivitis (12.2%). At the start of treatment and at the last visit, the mean EASI was 30.8 and 4.1, respectively, mean BSA was 56% and 8%, respectively, and mean DLQI 18.2 and 3.7 respectively. In 2023, a total of 496 patients started the biological treatment. At the end of 2023, a total of 1,239 patients were treated and the average duration of treatment was 1.6 years, the most common medication was Dupixent (81%). Conclusion: The analysis confirmed the high activity of diseases according to objective evaluation and the significant negative impact on the quality of life before initiation of targeted treatment, with a decrease in the evaluated scores during treatment. At the same time, it demonstrates a high prevalence of comorbidities and risk factors and a long diseases duration before the introduction of targeted treatment.