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1.
J Drugs Dermatol ; 21(12): 1358-1360, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36468954

RESUMO

Hidradenitis suppurativa (HS) is a morbid, recurrent skin condition that presents a major challenge to clinical therapy. Investigation into the pathogenesis of HS has implicated local and systemic pro-inflammatory cytokines, particularly TNF-α and IL-17A, as major determinants of disease progression and severity. This has ushered in a revolution in HS therapy with biologics targeting these cytokines. We report a case of a 36-year-old man with extensive and treatment-resistant Hurley Stage 3 HS. After undergoing numerous unsuccessful trials of topical, systemic, and biologic therapies, secukinumab therapy with 150 mg weekly injections was initiated. HS clinical response was seen after 20 weeks and was maintained for almost two years. Secukinumab 150 mg or 300 mg once weekly may be an effective and safe therapeutic option for moderate-to-severe chronic HS. J Drugs Dermatol. 2022;21(12):1358-1360. doi:10.36849/JDD.6752.


Assuntos
Hidradenite Supurativa , Masculino , Humanos , Adulto , Hidradenite Supurativa/diagnóstico , Hidradenite Supurativa/tratamento farmacológico , Interleucina-17 , Inibidores de Interleucina , Citocinas
2.
BMJ Open ; 12(12): e063650, 2022 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-36564123

RESUMO

INTRODUCTION: Psoriatic arthritis (PsA) is a complex, immune-mediated disease associated with skin psoriasis that, if left untreated, can lead to joint destruction. Up to 30% of patients with psoriasis progress to PsA. In most cases, psoriasis precedes synovio-entheseal inflammation by an average of 5-7 years, providing a unique opportunity for early and potentially preventive intervention in a susceptible and identifiable population. Guselkumab is an effective IL-23p19 inhibitor Food and Drug Administration (FDA-approved for treatment of moderate-to-severe psoriasis and PsA. The Preventing Arthritis in a Multicentre Psoriasis At-Risk cohort (PAMPA) study aims to evaluate the efficacy of guselkumab in preventing PsA and decreasing musculoskeletal power Doppler ultrasound (PDUS) abnormalities in a population of patients with psoriasis who are at-increased risk for PsA progression. METHODS AND ANALYSIS: The PAMPA study is a multicentre, randomised, double-blind, placebo-controlled, interventional, preventive trial comparing PDUS involvement and conversion to PsA in patients with psoriasis at-increased risk for progression treated with guselkumab compared with non-biological standard of care. The study includes a screening period, a double-blind treatment period (24 weeks) and an open-label follow-up period (72 weeks). At baseline, 200 subjects will be randomised (1:1) to receive either guselkumab 100 mg (arm 1) or placebo switching to guselkumab 100 mg starting at week 24 (arm 2). Arm 3 will follow 150 at-risk psoriasis patients who decline biological therapy and randomisation. Changes from baseline in the PDUS score at week 24 and the difference in proportion of patients transitioning to PsA at 96 weeks will be examined as the coprimary endpoints. ETHICS AND DISSEMINATION: Ethics approval for this study was granted by the coordinating centre's (NYU School of Medicine) Institutional Review Board (IRB). Each participating site received approval through their own IRBs. The findings will be shared in peer-reviewed articles and scientific conference presentations. TRIAL REGISTRATION NUMBER: NCT05004727.


Assuntos
Artrite Psoriásica , Psoríase , Humanos , Artrite Psoriásica/tratamento farmacológico , Inibidores de Interleucina , Resultado do Tratamento , Psoríase/complicações , Psoríase/tratamento farmacológico , Método Duplo-Cego , Interleucina-23/uso terapêutico , Índice de Gravidade de Doença , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
3.
Front Immunol ; 13: 1046352, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389759

RESUMO

Background: Coronavirus disease 2019 (COVID-19) have brought great disaster to mankind, and there is currently no globally recognized specific drug or treatment. Severe COVID-19 may trigger a cytokine storm, manifested by increased levels of cytokines including interleukin-17 (IL-17), so a new strategy to treat COVID-19 may be to use existing IL-17 inhibitors, which have demonstrated efficacy, safety and tolerability in the treatment of psoriasis. However, the use of IL-17 inhibitors in patients with psoriasis during the COVID-19 pandemic remains controversial due to reports that IL-17 inhibitors may increase the risk of respiratory tract infections. Objectives: The systematic review and meta-analysis aimed to evaluate the effect of IL-17 inhibitors on the risk of COVID-19 infection, hospitalization, and mortality in patients with psoriasis. Methods: Databases (including Embase, PubMed, SCI-Web of Science, Scopus, CNKI, and the Cochrane Library) were searched up to August 23, 2022, for studies exploring differences in COVID-19 outcomes between psoriasis patients using IL-17 inhibitors and those using non-biologics. Two authors independently extracted data and assessed the risk of bias in a double-blind manner. The risk ratios (RRs) and 95% confidence intervals (CIs) were calculated and heterogeneities were determined by the Q test and I 2 statistic. And the numbers needed to treat (NNTs) were calculated to assess the clinical value of IL-17 inhibitors in preventing SARS-CoV-2 infection and treating COVID-19. Results: Nine observational studies involving 7,106 participants were included. The pooled effect showed no significant differences in the rates of SARS-CoV-2 infection (P = 0.94; I 2 = 19.5%), COVID-19 hospitalization (P = 0.64; I 2 = 0.0%), and COVID-19 mortality (P = 0.32; I 2 = 0.0%) in psoriasis patients using IL-17 inhibitors compared with using non-biologics. Subgroup analyses grouped by age and COVID-19 cases, respectively, revealed consistent results as above. Meanwhile, the pooled NNTs showed no significant differences between the two groups in the clinical value of preventing SARS-CoV-2 infection and treating COVID-19. Conclusion: The use of IL-17 inhibitors in patients with psoriasis does not increase the risk of SARS-CoV-2 infection or worsen the course of COVID-19. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022335195.


Assuntos
Psoríase , Humanos , Interleucina-17 , Inibidores de Interleucina , Pandemias , Anticorpos Monoclonais/uso terapêutico , SARS-CoV-2 , Psoríase/tratamento farmacológico , Hospitalização , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Musculoskeletal Care ; 20 Suppl 1: S12-S21, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36069174

RESUMO

BACKGROUND: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis characterised by musculoskeletal and extra-articular manifestations, most notably psoriasis. While the underlying pathogenetic mechanisms are not yet fully understood, a central role has been identified for the IL-23/IL-17 pathway. OBJECTIVES: We briefly describe the role of IL-23 in the pathogenesis of PsA and go on to describe the available anti-IL-23 agents and their place in the management of PsA. METHODS: This is a narrative review of the current literature, focussing on the results of the phase 3 studies in PsA for the IL-12/23 p40 inhibitor ustekinumab and the more recent IL-23 p19 inhibitors guselkumab, risankizumab and tildrakizumab. RESULTS: IL-23 triggers expression of IL-17 and other effector cytokines in a variety of cells, leading to tissue inflammation and injury. Targeting IL-23, particularly with p19 inhibitors, appears to be an effective and safe strategy for multiple clinical domains in PsA, most notably the skin, with some differences in efficacy emerging between these agents. CONCLUSION: The development of IL-23 inhibitors represents a significant advance in the management of psoriatic disease. In the absence of head-to-head studies, future data emerging from real-world experiences of individual IL-23 p19 inhibitors will help inform the use of these agents in relation to other biologics in PsA.


Assuntos
Artrite Psoriásica , Inibidores de Interleucina , Humanos , Artrite Psoriásica/tratamento farmacológico , Inibidores de Interleucina/uso terapêutico , Interleucina-17/metabolismo , Subunidade p19 da Interleucina-23/metabolismo , Ustekinumab/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Interleucina-23/metabolismo
6.
Front Immunol ; 13: 923362, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35967348

RESUMO

Background: Several clinical trials have evaluated the efficacy and safety of interleukin-13 (IL-13) with lebrikizumab and tralokinumab in patients with moderate to severe atopic dermatitis (AD). However, the safety and efficacy of IL-13 inhibitors as a potent biologic for AD remain elusive. Objective: To assess the efficacy and safety of IL-13 inhibitors in moderate to severe AD. Method: Randomized clinical trials (RCTs), comparing IL-13 inhibitors vs placebo treatment in patients with moderate to severe AD, were identified from public database from its inception to November 9th, 2021. The study was registered in PROSPERO (CRD42021254920). Results: Six studies reporting 7 RCTs involving 2946 patients with moderate-to-severe AD were included for the pooled analysis. Compared with placebo, antagonizing IL-13 with lebrikizumab and tralokinumab showed a greater improvement in percentage change of EASI (MD -20.37, 95%CI -32.28, -8.47), and a larger proportion of patients achieving numerical rating scale (NRS) with more than 4-points improvement (RR 1.59, 95%CI 1.23, 2.05). Additionally, IL-13 inhibitors also improved impaired dermatology life quality index (DLQI) (MD -14.49, 95%CI -19.23, -9.75). In terms of safety, both lebrikizumab and tralokinumab were well tolerated, with the except that they were linked to an increased risk of conjunctivitis compared to placebo treatment. Conclusion: Antagonizing IL-13 with lebrikizumab and tralokinumab have demonstrated encouraging clinical efficacy against moderate-to-severe AD with excellent safety profile, albeit they did come with a higher risk of conjunctivitis than placebo treatment. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier ID=CRD42021254920.


Assuntos
Conjuntivite , Dermatite Atópica , Dermatite Atópica/tratamento farmacológico , Humanos , Inibidores de Interleucina , Interleucina-13 , Resultado do Tratamento
7.
Am J Clin Dermatol ; 23(6): 891-904, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35976568

RESUMO

BACKGROUND: Drug survival, defined as the length of time from initiation to discontinuation of a given therapy, allows comparisons between drugs, helps to predict patient's likelihood of remaining on a specific treatment, and achieving the best decision for each patient in daily clinical practice. OBJECTIVE: The aim of this study was to provide data on drug survival of secukinumab, ixekizumab, brodalumab, guselkumab, tildrakizumab, and risankizumab in a large international cohort, and to identify clinical predictors that might have an impact on the drug survival of these drugs. METHODS: This was a retrospective, multicentric, multi-country study that provides data of adult patients with moderate to severe psoriasis who started treatment with an interleukin (IL)-17 or IL-23 inhibitor between 1 February 2015 and 31 October 2021. Data were collected from 19 distinct hospital and non-hospital-based dermatology centers from Canada, Czech Republic, Italy, Greece, Portugal, Spain, and Switzerland. Kaplan-Meier estimator and proportional hazard Cox regression models were used for drug survival analysis. RESULTS: A total of 4866 treatment courses (4178 patients)-overall time of exposure of 9500 patient-years-were included in this study, with 3164 corresponding to an IL-17 inhibitor (secukinumab, ixekizumab, brodalumab) and 1702 corresponding to an IL-23 inhibitor (guselkumab, risankizumab, tildrakizumab). IL-23 inhibitors had the highest drug survival rates during the entire study period. After 24 months of treatment, the cumulative probabilities of drug survival were 0.92 (95% confidence interval [CI] 0.89-0.95) for risankizumab, 0.90 (95% CI 0.88-0.92) for guselkumab, 0.80 (95% CI 0.76-0.84) for brodalumab, 0.79 (95% CI 0.76-0.82) for ixekizumab, and 0.75 (95% CI 0.73-0.77) for secukinumab. At 36 months, only guselkumab [0.88 (95% CI 0.85-0.91)], ixekizumab [0.73 (95% CI 0.70-0.76)], and secukinumab [0.67 (95% CI 0.65-0.70)] had more than 40 patients at risk of drug discontinuation. Only two drugs had more than 40 patients at risk of drug discontinuation at 48 months, with ixekizumab demonstrating to have a higher cumulative probability of drug survival [0.71 (95% CI 0.68-0.75)] when compared with secukinumab [0.63 (95% CI 0.60-0.66)]. Secondary failure was the main cause for drug discontinuation. According to the final multivariable model, patients receiving risankizumab, guselkumab, and ixekizumab were significantly less likely to discontinue treatment than those receiving secukinumab. Previous exposure to biologic agents, absent family history of psoriasis, higher baseline body mass index (BMI), and higher baseline Psoriasis Area and Severity Index (PASI) were identified as predictors of drug discontinuation. CONCLUSION: The cumulative probability of drug survival of both IL-17 and IL-23 inhibitors was higher than 75% at 24 months, with risankizumab and guselkumab demonstrating to have overall cumulative probabilities ≥ 90%. Biological agent chosen, prior exposure to biologic agents, higher baseline BMI and PASI values, and absence of family history of psoriasis were identified as predictors for drug discontinuation. Risankizumab, guselkumab, and ixekizumab were less likely to be discontinued than secukinumab.


Assuntos
Interleucina-17 , Psoríase , Adulto , Humanos , Inibidores de Interleucina , Interleucina-23 , Psoríase/tratamento farmacológico , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento
8.
Yale J Biol Med ; 95(2): 249-255, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35782480

RESUMO

Novel biologic therapies have revolutionized the treatment of psoriasis and atopic dermatitis. Although they are generally safe, they are immunomodulatory and therefore unique considerations apply in regards to infections and vaccine administration. This review aims to provide a clear and practical guide for dermatologists or other healthcare providers to reference when caring for psoriasis or atopic dermatitis patients being treated with biologic therapies using currently available guidelines and clinical data. Vaccinations for approved biologics including TNFα, IL-12/23, IL-23, IL-17, and IL-4/13 inhibitors will be discussed, with a special note on current COVID-19 vaccination recommendations.


Assuntos
COVID-19 , Dermatite Atópica , Psoríase , Terapia Biológica , Vacinas contra COVID-19 , Dermatite Atópica/tratamento farmacológico , Humanos , Inibidores de Interleucina , Psoríase/tratamento farmacológico , Vacinação
10.
Zhonghua Shao Shang Za Zhi ; 38(6): 574-579, 2022 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-35764585

RESUMO

Pyoderma gangrenosum (PG) is a rare chronic inflammatory non-infectious skin dermatosis, and there is no clear treatment guideline for this disease at home and abroad. There are a variety of clinical treatment methods for PG, including local therapy and systemic application of glucocorticoids, immunosuppressants, intravenous immuno- globulin, and biologics. Glucocorticoids are the first-line drugs commonly used in clinical practice, and immunosuppressants can be used alone or in combination with glucocorticoids. In recent years, more and more evidence has shown that biologics are a new trend in the treatment of PG, mainly including tumor necrosis factor α inhibitors, interleukin-1 (IL-1) inhibitors, IL-12/23 inhibitors, IL-17 inhibitors, rituximab, and small molecular inhibitors. This article summarizes the current status and latest progress in the treatment of PG, hoping to provide clinicians with ideas for the treatment of PG.


Assuntos
Produtos Biológicos , Pioderma Gangrenoso , Glucocorticoides , Humanos , Imunossupressores , Imunoterapia , Inibidores de Interleucina , Pioderma Gangrenoso/tratamento farmacológico
11.
J Dermatolog Treat ; 33(7): 2963-2974, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35695280

RESUMO

BACKGROUND: Off-label uses of biologics in the treatment of psoriasis are usually implemented in limited-resource settings and studies regarding their response profiles are limited. METHOD: This was a retrospective study performed in moderate-to-severe plaque-type psoriasis patients who had been treated with either secukinumab, ixekizumab or brodalumab at a university hospital in Thailand between 1 January 2017 and 1 April 2021. RESULTS: A total of 142 patients were included in the data analysis consisting of three groups of 48 patients, 86 patients, and 8 patients treated by secukinumab, ixekizumab, and brodalumab, respectively. Patients were then classified into five groups according to the dosing pattern they received; on-label, off-label with induction, off-label with specific pattern, off-label with irregular dosing interval <8 weeks and >8 weeks. Considering both secukinumab and ixekizumab, the adjusted hazard ratios (95%CI) for complete skin clearance of the four off-label regimens were 2.2(0.9-5.2), 1.9 (0.9-3.9), 1.0 (0.4-2.2), and 1.6 (0.7-3.6), compared to on-label regimen, respectively. In each biologic drug, almost all off-label dosing regimens demonstrated higher adjusted hazard ratios compared to on-label regimen. CONCLUSION: Off-label, patient-oriented regimens could be a promising choice of IL-17 inhibitors for administration in special settings. Off-label regimens are not inferior in terms of skin clearance to an on-label regimen in the efficacy of psoriasis treatment of secukinumab and ixekizumab but do cause more flares. The decision to use off-label regimens must account for the benefits and associated risks.


Assuntos
Produtos Biológicos , Psoríase , Humanos , Interleucina-17 , Uso Off-Label , Anticorpos Monoclonais/uso terapêutico , Inibidores de Interleucina , Estudos Retrospectivos , Tailândia , Índice de Gravidade de Doença , Psoríase/tratamento farmacológico , Psoríase/induzido quimicamente , Produtos Biológicos/uso terapêutico , Resultado do Tratamento
12.
Clin Exp Dermatol ; 47(9): 1627-1635, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35466472

RESUMO

BACKGROUND: Tumour necrosis factor inhibitors (TNFi) were the first biologics approved for the treatment of psoriasis (PsO) and psoriatic arthritis (PsA). However, some patients are intolerant of or unresponsive to TNFi. AIM: To investigate the therapeutic effect of interleukin (IL)-17 and IL-12/23 inhibitors in patients with PsO or psoriatic arthritis PsA who were intolerant of or had responded inadequately to TNFi therapy (TNFi-experienced patients). METHODS: A systematic review of randomized controlled trials searched from the PubMed, Cochrane Library and Embase databases was conducted on 17 May 2021. Responses of 75% and 90% improvement on Psoriasis Area and Severity Index (PASI75, PASI90), 20%, 50% and 70% improvement on the American College of Rheumatology response criteria (ACR20, ACR50, ACR70), and full resolution of dactylitis/enthesitis were used to assess the treatment efficacy. RESULTS: In total, 7 studies with a total of 3398 patients with PsA were included, 1330 of whom were intolerant of or had responded inadequately to TNFi. All studies were categorized as having low risk of bias. For IL-17A inhibitors, there were significantly higher achievements in all of the endpoints compared with placebo, but the proportions of patients achieving these endpoints were lower in TNFi-experienced patients compared with TNFi-naïve patients. However, the differences between TNFi-experienced and TNFi-naïve patients were significant only for ACR responses and for full resolution of enthesitis. For IL-12/23 inhibitors, only the results for ACR20 response were reported. Significantly more TNFi-experienced patients achieved ACR20 response compared with patients receiving placebo, and the differences in treatment efficacy between TNFi-experienced and TFNi-naïve patients was not significant. CONCLUSION: IL-17A and IL-12/23 inhibitors still had efficacy for patients with PsO or PsA had failed or were intolerant to TNFi therapy; however, the efficacy was lower than that in TNFi-naïve patients. Further studies to confirm these findings are warranted.


Assuntos
Antirreumáticos , Artrite Psoriásica , Neoplasias , Psoríase , Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/patologia , Humanos , Inibidores de Interleucina , Interleucina-12 , Interleucina-17 , Interleucina-23 , Necrose/tratamento farmacológico , Psoríase/tratamento farmacológico , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral
13.
Eur J Intern Med ; 101: 41-48, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35422374

RESUMO

OBJECTIVE: To assess the efficacy of IL-6 inhibitors compared to standard of care (SOC) in COVID-19 patients. DATA SOURCES: A systematic review of the MEDLINE and Scopus databases (last search: October 8th, 2021) was performed according to the PRISMA statement. STUDY SELECTION: Randomized control trials (RCTs) comparing IL-6 inhibitors to SOC in hospitalized COVID-19 patients were deemed eligible. DATA EXTRACTION AND SYNTHESIS: Individual patient data were extracted from the Kaplan-Meier curves or were obtained from authors of included studies. Additionally, the reviewers independently abstracted data and assessed study quality of each eligible report. RESULTS: Eleven studies were identified, incorporating 7467 patients (IL-6 inhibitors: 4103, SOC: 3364). IL-6 inhibitors were associated with decreased risk for death compared to SOC at the one-stage meta-analysis (Hazard Ratio [HR]: 0.75, 95% Confidence interval [CI]: 0.69-0.82, p<0.0001) and the two-stage meta-analysis (HR: 0.85, 95%CI: 0.77-0.93, p<0.001, I2 = 0.0%). Meta-regression analysis revealed that the difference in OS between the two groups was not influenced by the mean age of patients. At secondary meta-analyses, IL-6 inhibitors were associated with decreased odds for intubation OR:0.74, 95%CI:0.65-0.85, p<0.001, I2=0.0%). IL-6 inhibitors were associated with increased odds for discharge compared to SOC (OR:1.28, 95% CI:1.15-1.42, p<0.001, I2=0.0%). CONCLUSIONS AND RELEVANCE: This meta-analysis of individual patient data from randomized trials shows that IL-6 inhibitors significantly reduce the risk of death compared to SOC. IL-6 inhibitors are also associated with better outcomes in terms of intubation and discharge rates compared to SOC.


Assuntos
Coronavirus , Humanos , Inibidores de Interleucina , Interleucina-6 , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
Cas Lek Cesk ; 161(1): 3-10, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35354288

RESUMO

Monogenic periodic fever syndromes are heterogeneous group of autoinflammatory diseases including distinct syndromes, such as cryopyrin-associated periodic syndrome (CAPS), tumor necrosis factor alpha receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency/hyper IgD syndrome (MKD/HIDS), and familial Mediterranean fever (FMF). Individual diseases differ in pathogenesis, clinical manifestations, and severity. However, cytokines from the interleukin 1 (IL-1) family play a key role in all of them. Inhibition of these cytokines, especially IL-1, thus plays a crucial role in their treatment. At present, we have a wide range of drugs that differ in structure, mechanism of action, efficacy, and spectrum of side effects. The most available are anakinra, canakinumab and rilonacept. Moreover, several clinical trials are currently underway with other very promising drugs, such as gevokizumab, tadekinig alfa or tranilast. In the following review, we provide a new perspective on the efficacy and safety of IL-1 inhibitors that have provided the novel results coming from recently published clinical trials.


Assuntos
Síndromes Periódicas Associadas à Criopirina , Doenças Hereditárias Autoinflamatórias , Deficiência de Mevalonato Quinase , Síndromes Periódicas Associadas à Criopirina/tratamento farmacológico , Doenças Hereditárias Autoinflamatórias/tratamento farmacológico , Humanos , Inibidores de Interleucina , Interleucina-1/uso terapêutico , Deficiência de Mevalonato Quinase/tratamento farmacológico
15.
J Eur Acad Dermatol Venereol ; 36(8): 1171-1177, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35246887

RESUMO

Anti-drug antibodies (ADAs) can form with certain biological medications, but their clinical significance is not fully understood. ADA formation in psoriasis patients treated with IL-23 inhibitors was evaluated, looking at the incidence of ADAs, impact on clinical outcomes and association with adverse events. A systematic search of PubMed, Cochrane and Embase databases yielded 318 articles, which were manually reviewed. A total of 19 articles met the eligibility criteria. The incidence of ADAs with the IL-23 inhibitors was as follows: 4.1-14.7% with guselkumab, 141-31% with risankizumab and 6.51-18% with tildrakizumab. The incidence of neutralizing antibodies ranged from 01-0.6% with guselkumab, 21-16% with risankizumab and 2.5 to 3.2% with tildrakizumab. There was no evidence of reduced efficacy of psoriasis treatment with ADA presence alone. However, some studies found a reduction in clinical response with high ADA titres or with the presence of neutralizing antibodies. A few studies reported that patients with ADAs to guselkumab and risankizumab had a higher incidence of injection site reactions (ISRs). There do not appear to be other adverse events associated with ADAs with IL-23 inhibitors. Testing for presence of ADAs alone in this patient group does not appear to be predictive of treatment response. Clinically, it may be more productive to test for neutralizing antibodies or ADA titre values, although further investigation is required to show a definitive correlation.


Assuntos
Inibidores de Interleucina , Psoríase , Anticorpos Neutralizantes/uso terapêutico , Humanos , Interleucina-23 , Psoríase/tratamento farmacológico
16.
Ann Rheum Dis ; 81(6): 823-830, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35210262

RESUMO

OBJECTIVE: We evaluated real-world treatment persistence and effectiveness at 1 year following initiation of IL-12/23 inhibitor ustekinumab or a tumour necrosis factor inhibitor (TNFi) for psoriatic arthritis (PsA). METHODS: PsABio (NCT02627768), a prospective, observational study, followed patients with PsA prescribed first-line to third-line ustekinumab or TNFi. Drug persistence, effectiveness (achievement of clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) low disease activity (LDA)/remission and minimal disease activity/very low disease activity (MDA/VLDA)), and safety were assessed every 6 months. In addition to descriptive statistics, propensity score (PS)-adjusted comparisons across cohorts were performed. RESULTS: At 1 year, overall persistence was similar in the ustekinumab (n=317/438, 72.4%) and TNFi (n=321/455, 70.5%) groups. PS-adjusted HR (95% CI) for stopping/switching ustekinumab versus TNFi was 0.82 (0.60; 1.13). cDAPSA LDA (including remission)/remission was achieved in 55.9%/22.1% of ustekinumab-treated and 67.1%/31.7% of TNFi-treated patients; PS-adjusted ORs (95% CI) were 0.80 (0.57; 1.10) for cDAPSA LDA and 0.73 (0.49; 1.07) for remission. MDA/VLDA was achieved in 34.2%/11.9% of ustekinumab-treated and 43.1%/12.6% of TNFi-treated patients; PS-adjusted ORs (95% CI) were 0.89 (0.63; 1.26) for MDA and 0.90 (0.54; 1.49) for VLDA. The safety profiles were similar in both groups. CONCLUSION: In the real-world PsABio Study, after 1 year of treatment, although unadjusted persistence was numerically slightly higher for ustekinumab versus TNFi and unadjusted effectiveness was numerically slightly higher for TNFi versus ustekinumab, the PS-adjusted comparisons demonstrated comparable overall persistence, effectiveness and safety for both modes of action in PsA.


Assuntos
Antirreumáticos , Artrite Psoriásica , Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Humanos , Inibidores de Interleucina , Interleucina-12 , Estudos Prospectivos , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral , Ustekinumab/uso terapêutico
17.
Inflammopharmacology ; 30(2): 435-451, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35188599

RESUMO

BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease characterized by immune system dysregulation and inflammation in the joints. Interleukin (IL)-17 inhibitors are new biological drugs used to treat AS. In this study, we aimed to assess the risk of immune system-related AEs due to targeting IL-17 or IL-17R. METHODS: The CENTRAL, PubMed, Scopus, Google Scholar, Clinical Trials Registry, and ICTRP were searched for randomized clinical trials (RCTs) and non-RCTs until February 2021. The risk of irAEs in patients treated with IL-17 inhibitors compared to the placebo or a drug-free control was evaluated. In studies that reported AEs of the IL-17 inhibitors at several different time points, we compared the number of cases/100 patient-year in which irAEs were reported. Subgroup analyses were also performed based on the dose and type of drugs. RESULTS: Thirteen studies of 1848 AS patients treated by IL-17 inhibitors (secukinumab, ixekizumab, bimekizumab, and netakimab) and 764 participants who received a placebo were included. The risk of some AEs related to immune function in patients under IL-17 inhibitors treatment was significantly higher than that of the placebo group, including infection and infestation (risk difference RD = 0.09, P = 0.02), nasopharyngitis (RD = 0.04, P < 0.001), opportunistic infections (RD = 0.01, P = 0.04), and neutropenia (RD = 0.04, P = 0.03). Besides, the results of the Cochran Q test showed that there were significant differences between the occurrence of some AEs over time, including infection and infestations (p < 0.001, RCTs), upper respiratory tract infections (p < 0.001, non-RCTs), urinary tract infections (p < 0.001, non-RCTs), and diarrhea (p < 0.01, RCTs). CONCLUSIONS: The most common immune system-related AEs in patients treated with IL-17 inhibitors are mucosal and opportunistic infections.


Assuntos
Espondilite Anquilosante , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Humanos , Inibidores de Interleucina , Espondilite Anquilosante/tratamento farmacológico
19.
J Dermatolog Treat ; 33(2): 1091-1096, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32713225

RESUMO

BACKGROUND: Biological agent treatments represent a relatively new field and their effects on routine laboratory parameters are not fully known as there has been little research in the area. In our study, we aimed to evaluate the differences between the two main biological treatment groups and their effects on routine laboratory parameters. METHODS: Patients were enrolled when they had received treatment for more than six months with biological treatments between January 2013 and April 2020. The available data on routine laboratory parameters were collected by routine blood tests before the treatment, at three months, and at the final evaluation. RESULTS: When the changes in routine laboratory parameters were evaluated by treatment, it was found that the NLR and CRP values decreased statistically significantly in the anti-TNF group compared to the IL inhibitor group. In addition, strong suppression of these inflammation parameters means strong suppression of the immune system response. In addition, AST, ALT, and creatinine values were found to be statistically significantly higher in the anti-TNF group compared to the IL inhibitor group. CONCLUSIONS: In our study, anti-TNF treatments are shown to be more effective in reducing inflammation parameters while IL antagonists are safer in terms of biochemical parameters.


Assuntos
Psoríase , Inibidores do Fator de Necrose Tumoral , Humanos , Inibidores de Interleucina , Psoríase/tratamento farmacológico , Fator de Necrose Tumoral alfa
20.
J Dermatolog Treat ; 33(3): 1252-1256, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-32962478

RESUMO

PURPOSE: This review article aims to compare global dermatologic organizations and the clinical practice guidelines available for the use of interleukin (IL)-23 inhibitors in the treatment of psoriasis. MATERIALS AND METHODS: A literature review encompassing systemic therapies for the treatment of psoriasis was conducted. Guidelines from the American Academy of Dermatology (AAD)-National Psoriasis Foundation (NPF), the National Institute for Health and Care Excellence (NICE), and the British Association of Dermatologists (BAD) served as the main comparators in this review. RESULTS: Of the American and European guidelines available for use of IL-23 inhibitors, several organizations are in agreement regarding the dosage and indications of guselkumab, tildrakizumab, and risankizumab. However, there are differences as well as insufficient recommendations concerning laboratory monitoring and screenings as well as contraindications to therapy. CONCLUSION: IL-23 inhibitors are safe and efficacious therapeutic options for patients with psoriasis and should be considered as a potential first-line therapy alone or in combination with topical medications, phototherapy, and other systemic non-biologic agents. Consideration should be given to the evidence-based guidelines of global dermatologic organizations to help guide therapeutic decisions.


Assuntos
Fármacos Dermatológicos , Inibidores de Interleucina , Psoríase , Fármacos Dermatológicos/uso terapêutico , Humanos , Inibidores de Interleucina/uso terapêutico , Interleucina-23/antagonistas & inibidores , Fototerapia , Guias de Prática Clínica como Assunto , Psoríase/tratamento farmacológico , Reino Unido , Estados Unidos
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