OBJECTIVES: To compare the drug survival of etanercept to monoclonal tumour necrosis factor-α inhibitors in rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. METHODS: Patients initiating first line biological therapy with tumour necrosis factor-α were propensity score matched and compared for drug survival with a Kaplan-Meier analysis. RESULTS: We matched 657 to 657 patients in rheumatoid arthritis, the median survival time on etanercept was 44.6 months vs. 36.8 months on monoclonal antibody tumour necrosis factor-α inhibitors, with a hazard ratio of 0.94, p = 0.416 We matched 187 to 356 patients in ankylosing spondylitis, the median survival time on etanercept was 75.1 compared to 68.0 months, hazard ratio of 0.78, p = 0.087 We matched 81 to 160 psoriatic arthritis patients, the median survival time on etanercept was 35.8. compared to 65.7 months, hazard ratio 1.61, p = 0.011. Patients treated with etanercept had significantly worse psoriasis scoring during follow up. CONCLUSIONS: We found comparable survival in rheumatoid arthritis and ankylosing spondylitis. In psoriatic arthritis, we found significantly shorter survival on etanercept, possibly due to worse response of skin and nail manifestations.

• MeSH
• adalimumab terapeutické užití   MeSH
• ankylózující spondylitida * farmakoterapie   mortalita   MeSH
• antirevmatika * terapeutické užití   MeSH
• dospělí MeSH
• etanercept * terapeutické užití   MeSH
• infliximab terapeutické užití   MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• monoklonální protilátky terapeutické užití   MeSH
• psoriatická artritida * farmakoterapie   mortalita   MeSH
• registrace * MeSH
• revmatoidní artritida * farmakoterapie   mortalita   MeSH
• senioři MeSH
• tendenční skóre * MeSH
• TNF-alfa * antagonisté a inhibitory   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Geografické názvy
• Česká republika MeSH

The aim was to explore factors associated with intestinal tissue levels of anti-TNF alpha (anti-TNF), anti-TNF antibodies, and cytokines in pediatric patients with Crohn Disease (CD). In a prospective exploratory study of CD patients undergoing ileocecal resection or colonoscopy between 6/2020 and 1/2023, we analysed tissue levels of anti-TNF, anti-TNF antibodies, and cytokines (TNF-α, IL-17, IL-1β, IFN-γ) from intestinal biopsies. Mixed-effects regression models, adjusted for potential confounders, were used. Data from 27 CD patients (18 females, 66.7%) were analysed. Fourteen (52%) received adalimumab (ADA) and thirteen received infliximab (IFX), with a median therapy duration of 17 (IQR 4.5-41.5) months. Higher levels of free anti-TNF were found in macroscopically inflamed tissue compared to non-inflamed tissue (β = 3.42, 95% CI 1.05-6.10). No significant association was found between serum and tissue anti-TNF levels (β= -0.06, 95% CI - 0.70-0.58). Patients treated longer with anti-TNF had increased IL-17 levels (β = 0.19, 95% CI 0.05-0.33), independent of disease duration and age. IFN-γ levels were linked with both follow-up duration and anti-TNF length. Our study shows significantly higher free drug levels in inflamed tissue. Long-term anti-TNF treatment has been linked to increased IL-17 levels, suggesting a possible impact on the cytokine response pathway. We did not observe a relationship between serum and tissue anti-TNF levels.

• MeSH
• adalimumab * terapeutické užití   MeSH
• Crohnova nemoc * farmakoterapie   metabolismus   krev   patologie   MeSH
• cytokiny * metabolismus   krev   MeSH
• dítě MeSH
• infliximab * terapeutické užití   MeSH
• lidé MeSH
• mladiství MeSH
• prospektivní studie MeSH
• střeva patologie   účinky léků   MeSH
• střevní sliznice metabolismus   patologie   MeSH
• TNF-alfa * antagonisté a inhibitory   metabolismus   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: We aimed to evaluate the predictors of sustainability of biologic drugs for paediatric patients with Crohn's disease (CD). METHODS: The Czech National Prospective Registry of Biologic and Targeted Therapy of Inflammatory Bowel Disease (CREdIT) was used to identify the biologic treatment courses in paediatric patients with CD. Mixed-effects Cox models and propensity score analyses were employed to evaluate predictors of treatment sustainability. RESULTS: Among the 558 observations of 473 patients, 264 were treated with adalimumab (47%), 240 with infliximab (43%), 41 with ustekinumab (7%), and 13 with vedolizumab (2%). Multivariable analysis revealed higher discontinuation risk with infliximab compared to adalimumab (HR = 0.600, 95%CI 0.389-0.926), both overall and in first-line treatment (HR = 0.302, 95%CI 0.103-0.890). Infliximab versus adalimumab was associated with shorter time to escalation (HR = 0.094, 95%CI 0.043-0.203). Propensity-score analysis demonstrated lower sustainability of infliximab (HR = 0.563, 95%CI 1.159-2.725). The time since diagnosis to treatment initiation (HR = 0.852, 95%CI 0.781-0.926) was the most important predictor. Baseline immunosuppressive therapy prolonged sustainability with infliximab (HR = 2.899, 95%CI 1.311-6.410). CONCLUSIONS: Given the results suggesting shorter sustainability, the need for earlier intensification and thus higher drug exposure, and the greater need for immunosuppression with infliximab than with adalimumab, the choice of these drugs cannot be considered completely equitable. IMPACT: Our study identified predictors of sustainability of biologic treatment in paediatric patients with Crohn's disease, including adalimumab (versus infliximab), early initiation of biologic treatment, and normalised baseline haemoglobin levels. Infliximab treatment was associated with earlier intensification, higher drug exposure, and a greater need for immunosuppression. Parents and patients should be fully informed of the disadvantages of intravenous infliximab versus adalimumab during the decision-making process. This study emphasises the importance of not delaying the initiation of biologic therapy in paediatric patients with Crohn's disease.

• MeSH
• adalimumab * terapeutické užití   MeSH
• biologické přípravky terapeutické užití   MeSH
• Crohnova nemoc * farmakoterapie   MeSH
• dítě MeSH
• humanizované monoklonální protilátky terapeutické užití   MeSH
• infliximab * terapeutické užití   MeSH
• lidé MeSH
• mladiství MeSH
• proporcionální rizikové modely MeSH
• prospektivní studie MeSH
• registrace * MeSH
• tendenční skóre MeSH
• ustekinumab terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Although biologic agents are very effective, long-term comparative studies demonstrating their safety relative to one another are still lacking. METHODS: A total of 124 patients with psoriasis were followed up for 30 months; 74 received anti-TNF-alpha inhibitors (adalimumab, etanercept, infliximab), 33 were on ustekinumab, and 17 were treated with secukinumab. The rates of adverse events in these groups were recorded and statistically analyzed. RESULTS: Infliximab-treated patients showed a high occurrence of asymptomatic, but increased liver enzymes, fatigue, and respiratory as well as dermatologic infections. Adalimumab-treated patients were more often affected by musculoskeletal disorders and infections of all types. Patients treated with secukinumab presented with higher rates of cardiovascular disorders as well as respiratory and dermatologic infections. The group receiving etanercept was more often diagnosed with musculoskeletal and reproductive disorders, specifically menstrual disorders. The rates of therapy discontinuation and serious adverse events did not reach statistically significant values. CONCLUSION: A higher incidence of adverse events was observed among adalimumab-, and infliximab-treated patients, with ustekinumab found to have the safest profile. Our results demonstrate that a personalized approach, including evaluation of a patient's risk profile, is necessary before commencing a biologic. Further research is warranted to confirm the findings of our study.

• MeSH
• adalimumab * škodlivé účinky   terapeutické užití   MeSH
• dermatologické látky škodlivé účinky   terapeutické užití   MeSH
• dospělí MeSH
• etanercept * škodlivé účinky   terapeutické užití   MeSH
• humanizované monoklonální protilátky * škodlivé účinky   terapeutické užití   MeSH
• infliximab * škodlivé účinky   terapeutické užití   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• monoklonální protilátky škodlivé účinky   terapeutické užití   MeSH
• prospektivní studie MeSH
• psoriáza * farmakoterapie   MeSH
• ustekinumab * terapeutické užití   škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

Cílená biologická terapie přinesla dramatickou změnu v léčbě autoimunitních zánětlivých onemocnění. Široké spektrum využití těchto léčiv je ve spojení s novou třídou vedlejších účinků léčby, také někdy nazývaných paradoxní reakce. Cílovým orgánem těchto reakcí je velmi často kůže. Článek prezentuje pacientku s Morbus Crohn, léčenou biologiky, s postupnou tvorbou 3 kožních autoimunitních onemocnění a jejich úspěšnou léčbou risankizumabem.

Targeted biological therapy has brought about a dramatic change in the treatment of autoimmune inflammatory diseases. The wide spectrum of use of these drugs is associated with a new class of treatment side effects, also sometimes called paradoxical reactions. The target organ of these reactions is very often the skin. The article presents a patient with Crohn's disease, treated with biologics, with the gradual development of 3 skin autoimmune diseases and their successful treatment with risankizumab.

• Klíčová slova
• risankizumab,
• MeSH
• biologická terapie metody   škodlivé účinky   MeSH
• Crohnova nemoc * farmakoterapie   komplikace   MeSH
• dospělí MeSH
• hidradenitis suppurativa chemicky indukované   farmakoterapie   komplikace   patologie   MeSH
• infliximab aplikace a dávkování   škodlivé účinky   MeSH
• kožní nemoci chemicky indukované   farmakoterapie   komplikace   patologie   MeSH
• lidé MeSH
• monoklonální protilátky * aplikace a dávkování   ekonomika   MeSH
• progrese nemoci MeSH
• psoriáza chemicky indukované   farmakoterapie   komplikace   patologie   MeSH
• ustekinumab aplikace a dávkování   škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

PURPOSE: Immunogenicity is a major reason for secondary loss of response to infliximab (IFX). Recent work suggested potentially lower immunogenicity of subcutaneous (SC) compared to intravenous (IV) IFX. However, it is unknown whether re-exposure to IFX SC after secondary loss of response and immunogenicity to its intravenous formulation is safe and effective. METHODS: In a retrospective cohort study conducted at two medical centers, patients with clinically (Harvey-Bradshaw Index ≥ 5) and/or biochemically (fecal calprotectin > 250 μg/g) active Crohn's disease (CD) and previous immunogenic failure of IFX IV underwent exposure to IFX SC. Harvey-Bradshaw Index, fecal calprotectin, IFX serum concentration, and anti-drug antibodies were assessed until month 12. RESULTS: Twenty CD patients were included. The majority of patients (90%) had previous treatment with three or more biologics. Fifteen (75%) and ten (50%) of 20 patients continued IFX SC treatment until months 6 and 12, respectively. No immediate hypersensitivity reactions were observed. Two patients discontinued IFX SC treatment because of delayed hypersensitivity at week 2 and week 4. IFX serum concentrations increased from baseline to month 12, while anti-drug antibody levels decreased. Combined clinical and biochemical remission at month 12 was observed in seven of 20 patients (35%). CONCLUSION: Subcutaneous infliximab treatment of Crohn's disease patients with previous immunogenic failure of intravenous infliximab was well tolerated and effective in a cohort of patients with refractory Crohn's disease.

• MeSH
• Crohnova nemoc * farmakoterapie   imunologie   MeSH
• dospělí MeSH
• feces chemie   MeSH
• infliximab * terapeutické užití   imunologie   aplikace a dávkování   MeSH
• injekce subkutánní MeSH
• intravenózní podání MeSH
• leukocytární L1-antigenní komplex analýza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• neúspěšná terapie MeSH
• retrospektivní studie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Infliximab selectively targets recently activated effector cells and, as an induction agent, might enable the safe elimination of mycophenolate from maintenance immunosuppression in kidney transplantation. METHODS: This is a phase II international multicenter open-label single-arm confidence interval (CI)-based clinical trial of the BIO-DrIM EU consortium aimed at assessing the efficacy and safety of rabbit antithymocyte globulin and infliximab induction in kidney transplantation. Sixty-seven primary kidney transplant recipients at low risk (panel-reactive antibodies <20%, no donor-specific antibodies [DSA]) received rabbit antithymocyte globulin (2 × 1.5 mg/kg, postoperative days 0 and 1) and infliximab (5 mg/kg, postoperative day 2), followed by mycophenolate-free tacrolimus-based immunosuppression for 12 mo. The primary endpoint was efficacy failure, defined as a composite of acute rejection, graft loss, or poor graft function (estimated glomerular filtration rate <40 mL/min) at 12 mo and was based on the endpoint of the comparator study. Additionally, a historical propensity-matched control cohort was established. RESULTS: Primary endpoint occurred in 22 of 67 patients (32.84%), with upper bound of an exact 1-sided 95% CI of 43.47%, which met the predefined criteria (efficacy failure of <40% and upper-bound 95% CI of <50%) and was similar in the historical matched cohort. By 12 mo, 79.1% of patients remained on the study protocol. Lower rates of BK replication (6% versus 22.4%; P = 0.013) but higher rates of de novo DSAs (11.9% versus 1.5%; P = 0.039) were observed in the study cohort. CONCLUSIONS: A similar efficacy of the study immunosuppression regimen to the comparator study and the historical matched cohort was found. However, a higher de novo DSA emergence points to an increased risk of antibody-mediated rejection (NCT04114188).

• MeSH
• antilymfocytární sérum * MeSH
• imunosupresiva škodlivé účinky   MeSH
• imunosupresivní léčba MeSH
• infliximab škodlivé účinky   MeSH
• inhibitory enzymů MeSH
• lidé MeSH
• přežívání štěpu MeSH
• protilátky MeSH
• rejekce štěpu prevence a kontrola   MeSH
• takrolimus * škodlivé účinky   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH

x

x

• MeSH
• biosimilární léčivé přípravky * farmakokinetika   MeSH
• dospělí MeSH
• infliximab * farmakologie   imunologie   MeSH
• injekce subkutánní MeSH
• lidé MeSH
• psoriáza * farmakoterapie   patofyziologie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

• MeSH
• ankylózující spondylitida farmakoterapie   MeSH
• biosimilární léčivé přípravky aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• infliximab * aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• injekce subkutánní MeSH
• lidé středního věku MeSH
• lidé MeSH
• psoriatická artritida farmakoterapie   MeSH
• revmatoidní artritida farmakoterapie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

BACKGROUND: Mucosal healing (MH) has become a perspective treatment target in patients with Crohn's disease (CD). Data about the impact of MH on long-term outcome in pediatric patients are still scarce. METHODS: Seventy-six pediatric patients with CD were evaluated retrospectively (2000-2015) in a tertiary care center. Based on MH achievement, they were divided into two groups (MH, N.=17; and No MH, N.=59). The primary endpoint was to assess the association of MH and the need for CD-related hospitalizations or surgery in pediatric patients with CD. RESULTS: The number of hospitalized patients was 24% in the MH group and 42% in the No MH group (P=0.26). The total number of CD-related hospitalizations was not significant between the MH group and the No MH group (5 vs. 41, P=0.15). The time to the first hospitalization was 24 months in MH and 21 months in No MH (P>0.99). About 24% of the patients in the MH group and 39% patients in the No MH group underwent CD-related operation (P=0.39). Time to the first operation was 43 months for MH and 19 months for the No MH group (P=0.13). The follow-up period was 91 months in the MH group and 80 months in the No MH group (P=0.74). The use of infliximab was positively associated with MH (P=0.002). CONCLUSIONS: MH was not associated with fewer CD-related hospitalizations or operations in pediatric patients with CD during seven years of follow-up.

• MeSH
• časové faktory MeSH
• centra terciární péče MeSH
• Crohnova nemoc * terapie   MeSH
• dítě MeSH
• hojení ran MeSH
• hospitalizace * statistika a číselné údaje   MeSH
• infliximab terapeutické užití   MeSH
• lidé MeSH
• mladiství MeSH
• následné studie MeSH
• retrospektivní studie MeSH
• střevní sliznice * patologie   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH