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

BACKGROUND: While indirect comparison of infliximab (IFX) and vedolizumab (VDZ) in adults with Crohn's disease (CD) or ulcerative colitis (UC) shows that IFX has better effectiveness during induction, and comparable efficacy during maintenance treatment, comparative data specific to subcutaneous (SC) IFX (i.e., CT-P13 SC) versus VDZ are limited. AIM: Pooled analysis of randomised studies to compare efficacy and safety with IFX SC and VDZ in moderate-to-severe inflammatory bowel disease. METHODS: Parallel-group, randomised studies evaluating IFX SC and VDZ in patients with moderate-to-severe CD or UC were identified. Eligible studies reported ≥ 1 prespecified outcome of interest at Week 6 (reflecting treatment during the induction phase) and/or at 1 year (Weeks 50-54; reflecting treatment during the maintenance phase). Prespecified efficacy and safety outcomes considered in this pooled analysis included the proportions of patients achieving disease-specific clinical responses, clinical remission, or discontinuing due to lack of efficacy, and the proportions of patients experiencing adverse events (AEs), serious AEs, infections, serious infections, or discontinuing due to AEs. Data from multiple studies or study arms were extracted and pooled using a random-effect model; comparative analyses were performed separately for patients with CD and UC. RESULTS: We identified three eligible CD trials and four eligible UC trials that assigned over 1200 participants per disease cohort to either IFX SC or VDZ. In patients with CD, intravenous induction therapy with IFX demonstrated better efficacy (non-overlapping 95% confidence intervals [CIs]) compared with VDZ; during the maintenance phase, IFX SC showed numerically better efficacy (overlapping 95% CIs) than VDZ. A lower proportion of IFX SC-treated patients discontinued therapy due to lack of efficacy over 1 year. In patients with UC, efficacy profiles were similar with IFX SC and VDZ during the induction and maintenance phases, and a lower proportion of IFX SC-treated patients discontinued therapy due to lack of efficacy over 1 year. In both cohorts, safety profiles for IFX SC and VDZ were generally comparable during 1 year. CONCLUSION: IFX SC demonstrated better efficacy than VDZ in patients with CD, and similar efficacy to VDZ in patients with UC; 1-year safety was comparable with IFX SC and VDZ.

• MeSH
• Crohnova nemoc * farmakoterapie   MeSH
• dospělí MeSH
• gastrointestinální látky škodlivé účinky   MeSH
• humanizované monoklonální protilátky * MeSH
• indukce remise MeSH
• infliximab škodlivé účinky   MeSH
• lidé MeSH
• randomizované kontrolované studie jako téma MeSH
• ulcerózní kolitida * farmakoterapie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

We report the first described case of pulmonary tularaemia in the pediatric patient receiving infliximab for ulcerative colitis. We highlight the importance of considering Francisella tularensis in diagnostically challenging cases of persistent respiratory symptoms to facilitate early diagnosis and adequate therapy. The TCR-γδ + DN T cells are gaining important role in clinical practice. Polymerase chain reaction assays and serology guarantee early recognition.

• MeSH
• dítě MeSH
• Francisella tularensis * genetika   MeSH
• idiopatické střevní záněty * diagnóza   farmakoterapie   MeSH
• infliximab škodlivé účinky   MeSH
• lidé MeSH
• mladiství MeSH
• polymerázová řetězová reakce MeSH
• tularemie * diagnóza   farmakoterapie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH

Narůstající počet nemocných s idiopatickými střevními záněty na biologické léčbě s sebou přináší přirozeně i častější manifestaci nežádoucích účinků. Zejména u pacientů, kteří z této terapie profitují, je možno výskyt nežádoucích účinků eliminovat změnou aplikační formy preparátu a úpravou konkomitantní terapie. V kazuistice je prezentovaný případ 49leté ženy s chronickým těžkým průběhem ulcerózní kolitidy a opakovaným výskytem závažných infekčních komplikací na kombinaci biologické a imunosupresivní terapie. Po změně na subkutánní aplikační formu infliximabu bylo možno souběžnou imunosupresivní terapii vysadit, úspěšně tak předejít závažným infekčním komplikacím při současném udržení remise střevního zánětu a tím výrazně zvýšit kvalitu života nemocné.

The growing number of patients with inflammatory bowel disease on biological treatment naturally entails a more frequent manifestation of adverse effects. Especially in patients who benefit from this therapy, it is possible to eliminate the occurrence of adverse effects by changing the application form of the preparation and adjusting the concomitant therapy. The case report presents the case of a 49-year-old woman with a chronic, severe course of ulcerative colitis and repeated occurrence of serious infectious complications when biological and immunosuppressive therapies were combined. After changing to the subcutaneous application form of infliximab, it was possible to discontinue the concurrent immunosuppressive therapy, thus successfully preventing serious infectious complications while simultaneously maintaining the remission of intestinal inflammation and thereby significantly increasing the patient's quality of life.

• MeSH
• biologická terapie škodlivé účinky   MeSH
• infliximab * škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nežádoucí účinky léčiv MeSH
• ulcerózní kolitida * farmakoterapie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

• MeSH
• alopurinol aplikace a dávkování   škodlivé účinky   MeSH
• azathioprin aplikace a dávkování   škodlivé účinky   MeSH
• Crohnova nemoc * farmakoterapie   imunologie   komplikace   MeSH
• dospělí MeSH
• infliximab * aplikace a dávkování   imunologie   škodlivé účinky   MeSH
• kombinovaná farmakoterapie MeSH
• lékové postižení jater etiologie   MeSH
• leukocytární L1-antigenní komplex analýza   MeSH
• lidé MeSH
• náhrada léků MeSH
• terapie neúspěšná MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

• MeSH
• biologická terapie * škodlivé účinky   MeSH
• dospělí MeSH
• idiopatické střevní záněty * farmakoterapie   MeSH
• infliximab škodlivé účinky   terapeutické užití   MeSH
• kožní nemoci chemicky indukované   MeSH
• lidé MeSH
• nežádoucí účinky léčiv MeSH
• ulcerózní kolitida farmakoterapie   MeSH
• ustekinumab terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

• Klíčová slova
• tofacitinib,
• MeSH
• biochemie metody   MeSH
• diagnostické zobrazování MeSH
• infliximab škodlivé účinky   účinky léků   MeSH
• inhibitory Janus kinas terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• ulcerózní kolitida * farmakoterapie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

BACKGROUND AND AIMS: There are limited comparative data for infliximab and vedolizumab in inflammatory bowel disease patients. METHODS: We conducted a systematic review and meta-analysis to compare the efficacy and safety of infliximab and vedolizumab in adult patients with moderate-to-severe Crohn's disease or ulcerative colitis. RESULTS: We identified six eligible Crohn's disease and seven eligible ulcerative colitis trials that randomised over 1900 participants per disease cohort to infliximab or vedolizumab. In the Crohn's disease and ulcerative colitis cohorts, infliximab yielded better efficacy than vedolizumab for all analysed outcomes (CDAI-70, CDAI-100 responses, and clinical remission for Crohn's disease and clinical response and clinical remission for ulcerative colitis) during the induction phase, with non-overlapping 95% confidence intervals. In the maintenance phase, similar proportions of infliximab- or vedolizumab-treated patients achieved clinical response, clinical remission, or mucosal healing in both Crohn's disease and ulcerative colitis. For the safety outcomes, rates of adverse events, serious adverse events, and discontinuations due to adverse events were similar in infliximab- and vedolizumab-treated patients in both diseases. The infection rate was higher in infliximab for Crohn's disease and higher in vedolizumab when treating patients with ulcerative colitis. There was no difference between the treatments in the proportions of patients who reported serious infections in both indications. CONCLUSIONS: Indirect comparison of infliximab and vedolizumab trials in adult patients with moderate-to severe Crohn's disease or ulcerative colitis demonstrated that infliximab has better efficacy in the induction phase and comparable efficacy during the maintenance phase and overall safety profile compared to vedolizumab.

• MeSH
• Crohnova nemoc * chemicky indukované   farmakoterapie   MeSH
• dospělí MeSH
• gastrointestinální látky škodlivé účinky   MeSH
• humanizované monoklonální protilátky MeSH
• idiopatické střevní záněty * chemicky indukované   farmakoterapie   MeSH
• infliximab škodlivé účinky   MeSH
• lidé MeSH
• ulcerózní kolitida * chemicky indukované   farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• systematický přehled MeSH

Studies showing a substantial frequency of dermatologic complications in paediatric Crohn's disease (CD) patients on anti-tumour necrosis factor (TNF) therapy preferentially include patients treated with infliximab. We aimed to identify risk factors for the cumulative incidence of skin complications in a paediatric cohort receiving either adalimumab or infliximab and found an association between current skin complications and the patient's current clinical condition. This study retrospectively evaluated dermatologic complications in an inception cohort of 100 paediatric CD patients receiving the first anti-TNF (Motol PIBD cohort). Patient data were collected every 3 months. The lesions were classified as psoriatic, atopic dermatitis, or others. We used Cox regression to evaluate the association between predefined variables and the time to complication and a generalised linear mixed model to assess the association between the patient's current condition and the occurrence of complications. Among the 89 included children, 35 (39%) presented with dermatologic lesions. The only predictor associated with any complication was infliximab (versus adalimumab) therapy (hazard ratio [HR]: 2.07; 95% confidence interval [CI]: 1.03-4.17; p = 0.04). Infliximab therapy (HR: 5.5; 95%CI: 1.59-19.06; p = 0.01) and a family history of atopy (HR: 3.4; 95%CI 1.35-8.57, p = 0.002) were associated with early manifestation of atopic dermatitis. Lower C-reactive protein levels (odds ratio [OR], 0.947; 95% CI, - 0.898 to 0.998; p = 0.046) and infliximab (versus adalimumab) were associated with the occurrence of any dermatologic complications (OR, 5.93; 95% CI, 1.59-22.07; p = 0.008).Conclusion: The frequency of skin complications seems high in paediatric CD patients treated with anti-TNF and is even higher in those treated with infliximab. What is Known: •The dermatologic complications occur during treatment with anti-tumour necrosis factor. •The frequency of skin complications in paediatric patients with Crohn's disease is high. What is New: •Infliximab (vs. adalimumab) was identified as a strong risk factor for the cumulative incidence of skin complications. •Lower C-reactive protein levels were associated with the current occurrence of dermatologic complications.

• MeSH
• Crohnova nemoc * komplikace   farmakoterapie   MeSH
• dítě MeSH
• infliximab škodlivé účinky   MeSH
• inhibitory TNF * MeSH
• lidé MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• TNF-alfa MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Posterior reversible encephalopathy syndrom (PRES) je akutně vzniklá, klinicko-neuroradiologická jednotka definovaná jako vazogenní edém mozku v souvislosti s neurotoxickým postižením. Prezentována je kazuistika osmiletého chlapce s těžkou formou ulcerózní kolitidy a celiakií, který byl léčen kombinovanou terapií infliximabem a azatioprinem. Desátý den po aplikaci infliximabu se rozvinul 45 minut trvající stav bezvědomí s generalizovanými křečemi a miózou zornic, provázený arteriální hypertenzí. Chlapec byl léčen antikonvulzivy a antihypertenzivy. Stav vědomí se upravil ad integrum. Magnetická rezonance (MR) mozku nalezla ložiskové hypersignální změny kortikálně a subkortikálně, uložené symetricky v okcipitálních a frontoparietálních oblastech. Lumbální punkce byla negativní. Při kontrolní MR v odstupu týdne se nález zcela znormalizoval. Stav byl zhodnocen jako PRES, který se vyvinul jako komplikace léčby (infliximab, azatioprin) u pacienta s chronicky aktivní ulcerózní kolitidou. Případ ukazuje na možné riziko rozvoje neurologických potíží typu PRES u pacientů s nespecifickým střevním zánětem, jejichž klinický stav není kompenzován, dostávají imunosupresivní nebo biologickou léčbu a/ nebo se u nich rozvine arteriální hypertenze.

Posterior Reversible Encephalopathy Syndrome (PRES) is a clinical-neuroradiological entity with acute onset, defined as a vasogenic brain edema associated with neurotoxic impairment. We report the case of an eight-year-old boy with severe ulcerative colitis and celiac disease, who was treated with infliximab and azathioprine. On the 10th day after infliximab administration, a 45-minute unconsciousness developed with generalized convulsions and pupil miosis, accompanied by arterial hypertension. The boy was treated with anticonvulsants and antihypertensives. The state of consciousness improved ad integrum. Magnetic resonance imaging (MRI) of the brain revealed symmetric areas of high-intensity signal involving occipital and fronto-parietal lobes. Lumbar puncture was negative. Repeat MRI, seven days from the onset, showed resolution of the previous changes. The condition was assessed as PRES that developed as a complication of treatment (infliximab, azathioprine) in a patient with active ulcerative colitis. The case indicates a possible risk of developing PRES in patients with uncompensated inflammatory bowel disease, receiving immunosuppressive and/ or bio­logical treatment and/ or developing arterial hypertension.

• MeSH
• azathioprin škodlivé účinky   terapeutické užití   MeSH
• dítě MeSH
• infliximab škodlivé účinky   terapeutické užití   MeSH
• lidé MeSH
• neurozobrazování metody   MeSH
• syndrom zadní leukoencefalopatie * chemicky indukované   diagnóza   terapie   MeSH
• ulcerózní kolitida * diagnóza   farmakoterapie   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH