Evidence on serological responses to vaccination in children exposed to ustekinumab (UST) or vedolizumab (VDZ) in utero is lacking. This multicentre prospective study aimed to assess the impact of prenatal exposure to UST or VDZ due to maternal inflammatory bowel disease (IBD) on serological responses to vaccination and other immunological parameters in exposed children. Children aged ≥ 1 year who were exposed in utero to UST or VDZ and completed at least 1-year of mandatory vaccination were included. We assessed the serological response to vaccination (non-live: tetanus, diphtheria, and Haemophilus influenzae B; live: mumps, rubella, and measles), whole blood count, and immunoglobulin levels. The control group comprised unexposed children born to mothers without IBD. A total of 23 children (median age, 25 months) exposed to UST (n = 13) or VDZ (n = 10) and 10 controls (median age, 37 months) were included. The serological response to vaccination was comparable between the UST and VDZ groups and controls, with an adequate serological response rate of ≥ 80%. Only children exposed to UST showed a slightly reduced serological response to mumps (67% vs. 86% in controls), whereas all children exposed to VDZ showed an adequate response. The majority of the exposed children had normal levels of individual immunoglobulin classes, similar to the controls. No severe pathology was observed in any of the children.Conclusion: Despite the limited sample size, our findings suggest that in utero exposure to VDZ or UST does not significantly impair the vaccine response or broader immunological parameters in exposed children.

• MeSH
• dítě MeSH
• gastrointestinální látky terapeutické užití   škodlivé účinky   MeSH
• humanizované monoklonální protilátky * škodlivé účinky   terapeutické užití   MeSH
• idiopatické střevní záněty * farmakoterapie   imunologie   MeSH
• kojenec MeSH
• lidé MeSH
• předškolní dítě MeSH
• prospektivní studie MeSH
• průřezové studie MeSH
• studie případů a kontrol MeSH
• těhotenství MeSH
• ustekinumab * terapeutické užití   škodlivé účinky   MeSH
• vakcinace * škodlivé účinky   MeSH
• zpožděný efekt prenatální expozice * chemicky indukované   imunologie   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články 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

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

• MeSH
• antibakteriální látky terapeutické užití   MeSH
• biologická terapie metody   MeSH
• Crohnova nemoc * diagnóza   farmakoterapie   patologie   MeSH
• enterální výživa metody   MeSH
• gastrointestinální látky aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• hormony kůry nadledvin aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• imunosupresiva aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• inhibitory TNF aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• léková kontraindikace MeSH
• lidé MeSH
• methotrexát aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• parenterální výživa metody   MeSH
• Check Tag
• lidé MeSH

BACKGROUND AND AIMS: Evidence on the safety of newer biologics during pregnancy is limited. We aimed to assess the safety of ustekinumab and vedolizumab treatment during gestation on pregnancy and infant outcome. Furthermore, we evaluated the placental transfer of these agents. METHODS: We performed a prospective, multicentre, observational study in consecutive women with inflammatory bowel disease exposed to ustekinumab or vedolizumab 2 months prior to conception or during pregnancy. Pregnancy, neonatal, and infant outcomes were evaluated and compared with the anti-tumour necrosis factor [TNF]-exposed control group. Drug levels were assessed in maternal and cord blood at delivery. RESULTS: We included 54 and 39 pregnancies exposed to ustekinumab and vedolizumab, respectively. In the ustekinumab group, 43 [79.9%] resulted in live births, and 11 [20.4%] led to spontaneous abortion. Thirty-five [89.7%] pregnancies on vedolizumab ended in a live birth, two [5.1%] in spontaneous, and two [5.1%] in therapeutic abortion. No significant difference in pregnancy outcome between either the vedolizumab or the ustekinumab group and controls was observed [p >0.05]. Similarly, there was no negative safety signal in the postnatal outcome of exposed children regarding growth, psychomotor development, and risk of allergy/atopy or infectious complications. The median infant-to-maternal ratio of ustekinumab levels was 1.67 and it was 0.59 in vedolizumab. CONCLUSIONS: Use of ustekinumab and vedolizumab in pregnancy seems to be safe, with favuorable pregnancy and postnatal infant outcomes. Placental transfer differed between these two drugs, with ustekinumab having similar and vedolizumab having inverse infant-to-maternal ratio of drug levels compared with anti-TNF preparations.

• MeSH
• gastrointestinální látky škodlivé účinky   terapeutické užití   MeSH
• humanizované monoklonální protilátky * škodlivé účinky   terapeutické užití   MeSH
• idiopatické střevní záněty * farmakoterapie   MeSH
• inhibitory TNF škodlivé účinky   terapeutické užití   MeSH
• kojenec MeSH
• lidé MeSH
• matka - expozice noxám MeSH
• novorozenec MeSH
• placenta MeSH
• prospektivní studie MeSH
• těhotenství MeSH
• ustekinumab * škodlivé účinky   terapeutické užití   MeSH
• výsledek těhotenství MeSH
• výsledek terapie MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH

BACKGROUND AND AIMS: Ontamalimab, a fully-human monoclonal antibody targeting MAdCAM-1, induced remission in patients with moderate-to-severe ulcerative colitis [UC] in the TURANDOT study. We aimed to assess long-term safety, tolerability, and efficacy of ontamalimab in TURANDOT II. METHODS: TURANDOT II was a phase 2, multicentre, open-label [OL] study in patients with moderate-to-severe UC who completed TURANDOT on placebo or ontamalimab (NCT01771809). Patients were randomised to 75 mg or 225 mg ontamalimab every 4 weeks for 72 weeks [OL1]. The dosage could be increased to 225 mg from Week 8 at the investigator's discretion. All patients then received 75 mg every 4 weeks for 72 weeks [OL2], followed by 6-month safety follow-up. The primary objective was safety, measured by adverse events [AEs], serious AEs [SAEs], and AEs leading to withdrawal. Mucosal healing [MH; centrally read endoscopy] was assessed. RESULTS: Of 330 patients, 180 completed OL1; 94 escalated to 225 mg; 127 completed OL2. Overall, 36.1% experienced drug-related AEs. The most common SAE [10.0%] was worsening/ongoing UC; 5.5% of patients had serious infections, the most common being gastroenteritis [0.9%]. One death and four cancers [all unrelated to ontamalimab] occurred. No PML [progressive multifocal leukoencephalopathy]/lymphoproliferative disorders occurred. Geometric mean high-sensitivity C-reactive protein [hsCRP] and faecal calprotectin decreased across OL1 in both dose groups. The proportion of patients assigned to placebo in TURANDOT achieving MH increased from 8.8% [6/68] at baseline to 35.3% at Week 16 [24/68; non-responder imputation]. The corresponding increase in the ontamalimab group was from 23.3% [61/262] to 26.7% [70/262]. CONCLUSIONS: Ontamalimab was well tolerated up to 144 weeks in patients with moderate-to-severe UC, with good safety and efficacy.

• MeSH
• C-reaktivní protein analýza   MeSH
• dospělí MeSH
• gastrointestinální endoskopie metody   statistika a číselné údaje   MeSH
• gastrointestinální látky aplikace a dávkování   škodlivé účinky   MeSH
• humanizované monoklonální protilátky * aplikace a dávkování   škodlivé účinky   MeSH
• imunologická odpověď na dávku MeSH
• leukocytární L1-antigenní komplex analýza   MeSH
• lidé MeSH
• molekuly buněčné adheze antagonisté a inhibitory   MeSH
• monitorování léčiv * metody   statistika a číselné údaje   MeSH
• mukoproteiny antagonisté a inhibitory   MeSH
• ulcerózní kolitida * diagnóza   farmakoterapie   imunologie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

BACKGROUND AND AIMS: Vedolizumab was shown to be safe and effective for the treatment of Crohn's disease [CD] and ulcerative colitis [UC] in the GEMINI Long-Term Safety [LTS] study. The vedolizumab Extended Access Program [XAP] provides patients with continued treatment. This XAP pharmacokinetics [PK] sub-study investigated vedolizumab efficacy, safety, and PK. METHODS: Vedolizumab dosing frequency was reduced from every 4 weeks [Q4W] to every 8 weeks [Q8W] at XAP enrolment, and patients were followed for 56 weeks. Outcomes included: efficacy, loss of clinical benefit, and re-escalation to Q4W dosing; and vedolizumab PK, immunogenicity, and adverse events. RESULTS: Among 167 enrolled patients [CD = 88, UC = 79], 80 [91%] with CD and 73 [92%] with UC completed 56 weeks; 76 [86%] and 71 [90%] with CD and UC, respectively, remained on Q8W dosing for 56 weeks. Clinical remission, corticosteroid-free clinical remission, and C-reactive protein levels were stable among patients remaining on Q8W through Week 56. Four patients with CD and two with UC resumed Q4W dosing [three with CD regained clinical response]. Patients with CD who completed Week 56 on Q8W dosing had median trough vedolizumab concentrations of 43.6 µg/mL at enrolment and 10.4 µg/mL at Week 56; concentrations were 42.4 µg/mL and 13.3 µg/mL, respectively, in patients with UC. Treatment-related adverse events were infrequent; no new or serious adverse events related to vedolizumab were reported. CONCLUSIONS: In the XAP-PK sub-study, adherence to Q8W dosing was high, with no loss of efficacy; very few patients required re-escalation to Q4W. There were no new safety signals.

• MeSH
• Crohnova nemoc * diagnóza   farmakoterapie   imunologie   MeSH
• dospělí MeSH
• gastrointestinální látky aplikace a dávkování   škodlivé účinky   farmakokinetika   MeSH
• humanizované monoklonální protilátky * aplikace a dávkování   škodlivé účinky   farmakokinetika   MeSH
• imunologická odpověď na dávku MeSH
• integriny antagonisté a inhibitory   MeSH
• intravenózní infuze MeSH
• lidé MeSH
• monitorování léčiv metody   MeSH
• ulcerózní kolitida * diagnóza   farmakoterapie   imunologie   MeSH
• vysazování léků metody   MeSH
• výsledky a postupy - zhodnocení (zdravotní péče) MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze IV MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH

• Klíčová slova
• vedolizumab,
• MeSH
• alergie komplikace   MeSH
• bariatrická chirurgie MeSH
• gastroezofageální reflux MeSH
• gastrointestinální látky aplikace a dávkování   škodlivé účinky   MeSH
• humanizované monoklonální protilátky aplikace a dávkování   škodlivé účinky   MeSH
• klinická studie jako téma MeSH
• klinické zkoušky, fáze III jako téma MeSH
• komorbidita MeSH
• komplikace diabetu MeSH
• lidé MeSH
• multicentrické studie jako téma MeSH
• nádory slinivky břišní epidemiologie   prevence a kontrola   MeSH
• obezita komplikace   MeSH
• rizikové faktory MeSH
• syndrom dráždivého tračníku MeSH
• ulcerózní kolitida farmakoterapie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH

• Klíčová slova
• etrolizumab, ozanimob,
• MeSH
• dospělí MeSH
• gastroenterologie * MeSH
• gastrointestinální látky škodlivé účinky   terapeutické užití   MeSH
• humanizované monoklonální protilátky terapeutické užití   MeSH
• infliximab terapeutické užití   MeSH
• klinické zkoušky, fáze III jako téma MeSH
• lidé MeSH
• odměny a ceny * MeSH
• randomizované kontrolované studie jako téma MeSH
• ulcerózní kolitida farmakoterapie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH

• MeSH
• ankylózující spondylitida imunologie   MeSH
• cytokiny imunologie   MeSH
• dysbióza komplikace   MeSH
• entezopatie diagnostické zobrazování   komplikace   MeSH
• gastrointestinální látky škodlivé účinky   MeSH
• humanizované monoklonální protilátky škodlivé účinky   MeSH
• idiopatické střevní záněty farmakoterapie   MeSH
• interleukin-17 imunologie   MeSH
• interleukin-23 - podjednotka p19 imunologie   MeSH
• lidé MeSH
• psoriatická artritida imunologie   MeSH
• spondylartritida * diagnostické zobrazování   etiologie   imunologie   MeSH
• střevní mikroflóra MeSH
• TNF-alfa antagonisté a inhibitory   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH