BACKGROUND: STARDUST, a phase 3b randomised trial, compared ustekinumab therapeutic strategies in patients with Crohn's disease (CD) using early endoscopic assessment and treat-to-target (T2T) versus standard of care (SoC). AIM: To assess the efficacy of ustekinumab extended treatment in a long-term extension (LTE) of up to 104 weeks with dosing adapted according to clinical, biomarker and endoscopy outcomes. METHODS: Adults with moderately-to-severely active CD received intravenous ustekinumab approximating 6 mg/kg at Week 0 and subcutaneous ustekinumab 90 mg at Week 8. At Week 16, 440 ≥70-point responders were randomised to T2T or SoC and 323 entered the LTE. At Week 48, a unified, protocol-defined ustekinumab dose frequency escalation/de-escalation was applied based on achieving endoscopic remission and corticosteroid-free clinical remission. Achieving corticosteroid-free clinical remission and biomarker remission at consecutive visits determined ustekinumab dosing frequency. Dichotomous variables were analysed using non-responder imputation. RESULTS: Among patients who entered the LTE, 7.7%, 48.6% and 43.7% received doses every 4, 8 and 12 weeks, respectively. Ustekinumab dose frequency was escalated in 23.5% and de-escalated in 19.7%. Endoscopic response and remission rates were 28.9% and 10.73% (all randomised) and 39.3% and 14.6% (patients entering the LTE), respectively, at Week 104. Clinical remissiona rates at week 104 were 50.2% (all randomised) and 68.4% (patients entering the LTE). There were no new safety signals. CONCLUSION: STARDUST LTE is the first interventional ustekinumab efficacy study to show a favourable benefit-risk profile with preservation of clinical and endoscopic outcomes through Week 104 using flexible, algorithm-driven dose adjustment including de-escalation.
- MeSH
- biologické markery analýza MeSH
- Crohnova nemoc * farmakoterapie MeSH
- dospělí MeSH
- gastrointestinální endoskopie MeSH
- indukce remise MeSH
- lidé MeSH
- ustekinumab * terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III 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
- MeSH
- biosimilární léčivé přípravky * farmakologie klasifikace terapeutické užití MeSH
- humanizované monoklonální protilátky farmakologie klasifikace terapeutické užití MeSH
- klinická studie jako téma MeSH
- lidé MeSH
- schvalování léčiv MeSH
- ustekinumab * farmakologie terapeutické užití MeSH
- způsoby aplikace léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
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
Ustekinumab is an effective therapy for adult Crohn's disease (CD), but data in paediatric CD patients are scarce. The aim of the study was to describe the real-life effectiveness and safety of ustekinumab in paediatric CD. This is a multicentre review of children with Crohn's disease treated with ustekinumab. The aim of our study was to describe the effectiveness and safety of ustekinumab in paediatric real-life practice. This is a study of the Paediatric IBD (inflammatory bowel disease) Porto group of ESPGHAN. Corticosteroid (CS)- and exclusive enteral nutrition (EEN)-free remission, defined as weighted Paediatric Crohn's Disease Activity Index (wPCDAI) < 12.5, and physician global assessment (PGA) were determined at weeks 12 and 52. A total of 101 children were included at a median age of 15.4 years (IQR 12.7-17.2) with a median follow-up of 7.4 months (IQR 5.6-11.8). Ninety-nine percent had received prior anti-TNF, 63% ≥ 2 anti-TNFα therapies and 22% vedolizumab. Baseline median wPCDAI was 39 (IQR 25-57.5) (71 (70%) patients with moderate-severe activity). Weeks 12 and 52 CS- and EEN-free remission were both 40.5%. Clinical response at week 6, iv induction route and older age at onset of ustekinumab treatment were predictive factors associated with clinical remission at week 12. Seven minor adverse events probably related to ustekinumab were reported. One patient died from an unrelated cause. Conclusion: Our results suggest that ustekinumab is effective and safe in children with chronically active or refractory CD. What is Known: • Ustekinumab is an effective therapy for adult moderate to severe Crohn's disease (CD). • Off-label use of ustekinumab in children is increasing especially in anti-TNF refractory CD. What is New: • Is the largest cohort of real-world use of ustekinumab in paediatric CD to date. • Clinical response at week 6, iv induction and older age at onset of ustekinumab were predictive factors associated with clinical response at week 12.
- MeSH
- Crohnova nemoc * farmakoterapie MeSH
- dítě MeSH
- indukce remise MeSH
- lidé MeSH
- mladiství MeSH
- retrospektivní studie MeSH
- stupeň závažnosti nemoci 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
- multicentrická studie MeSH
- Klíčová slova
- vedolizumab,
- MeSH
- adalimumab aplikace a dávkování farmakologie terapeutické užití MeSH
- biologická terapie metody MeSH
- humanizované monoklonální protilátky aplikace a dávkování farmakologie terapeutické užití MeSH
- idiopatické střevní záněty * farmakoterapie MeSH
- infliximab aplikace a dávkování farmakologie terapeutické užití MeSH
- lidé MeSH
- monitorování léčiv metody MeSH
- ustekinumab aplikace a dávkování farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- směrnice pro lékařskou praxi MeSH
Psoriatická artritida je chronická zánětlivá artritida, kterou lze řadit mezi spondyloartritidy. Jedná se o systémové autoimunitní onemocnění, u kterého je charakteristická heterogenita zánětlivého postižení zejména v oblasti úponů (entezitida), dále postižení periferních a axiálních skloubení, která jsou asociována s klinickými projevy v oblasti kůže, nehtů, střevní sliznice a duhovek. Doporučení léčby pro psoriatickou artritidu sestává z konvenčních syntetických chorobu modifikujících léků (conventional synthetic disease modifying anti-rheumatic drug, csDMARD), biologických chorobu modifikujících antirevmatických léků (biological disease modifying anti-rheumatic drug, bDMARD), inhibitorů Janusových kináz a inhibitorů fosfodiesterázy 4. V současnosti nejsou plně k dispozici komparativní studie mezi jednotlivými molekulami. Psoriatická artritida je často asociována s komorbiditami, jako jsou osteoporóza, uveitidy, kardiovaskulární onemocnění. Pro heterogenitu klinických projevů lze léčebně využít takové léčebné možnosti, které cílí na jednotlivé domény klinického postižení a mohou bránit rentgenové progresi.
Psoriatic arthritis (PsA) is a chronic inflammatory condition with articular and extra-articular manifestations: peripheral arthritis, axial disease, enthesitis, dactylitis, psoriasis, inflammatory bowel disease and uveitis. Anti-tumour necrosis factors (anti-TNF) have demonstrated clinical efficacies exceeding those of conventional disease-modifying anti-rheumatic drugs (csDMARD). New understanding in pathogenic pathways have led to novel therapeutic targets. The prevention of joint deformity is among the most important treatment goals of psoriatic arthritis. Some biological disease modifying anti-rheumatic drugs (bDMARD) have been demonstrated to be effective for both the skin and joints, as well as for slowing radiographic progression. However, there has been a lack of direct comparisons of bDMARDs. Psoriatic arthritis is associated with comorbidities such as osteoporosis, uveitis, subclinical bowel inflammation, and cardiovascular disease. Given this heterogeneity, its diagnosis has been difficult. Here we present use of screening tools to aid in early diagnosis, recent findings on pathogenesis, and new therapeutic approaches including new biologic medications.
- MeSH
- inhibitory Janus kinas farmakologie terapeutické užití MeSH
- inhibitory TNF aplikace a dávkování farmakologie terapeutické užití MeSH
- interleukin-17 antagonisté a inhibitory aplikace a dávkování farmakologie MeSH
- lidé MeSH
- psoriatická artritida * diagnóza farmakoterapie komplikace patologie MeSH
- psoriáza farmakoterapie komplikace MeSH
- ustekinumab farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
BACKGROUND & AIMS: In this STARDUST substudy, the effect of ustekinumab on transmural bowel inflammation was assessed in adults with moderate-to-severe Crohn's disease (CD) by using intestinal ultrasound (IUS), a noninvasive imaging procedure. METHODS: STARDUST was an international, multicenter, phase 3b, interventional, randomized controlled trial specifically designed to compare treat-to-target and standard-of-care treatment strategies in ustekinumab-treated CD patients. In this substudy, the most affected bowel segment at baseline by IUS was used for all analyses. Key IUS endpoints (centrally read, parameter-blinded) were IUS response, transmural remission, bowel wall thickness (BWT), blood flow, bowel wall stratification, and inflammatory fat. RESULTS: Seventy-seven patients were evaluated. IUS response could be determined 4 weeks after treatment initiation, with progressive improvement through week 48. IUS response and transmural remission rates at week 48 were 46.3% and 24.1%, respectively. IUS response, transmural remission, BWT, and blood flow normalization rates were more pronounced in the colon and biologic-naive patients. Fair/moderate reliability (κ = 0.21-0.51) was observed between week 4 IUS response and week 48 overall endoscopic response and fecal calprotectin/complete biomarker outcomes. Endoscopy and IUS baseline agreement was >90% in determining the terminal ileum as the most affected bowel segment. IUS response absence at week 4 was associated with no endoscopic response (based on the simplified endoscopic score for Crohn's disease terminal ileum subscore) at week 48 (negative predictive value = 73%). CONCLUSIONS: In this first international, multicenter, interventional study, IUS showed that ustekinumab-treated CD patients achieved progressive IUS response (46.3%) and transmural remission (24.1%) through week 48, with a more robust response in the colon and biologic-naive patients. CLINICALTRIALS: gov number: NCT03107793.
- MeSH
- biologické přípravky * MeSH
- Crohnova nemoc * diagnostické zobrazování farmakoterapie MeSH
- dospělí MeSH
- indukce remise MeSH
- kolon MeSH
- lidé MeSH
- reprodukovatelnost výsledků MeSH
- ustekinumab terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
