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
- retrospektivní studie MeSH
- terapie neúspěšná 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
- 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
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
Úvod a ciele: Nedávno bol schválený prvý subkutánny infliximab (IFX), CTP-13, v indikácii IBD. Pilotná štúdia preukázala noninferioritu subkutánneho infliximabu voči intravenóznej forme z hľadiska účinnosti, pričom neboli pozorované žiadne neočakávané nežiaduce účinky liečby. Cieľom štúdie bolo zhodnotiť účinnosť liečby, farmakokinetiku a bezpečnosť po prechode z intravenóznej na subkutánnu liečbu infliximabom. Metódy: Táto retrospektívna kohortová štúdia zah?ňala všetkých pacientov s Crohnovou chorobou (CD) a ulceróznou kolitídou (UC) sledovaných v IBD centre, ktorí prešli z intravenózneho na subkutánny IFX medzi septembrom 2022 a septembrom 2023. Klinická aktivita ochorenia podľa HBI a pMayo, sIBDQ, fekálny kalprotektín, perzistencia liečby, bezpečnosť a farmakokinetika boli hodnotené v 24. a 56. týždni po prechode na subkutánny infliximab. Výsledky: Kohorta pozostávala z 107 pacientov (63 CD a 44 UC). Indexy kvality života a klinickej aktivity ochorenia zostali nezmenené pri CD aj UC. Fekálny kalprotektín sa významne znížil pri CD, ale nie pri UC. Pacienti, ktorým bol IV IFX podávaný v štandardnom režime, ako aj tí na intenzifikovaných režimoch, vykazovali podobné výsledky pri štandardnom SC dávkovaní. Nevyskytli sa žiadne závažné nežiaduce udalosti. Prechodné injekčné reakcie sa vyskytli u 4,7 % pacientov. Medián najnižších hladín infliximabu sa významne zvýšil po prechode na subkutánnu formu. Záver: Prechod z intravenózneho infliximabu na subkutánny je bezpečnou a účinnou možnosťou liečby pacientov so zápalovým ochorením čriev vrátane tých s aktivitou ochorenia a/alebo na intenzifikovanom intravenóznom režime infliximabu.
Background and aims: Recently, the first subcutaneous infliximab (IFX), CTP-13, was approved in the indication of IBD. Pivotal study established noninferiority of subcutaneous infliximab to intravenous formulation in terms of efficacy, with no unexpected safety signals observed. The aims of the study were to evaluate persistency of treatment, pharmacokinetics and safety following a switch from intravenous to subcutaneous infliximab treatment. Methods: This retrospective, single-centre cohort study, recruited all Crohn’s disease (CD) and ulcerative colitis (UC) patients who transitioned from intravenous to subcutaneous IFX between September 2022 and September 2023. Clinical disease activity according to HBI and pMayo, sIBDQ, faecal calprotectin, drug persistence, safety and pharmacokinetics were evaluated at week 24 and 56 after the switch to subcutaneous infliximab. Results: A number of 107 patients was included (63 CD and 44 UC). Quality of life and clinical disease activity scores remained unchanged both in CD and UC. Faecal calprotectin decreased significantly in CD but not in UC. Patients that had been on standard compared to intensified IV infliximab dosing displayed similar outcomes on standard SC dosing. No serious adverse events occurred. Transient local injection reactions were experienced by 4.7% of patients. Median infliximab trough levels significantly increased after the switch to subcutaneous formulation. Conclusion: The switch from intravenous to subcutaneous infliximab is a safe and effective option for the treatment of inflammatory bowel diseases including those with active disease and/or on intensified intravenous infliximab regime.
- MeSH
- biologické přípravky aplikace a dávkování farmakologie terapeutické užití MeSH
- Crohnova nemoc * farmakoterapie MeSH
- infliximab * aplikace a dávkování farmakologie terapeutické užití MeSH
- intravenózní podání MeSH
- lidé MeSH
- retrospektivní studie MeSH
- subkutánní infuze MeSH
- ulcerózní kolitida * farmakoterapie MeSH
- Check Tag
- lidé MeSH
