Tato kazuistika popisuje léčbu pacienta s relabující-remitující formou roztroušené sklerózy (RR-RS), který zároveň trpí Crohnovou nemocí. Po počáteční terapii glatiramer-acetátem a interferonem beta-1a došlo u pacienta k pokračující aktivitě onemocnění, která si vyžádala změnu léčby. S ohledem na potřebu vysoce účinné terapie a pacientovu preferenci méně častých návštěv zdravotnického zařízení byla v dubnu 2022 zahájena léčba ponesimodem. Po více než dvouleté léčbě pacient zůstává klinicky stabilní, bez nových atak či progrese nemoci, a Crohnova nemoc je v remisi. Pacient dobře toleruje léčbu a vede plnohodnotný život, což potvrzuje účinnost a bezpečnost ponesimodu jako vhodné volby pro pacienty s aktivní RS a komorbiditami.
This case report describes the treatment of a patient with relapsing-remitting multiple sclerosis (RR-RS) who also suffers from Crohn's disease. After initial therapy with glatiramer acetate and interferon beta-1a, the patient had ongoing disease activity that required a change in treatment. Considering the need for highly effective therapy and the patient's preference for less frequent visits to the medical facility, treatment with ponesimod was started in April 2022. After more than two years of treatment, the patient remains clinically stable, without new relapses or disease progression, and Crohn's disease is in remission. The patient tolerates the treatment well and leads a full life, which confirms the efficacy and safety of ponesimod as a suitable choice for patients with active MS and comorbidities.
- Klíčová slova
- ponesimod,
- MeSH
- Crohnova nemoc diagnóza farmakoterapie MeSH
- demyelinizační nemoci diagnostické zobrazování MeSH
- dospělí MeSH
- kvalita života MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- progrese nemoci MeSH
- receptory sfingosin-1-fosfátu * antagonisté a inhibitory terapeutické užití MeSH
- relabující-remitující roztroušená skleróza * diagnóza farmakoterapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
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
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
Crohnova choroba a ulcerózní kolitida jsou chronická, zánětlivá střevní onemocnění medikamentózně a chirurgicky nevy- léčitelná. V posledních 20 letech došlo k dramatickému vývoji především léčby medikamentózní. V biologické léčbě byly zavedeny nové preparáty s mechanismem účinku cíleným na molekuly s klíčovým postavením v patogenezi idiopatických střevních zánětů.
Crohn's disease and ulcerative colitis are chronic, inflammatory bowel disease medically and surgically incurable. In the last 20 years, there has been a dramatic development, especially of medicamentous treatment. In biological therapy, new agents have been introduced with a mechanism of action targeted on molecules of key role in the pathogenesis of inflammatory bowel disease.
- MeSH
- biologická terapie metody MeSH
- biosimilární léčivé přípravky terapeutické užití MeSH
- Crohnova nemoc farmakoterapie MeSH
- idiopatické střevní záněty * farmakoterapie MeSH
- individualizovaná medicína MeSH
- inhibitory interleukinu terapeutické užití MeSH
- inhibitory Janus kinas aplikace a dávkování terapeutické užití MeSH
- inhibitory TNF aplikace a dávkování terapeutické užití MeSH
- lidé MeSH
- molekuly buněčné adheze antagonisté a inhibitory MeSH
- receptory sfingosin-1-fosfátu antagonisté a inhibitory MeSH
- ulcerózní kolitida farmakoterapie MeSH
- Check Tag
- lidé 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
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
