- Klíčová slova
- mirikizumab,
- MeSH
- cílená molekulární terapie metody MeSH
- dospělí MeSH
- humanizované monoklonální protilátky farmakologie klasifikace terapeutické užití MeSH
- interleukin-23 * antagonisté a inhibitory terapeutické užití MeSH
- kombinovaná farmakoterapie metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- ulcerózní kolitida * diagnostické zobrazování diagnóza farmakoterapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- Klíčová slova
- ustekinumab CT-P43,
- MeSH
- biosimilární léčivé přípravky * farmakologie klasifikace terapeutické užití MeSH
- cílená molekulární terapie metody MeSH
- Crohnova nemoc farmakoterapie MeSH
- humanizované monoklonální protilátky farmakologie klasifikace terapeutické užití MeSH
- klinická studie jako téma MeSH
- lidé MeSH
- náklady na zdravotní péči MeSH
- ustekinumab * aplikace a dávkování farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Background/Objectives: Data on the real-world effectiveness and safety of selective JAK inhibitors (JAKis) in ulcerative colitis (UC) and Crohn's disease (CD) are limited. Methods: We conducted a multicentre, retrospective study to assess clinical, biochemical, and endoscopic outcomes of selective JAKis in bio-experienced UC and CD. Results: A total of 246 patients (mean age: 40.5 ± 14.5 years; 131 UC and 115 CD) were included with a median follow-up of 7.5 months. Among the CD patients receiving upadacitinib (n = 115), 76.2% achieved clinical remission (CR) at week 12. Furthermore, 59.5% of the upadacitinib-treated UC patients (n = 100) experienced CR at week 8. Corticosteroid-free CR (CSFCR) was achieved by 76.9% of the CD patients and 80.6% of the UC patients at week 24, while 50.0% and 36.1% experienced endoscopic remission. At week 52, 66.7% of the CD and 86.2% of the UC patients achieved CSFCR, whereas 54.5% and 52.9% had endoscopic remission. In UC, the effectiveness of upadacitinib was not compromised by prior tofacitinib failure, while the upadacitinib-treated CD patients with stricturing and penetrating disease were less likely to achieve CR by the end of the induction phase (p = 0.04). C-reactive protein (p[CD] < 0.0001; p[UC] < 0.0001) and faecal calprotectin (p[CD] < 0.0001; p[UC] = 0.02) decreased significantly in both patient groups as early as week 2. Among the filgotinib-treated UC patients (n = 31), 28.6% were in CR at week 12. At week 24 and 52, 59.1% and 60% achieved CSFCR, while 0.0% and 20.0% had endoscopic remission. Both C-reactive protein (p = 0.04) and faecal calprotectin (p = 0.04) decreased significantly by week 12. Hyperlipidaemia (9.7-9.8%) was the most common adverse event. Conclusions: Selective JAKis are rapidly effective and safe for treating refractory, moderate-to-severe CD and UC.
- Publikační typ
- časopisecké články 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
- MeSH
- adenom diagnóza terapie MeSH
- anastomóza chirurgická MeSH
- dospělí MeSH
- familiární adenomatózní polypóza * chirurgie diagnostické zobrazování komplikace MeSH
- kolektomie MeSH
- lidé MeSH
- meduloblastom * chirurgie diagnóza terapie MeSH
- peritonitida diagnóza terapie MeSH
- pouch MeSH
- tlusté střevo chirurgie patologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Inhibitory Janusovy kinázy byly zavedeny do terapeutického armamentária idiopatických střevních zánětů v roce 2018. Prvním lékem byl tofacitinib a v posledních dvou letech byl dále schválen filgotinib (preferenční inhibitor JAK1) a upadacitinib (selektivní inhibitor JAK1). Inhibitory JAK se využívají především u nemocných s ulcerózní kolitidou, u které představují účinnou 2. linii léčby po selhání alespoň jednoho biologika. Tofacitinib a upadacitinib se uplatňují také jako záchranná terapie u nemocných s ulcerózní kolitidou, u nichž selhalo intravenózní podávání kortikosteroidů. Výjimečné postavení má upadacitinib, neboť jako jediný ze skupiny inhibitorů JAK má také uplatnění u Crohnovy choroby
JAKs inhibitors have been introduced into therapeutic armamentarium of inflammatory bowel disease in 2018. The first molecule was tofacitinib and in the last two years filgotinib (preferential JAK1 inhibitor) and upadacitinib (selective JAK1 inhibitor) were also introduced. JAKs inhibitors are used in ulcerative colitis patients especially in those who failed in one biological therapy. Tofacitinib and upadacitinib are effective as a rescue therapy in patients with acute severe ulcerative colitis, which failed on intravenously applied corticosteroids. Upadacitinib has an extraordinary position because it was also approved for medicamentous therapy in Crohn’s disease patients.
- Klíčová slova
- tofacitinib, upadacitinib, fligotinib,
- MeSH
- idiopatické střevní záněty * farmakoterapie MeSH
- inhibitory Janus kinas farmakologie terapeutické užití MeSH
- klinická studie jako téma MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
