BACKGROUND AND AIMS: Anti-tumor necrosis factor-α inhibitors (anti-TNFs) are the established treatment for perianal Crohn's disease (pCD), but relapse and non-response are common. Data on second- and third-line biologics are limited. We present the first direct comparison of second- and third-line biologics in pCD patients with active perianal disease previously treated with first-line anti-TNFs. METHODS: A multicenter retrospective cohort study included adult patients with pCD who failed first-line anti-TNF. The primary outcome was clinical perianal response, with secondary outcomes of radiological response (magnetic resonance imaging or transrectal ultrasound) and healing, and clinical remission. Propensity score matching (PSM) was used to adjust for baseline differences. RESULTS: A total of 486 pCD patients from 23 IBD centers were included, with 333/486 (68.5%) and 216/263 (82.1%) matched by PSM in the second and third-line treatment groups, respectively. In the second-line group, 62/78 (79.5%) of ustekinumab (UST)-treated patients achieved clinical perianal response, compared to 46/78 (58.9%) with vedolizumab (VDZ) (OR 4.47, 95% CI, 1.94-10.28, P < .001) and 38/78 (48.7%) with anti-TNFs (OR 5.29, 95% CI, 2.39-11.71, P < .001). In the third-line group, 38/49 (77.6%) of UST-treated patients achieved clinical perianal response, compared to 29/49 (59.2%) with VDZ (OR 9.96, 95% CI, 2.6-38.4, P < .001) and 27/49 (55.1%) with anti-TNFs (OR 12.03, 95% CI, 2.99-48.47, P < .001). UST-treated patients also had higher radiological response rates than VDZ (OR 3.28, 95% CI, 1.07-10.07, P = .038). CONCLUSION: In pCD patients failing anti-TNFs as first-line treatment, ustekinumab may be more effective than vedolizumab or another anti-TNF as second or third-line therapy.
- MeSH
- biologické přípravky * terapeutické užití MeSH
- Crohnova nemoc * farmakoterapie diagnostické zobrazování MeSH
- dospělí MeSH
- gastrointestinální látky * terapeutické užití MeSH
- humanizované monoklonální protilátky terapeutické užití MeSH
- indukce remise MeSH
- inhibitory TNF terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- nemoci anu * farmakoterapie MeSH
- retrospektivní studie MeSH
- tendenční skóre MeSH
- ustekinumab * terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- MeSH
- gastroenterologie * MeSH
- společnosti lékařské MeSH
- Publikační typ
- biografie MeSH
- O autorovi
- Scheiner, Jiří, 1893-1950 Autorita
BACKGROUND: Many ulcerative colitis (UC) patients require the use of second-line agents after the failure of anti-TNF therapy. RESEARCH DESIGN AND METHODS: We conducted a multicenter, retrospective study including 683 chronically active, moderate-to-severe UC patients who failed first-line anti-TNFs. The rate of treatment persistence and colectomy-free survival was assessed up to 3 years after the initiation of second-line therapy. Predictors for colectomy and persistence were investigated. RESULTS: After the failure of the first-line anti-TNF, ustekinumab had superior persistence and colectomy-free survival rates compared to tofacitinib (p = 0.05; p = 0.001) and vedolizumab (p = 0.02; p = 0.05), but significant difference was only found in persistence rates in comparison with anti-TNFs (p < 0.001). Regardless of the number of prior anti-TNFs, significantly higher persistence (p = 0.05) and colectomy-free survival rates (p = 0.01) were observed over 2 years with ustekinumab than with vedolizumab or tofacitinib, whereas ustekinumab's superiority over tofacitinib seemed to disappear by the third year. Hypoalbuminaemia (p = 0.002) and shorter disease duration at second-line initiation (p = 0.03) increased, while concomitant immunomodulators (p = 0.05) reduced the risk for colectomy. Shorter disease duration (p = 0.01) and primary non-response to the previously used anti-TNF (p < 0.001) negatively influenced persistence with second-line non-TNF-targeted agents. CONCLUSION: After first-line anti-TNF failure, switching to a non-anti-TNF agent is worth considering in moderate-to-severe UC.
- MeSH
- chronická nemoc MeSH
- dospělí MeSH
- gastrointestinální látky * terapeutické užití aplikace a dávkování MeSH
- humanizované monoklonální protilátky terapeutické užití aplikace a dávkování MeSH
- kohortové studie MeSH
- kolektomie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- neúspěšná terapie MeSH
- piperidiny terapeutické užití aplikace a dávkování MeSH
- pyrimidiny terapeutické užití aplikace a dávkování MeSH
- pyrrolidiny terapeutické užití aplikace a dávkování MeSH
- retrospektivní studie MeSH
- senioři MeSH
- stupeň závažnosti nemoci MeSH
- TNF-alfa * antagonisté a inhibitory MeSH
- ulcerózní kolitida * farmakoterapie chirurgie MeSH
- ustekinumab terapeutické užití aplikace a dávkování MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- srovnávací studie MeSH
OBJECTIVES: Elderly hospitalized patients with inflammatory bowel disease (IBD) flare and concurrent Clostridioides difficile infection (CDI) are considered at high risk of IBD-related complications. We aimed to evaluate the short-,intermediate-, and long-term post-discharge complications among these patients. METHODS: A retrospective multicenter cohort study assessing outcomes of elderly individuals (≥60 years) hospitalized for an IBD flare who were tested for CDI (either positive or negative) and discharged. The primary outcome was the 3-month post-discharge IBD-related complication rates defined as steroid dependency, re-admissions (emergency department or hospitalization), IBD-related surgery, or mortality. We assessed post-discharge IBD-related complications within 6 month and mortality at 12 month among secondary outcomes. Risk factors for complication were assessed by multivariable logistic regression. RESULTS: In a cohort of 654 patients hospitalized for IBD {age 68.9 (interquartile range [IQR]): 63.9-75.2 years, 60.9% ulcerative colitis (UC)}, 23.4% were CDI-positive. Post-discharge complication rates at 3 and 6 months, and 12 months mortality, did not differ significantly between CDI-positive and CDI-negative patients (32% vs 33.1%, p = 0.8; 40.5% vs 42.5%, p = 0.66; and 4.6% vs 8%, p = 0.153, respectively). The Charlson comorbidity index was the only significant risk factor for complications within 3 months (aOR 1.1), whereas mesalamine (5-aminosalicylic acid [5-ASA]) use was protective (aOR 0.6). An UC diagnosis was the sole risk factor for complication at 6 months (aOR 1.5). Clostridioides difficile infection did not significantly impact outcomes or interact with IBD type. CONCLUSIONS: In elderly IBD patients hospitalized for IBD flare and subsequently discharged, a concurrent CDI infection was not associated with post-discharge IBD-related complications or mortality up to 1 year.
- MeSH
- Clostridioides difficile MeSH
- hospitalizace statistika a číselné údaje MeSH
- idiopatické střevní záněty * komplikace MeSH
- klostridiové infekce * komplikace epidemiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- propuštění pacienta MeSH
- retrospektivní studie MeSH
- rizikové faktory MeSH
- senioři MeSH
- syndrom vzplanutí nemoci MeSH
- znovupřijetí pacienta statistika a číselné údaje MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
BACKGROUND AND AIMS: Janus kinase (JAK) inhibitors, such as tofacitinib, are potent anti-inflammatory agents used in the treatment of ulcerative colitis (UC). Current guidelines recommend avoiding their use during pregnancy due to safety concerns, as well as during breastfeeding due to the potential excretion into breast milk. METHODS: This case report describes the impact of in utero exposure to tofacitinib during pregnancy and subsequent exposure via breastfeeding on the immune development of the exposed infant. RESULTS: A 37-year-old woman with UC, who was being treated with tofacitinib and vedolizumab, became pregnant and continued both medications, with the tofacitinib dosage reduced from 10 to 5 mg BID at gestational week 28. The infant was born healthy, with normal growth and development, and received all scheduled non-live vaccinations. At 15 months, immune parameters-including response to vaccination-were evaluated. The results showed normal immunoglobulin levels and an adequate serologic response to vaccination, with no signs of immune dysfunction. CONCLUSIONS: This case suggests that prolonged prenatal and postnatal exposure to tofacitinib may not adversely affect infant immune development. However, caution is advised due to the limited number of documented cases. Further research is needed to fully understand the long-term implications of JAK inhibitor exposure during pregnancy and breastfeeding.
- MeSH
- dospělí MeSH
- humanizované monoklonální protilátky terapeutické užití MeSH
- inhibitory Janus kinas * škodlivé účinky MeSH
- inhibitory proteinkinas škodlivé účinky terapeutické užití MeSH
- kojenec MeSH
- kojení * MeSH
- komplikace těhotenství farmakoterapie MeSH
- lidé MeSH
- novorozenec MeSH
- piperidiny * škodlivé účinky terapeutické užití MeSH
- pyrimidiny * škodlivé účinky terapeutické užití MeSH
- pyrroly škodlivé účinky terapeutické užití MeSH
- těhotenství MeSH
- ulcerózní kolitida * farmakoterapie MeSH
- zpožděný efekt prenatální expozice * imunologie chemicky indukované MeSH
- Check Tag
- dospělí MeSH
- kojenec MeSH
- lidé MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
