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Clinical Gastroenterology and... Jan 2024Several advanced therapies (biologic therapies and small molecules) have been approved for the treatment of moderate-to-severe ulcerative colitis. The registration...
BACKGROUND & AIMS
Several advanced therapies (biologic therapies and small molecules) have been approved for the treatment of moderate-to-severe ulcerative colitis. The registration trials for these agents typically excluded patients with isolated proctitis, leaving an evidence gap. We evaluated efficacy and safety of advanced therapies in patients with ulcerative proctitis (UP).
METHODS
This multicenter retrospective cohort study included consecutive patients with active UP (Mayo endoscopy subscore of ≥2, rectal inflammation up to 15 cm) initiating advanced therapy, after failing conventional therapy. The primary end point was short-term steroid-free clinical remission (total Mayo score ≤2 with no individual subscore >1). In addition, drug persistence and relapse-free and colectomy-free survival were assessed. Both binary logistic and Cox regression analyses were performed.
RESULTS
In total, 167 consecutive patients (52.0% female; median age 41.0 years; 82.0% bionaive) underwent 223 courses of therapy for UP (38 adalimumab, 14 golimumab, 54 infliximab, 9 ustekinumab, 99 vedolizumab, 9 tofacitinib). The primary end point was achieved with 36.3% of the treatment courses, and based on multivariate analysis, more commonly attained in bionaive patients (P = .001), patients treated with vedolizumab (P = .001), patients with moderate endoscopic disease activity (P = .002), and a body mass index <25 kg/m (P = .018). Drug persistence was significantly higher in patients treated with vedolizumab (P < .001) and patients with a shorter disease duration (P = .006). No new safety signals were observed.
CONCLUSIONS
Advanced therapies are also efficacious and safe in patients with ulcerative colitis limited to the rectum. Therefore, the inclusion of patients with UP in future randomized-controlled trials should be considered.
Topics: Humans; Female; Adult; Male; Colitis, Ulcerative; Retrospective Studies; Belgium; Adalimumab; Biological Therapy; Treatment Outcome
PubMed: 37442318
DOI: 10.1016/j.cgh.2023.06.023 -
Journal of Crohn's & Colitis Dec 2023Ulcerative proctitis [UP] is an uncommon presentation in paediatric patients with ulcerative colitis. We aimed to characterize the clinical features and natural history...
BACKGROUND AND AIMS
Ulcerative proctitis [UP] is an uncommon presentation in paediatric patients with ulcerative colitis. We aimed to characterize the clinical features and natural history of UP in children, and to identify predictors of poor outcomes.
METHODS
This was a retrospective study involving 37 sites affiliated with the IBD Porto Group of ESPGHAN. Data were collected from patients aged <18 years diagnosed with UP between January 1, 2016 and December 31, 2020.
RESULTS
We identified 196 patients with UP (median age at diagnosis 14.6 years [interquartile range, IQR 12.5-16.0]), with a median follow-up of 2.7 years [IQR 1.7-3.8]. The most common presenting symptoms were bloody stools [95%], abdominal pain [61%] and diarrhoea [47%]. At diagnosis, the median paediatric ulcerative colitis activity index [PUCAI] score was 25 [IQR 20-35], but most patients exhibited moderate-severe endoscopic inflammation. By the end of induction, 5-aminosalicylic acid administration orally, topically or both resulted in clinical remission rates of 48%, 48%, and 73%, respectively. The rates of treatment escalation to biologics at 1, 3, and 5 years were 10%, 22%, and 43%, respectively. In multivariate analysis, the PUCAI score at diagnosis was significantly associated with initiation of systemic steroids, or biologics, and subsequent acute severe colitis events and inflammatory bowel disease-associated admission, with a score ≥35 providing an increased risk for poor outcomes. By the end of follow-up, 3.1% of patients underwent colectomy. Patients with UP that experienced proximal disease progression during follow-up [48%] had significantly higher rates of a caecal patch at diagnosis and higher PUCAI score by the end of induction, compared to those without progression.
CONCLUSION
Paediatric patients with UP exhibit high rates of treatment escalation and proximal disease extension.
Topics: Humans; Child; Adolescent; Retrospective Studies; Colitis, Ulcerative; Inflammatory Bowel Diseases; Proctitis; Biological Products
PubMed: 37392064
DOI: 10.1093/ecco-jcc/jjad111 -
Health Science Reports Oct 2023The 2022-mpox outbreak has spread worldwide in a short time. Integrated knowledge of the epidemiology, clinical characteristics, and transmission of mpox are limited....
BACKGROUND AND AIMS
The 2022-mpox outbreak has spread worldwide in a short time. Integrated knowledge of the epidemiology, clinical characteristics, and transmission of mpox are limited. This systematic review of peer-reviewed articles and gray literature was conducted to shed light on the epidemiology, clinical features, and transmission of 2022-mpox outbreak.
METHODS
We identified 45 peer-reviewed manuscripts for data analysis. The standards of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) Statement and Cochrane Collaboration were followed for conducting the study.
RESULTS
The case number of mpox has increased about 100 times worldwide. About 99% of the cases in 2022 outbreak was from non-endemic regions. Men (70%-98% cases) were mostly infected with homosexual and bisexual behavior (30%-60%). The ages of the infected people ranged between 30 and 40 years. The presence of HIV and sexually transmitted infections among 30%-60% of cases were reported. Human-to-human transmission via direct contact and different body fluids were involved in the majority of the cases (90%-100%). Lesions in genitals, perianal, and anogenital areas were more prevalent. Unusually, pharyngitis (15%-40%) and proctitis (20%-40%) were more common during 2022 outbreak than pre-2022 outbreaks. Brincidofovir is approved for the treatment of smallpox by FDA (USA). Two vaccines, including JYNNEOSTM and ACAM2000®, are approved and used for pre- and post-prophylaxis in cases. About 100% of the cases in non-endemic regions were associated with isolates of IIb clade with a divergence of 0.0018-0.0035. Isolates from B.1 lineage were the most predominant followed by B.1.2 and B.1.10.
CONCLUSION
This study will add integrated knowledge of the epidemiology, clinical features, and transmission of mpox.
PubMed: 37808926
DOI: 10.1002/hsr2.1603 -
Annual Review of Medicine Jan 2024Mpox, previously known as monkeypox, is caused by an related to the variola virus that causes smallpox. Prior to 2022, mpox was considered a zoonotic disease endemic to... (Review)
Review
Mpox, previously known as monkeypox, is caused by an related to the variola virus that causes smallpox. Prior to 2022, mpox was considered a zoonotic disease endemic to central and west Africa. Since May 2022, more than 86,000 cases of mpox from 110 countries have been identified across the world, predominantly in men who have sex with men, most often acquired through close physical contact or during sexual activity. The classical clinical presentation of mpox is a prodrome including fever, lethargy, and lymphadenopathy followed by a characteristic vesiculopustular rash. The recent 2022 outbreak included novel presentations of mpox with a predominance of anogenital lesions, mucosal lesions, and other features such as anorectal pain, proctitis, oropharyngeal lesions, tonsillitis, and multiphasic skin lesions. We describe the demographics and clinical spectrum of classical and novel mpox, outlining the potential complications and management.
Topics: Male; Animals; Humans; Homosexuality, Male; Mpox (monkeypox); Sexual and Gender Minorities; Zoonoses; Disease Outbreaks
PubMed: 37788486
DOI: 10.1146/annurev-med-080122-030714 -
Journal of Crohn's & Colitis Apr 2024Pivotal trials in ulcerative colitis have historically excluded patients with isolated proctitis. Etrasimod is an oral, oncedaily, selective sphingosine 1phosphate1,4,5...
BACKGROUND AND AIMS
Pivotal trials in ulcerative colitis have historically excluded patients with isolated proctitis. Etrasimod is an oral, oncedaily, selective sphingosine 1phosphate1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis. This post hoc analysis assessed efficacy and safety of etrasimod 2 mg once daily in patients with isolated proctitis (centrally read) from the phase 3 ELEVATE UC 52 and ELEVATE UC 12 trials.
METHODS
Patients, including those with isolated proctitis (<10 cm rectal involvement) who met all other inclusion criteria in ELEVATE UC 52 and ELEVATE UC 12, were randomised 2:1 to receive etrasimod or placebo. Primary, secondary and other identified efficacy endpoints and safety were assessed.
RESULTS
We analysed data from 64 and 723 patients at Week 12 (both trials pooled), and 36 and 397 patients at Week 52 (ELEVATE UC 52 only) with isolated proctitis and more extensive colitis (≥10 cm rectal involvement), respectively. Patients with isolated proctitis receiving etrasimod demonstrated significant improvements versus placebo, including clinical remission rates at Weeks 12 (42.9% vs 13.6%) and 52 (44.4% vs 11.1%), endoscopic improvement (52.4% vs 22.7%) at Week 12 and bowel urgency numerical rating scale score at Week 12 (all p<0.01). Generally similar trends were observed in patients with more extensive colitis. Safety was consistent across subgroups, with no new findings.
CONCLUSIONS
Etrasimod demonstrated significant improvements versus placebo in patients with isolated proctitis, and those with more extensive disease, in most efficacy endpoints at Week 12 and 52.
PubMed: 38613425
DOI: 10.1093/ecco-jcc/jjae038 -
British Journal of Hospital Medicine... Oct 2023
Topics: Humans; Constipation; Fecal Impaction; Proctitis
PubMed: 37906064
DOI: 10.12968/hmed.2023.0173 -
Journal of Crohn's & Colitis Mar 2024Although ulcerative proctitis [UP] can dramatically impair quality of life, treatment efficacy has been poorly investigated in UP as it was historically excluded from...
BACKGROUND
Although ulcerative proctitis [UP] can dramatically impair quality of life, treatment efficacy has been poorly investigated in UP as it was historically excluded from phase 2/3 randomised controlled trials in ulcerative colitis. Our aim was to assess the effectiveness and safety of tofacitinib for the treatment of UP.
METHODS
We conducted a retrospective, multicentre study in 17 GETAID centres, including consecutive patients with UP treated with tofacitinib. The primary endpoint was steroid-free remission between Week 8 and Week 14, defined as a partial Mayo score of 2 [and no individual subscore above 1]. Secondary outcomes included clinical response and steroid-free remission after induction and at 1 year.
RESULTS
All the 35 enrolled patients previously received anti-tumour necrosis factor [TNF] therapy and 88.6% were exposed to at least two lines of biologics. At baseline, the median partial Mayo score was 7 (intequartile range [IQR] [5.5-7]). After induction [W8-W14], 42.9% and 60.0% of patients achieved steroid-free remission and clinical response, respectively. At 1 year, the steroid-free clinical remission and clinical response rates were 39.4% and 45.5%, respectively, and 51.2% [17/33] were still receiving tofacitinib treatment. Survival without tofacitinib withdrawal was estimated at 50.4% (95% confidence interval [CI] [35.5-71.6]) at 1 year. Only a lower partial Mayo at baseline was independently associated with remission at induction (0dds ratio [OR] = 0.56 for an increase of 1, (95% CI [0.33-0.95], p = 0.03). Five [14.3%] adverse events were reported, with one leading to treatment withdrawal [septic shock secondary to cholecystitis].
CONCLUSION
Tofacitinib may offer a therapeutic option for patients with refractory UP.
Topics: Humans; Tumor Necrosis Factor Inhibitors; Retrospective Studies; Quality of Life; Proctitis; Piperidines; Pyrimidines
PubMed: 37796025
DOI: 10.1093/ecco-jcc/jjad169 -
Inflammatory Bowel Diseases Dec 2023There is growing evidence of the role of the mycobiome in inflammatory bowel disease (IBD). Variations within phenotypes and activity and with prognosis have been poorly...
BACKGROUND
There is growing evidence of the role of the mycobiome in inflammatory bowel disease (IBD). Variations within phenotypes and activity and with prognosis have been poorly studied.
METHODS
A total of 111 individuals were prospectively enrolled: 89 IBD patients (52 ulcerative colitis and 37 Crohn's disease [CD]) and 22 healthy individuals. Disease characteristics were collected and a fecal calprotectin >100 μg/mg was considered indicative of activity. A subset of patients was followed for 6 ± 2 years. Disease course was designated as either complicated or uncomplicated based on the need of intensified medication and/or surgery. ITS sequencing was performed targeting the ITS1 region.
RESULTS
We found lower Ascomycota/Basidiomycota ratio in IBD. Patients showed a marked increase in Candida dublinensis and Ca albicans and were depleted of Aspergillus rubrobrunneus and Penicillium brevicompactum (P ≤ .001) Saccharomyces was predominant in total colitis and Penicillium in proctitis. Several Penicillium species were depleted in total colitis vs proctitis. Ileal CD patients were enriched in Debaromyces hansenii and depleted of Ca tropicalis (P ≤ .001). Ca albicans was overrepresented in inflammatory (B1) vs fibrostenosing (B2) CD. Ca dublinensis was more abundant in active patients and correlated positively with fecal calprotectin and neutrophil gelatinase-associated lipocalin, while S pastorianus correlated inversely with activity. Ca sake was associated with complicated disease and increased abundance of Cryptococcus carnescens with the need for surgery in CD.
CONCLUSIONS
This study shows important differences in the mycobiome in IBD and within phenotypes. Selected fungal species were associated with complicated disease and the need of surgery in CD. This work adds to our understanding of the role of fungi in IBD, with potential clinical implications.
PubMed: 38103028
DOI: 10.1093/ibd/izad289 -
Cancers Nov 2023Although prostate cancer treatment is increasingly effective, its toxicities pose a major concern. The aim of our study was to assess the rate of adverse events (AEs)...
Although prostate cancer treatment is increasingly effective, its toxicities pose a major concern. The aim of our study was to assess the rate of adverse events (AEs) and the prognostic value of dose-volume histogram (DVH) parameters for the occurrence of treatment toxicity in patients treated with post-prostatectomy prostate bed radiotherapy (RT). The AEs were scored according to the CTCAE v.5.0. The rectum and bladder were contoured according to the RTOG Guidelines. The DVH parameters were assessed using data exported from the ECLIPSE treatment-planning system. Genitourinary (GU) and gastrointestinal (GI) toxicity were analysed using consecutive dose thresholds for the percentage of an organ at risk (OAR) receiving a given dose and the QUANTEC dose constraints. A total of 213 patients were included in the final analysis. Acute grade 2 or higher (≥G2) GU AEs occurred in 18.7% and late in 21.3% of patients. Acute ≥G2 GI toxicity occurred in 11.7% and late ≥G2 in 11.2% of the patients. Five patients experienced grade 4 AEs. The most common adverse effects were diarrhoea, proctitis, cystitis, and dysuria. The most significant predictors of acute ≥G2 GI toxicity were rectum V47 and V46 ( < 0.001 and < 0.001) and rectum wall V46 ( = 0.001), whereas the most significant predictors of late ≥G2 GI AEs were rectum wall V47 and V48 ( = 0.019 and = 0.021). None of the bladder or bladder wall parameters was significantly associated with the risk of acute toxicity. The minimum doses to bladder wall ( = 0.004) and bladder ( = 0.005) were the most significant predictors of late ≥G2 GU toxicity. Postoperative radiotherapy is associated with a clinically relevant risk of AEs, which is associated with DVH parameters, and remains even in patients who fulfil commonly accepted dose constraints. Considering the lack of survival benefit of postoperative adjuvant RT, our results support delaying treatment through an early salvage approach to avoid or defer toxicity.
PubMed: 38001594
DOI: 10.3390/cancers15225334