Abstract
Background
Risankizumab is approved for moderate to severe Crohn’s disease (CD). The GETAID recently reported the real-world effectiveness of risankizumab as induction therapy for refractory ...CD. The aim of this study was to assess the long-term effectiveness and safety of risankizumab maintenance treatment in a large real-world cohort of patients with CD.
Methods
From May 2021 to August 2023, all consecutive CD patients treated with risankizumab in 25 GETAID centers have been retrospectively included. Only patients who received risankizumab 600 mg IV at week 0,4 and 8 as induction and SC 360 mg every 8 weeks as maintenance treatment were included. The primary outcome measure was steroid-free clinical remission (Harvey Bradshaw Index (HBI) <5) at week 52. Secondary outcomes included clinical response (≥ 3-point decrease of HB score and/or (HB) score < 5), endoscopic (no ulcers) and/or radiologic remission (normal intestinal ultra-sound or MRI), need for CD-related surgery, and adverse events.
Results
All patients had received at least three biologics and 108 (62%) had previous intestinal resection. Of the 174 patients included, 172 (99%), 162 (93%), and 167 (96%) had been previously exposed to anti-TNF, vedolizumab, and ustekinumab, respectively. Respectively 66 (38%) and 24 (14%) patients were on corticosteroids and immunosuppressants at risankizumab initiation. Median follow-up was 13.7 (10.0-18.1) months. The rates of steroid-free clinical remission and clinical remission at 52 weeks were 46% (60/131) and 50% (65/131), respectively. Absence/mild abdominal pain with normal stool frequency was observed in 48% (54/112) of patients at week 52. Among the 79 (45%) patients who had an endoscopic (n=67) and/or radiological (MRI, n=56 and IUS, n=15) evaluation during follow-up, response and remission were observed in 27 (34%) and 17 (22%) patients, respectively. Risankizumab persistence rates were 94%, 89%, and 79% at weeks 12, 26, and 52, respectively. At the end of follow-up, 45 (45/174, 26%) patients had discontinued risankizumab (loss of response, 42%; primary failure, 37%; intolerance, 13%). Thirty-six patients (36/174, 20.9%) were hospitalized and 22 (22/174, 12.6%) required intestinal resection. No factors were associated with steroid-free clinical remission at week 52. Twenty-five (14%) patients had an adverse event and 26 (15%) serious adverse events (CD flare, n=17). One death (myocardial infarction) and one cancer (papillary thyroid carcinoma) were observed.
Conclusion
This is the first real-life study to report long-term outcomes in patients with refractory CD treated with risankizumab. Half of the patients achieved steroid-free clinical remission after one year, and the safety profile was consistent with the literature.
Summary Late complications arising after bile duct injury (BDI) include biliary strictures, hepatic atrophy, cholangitis and intra-hepatic lithiasis. Later, fibrosis or even secondary biliary ...cirrhosis and portal hypertension can develop, enhanced by prolonged biliary obstruction associated with recurrent cholangitis. Secondary biliary cirrhosis resulting in associated hepatic failure or digestive tract bleeding due to portal hypertension is a substantial risk factor for morbidity and mortality after bile duct repair. Parameters that determine the management of late complications of BDI include the type of biliary injury, associated vascular injury, hepatic atrophy, the presence of intra-hepatic strictures or lithiasis, repetitive infectious complications, the quality of underlying parenchyma (fibrosis, secondary biliary cirrhosis) and the presence of portal hypertension. Endoscopic drainage is indicated for patients with uncontrolled acute sepsis, patients at high operative risk, patients with cirrhosis who are not eligible for liver transplantation and patients who have previously undergone several attempts at repair. Roux-en-Y hepaticojejunostomy, whether de novo or as an iterative repair, is the technique of reference for post-cholecystectomy BDI. Hepatic resection is indicated in only rare instances, mainly in case of extended hilar stricture, multiple stone retention in one sector of the liver or in patients for whom the repair is deemed technically difficult. Liver transplantation is indicated only in exceptional circumstances, when secondary biliary cirrhosis is associated with liver failure and portal hypertension.
Standard high-volume polyethylene glycol PEG bowel preparations PEG-4L are recommended for patients with inflammatory bowel disease IBD undergoing colonoscopy. However, low-volume preparations ≤2 L ...of active volume are often used in clinical practice. The aim of this study was to evaluate the efficacy, tolerability, and safety of the various bowel preparations for patients with IBD, including low-volume preparations.
We conducted a French prospective multicentre observational study over a period of 1 month. Patients aged 18-75 years with IBD with an indication of colonoscopy independent of the study were enrolled. The choice of the preparation was left to the investigators, as per their usual protocol. The patients' characteristics, disease, and colonoscopy characteristics were recorded, and they were given self-reported questionnaires.
Twenty-five public and private hospitals enrolled 278 patients. Among them, 46 had a disease flare and 41 had bowel stenoses. Bowel preparations for colonoscopy were as follows: 42% received PEG-2L, 29% received sodium picosulfate Pico, 15% received PEG-4L, and 14% had other preparations. The preparation did not reach the Boston's score efficacy outcome in the PEG-4L group in 51.2% of the patients p = 0.0011. The preparation intake was complete for 59.5% in the PEG-4L group, compared with 82.9% in the PEG-2L group and 93.8% in the Pico group p < 0.0001. Tolerability, as assessed by the patients' VAS, was significantly better for both Pico and PEG-2L compared with PEG-4L, and better for Pico compared with PEG-2L p = 0.008; p = 0.0003. In multivariate analyses, low-volume preparations were independent factors of efficacy and tolerability. Adverse events occurred in 4.3% of the patients.
Preparations with PEG-2L and Pico were equally safe, with better efficacy and tolerability outcomes compared with PEG-4L preparations. The best efficacy/tolerance/safety profile was achieved with the Pico preparation.
ESGE recommends offering stone extraction to all patients with common bile duct stones, symptomatic or not, who are fit enough to tolerate the intervention.Strong recommendation, low quality ...evidence.ESGE recommends liver function tests and abdominal ultrasonography as the initial diagnostic steps for suspected common bile duct stones. Combining these tests defines the probability of having common bile duct stones.Strong recommendation, moderate quality evidence.ESGE recommends endoscopic ultrasonography or magnetic resonance cholangiopancreatography to diagnose common bile duct stones in patients with persistent clinical suspicion but insufficient evidence of stones on abdominal ultrasonography.Strong recommendation, moderate quality evidence.ESGE recommends the following timing for biliary drainage, preferably endoscopic, in patients with acute cholangitis, classified according to the 2018 revision of the Tokyo Guidelines:- severe, as soon as possible and within 12 hours for patients with septic shock- moderate, within 48 - 72 hours- mild, elective.Strong recommendation, low quality evidence.ESGE recommends endoscopic placement of a temporary biliary plastic stent in patients with irretrievable biliary stones that warrant biliary drainage.Strong recommendation, moderate quality of evidence.ESGE recommends limited sphincterotomy combined with endoscopic papillary large-balloon dilation as the first-line approach to remove difficult common bile duct stones. Strong recommendation, high quality evidence.ESGE recommends the use of cholangioscopy-assisted intraluminal lithotripsy (electrohydraulic or laser) as an effective and safe treatment of difficult bile duct stones.Strong recommendation, moderate quality evidence.ESGE recommends performing a laparoscopic cholecystectomy within 2 weeks from ERCP for patients treated for choledocholithiasis to reduce the conversion rate and the risk of recurrent biliary events. Strong recommendation, moderate quality evidence.
Recent developments in therapeutic endoscopic ultrasound (EUS) have enabled new approaches to the management of refractory gastrointestinal bleeding, including EUS-guided sclerotherapy and vessel ...embolization. Few cases have been reported in the literature. Eight patients were admitted for severe, refractory gastrointestinal bleeding, seven of whom were actively bleeding. Causes of bleeding were gastric varices secondary to portal hypertension (n = 3); gastroduodenal artery aneurysm or fundal aneurysmal arterial malformation (n = 3); and Dieulafoy's ulcer (n = 2); the latter five patients having arterial bleeding. During the procedures, the bleeding vessel was punctured with a 19-gauge needle then injected with a sclerosing agent (cyanoacrylate glue n = 6 or polidocanol 2 % n = 2) under Doppler control. The median follow-up time was 9 months (3 - 18 months). In all 10 endoscopic procedures were performed. The procedure was successful at the first attempt in seven out of eight patients (87.5 %). No clinical complications were observed, although in one case there was diffusion of cyanoacrylate in the hepatic artery. The seven successful cases all showed immediate and complete disappearance of the Doppler flow signal at the end of the procedure. This retrospective study highlights the utility of EUS-guided vascular therapy. However, more large randomized studies should be conducted to confirm these results.
Abstract
Background
Prospective data after switch from intravenous infliximab (IV-IFX) to subcutaneous (SC-IFX) in Inflammatory Bowel Disease (IBD) is needed. The aim of this prospective multicenter ...cohort was to describe SC-IFX persistence, efficacy and tolerance after switch from IV-IFX.
Methods
IBD patients in steroid-free clinical remission (defined by a Harvey Bradshaw index (HBI) ≤ 4 for Crohn’s disease (CD), and partial Mayo Score (PMS) ≤ 2 with no subscore >1 for ulcerative colitis UC)) for at least 6 months on IV-IFX, were enrolled in this prospective cohort if they switched to SC-IFX.
Clinical (HBI, PMS), biological (CRP, fecal calprotectin (FC)) and pharmacokinetic evaluations were performed at 3, 6, 12 and 24 months from switch. In case of clinical or biological relapse, as per physicians’ judgement, SC-IFX dose could be increased, or drug changed.
Primary endpoint was SC-IFX persistence at week 48 (W48). Secondary endpoints comprised steroid-free clinical remission at W48, proportion of patients who switched back to IV-IFX, HBI and PMS changes and FC, CRP and infliximab serum level changes. Statistical comparisons were performed using Fisher’s exact test. Survival without treatment discontinuation was analysed using a Kaplan-Meyer curve.
Results
426 patients were included (72.4% CD, 45.1% female, median age 37 years), with a median time from diagnosis of 143 months in CD, 154 months in UC. At baseline, 74% were on IV-IFX standard dose (5mg/kg every 8-week) and 68 (16%) received combination therapy with an immunosuppressant.
Among patients with complete data until W48, SC-IFX persistence was 95.3% (CI, 93.2-97.5). 319/367 (89.9%) were on steroid-free clinical remission.
From baseline to W48, median HBI and PMS scores were 0, CRP did not change significantly, median FC rate decreased significantly from 52µg/g to 36 µg/g (p=0.015). Mean Infliximab trough level at inclusion was 7.97µg/mL, while it reached 17.96µg/mL at W48 (p<0.0001).
23 (5.4%) patients had an increase of SC-IFX dose and 22 (5.2%) stopped SC-IFX, of which 6 patients switched back to IV-IFX. SC-IFX persistence was significantly higher among patients treated with SC-IFX monotherapy (98.8%) as compared to those on combination therapy (90.0%) (HR=0.14 0.04-0.53).
Adverse events were reported in 181/426 patients (42.4%), 12 led to treatment discontinuation. Nine severe adverse events (2%) were reported. Three patients (0.7%) had IBD-related surgery and 8 (1.9%) IBD-related hospitalization.
Conclusion
In this large multicenter prospective cohort of IBD patients in remission, one-year persistence of SC-IFX after switch from IV-IFX was 95.3%, supporting excellent efficacy and tolerance of SC-IFX.
Abstract
Background
Phase III trials have demonstrated the efficacy of risankizumab in moderate-to-severe Crohn’s disease (CD), but no real-world data are currently available. We aimed to assess the ...short-term effectiveness and safety of risankizumab in patients with CD.
Methods
From May 2021 to May 2022, all patients with refractory luminal CD treated with risankizumab in 22 French GETAID centers were retrospectively included. The primary endpoint was steroid-free clinical remission at week 12 (Harvey-Bradshaw (HB) score < 5). Secondary endpoints included clinical response (≥ 3-point decrease of HB score and/or (HB) score < 5), biological remission (CRP ≤ 5 mg/L), need for CD-related surgery, and adverse events.
Results
Among the 100 patients included, all have been previously exposed to anti-TNF agents, 94 to vedolizumab, 98 to ustekinumab (all exposed to at least three biologics) and 61 had previous intestinal resection. All but three (97%) received a 600 mg risankizumab intravenous induction at weeks 0-4-8. At week 12, steroid-free clinical remission was observed in 45.8% of patients, clinical remission in 58% and clinical response in 78.5%. Absence/mild abdominal pain with normal stool frequency was noted in 50% of patients at week 12. Biological remission was observed in 50% of patients. Six patients discontinued risankizumab before the week 12 visit due to lack of efficacy. CD-related hospitalization was needed in six patients, and three underwent intestinal resection. In multivariable analysis, only a history of ustekinumab loss of response (vs primary failure) (Odds Ratio (OR), 2.80 ; 95%CI, 1.07 – 7.82; p=0.041) was significantly associated with clinical remission at week 12. Twenty adverse events (AE) occurred in 20 patients including 7 serious AE corresponding to 6 CD exacerbation and one severe hypertension.
Conclusion
In a cohort of highly refractory patients with luminal CD and multiple prior drug failures including ustekinumab, risankizumab induction provided clinical response in about 3 out of 4 patients and steroid-free clinical remission in about half of patients.
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