INSPECT: A Retrospective Study to Evaluate Long-term Effectiveness and Safety of Darvadstrocel in Patients With Perianal Fistulizing Crohn’s Disease Treated in the ADMIRE-CD Trial
Julían PanésGerd BoumaMarc FerranteTorsten KucharzikMaria NachuryFernando de JuanWalter ReinischFrancesco SelvaggiJörg TschmelitschNeil R. BrettMartin LadouceurMatthias BinekGary HantsbargerSarah Campbell‐HillChitra KarkiChristianne J. Buskens
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Abstract Background The efficacy of a single administration of darvadstrocel (expanded allogeneic adipose-derived mesenchymal stem cells) for treating complex perianal fistulas in patients with Crohn’s disease was demonstrated in a randomized, double-blind trial (ADMIRE-CD [Adipose Derived Mesenchymal Stem Cells for Induction of Remission in Perianal Fistulizing Crohn\'s Disease] trial). The current chart review study (INSPECT [A retrospectIve chart review study evaluatINg the longer-term effectiveneSs of darvadstrocel in PatiEnts who CompleTed ADMIRE-CD]) evaluated the longer-term effectiveness and safety of darvadstrocel. Methods Eligible patients had completed at least 52 weeks in the ADMIRE-CD trial. Data on clinical remission and fistula relapse outcomes were collected retrospectively at 104 and 156 weeks after treatment. Adverse events of special interest (tumorigenicity and ectopic tissue formation) were collected up to 208 weeks after treatment. Results Eighty-nine patients were included (43 darvadstrocel patients, 46 control subjects). At 52, 104, and 156 weeks posttreatment, clinical remission was observed in 29 (67.4%) of 43, 23 (53.5%) of 43, and 23 (53.5%) of 43 darvadstrocel-treated patients, compared with 24 (52.2%) of 46, 20 (43.5%) of 46, and 21 (45.7%) of 46 control subjects, respectively. In patients with clinical remission at week 52, this remission was sustained at 104 and 156 weeks after treatment in 19 (65.5%) of 29 and 16 (55.2%) of 29 darvadstrocel-treated patients and in 17 (70.8%) of 24 and 13 (54.2%) of 24 control subjects, respectively. Time to fistula relapse and incidence of fistula relapse or new fistula occurrence were not significantly different between groups. Tumorigenicity was reported for 1 (2.2%) patient in the control group (malignant epidermoid carcinoma). No ectopic tissue formation was reported. Conclusions Real-world follow-up of patients from the ADMIRE-CD trial indicates that clinical remission of complex perianal fistulas can be sustained in the long term irrespective of whether it is achieved through darvadstrocel administration or maintenance treatment regimens and confirms a favorable long-term safety profile of darvadstrocel.Crohn disease
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Crohn's disease is a lifelong illness characterized by chronic recurrent flares. The precise etiology of Crohn's disease is unknown. However, it appears to involve an enhanced systemic immune response and intensified local intestinal mucosal inflammatory activity, mediated through various inflammatory cells and an array of proinflammatory cytokines. Corticosteroids have been the mainstay of treatment of Crohn's disease. The controlled trials of the National Cooperative Crohn's Disease Study and the European Cooperative Crohn's Disease Study established that corticosteroids were effective for the induction of remission in Crohn's disease for the duration of the studies (6-17 wk). However, corticosteroids have not been shown to have an impact on the maintenance of long term remission in patients with Crohn's disease. In addition, they are associated with a high potential for dependence and serious toxic side effects. Alternative classes of medical therapy for Crohn's disease, including modified corticosteroids and a group of new biological therapies, have proven to be efficacious in the management of active and/or quiescent Crohn's disease.
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Background: Noninvasive electrical stimulation (ES) could have therapeutic potential in stroke recovery. However, there is no comprehensive evaluation of adverse events. This study systematically searched the literature to document frequency and prevalence of adverse events. A secondary aim was to explore associations between adverse events and ES parameters or participant characteristics.Methods: Databases were searched for studies evaluating ES in adults with stroke. All included studies were required to report on adverse events. Extracted data were: (1) study design; (2) adverse events; (3) participant characteristics; (4) ES parameters.Results: Seventy-five studies were included. Adverse events were minor in nature. The most frequently reported adverse events were tingling (37.3% of papers), burning (18.7%), headaches (14.7%) and fatigue (14.7%). Cathodal stimulation was associated with greater frequency of itching (p = .02), intensities of 1–2 mA with increased tingling (p = .04) and discomfort (p = .03), and current density <0.4mA/cm2 with greater discomfort (p = .03). Tingling was the most prevalent adverse event (18.1% of participants), with prevalence data not differing between active and control conditions (all p ≥ 0.37). Individual participants were more likely to report adverse events with increasing current density (r = 0.99, p = .001). Two severe adverse events were noted (a seizure and percutaneous endoscopic gastrostomy placement).Conclusion: ES appears safe in people with stroke as reported adverse events were predominantly minor in nature. An adverse events questionnaire is proposed to enable a more comprehensive and nuanced analysis of the frequency and prevalence of adverse events.
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The second branchial fistula and thyroglossal fistula are relatively common lesions. In this paper the author reported 18 cases with second branchial fistula and thyroglossal fistula. During operation, a extradural catheter was put into the fistula. The fistula was then easy to be recognized and separated owing to the duct in the fistula. The fistula was completely excised and none developed complications or recurrence. The author believed that insertion of an extradural catheter into the fistula can make the excision simple, convenient and safe.
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large-scale multicentre clinical trials conducted by cooperative groups have generated a lot of evidence to establish better standard treatments. The Clinical Trials Act was enforced on 1 April 2018, in Japan, and it has remarkably increased the operational burden on investigators, but its long-term impact on cancer cooperative groups is unknown.
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Exclusive enteral nutrition (EEN) is a first-line treatment in active, mild to moderate Crohn’s disease (CD) in children. The Crohn’s disease exclusion diet (CDED), which avoids products known to have a pro-inflammatory effect on the intestinal mucosa, presents similar effectiveness to EEN for inducing remission in the paediatric population. The aim of the study was to evaluate the effectiveness of the CDED in inducing remission in adult patients. Between March 2020 and May 2021, 32 patients in a gastroenterology outpatient centre were treated according to the assumptions of the CDED. The patients were seen at baseline, at week 6, and at week 12 of the study. During the visits, anthropometric measurements and laboratory tests were performed, Crohn’s disease activity index (CDAI) was calculated, and the Inflammatory Bowel Disease Questionnaire (IBDQ) was completed. The study included a total of 32 participants, 18 women (56.3%) and 14 men (43.7%). Clinical remission was obtained in 76.7% patients after 6 weeks and in 82.1% after 12 weeks of therapy. Calprotectin levels were significantly lower in the second follow-up compared with baseline (p = 0.021). The CDED is an effective therapy for inducing remission in the adult CD population.
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