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International Journal of Pharmaceutics:... Dec 2023Infliximab is a monoclonal antibody that plays an important role in the management and treatment of chronic inflammatory bowel diseases (IBD). Due to its macromolecular...
Infliximab is a monoclonal antibody that plays an important role in the management and treatment of chronic inflammatory bowel diseases (IBD). Due to its macromolecular structure, its delivery through the oral route is challenging, limiting its administration to only via the parenteral route. The rectal route offers an alternative way for administering infliximab, allowing it to be localised at the disease site and circumventing its passage across the alimentary canal and thus, maintaining its integrity and bioactivity. Three-dimensional (3D) printing is an advanced production technology that permits the creation of dose-flexible drug products from digital designs. The current study assessed the feasibility of utilising semi-solid extrusion 3D printing for the fabrication of infliximab-loaded suppositories for the local treatment of IBD. Various printing inks composed of Gelucire® (48/16 or 44/14) mixed with coconut oil and/or purified water were investigated. It was shown that following reconstitution in water, the infliximab solution can be directly incorporated into the printing ink of Gelucire® 48/16 and can withstand the extrusion process, resulting in well-defined suppositories. Since water content and temperature are critical for safeguarding infliximab's potency, the effect of changing the composition of the printing inks and printing parameters on infliximab's biologic efficiency was evaluated by measuring its binding capacity (i.e., the amount of infliximab that actively binds to its antigen to exert an effect). Despite drug loading assays showing that infliximab remains intact following printing, it was found that the incorporation of water in isolation results in only ∼65% binding capacity. However, when oil is added to the mixture, infliximab's binding capacity increases up to ∼85%. These promising results demonstrate that 3D printing has the potential to be exploited as a novel platform for fabricating dosage forms containing biopharmaceuticals, avoiding patients' compliance issues observed with injectables and addressing their unmet needs.
PubMed: 37396625
DOI: 10.1016/j.ijpx.2023.100176 -
The American Surgeon Sep 2021Perianal Crohn's disease (CD) is a complex manifestation of CD that affects approximately 10% of patients. The spectrum of disease is quite variable, ranging from... (Review)
Review
Perianal Crohn's disease (CD) is a complex manifestation of CD that affects approximately 10% of patients. The spectrum of disease is quite variable, ranging from relatively mild disease to severe, aggressive manifestations that result in frequent hospitalizations, multiple surgeries, and poor quality of life. Despite significant recent advances in surgical and medical management, treatment remains challenging and frequently requires a multidisciplinary medical-surgical approach. The goal of this article is to review the current literature regarding the work-up, treatment, and future directions of therapy. Crucial features of effective management include the precise identification of manifestations, control of sepsis, limiting rectal inflammation, frequently with use of antitumor necrosis factor agents, and avoidance of extensive surgery.
Topics: Anus Diseases; Biological Products; Crohn Disease; Drainage; Enterostomy; Fibrin Tissue Adhesive; Humans; Inflammation; Ligation; Mesenchymal Stem Cell Transplantation; Proctectomy; Sepsis; Surgical Flaps; Tumor Necrosis Factor-alpha
PubMed: 33345571
DOI: 10.1177/0003134820956331 -
Tidsskrift For Den Norske Laegeforening... Jan 2019
Review
Topics: Anti-Bacterial Agents; Crohn Disease; Drug Therapy, Combination; Gastrointestinal Agents; Humans; Immunosuppressive Agents; Rectal Fistula; Tumor Necrosis Factor-alpha
PubMed: 30644688
DOI: 10.4045/tidsskr.17.1055 -
Gut Jun 2018Perianal fistulae in patients with Crohn's disease (CD) can be associated with significant morbidity resulting in negative impact on quality of life. The last two... (Review)
Review
Perianal fistulae in patients with Crohn's disease (CD) can be associated with significant morbidity resulting in negative impact on quality of life. The last two decades have seen significant advancements in the management of perianal fistulas in CD, which has evolved into a multidisciplinary approach that includes gastroenterologists, colorectal surgeons, endoscopists and radiologists. Despite the introduction of new medical therapies such as antitumour necrosis factor and novel models of care delivery, the best fistula healing rates reported with combined medical and surgical approaches are approximately 50%. More recently, newer biologics, cell-based therapies as well as novel endoscopic and surgical techniques have been introduced raising new hopes that outcomes can be improved upon. In this review, we describe the modern management and the most recent advances in the management of complex perianal fistulising CD, which will likely impact clinical practice. We will explore optimal use of both older and newer biological agents, as well as new data on cell-based therapies. In addition, new techniques in endoscopic and surgical approaches will be discussed.
Topics: Biological Therapy; Combined Modality Therapy; Crohn Disease; Endoscopy; Humans; Mesenchymal Stem Cell Transplantation; Rectal Fistula
PubMed: 29331943
DOI: 10.1136/gutjnl-2017-314918 -
Techniques in Coloproctology Sep 2017Anoperineal lesion (APL) occurrence is a significant event in the evolution of Crohn's disease (CD). Management should involve a multidisciplinary approach combining the... (Review)
Review
BACKGROUND
Anoperineal lesion (APL) occurrence is a significant event in the evolution of Crohn's disease (CD). Management should involve a multidisciplinary approach combining the knowledge of the gastroenterologist, the colorectal surgeon and the radiologist who have appropriate experience in this area. Given the low level of evidence of available medical and surgical strategies, the aim of this work was to establish a French expert consensus on management of anal Crohn's disease. These recommendations were led under the aegis of the Société Nationale Française de Colo-Proctologie (SNFCP). They report a consensus on the management of perianal Crohn's disease lesions, including fistulas, ulceration and anorectal stenosis and propose an appropriate treatment strategy, as well as sphincter-preserving and multidisciplinary management.
METHODOLOGY
A panel of French gastroenterologists and colorectal surgeons with expertise in inflammatory bowel diseases reviewed the literature in order to provide practical management pathways for perianal CD. Analysis of the literature was made according to the recommendations of the Haute Autorité de Santé (HAS) to establish a level of proof for each publication and then to propose a rank of recommendation. When lack of factual data precluded ranking according to the HAS, proposals based on expert opinion were written. Therefore, once all the authors agreed on a consensual statement, it was then submitted to all the members of the SNFCP. As initial literature review stopped in December 2014, more recent European or international guidelines have been published since and were included in the analysis.
RESULTS
MRI is recommended for complex secondary lesions, particularly after failure of previous medical and/or surgical treatments. For severe anal ulceration in Crohn's disease, maximal medical treatment with anti-TNF agent is recommended. After prolonged drainage of simple anal fistula by a flexible elastic loop or loosely tied seton, and after obtaining luminal and perineal remission by immunosuppressive therapy and/or anti-TNF agents, the surgical treatment options to be discussed are simple seton removal or injection of the fistula tract with biological glue. After prolonged loose-seton drainage of the complex anal fistula in Crohn's disease, and after obtaining luminal and perineal remission with anti-TNF ± immunosuppressive therapy, surgical treatment options are simple removal of seton and rectal advancement flap. Colostomy is indicated as a last option for severe APL, possibly associated with a proctectomy if there is refractory rectal involvement after failure of other medical and surgical treatments. The evaluation of anorectal stenosis of Crohn's disease (ARSCD) requires a physical examination, sometimes under anesthesia, plus endoscopy with biopsies and MRI to describe the stenosis itself, to identify associated inflammatory, infectious or dysplastic lesions, and to search for injury or fibrosis of the sphincter. Therapeutic strategy for ARSCD requires medical-surgical cooperation.
Topics: Adult; Anal Canal; Anus Neoplasms; Combined Modality Therapy; Consensus; Crohn Disease; Digestive System Surgical Procedures; Drainage; Female; France; Gastrointestinal Agents; Humans; Male; Perineum; Practice Guidelines as Topic; Rectal Fistula; Treatment Outcome; Tumor Necrosis Factor-alpha
PubMed: 28929282
DOI: 10.1007/s10151-017-1684-y -
Gastroenterology Jul 2022
Topics: Humans; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha
PubMed: 35525321
DOI: 10.1053/j.gastro.2022.04.050 -
ANZ Journal of Surgery Apr 2021
Topics: Humans; Necrosis; Rectal Prolapse
PubMed: 33241593
DOI: 10.1111/ans.16259 -
Revista Espanola de Enfermedades... Feb 2024Ogilvie syndrome is a functional disorder of colonic motility that causes acute and progressive dilation, which can lead to necrosis and perforation. Early diagnosis and...
Ogilvie syndrome is a functional disorder of colonic motility that causes acute and progressive dilation, which can lead to necrosis and perforation. Early diagnosis and management are essential to avoid serious complications. The case of a patient with Ogilvie syndrome refractory to medical and endoscopic treatment that required surgery is presented. This is a 68-year-old man with decreased level of consciousness and abdominal distension for 3 days. Last bowel movement 4 days ago. The data and tests appear in table 1. We are faced with a patient with neurological alteration and hemodynamically unstable secondary to complicated Ogilvie syndrome. After admission to the ICU, where a 2.5 mg bolus of neostigmine was administered, he was transferred to the ward. Despite 250 mg of intravenous erythromycin every 6 hours together with metoclopramide every 8 hours, high doses of polyethylene glycol and daily cleansing enemas and rectal catheterization, only a brief and mild improvement is achieved. Given the failure of conservative measures, colectomy was performed, achieving complete resolution. Ogilvie syndrome is a functional disorder1 that usually associates predisposing factors that impact intestinal motility 2 ; In our case: bedridden, the use of anticholinergics, hydroelectric alteration both due to the use of antidepressants and the creation of a third space secondary to colonic dilation and severe intestinal ischemia². In one third it is resolved by early correction of the triggering factors, adding neostigmine if necessary with high rates of effectiveness¹. In our case, a second bolus of neostigmine could have been administered or even as an infusion since greater efficacy has been demonstrated in this way given its short half-life². Electrolyte imbalance is a predictor of poor response to neostigmine, a factor that was associated with our patient 3. Colonic decompression and finally surgery are reserved as a last measure, being necessary in a very small percentage as in this case 1. As a preventive measure, the administration of 29.5 g of oral polyethylene glycol per day has been effective 4. Therefore, we should suspect Ogilvie syndrome in patients with predisposing factors who present acute dilation of the colon without mechanical obstruction, and although it usually resolves with medical and endoscopic treatment, we should not delay surgery to avoid complications.
PubMed: 38305678
DOI: 10.17235/reed.2024.10287/2024 -
World Journal of Gastroenterology Jul 2021Perianal Crohn's disease remains a challenging condition to treat and can have a substantial negative impact on quality of life. It often requires combined surgical and... (Review)
Review
Perianal Crohn's disease remains a challenging condition to treat and can have a substantial negative impact on quality of life. It often requires combined surgical and medical interventions. Anti-tumor necrosis factor (anti-TNF) therapy, including infliximab and adalimumab, remain preferred medical therapies for perianal Crohn's disease. Infliximab has been shown to be efficacious in improving fistula closure rates in randomized controlled trials. Clinicians can be faced with a number of questions relating to the optimal use of anti-TNF therapy in perianal Crohn's disease. Specific issues include evaluation for the presence of perianal sepsis, the treatment target of therapy, the ideal time to commence treatment, whether additional medical therapy should be used in conjunction with anti-TNF therapy, and the duration of treatment. This article will discuss key studies which can assist clinicians in addressing these matters when they are considering or have already commenced anti-TNF therapy for the treatment of perianal Crohn's disease. It will also discuss current evidence regarding the use of vedolizumab and ustekinumab in patients who are failing to achieve a response to anti-TNF therapy for perianal Crohn's disease. Lastly, new therapies such as local injection of mesenchymal stem cell therapy will be discussed.
Topics: Crohn Disease; Humans; Infliximab; Quality of Life; Rectal Fistula; Treatment Outcome; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha
PubMed: 34321838
DOI: 10.3748/wjg.v27.i25.3693 -
The American Journal of Gastroenterology Jun 2023The prevalence of penetrating complications in Crohn's disease (CD) increases progressively over time, but evidence on the medical treatment in this setting is limited....
INTRODUCTION
The prevalence of penetrating complications in Crohn's disease (CD) increases progressively over time, but evidence on the medical treatment in this setting is limited. The aim of this study was to evaluate the effectiveness of biologic agents in CD complicated with internal fistulizing disease.
METHODS
Adult patients with CD-related fistulae who received at least 1 biologic agent for this condition from the prospectively maintained ENEIDA registry were included. Exclusion criteria involved those receiving biologics for perianal disease, enterocutaneous, rectovaginal, anastomotic, or peristomal fistulae. The primary end point was fistula-related surgery. Predictive factors associated with surgery and fistula closure were evaluated by multivariate logistic regression and survival analyses.
RESULTS
A total of 760 patients from 53 hospitals (673 receiving anti-tumor necrosis factors, 69 ustekinumab, and 18 vedolizumab) were included. After a median follow-up of 56 months (interquartile range, 26-102 months), 240 patients required surgery, with surgery rates of 32%, 41%, and 24% among those under anti-tumor necrosis factor, vedolizumab, or ustekinumab, respectively. Fistula closure was observed in 24% of patients. Older patients, ileocolonic disease, entero-urinary fistulae, or an intestinal stricture distal to the origin of the fistula were associated with a higher risk of surgery, whereas nonsmokers and combination therapy with an immunomodulator reduced this risk.
DISCUSSION
Biologic therapy is beneficial in approximately three-quarters of patients with fistulizing CD, achieving fistula closure in 24%. However, around one-third still undergo surgery due to refractory disease. Some patient- and lesion-related factors can identify patients who will obtain more benefit from these drugs.
Topics: Adult; Humans; Crohn Disease; Ustekinumab; Treatment Outcome; Fistula; Biological Therapy; Necrosis; Retrospective Studies; Rectal Fistula
PubMed: 36516073
DOI: 10.14309/ajg.0000000000002152