Long-term efficacy of infliximab maintenance therapy for perianal Crohn's disease

AIM: To assess the long-term efficacy of seton drainage with infliximab maintenance therapy in treatment of stricture for perianal Crohn’s disease (CD).METHODS: Sixty-two patients with perianal CD who required surgical treatment with or without infliximab between September 2000 and April 2010 were identified from our clinic’s database. The activities of the perianal lesions were evaluated using the modified perianal CD activity index (mPDAI) score. The primary endpoint was a clinical response at 12-15 wk after surgery as a short-term efficacy. Secondary endpoints were recurrence as reflected in the mPDAI score, defined as increased points in every major element. The clinical responses were classified as completely healed (mPDAI = 0), partially improved (mPDAI score decreased more than 4 points), and failure or recurrence (mPDAI score increased or decreased less than 3 points).RESULTS: There were 43 males and 19 females, of whom 26 were consecutively treated with infliximab after surgery as maintenance therapy. Complete healing was not seen. Failure was seen in 10/36 (27.8%) patients without infliximab and 4/26 (15.4%) patients with infliximab (P = 0.25). Partial improvement was seen in 26/36 (72.2%) patients without infliximab and 22/26 (88.5%) patients with infliximab (P = 0.25). Short-term improvement was achieved in 48/62 (77.4%) patients. Although the mPDAI score improved significantly with surgery regardless of infliximab, it decreased more from baseline in patients with infliximab (50.0%) than in those without infliximab (28.6%), (P = 0.003). In the long-term, recurrence rates were low regardless of infliximab in patients without anorectal stricture. In patients with anorectal stricture, cumulative recurrence incidences increased gradually and exceeded 40% at 5 years regardless of infliximab. No efficacy of infliximab treatment was found (P = 0.97). Although the cumulative rate of ostomy creation was also low in patients without stricture and high in patients with stricture, no protective efficacy was found with infliximab treatment (P = 0.6 without stricture, P = 0.22 with stricture).CONCLUSION: Infliximab treatment was demonstrated to have short-term efficacy for perianal lesions. Long-term benefit with infliximab was not proven, at least in patients with anorectal stricture.     

Long-term outcome of infliximab combined with surgery for perianal fistulizing Crohn’s disease

AIM:To evaluate the efficacy and long-term outcome of infliximab combined with surgery to treat perianal fistulizing Crohn’s disease(CD).METHODS:The work was performed as a prospective study.All patients received infliximab combined withsurgery to treat perianal fistulizing CD,which was followed by an immunosuppressive agent as maintenance therapy.RESULTS:A total of 28 patients with perianal fistulizing CD were included.At week 30,89.3%(25/28)of the patients were clinically cured with an average healing time of 31.4 d.The CD activity index decreased to70.07±77.54 from 205.47±111.13(P0.01)after infliximab treatment.The perianal CD activity index was decreased to 0.93±2.08 from 8.54±4.89(P0.01).C-reactive protein,erythrocyte sedimentation rate,platelets,and neutrophils all decreased significantly compared with the pretreatment levels(P0.01).Magnetic resonance imaging results for 16 patients after therapy showed that one patient had a persistent presacral-rectal fistula and another still had a cavity without clinical symptoms at follow-up.After a median follow-up of 26.4 mo(range:14-41 mo),96.4%(27/28)of the patients had a clinical cure.CONCLUSION:Infliximab combined with surgery is effective and safe in the treatment of perianal fistulizing CD,and this treatment was associated with better longterm outcomes.     

英夫利昔在克罗恩病诱导缓解中的作用及随访研究

目的 探讨英夫利昔(IFX)在克罗恩病诱导缓解中的作用并随访其诱导缓解的效果.方法 10例克罗恩病患者接受IFX(5 mg/kg)、5-氨基水杨酸(5-ASA)、硫唑嘌呤(AZA)诱导缓解和维持缓解治疗.在0、10、22和50周时进行克罗恩病活动指数(CDAI)、C-反应蛋白(CRP)、红细胞沉降率(ESR)、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总胆红素(TBil)、结合胆红素(CB)、肌酐(Scr)检测.在0、10和50周时进行克罗恩病简化内镜评分(SES-CD).记录不良反应.结果 10周时所有患者均获缓解,CDAI、CRP、ESR和SES-CD均较0周时显著降低(P值均＜0.01).1例患者在30周时因复发终止随访.50周时,有6例患者CDAI、CRP、ESR、SES-CD与10周时比较略增高,但差异无统计学意义(P值分别=0.2001、0.0600、0.1328、0.4230),与0周时比较则均显著降低(P值分别=0.0005、0.0087、0.0054、0.0163).所有患者均未出现严重不良反应.结论 IFX诱导CD缓解效果确切,部分CD患者在IFX诱导缓解后使用5-ASA和AZA维持缓解有效.     

Prevention of recurrence after surgery for Crohn’s disease: Efficacy of infliximab

After surgery for Crohn’s disease (CD), early endoscopic lesions are frequently observed despite no symptomatic recurrence. The severity of lesions found at postoperative endoscopy is reported to be a strong predictive factor for future clinical recurrence. If endoscopic lesions in the early postoperative period can be reduced with medications, symptomatic recurrence will likely be delayed and decreased. Before the introduction of biologic therapies, various medications were used for the maintenance of clinical remission after surgery; however, few demonstrated consistent efficacy. Infliximab is a recombinant anti-tumor necrosis factor-α antibody. Although infliximab is one of the most effective medications in the management of CD, its efficacy for early endoscopic lesions after surgery has not yet been assessed. The author and colleagues recently conducted a prospective study in order to investigate the impact of infliximab on early endoscopic lesions after resection for CD. We found that infliximab therapy showed clear suppressive effects on clinical and endoscopic disease activity in patients with early endoscopic lesions after resection.     

英夫利西单抗治疗克罗恩病的疗效分析

目的 探讨TNFα单克隆抗体英夫利西(infliximab,IFX)单抗治疗活动性克罗恩病(CD)的疗效与安全性.方法 对传统药物治疗后未能完全缓解、手术治疗后复发或对药物不耐受的CD患者,于0、2、6周时静脉输注IFX(5 mg/kg)诱导缓解治疗,并对第一次输注后14周内的临床疗效,包括疾病活动度、血生化指标及结肠镜表现作出评估.结果 10例患者接受了IFX治疗,其中男8例,女2例,中位年龄31.4岁.5例患者IFX治疗1周后即感症状得到改善,主观症状评分从2.2±0.6降为1.2±0.4(P<0.05);简化CD活动性指数(H-B指数)从6.6±1.6降为2.1±1.0(P<0.05);ESR、C反应蛋白、血清总蛋白及白蛋白也有明显改善;内镜下CD严重度指数也得到明显改善.治疗过程中未观察到输注反应;1例患者在第3次IFX输注后,血ALT及AST暂时性升高;1例患者输注后35周出现严重贫血(三系列均减少).结论 经3次IFX静脉输注方案治疗,本组患者的临床症状及结肠镜下表现可获得较快、较好的改善.IFX长期应用的安全性尚需进一步扩大样本的研究.     

Deep remission on magnetic resonance imaging impacts outcomes of perianal fistulizing Crohn’s disease

Background

The long-term management of perianal Crohn’s disease for patients on anti-TNF-α therapy remains challenging.

Evaluation of adalimumab therapy in multidisciplinary strategy for perianal Crohn's disease patients with infliximab failure

BackgroundInfliximab has improved the management of perianal Crohn's disease, but intolerance and loss of efficacy can occur. The use of a second antibody can be less effective.ObjectiveOur aim was to determine if the use of adalimumab, based on a multidisciplinary strategy, can enhance outcomes for patients with fistulizing disease and infliximab failure.Material and methodsSixteen patients with perianal disease and infliximab failure were treated with adalimumab. Complex fistulas were assessed using magnetic resonance imaging (MRI). Patients with severe conditions as determined by radiology were examined under anesthesia, and seton placement was performed when appropriate. Setons were removed when external discharge had ceased and there was no radiological evidence of fistula activity.ResultsNine patients (56%) underwent MRI. Setons were inserted in seven (43%). The baseline perianal disease activity index (PDAI) decreased after 4 weeks and remained at similar levels 24 and 48 weeks after treatment. The complete response rate was 50% after four weeks and 87.5% of these patients remained in remission after 48 weeks of treatment.ConclusionsFor patients with Crohn's perianal fistulas and infliximab failure, adalimumab as a multidisciplinary approach to management, using MRI to guide surgical drainage when necessary, results in a favourable response and low recurrence rate.     

Multidisciplinary and evidence-based management of fistulizing perianal Crohn's disease

Perianal symptoms are common in patients with Crohn's disease and cause considerable morbidity. The etiology of these symptoms include skin tags, ulcers, fissures, abscesses, fistulas or stenoses. Fistula is the most common perianal manifestation. Multiple treatment options exist although very few are evidence-based. The phases of treatment include: drainage of infection, assessment of Crohn's disease status and fistula tracts, medical therapy, and selective operative management. The impact of biological therapy on perianal Crohn's disease is uncertain given that outcomes are conflicting. Operative treatment to eradicate the fistula tract can be attempted once infection has resolved and Crohn's disease activity is controlled. The operative approach should be tailored according to the anatomy of the fistula tract. Definitive treatment is challenging with medical and operative treatment rarely leading to true healing with frequent complications and recurrence. Treatment success must be weighed against the risk of complications, specially anal sphincter injury. A full understanding of the etiology and all potential therapeutic options is critical for success. Multidisciplinary management of fistulizing perianal Crohn's disease is crucial toimprove outcomes.     

Recent advances in the management of perianal fistulizing Crohn’s disease: lessons for the clinic

Introduction: Managing fistulizing perianal disease is among the most challenging aspects of treating patients with Crohn’s disease. Perianal fistulas are indicative of poor long-term prognosis. They are commonly associated with significant morbidities and can have detrimental effects on quality of life. While durable fistula closure is ideal, it is uncommon.

In optimal circumstances, reported long-term fistula healing rates are only slightly higher than 50% and recurrence is common. Achieving these results requires a combined medical and surgical approach, highlighting the importance of a highly skilled and collaborative multidisciplinary team.

In recent years, advances in imaging, biologic therapies and surgical techniques have lent to growing enthusiasm amongst treatment teams, however the most advantageous approach is yet to be determined.

Areas covered: Here we review current management approaches, incorporating recent guidelines and novel therapies. Additionally, we discuss recently published and ongoing studies that will likely impact practice in the coming years.

Expert opinion: Investing in concerted collaborative multi-institutional efforts will be necessary to better define optimal timing and dosing of medical therapy, as well as to identify ideal timing and approach of surgical interventions. Standardizing outcome measures can facilitate these efforts. Clearly, experienced multidisciplinary teams will be paramount in this process.     

Modern surgical strategies for perianal Crohn's disease

One of the most challenging phenotypes of Crohn’s disease is perianal fistulizing disease (PFCD). It occurs in up to 50% of the patients who also have symptoms in other parts of the gastrointestinal tract, and in 5% of the cases it occurs as the first manifestation. It is associated with severe symptoms, such as pain, fecal incontinence, and a significant reduction in quality of life. The presence of perianal disease in conjunction with Crohn’s disease portends a significantly worse disease course. These patients require close monitoring to identify those at risk of worsening disease, suboptimal biological drug levels, and signs of developing neoplasm. The last 2 decades have seen significant advancements in the management of PFCD. More recently, newer biologics, cell-based therapies, and novel surgical techniques have been introduced in the hope of improved outcomes. However, in refractory cases, many patients face the decision of having a stoma made and/or a proctectomy performed. In this review, we describe modern surgical management and the most recent advances in the management of complex PFCD, which will likely impact clinical practice.     

英夫利西单抗治疗顽固性克罗恩病并短肠综合征1例

英夫利西单抗有助于防止克罗恩病的复发,是克罗恩病合并短肠综合征者的有效治疗手段,有助于防止剩余小肠受累,提高生活质量。     

英夫利西单抗治疗克罗恩病3例报道

英夫利西单抗目前是治疗克罗恩病的有效手段,特别是对五氨基水杨酸及激素耐药的病例,可以有效提高临床缓解率,其维持治疗尤其重要。     

Emerging treatments for complex perianal fistula in Crohn＇s disease

Complex perianal fistulas have a negative impact on the quality of life of sufferers and should be treated. Correct diagnosis, characterization and classification of the fistulas are essential to optimize treatment. Nevertheless, in the case of patients whose fistulas are associated with Crohn＇s disease, complete closure is particularly difficult to achieve. Systemic medical treatments （antibiotics, thiopurines and other immunomodulatory agents, and, more recently, anti-tumor necrosis factor-α agents such as infliximab） have been tried with varying degrees of success. Combined medical （including infliximab） and less aggressive surgical therapy （drainage and seton placement） offer the best outcomes in complex Crohn＇s fistulas while more aggressive surgical procedures such as fistulotomy or fistulectomy may increase the risk of incontinence. This review will focus on emerging novel treatments for perianal disease in Crohn＇s patients. These include locally applied infliximab or tacrolimus, fistula plugs, instillation of fibrin glue and the use of adult expanded adipose-derived stem cell injection. More welldesigned controlled studies are required to confirm the effectiveness of these emerging treatments.     

Establishing a rabbit model of perianal fistulizing Crohn’s disease

BACKGROUNDCrohn''s disease (CD) is a chronic nonspecific intestinal inflammatory disease. The aetiology and pathogenesis of CD are still unclear. Anal fistula is the main complication of CD and is a difficult problem to solve at present. The main limitation of developing new therapies is bound up with the short of preclinical security and effectiveness data. Therefore, an ideal animal model is needed to establish persistent anal fistula and an inflamed rectal mucosa.AIMTo improve the induction method of colitis and establish a reliable and reproducible perianal fistulizing Crohn’s disease animal model to evaluate new treatment strategies.METHODSTwenty male New Zealand rabbits underwent rectal enema with different doses of 2,4,6-trinitrobenzene sulfonic acid to induce proctitis. Group A was treated with an improved equal interval small dose increasing method. The dosage of group B was constant. Seven days later, the rabbits underwent surgical creation of a transsphincteric fistula. Then, three rabbits were randomly selected from each group every 7 d to remove the seton from the fistula. The rabbits were examined by endoscopy every 7 days, and biopsy forceps were used to obtain tissue samples from the obvious colon lesions for histological analysis. The disease activity index (DAI), colonoscopy and histological scores were recorded. Perianal endoscopic ultrasonography (EUS) was used to evaluate the healing of fistulas.RESULTSExcept for the DAI score, the colonoscopy and histological scores in group A were significantly higher than those in group B (P < 0.05). In the ideal model rabbit group, on the 7^th day after the removal of the seton, all animals had persistent lumens on EUS imaging, showing continuous full-thickness high signals. Histological inspection of the fistula showed acute and chronic inflammation, fibrosis, epithelialization and peripheral proctitis of the adjoining rectum.CONCLUSIONThe improved method of CD colitis induction successfully established a rabbit perianal fistula CD preclinical model, which was confirmed by endoscopy and pathology.     

Transperineal ultrasonography in perianal Crohn disease: A valuable imaging modality

Aims of treatment for Crohn disease have moved beyond the resolution of clinical symptoms to objective end points including endoscopic and radiological normality. Regular re-evaluation of disease status to safely, readily and reliably detect the presence of inflammation and complications is paramount. Improvements in sonographic technology over recent years have facilitated a growing enthusiasm among radiologists and gastroenterologists in the use of ultrasound for the assessment of inflammatory bowel disease. Transabdominal intestinal ultrasound is accurate, affordable and safe for the assessment of lumi-nal inflammation and complications in Crohn disease, and can be performed with or without the use of intravenous contrast enhancement. Perianal fistulizing disease is a common, complex and often treatment-refractory complication of Crohn disease, which requires regular radiological monitoring. Endoanal ultrasound is invasive, uncomfortable and yields limited assessment of the perineal region. Although magnetic resonance imaging of the pelvis is established, timely access may be a problem. Transperineal ultrasound has been described in small studies, and is an accurate, painless and cost-effective method for documenting perianal fluid collections, fistulas and sinus tracts. In the present article, the authors review the literature regarding perineal ultrasound for the assessment of perianal Crohn disease and use case examples to illustrate its clinical utility.     

英夫利西联合硫唑嘌呤治疗克罗恩病的临床及内镜随访

目的 观察英夫利西联合硫唑嘌呤治疗克罗恩病(CD)的疗效及黏膜愈合情况与预后的关系.方法 研究对象为广州中山大学附属第一医院接受英夫利西联合硫唑嘌呤治疗的20例活动性CD患者.根据CD活动指数分别评价治疗10周、30周、54周及2年时的临床疗效.根据内镜下黏膜应答情况分别评价治疗10周、30周、54周时的内镜下疗效.两组间比较采用方差分析或Fisher精确概率法.黏膜愈合影响因素采用Logistic回归分析.结果 治疗10周、30周、54周和2年时的无糖皮质激素临床缓解率分别为12/20、16/20、15/20和15/20,10周、30周和54周时的黏膜愈合率分别为8/20、12/20和10/20.Logistic多因素回归分析显示,年轻是影响治疗30周时黏膜愈合的惟一因素((OR=0.774,95％CI:0.630～0.950).30周时黏膜应答者与内镜下无效者在30周及2年时的无糖皮质激素临床缓解率(30周时为14/14比2/6,2年时为14/14比1/6)均差异有统计学意义(Fisher精确概率法,P均＜0.01).30周时获无糖皮质激素临床缓解的16例患者在54周时有4例停用英夫利西,其余12例继续英夫利西治疗,停用和续用英夫利西者的无糖皮质激素临床缓解率(4/4比11/12)和黏膜愈合率(2/4比7/12)均差异无统计学意义(P均＞0.05).结论 英夫利西联合硫唑嘌呤治疗可有效促进和维持CD黏膜愈合,黏膜应答者能维持较长期的无糖皮质激素临床缓解.     

Cost savings using a test-based de-escalation strategy for patients with Crohn’s disease in remission on optimized infliximab: A discrete event model study

Background

Drug de-escalation is considered in Crohn’s disease patients in sustained remission on optimized infliximab treatment.

Management of perianal fistulas in Crohn’s disease:An upto-date review

Perianal disease is one of the most disabling manifestations of Crohn’s disease.A multidisciplinary approach of gastroenterologist,colorectal surgeon and radiologist is necessary for its management.A correct diagnosis,based on endoscopy,magnetic resonance imaging,endoanal ultrasound and examination under anesthesia,is crucial for perianal fistula treatment.Available medical and surgical therapies are discussedin this review,including new local treatment modalities that are under investigation.     

Declining use of combination infliximab and immunomodulator for inflammatory bowel disease in the community setting

AIM To describe trends of combination therapy (CT) of infliximab (IFX) and immunomodulator (IMM) for inflammatory bowel disease(IBD) in the community setting. METHODS A retrospective study was conducted of all IBD patients referred for IFX infusion to our community infusion center between 04/01/01 and 12/31/14. CT was defined as use of IFX with either azathioprine, 6-mercaptopurine, or methotrexate. We analyzed trends of CT usage overall, for Crohn's disease (CD) and ulcerative colitis (UC), and for the subgroups of induction patients. We also analyzed the trends of CT use in these groups over the study period, and compared the rates of CT use prior to and after publication of the landmark SONIC trial.RESULTS Of 258 IBD patients identified during the 12 year study period, 60 (23.3%) received CT, including 35 of 133(26.3%) induction patients. Based on the CochranArmitage trend test, we observed decreasing CT use for IBD patients overall(P 0.0001) and IBD induction patients,(P = 0.0024). Of 154 CD patients, 37(24.68%) had CT, including 20 of 77 (26%) induction patients.The Cochran Armitage test showed a trend towards decreasing CT use for CD overall(P 0.0001) and CD induction,(P = 0.0024). Overall, 43.8% of CD patients received CT pre-SONIC vs 7.4% post-SONIC (P 0.0001). For CD induction, 40.0% received CT preSONIC vs 10.8% post-SONIC(P = 0.0035). Among the 93 patients with UC, 19 (20.4%) received CT. Of 50 induction patients, 14 (28.0%) received CT. The trend test of the 49 patients with a known year of induction again failed to demonstrate any significant trends in the use of CT(P = 0.6). CONCLUSION We observed a trend away from CT use in IBD. A disconnect appears to exist between expert opinion and evidence favoring CT with IFX and IMM, and evolving community practice.     

Management of patients with complex perianal fistulas in Crohn's disease: Optimal patient flow in the Italian clinical reality

Perianal fistulizing Crohn’s disease (PFCD) is a common, disabling and aggressive phenotype that negatively impacts on the quality of life of affected patients. Its successful treatment is still a struggle for both physicians and patients. Significant advances in the management of this condition have occurred in the last two decades holding promise for a better future. This culminated into the concept of a collaborative multidisciplinary approach using the latest medical therapies combined with modern surgical and endoscopic techniques. Despite this, PFCD management and treatment have not been standardized yet. Thus the gastroenterologist and surgeon have to be familiar with several approaches and/or techniques. The positioning of each therapeutic option will certainly evolve with new data, but for the time being it should be driven by patient’s characteristics, physician’s preference and/or experience, costs and availability in local practice. Additionally, patient’s perception of benefits and risks of treatment may differ from those of physicians and recognition of this difference is a starting point for difficult clinical decision-making.In this paper, a multidisciplinary group of Italian IBD experts explore and discuss current medical and surgical therapeutic options, highlighting areas of unmet needs in PFCD, with particular focus on the optimal patient flow within the Italian clinical reality.