Crohn's disease (CD) and Takayasu's arteritis (TA) are inflammatory granulomatous autoimmune disorders. Simultaneous occurrence of CD and TA in the same individual is rare. We report two cases treated with biologic agents. Case 1: A 16-year-old male presented with abdominal pain, nausea, vomiting. CT angiogram showed thickening of the terminal ileum, wall thickening and narrowing of multiple large and medium arteries including aorta and left common carotid. Colonoscopy with biopsy of the stenotic ileocecal valve confirmed CD. Resected carotid artery pathology was consistent with TA. Treatment was initially begun with prednisone, then methotrexate was started followed by infliximab. Due to side effects, methotrexate was switched to azathioprine. He remained asymptomatic. Case 2: A 38-year-old male with well-characterized Crohn's ileocolitis for 15 years, who had been treated with prednisone, mesalamine, sulfasalazine, and azathioprine presented with chest, upper back and abdominal pain. CT angiogram showed vasculitis of large and medium arteries, with stenosis of the right renal artery, and wall thickening of the sigmoid colon. He was diagnosed with TA. He underwent treatment with infliximab and adalumimab on different occasions, which were later discontinued due to fever, bacteremia and complications from sepsis. He remained on prednisone and azathioprine. In these two patients with both CD and TA the diagnoses were confirmed by imaging and pathologic findings. Both patients developed vascular complications. Tumor necrosis factor inhibitor therapy was effective in one patient but discontinued in the other due to infection. Further research into the association of CD and TA may provide clues to their etiologies and guide effective interventions.
Crohn's disease; Takayasu's arteritis; Coexisting; Anti-TNF alpha
A 46-year-old female patient with terminal ileum Crohn’s disease and ankylosing spondylitis presented with recurrent angioedema and urticaria. Investigations ruled out hereditary angioedema, and environmental or food allergen triggers. She was diagnosed with chronic idiopathic urticaria with angioedema, and was treated with a trial of intravenous immunoglobulin immunotherapy, danazol, prednisone and hydroxyzine. Due to ongoing bowel and arthritic complaints, she was started on infliximab infusions and within 2 treatments, she had complete resolution of the angioedema and urticaria, as well as of the bowel and arthritic symptoms. Unfortunately she developed allergic reactions to the infliximab and was switched to another anti-tumor necrosis factor (TNF)-α agent, adalimumab. Since then, she has had no further angioedema or urticaria, and her Crohn’s disease has been quiescent. This is the first known case report of chronic idiopathic urticaria with angioedema coexistent with Crohn’s disease that was successfully treated with anti-TNF-α agents.
Angioedema; Anti-tumor necrosis factor-α; Biologics; Crohn’s disease; Cytokines; Inflammatory bowel disease; Infliximab; Urticaria
Infliximab is a chimeric, monoclonal anti-tumour necrosis factor-alpha antibody. It has been previously demonstrated to be an effective treatment for patients with Crohn’s disease who do not achieve the desired response with conventional treatments. Although the etiology of ulcerative colitis (UC) differs from that of Crohn’s disease, randomized controlled trials have demonstrated that infliximab is also beneficial for the treatment of moderate to severe UC in patients who are either intolerant of or refractory to immunosuppressant agents or steroids, or those who are steroid-dependent. A review of the literature is followed by practical recommendations regarding infliximab that address the needs of clinicians and UC patients. Where there is a lack of evidence-based information, the expert panel provides its combined opinion derived from the members’ clinical experiences.
Drug administration schedule; Immunomodulatory agents; Inflammatory bowel disease; Infliximab; Monoclonal antibodies; Ulcerative colitis
Several studies have compared conventional open ileocolic resection with a laparoscopic-assisted approach. However, long-term outcome after laparoscopic-assisted ileocolic resection remains to be determined. This study was designed to compare long-term results of surgical recurrence, quality of life, body image, and cosmesis in patients who underwent laparoscopic-assisted or open ileocolic resection for Crohn’s disease.
Seventy-eight consecutive patients who underwent ileocolic resection during the period 1995 to 1998 were analyzed; 48 underwent a conventional open approach in the Academic Medical Centre (Amsterdam, The Netherlands) and 30 underwent a laparoscopic-assisted approach in the Leiden University Medical Centre (Leiden, The Netherlands). Primary outcome parameters were reoperation and readmission rate. Secondary outcome parameters were quality of life, body image, and cosmesis.
The two groups were comparable for characteristics of sex, age, and immunosuppressive therapy. Seventy-one patients had a complete follow-up of median 8.5 years. Resection for recurrent Crohn’s disease was performed in 6 of 27 (22 percent) and 10 of 44 (23 percent) patients in the laparoscopic and open groups, respectively. Reoperations for incisional hernia were only performed after conventional open ileocolic resection (3/44 = 6.8 percent). Quality of life and body image were comparable, but cosmesis scores were significantly higher in the laparoscopic group.
Despite small numbers, we found that surgical recurrence and quality of life after laparoscopic-assisted and open ileocolic resection were comparable. Incisional hernias occurred only after open ileocolic resection, and laparoscopic-assisted ileocolic resection resulted in a significantly better cosmesis.
Crohn’s disease; Laparoscopy; Ileocolic resection; Laparoscopic; CD; Long-term morbidity; Body image; Quality of life
Crohn’s disease (CD) is an idiopathic inflammatory bowel disease and has no known cure. CD symptoms are treated using an array of medicines, including biological agents such as infliximab. However, infliximab therapy is expensive; therefore, identifying variables that can help predict response to infliximab is worthwhile. The present article reviews the impact of tobacco smoking on the efficacy of infliximab in CD. Earlier studies have speculated that smoking has a negative effect on the response to infliximab in CD, but the current literature is largely unable to identify a significant relationship between the two. Although smoking is known to have a negative effect on the course of CD, as well as other organ systems, presently, a CD patient’s smoking status should not influence treatment decisions regarding infliximab therapy.
Crohn’s disease; Inflammatory bowel diseases; Infliximab therapy; Ulcerative colitis; Smoking
Orbital myositis is a rare extra-intestinal manifestation of inflammatory bowel disease. Seventeen cases of Crohn’s disease associated orbital myositis and 3 cases of ulcerative colitis associated orbital myositis have been reported in the published literature since 1970. We report the use of adalimumab (Abbott, Canada, Inc.) for orbital myositis in a patient with Crohn’s disease who discontinued infliximab (Janssen, Canada, Inc.) and review of the published literature.
A 35 year-old male with a 7-year history of Crohn’s disease was treated with an ileocolonic resection and re-anastomosis followed by infliximab which maintained full endoscopic and clinical remission for four years. After stopping the infliximab for infusion-related reactions he presented with 3-day history of severe right eye pain, pain with ocular movement, proptosis, and conjunctival injection. He had no intestinal symptoms and endoscopic assessment revealed no active luminal disease. CT of the orbit revealed an enlarged right medial rectus muscle with tendonous involvement and a diagnosis of orbital myositis was made. Treatment with 80 mg per day prednisone with tapering dose and adalimumab, induction and maintenance, resulted in rapid resolution of the orbital myositis and ocular symptoms with no recurrences on follow-up at 10 months.
The current case demonstrates a rare extraintestinal manifestation of Crohn’s disease, orbital myositis, and its temporal relationship to the discontinuance of infliximab therapy and its successful treatment, without recurrence with tapering prednisone and adalimumab.
Crohn’s disease; Ulcerative colitis; Orbital myositis; Extraintestinal manifestations; Inflammatory bowel disease; Infliximab; Adalimumab
Infliximab is a monoclonal antibody against tumor necrosis factor (TNF) which has become an established therapy for Crohn’s disease over the last 10 years. Given the similarities between Crohn’s disease and ulcerative colitis (UC), it is no surprise that gastroenterologists have used infliximab in patients with UC who have failed other therapies. Although the initial controlled trials with infliximab in steroid-refractory disease were unimpressive, subsequent controlled trials have demonstrated the efficacy of infliximab in both moderate to severe disease, and as rescue-therapy to avoid colectomy. The long-term remission rates, colectomy-sparing effects, and the impact of concomitant immunomodulator therapy, remain to be determined in these patients. Whether infliximab is a superior strategy to cyclosporine in patients with steroid-refractory disease is controversial. This review examines the data on the efficacy and safety of infliximab as an induction and maintenance agent for UC.
ulcerative colitis; infliximab; biologics
Mucosal healing is gaining more acceptance as a measure of disease activity in Crohn's disease and ulcerative colitis, and it is also gaining acceptance as an endpoint in clinical trials. Recent publications have correlated achievement of mucosal healing with good outcomes. Currently, there is no validated definition of what constitutes mucosal healing in inflammatory bowel disease. In clinical trials of ulcerative colitis, mucosal healing has been achieved with 5-aminosalicylates, corticosteroids, azathioprine, and infliximab. For Crohn's disease, mucosal healing has been achieved with corticosteroids, infliximab, and adalimumab, and mucosal healing has been maintained with infliximab. Achievement of long-term mucosal healing has been associated with a decreased risk of colectomy and colorectal cancer in ulcerative colitis patients, a decreased need for cortico-steroid treatment in Crohn's disease patients, and a trend toward a decreased need for hospitalization in Crohn's disease patients. Unfortunately, assessment of mucosal healing requires regular use of endoscopy, which is associated with increased costs, patient discomfort, and side effects. Biomarkers such as fecal calprotec-tin, fecal lactoferrin, serum C-reactive protein, and fecal S1 00A1 2 have been shown to correlate with disease activity in ulcerative colitis and Crohn's disease; in the future, these biomarkers might be used as surrogate markers for mucosal healing. Newer clinical trials are incorporating mucosal healing as an endpoint for evaluation of efficacy. However, before mucosal healing will be sufficient to guide therapy, clinicians need a standard definition of mucosal healing and a consistently used, prospectively validated scale with good interobserver agreement.
Mucosal healing; ulcerative colitis; Crohn's disease; anti—tumor necrosis factor agents; corticosteroids; colonoscopy
Background: There is little information about the effect of infliximab on the clinical course of liver disease in Crohn’s disease patients with concomitant hepatitis B virus (HBV) infection. Theoretically, immunosuppression induced by infliximab will facilitate viral replication which could be followed by a flare or exacerbation of disease when therapy is discontinued. There are no specific recommendations on surveillance and treatment of HBV before infliximab infusion. Two cases of severe hepatic failure related to infliximab infusions have been described in patients with rheumatic diseases.
Patients and methods: Hepatitis markers (C and B) and liver function tests were prospectively determined to 80 Crohn’s disease patients requiring infliximab infusion in three hospitals in Spain.
Results: Three Crohn’s disease patients with chronic HBV infection were identified. Two of the three patients with chronic HBV infection suffered severe reactivation of chronic hepatitis B after withdrawal of infliximab therapy and one died. A third patient, who was treated with lamivudine at the time of infliximab therapy, had no clinical or biochemical worsening of liver disease during or after therapy. From the remaining 80 patients, six received the hepatitis B vaccine. Three patients had antibodies to both hepatitis B surface antigen (anti-HBs) and hepatitis B core protein (anti-HBc) with normal aminotransferase levels, and one patient had positive anti-hepatitis C virus (HCV) antibodies, negative HCV RNA, and normal aminotransferase levels. Except for the patients with chronic HBV infection, no significant changes in hepatic function were detected.
Conclusions: Patients with Crohn’s disease who are candidates for infliximab therapy should be tested for hepatitis B serological markers before treatment and considered for prophylaxis of reactivation using antiviral therapy if positive.
Crohn’s disease; infliximab; chronic hepatitis B
AIM: To evaluate the effectiveness of infliximab as a second-line therapy in Crohn’s disease patients after adalimumab failure.
METHODS: A historical cohort study in a community-based gastroenterology practice evaluated Crohn’s disease patients treated with infliximab (induction plus maintenance) after adalimumab failure. Patients were identified using a large Spanish database (ENEIDA).
RESULTS: We included 15 Crohn’s disease patients who received infliximab after adalimumab failure. Five patients discontinued adalimumab due to loss of response, 3 due to adverse events and 7 due to partial response. After infliximab therapy was started, all patients who had interrupted adalimumab due to loss of efficacy regained response. All patients who discontinued adalimumab due to adverse events responded to infliximab and maintained this response; one of these patients had an uneventful course on infliximab, but 2 developed adverse events. None of the 7 patients who interrupted adalimumab due to partial response reached remission with infliximab.
CONCLUSION: Switching from adalimumab to infliximab may be useful in patients who develop adverse effects or loss of response, however, the benefit of infliximab in primary nonresponders was not established.
Adalimumab; Biologics; Crohn’s disease; Infliximab; Switch
Introduction. There is little information on the reasons for discontinuing infliximab treatment in patients with Crohn's disease. The aim of this study was to document these reasons to determine if any were preventable which would allow patients to continue the therapy. Aims & Methods. A review of the medical notes was conducted at the Norfolk and Norwich University Hospital on patients with Crohn's disease treated with infliximab between 2002–2008 to determine the reasons for stopping it. Results. A total of 65 patients were identified who had treatment with infliximab, of whom 23 (35.3%) had their therapy stopped. The reasons for discontinuation of infliximab in the 23 patients were: 47.8% side effects, 17.4% refractory disease, 13.0% achieved remission and did not receive long-term maintenance treatment, 4.34% pregnancy, 4.34% death, and unknown 13.0%. Conclusions. The main reasons for the discontinuation of infliximab were side effects rather than a lack of clinical response.
A liver abscess in Crohn’s disease is a rare but important entity that is associated with a poor prognosis and high mortality when treatment is delayed. We report a case of successful liver segmentectomy for a methicillin-resistant Staphylococcus aureus liver abscess in a patient with Crohn’s disease under infliximab treatment.
A 31-year-old Japanese man, who had been treated with infliximab infusions for Crohn’s disease, was referred to our hospital presenting with an abrupt onset of high fever and an elevated white blood cell count and serum C-reactive protein level. Computed tomography revealed a liver abscess occupying segment 8. The limited effect of percutaneous transhepatic abscess drainage and antibiotics led us to perform radical resection of the abscess. The patient recovered quickly after surgery and the postoperative course was uneventful.
The present case suggests that surgical removal of an abscess should be considered for patients under immunosuppression or refractory to conventional treatment.
Crohn’s disease (CD) is a chronic inflammatory bowel disease that can affect the entire gastrointestinal tract. Ultimately, up to 70% of all patients will need surgery, despite optimized medical therapy. Moreover, about half of the patients will need redo-surgery because of disease recurrence. The introduction of anti-tumor necrosis factor (TNF) drugs (Infliximab in 1998) revolutionized the treatment of CD. Different randomized trials assessed the efficacy of anti-TNF treatment not only to induce, but also to maintain, steroid-free remission. Furthermore, these agents can rapidly lead to mucosal healing. This aspect is important, as it is a major predictor for long-term disease control. Subgroup analyses of responding patients seemed to suggest a reduction in the need for surgery at median-term follow up (1-3 years). However if one looks at population surveys, one does not observe any decline in the need for surgery since the introduction of Infliximab in 1998. The short follow-up term and the exclusion of patients with imminent surgical need in the randomized trials could bias the results. Only 60% of patients respond to induction of anti-TNF therapy, moreover, some patients will actually develop resistance to biologicals. Many patients are diagnosed when stenosing disease has already occurred, obviating the need for biological therapy. In a further attempt to change the actual course of the disease, top down strategies have been progressively implemented. Whether this will indeed obviate surgery for a substantial group of patients remains unclear. For the time being, surgery will still play a pivotal role in the treatment of CD.
Crohn’s disease; Surgery; Biological agents; Anti-tumor necrosis factor drugs; Remission
Background and aims: Treatment with infliximab induces remission in about 70% of patients with steroid refractory Crohn's disease. Because Crohn's disease is considered to be mediated by uncontrolled activation of mucosal T lymphocytes, we hypothesised that infliximab could induce apoptosis of T lymphocytes.
Methods: Induction of apoptosis in vivo was studied in 10 patients with therapy refractory Crohn's disease. In vitro, resting or stimulated Jurkat T cells were incubated with infliximab.
Results: Infusion of infliximab (5 mg/kg) in steroid refractory patients with Crohn's disease induced a clinical response in 9/10 patients but did not influence expression of activation markers, homing receptors, memory cells, Fas expression, or Bax/Bcl-2 expression on peripheral blood T lymphocytes. In contrast, a significant increase in CD3 and TUNEL positive cells within colonic biopsies was detected 24 hours after infusion of infliximab, suggesting that infliximab stimulates apoptosis of activated T lymphocytes but not of resting T cells. To test this hypothesis, the effects of infliximab on Jurkat T cells were investigated. We observed that infliximab induced apoptosis and an increase in the Bax/Bcl-2 ratio of CD3/CD28 stimulated Jurkat T cells but not of unstimulated Jurkat cells.
Conclusions: Our data indicate that infliximab treatment causes a rapid and specific increase in apoptosis of T lymphocytes in the gut mucosa. These findings may explain the rapid and sustained therapeutic effects of infliximab in Crohn's disease.
apoptosis; T lymphocytes; Crohn's disease; infliximab; tumour necrosis factor
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 well-designed controlled studies are required to confirm the effectiveness of these emerging treatments.
Crohn’s disease; Perianal fistula; Drug therapy; Topical administration; Infliximab; Adalimumab; Adipose tissue; Stem cells
To test the safety, tolerability, and pharmacokinetics of the anti- TNF-α monoclonal antibody, infliximab, in subjects with intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD).
We conducted a multicenter, randomized, prospective trial of second IVIG infusion (2 g/kg) versus infliximab (5 mg/kg) in 24 children with acute KD and fever following initial treatment with IVIG. Primary outcome measures were infliximab safety, tolerability, and pharmacokinetics. Secondary outcome measures were duration of fever and changes in markers of inflammation.
Study drug infusions were associated with cessation of fever within 24 hours in 11 of 12 subjects treated with infliximab and 8 of 12 subjects retreated with IVIG. No infusion reactions or serious adverse events were attributed to either study drug. No significant differences were observed between treatment groups in the change from baseline for laboratory variables, fever, or echocardiographic assessment of coronary arteries.
Both infliximab and a second IVIG infusion were safe and well-tolerated in subjects with KD who were resistant to standard IVIG treatment. The optimal management of patients resistant to IVIG remains to be determined.
TNF-α; cytokine; monoclonal antibody; coronary artery aneurysm; infliximab; Kawasaki disease
The objective of this study was to analyze the safety of long-term infliximab treatment, with/without concomitant immunomodulators, across Crohn's disease (CD) and ulcerative colitis (UC) clinical trials.
To maximize sample size, we pooled primary safety data across 10 CD or UC trials, including five randomized, controlled trials contributing data from patients who received intravenous infliximab 5 or 10 mg/kg (n=1,713; ±azathioprine) or placebo (n=406; ±azathioprine). Pooled incidences and 95% confidence intervals (CIs) were determined for mortality, infection, and malignancy. Standardized incidence ratios and 95% CIs were also determined for malignancies using the Surveillance, Epidemiology, and End Results database.
We observed no increase in infections, serious infections, or malignancy with infliximab vs. placebo in these patients with inflammatory bowel disease (IBD). In patients with UC, but not CD, immunomodulator treatment (vs. treatment without immunomodulator) yielded a higher incidence (95% CI) of infections (120.07 (110.66, 130.08)/100 patient-years (pt-yrs) vs. 92.47 (84.54, 100.94)/100 pt-yrs). Among placebo-treated patients with CD, but not UC, those with immunomodulator use demonstrated a higher incidence (95% CI) of malignancy vs. no immunomodulator treatment (1.84 (0.22, 6.66)/100 pt-yrs vs. 0.00 (0.00, 0.00)/100 pt-yrs). Mortality and infection-related mortality appeared unaffected by infliximab or immunomodulator treatment.
Infliximab treatment of IBD did not appear to affect incidences of infection, mortality, or malignancy. Relative to patients with no immunomodulator use, immunomodulator-treated UC patients demonstrated a higher incidence of infection and immunomodulator-plus-placebo-treated CD patients demonstrated a higher incidence of malignancy.
A number of treatments have been shown to reduce the risk of postoperative recurrence of Crohn's disease (CD). The optimal strategy is unknown. The aim was to evaluate the comparative cost-effectiveness of postoperative strategies to prevent clinical recurrence of CD.
Three prophylactic strategies were compared to “no prophylaxis”; mesalamine, azathioprine (AZA) / 6-mercaptopurine (6-MP), and infliximab. The probability of clinical recurrence, endoscopic recurrence, and therapy discontinuation due to adverse drug reactions (ADRs) were extracted from randomized controlled trials (RCTs). Quality-of-life scores and treatment costs were derived from published data. The primary model evaluated quality-adjusted life years (QALYs) and cost-effectiveness at 1 year after surgery. Sensitivity analysis assessed the impact of a range of recurrence rates on cost-effectiveness. An exploratory analysis evaluated cost-effectiveness outcomes 5 years after surgery.
A strategy of “no prophylaxis” was the least expensive one at 1 and 5 years after surgery. Compared to this approach, AZA/6-MP had the most favorable incremental cost-effectiveness ratio (ICER) ($299,188/QALY gained), and yielded the highest net health benefits of the medication strategies at 1 year. Sensitivity analysis determined that the ICER of AZA/6-MP was preferable to mesalamine up to a recurrence rate of 52%, but mesalamine dominated at higher rates. In the 5-year exploratory analysis, mesalamine had the most favorable ICER over 5 years ($244,177/QALY gained).
Compared to no prophylactic treatment, AZA/6-MP has the most favorable ICER in the prevention of clinical recurrence of postoperative CD up to 1 year. At 5 years, mesalamine had the most favorable ICER in this model.
Crohn's disease; prophylaxis; decision analysis; cost-effectiveness
We evaluated the effect of potential clinical factors on surgical recurrence of ileal Crohn’s disease after initial ileocolic resection.
One hundred seventy-six patients with ileal Crohn’s disease who underwent an ileocolic resection with anastomosis were identified from our database. The outcome of interest was time from first to second ileocolic resection. Survival analysis was used to assess the significance of the Montreal phenotype classification, smoking habit, a family history of inflammatory bowel disease and other clinical variables.
In our final Cox model, a family history of inflammatory bowel disease (hazard ratio 2.24, 95 percent confidence interval 1.16–4.30, P=0.016), smoking at time of initial ileocolic resection (hazard ratio 2.08, 95 percent confidence interval 1.11–3.91, P=0.023) was associated with an increased risk of a second ileocolic resection while postoperative prescription of immunomodulators (hazard ratio 0.40, 95 percent confidence interval 0.18–0.88, P= 0.022) was associated with a decreased risk of a second ileocolic resection.
Both a family history of inflammatory bowel disease and smoking at the time of the initial ileocolic resection are associated with an increased risk of a second ileocolic resection. Postoperative prescription of immunomodulators is associated with a reduced risk of surgical recurrence. This study supports the concept that both genetic and environmental factors influence the risk of surgical recurrence of ileal Crohn’s disease.
Crohn’s disease; Ileocolic resection; Postoperative recurrence
Tumor necrosis factor α plays an important role in the pathogenesis of Crohn's disease (CD). The effects of infliximab on gastrointestinal bleeding in CD have not yet been fully evaluated. Herein we describe three CD cases who presented with gastrointestinal bleeding and received infliximab treatment. In case 1, double-balloon endoscopy showed a large ulcer with several irregularly shaped ulcers in the terminal ileum; 8 weeks after infliximab administration, complete healing of all lesions was observed. In case 2, double-balloon endoscopy showed linear ulcers and mucosal edema in the jejunum and ileum; 5 weeks after infliximab administration, all lesions were decreased in size and were healed. In case 3, double-balloon endoscopy revealed ulcerations and stenosis in the terminal ileum; 12 weeks after infliximab administration, ulcer healing and an increased diameter of the ileal stenosis were observed. These three cases have been receiving ongoing infliximab maintenance therapy and are currently symptom-free. Infliximab thus appears to be useful for treatment of gastrointestinal bleeding in CD patients.
Crohn's disease; Infliximab; Double-balloon endoscopy; Gastrointestinal bleeding
Activated granulocytes, monocytes, and platelets appear to be closely involved in active Crohn's disease (CD). Adsorptive granulocyte apheresis (GCAP) is a new treatment for inflammatory bowel disease. GCAP was used to treat a 23-year-old female patient with CD resistant to both infliximab (IFX) and azathioprine (AZA). At 16 years of age, the patient underwent a partial ileal resection for peritonitis caused by perforative ileitis. On pathological examination of the resected specimen, the diagnosis was CD. Mesalazine was started, but the patient did not comply with therapy. She was admitted to our hospital again in 2007 due to an acute exacerbation. IFX induction therapy was started. The combination of both AZA daily and IFX every 8 weeks was continued as maintenance therapy. However, she developed severe abdominal pain in September 2009. Computed tomography revealed ileitis and ascending colitis, and blood tests showed high inflammatory response marker levels. She was considered to have IFX- and AZA-resistant CD. Initial intravenous steroid therapy did not result in any improvement. Therefore, weekly GCAP therapy was given for 5 weeks, which immediately improved the inflammatory response markers. GCAP combined with prednisolone could be effective for IFX- and AZA-refractory CD.
Adsorptive granulocyte apheresis; Infliximab; Prednisolone; Azathioprine; Crohn's disease
Background. Single Port Laparoscopic Surgery (SPLS) is being increasingly employed in colorectal surgery for benign and malignant diseases. The particular role for SPLS in inflammatory bowel disease (IBD) has not been determined yet. In this review article we summarize technical aspects and short term results of SPLS resections in patients with Crohn's disease or ulcerative colitis. Methods. A systematic review of the literature until January 2012 was performed. Publications were assessed for operative techniques, equipment, surgical results, hospital stay, and readmissions. Results. 34 articles, published between 2010 and 2012, were identified reporting on 301 patients with IBD that underwent surgical treatment in SPLS technique. Surgical procedures included ileocolic resections, sigmoid resections, colectomies with end ileostomy or ileorectal anastomosis, and restorative proctocolectomies with ileum-pouch reconstruction. There was a wide variety in the surgical technique and the employed equipment. The overall complication profile was similar to reports on standard laparoscopic surgery in IBD. Conclusions. In experienced hands, single port laparoscopic surgery appears to be feasible and safe for the surgical treatment of selected patients with IBD. However, evidence from prospective randomized trials is required in order to clarify whether there is a further benefit apart from the avoidance of additional trocar incisions.
Infliximab’s efficacy in the induction and maintenance of remission in luminal Crohn’s disease has been confirmed by randomized, controlled trials. Less clearly described are long-term outcomes in the clinical practice setting since the establishment of regularly scheduled, every eight-week maintenance infliximab infusions. Existing reports describing clinical practice outcomes are limited by short durations of follow-up or by the use of episodic dosing, or focus on safety data rather than clinical outcomes.
To examine induction and maintenance responses to infliximab in an outpatient inflammatory bowel disease clinic.
A retrospective chart review was performed. Clinical outcomes were infliximab induction and maintenance responses, defined as the ability to stop and remain off corticosteroids while not requiring additional therapy for active disease.
One hundred thirty-three patients were identified with records sufficiently detailed to be analyzed. Of these, 117 patients (88%) demonstrated a clinical response to induction; 104 of 117 (89%) were on concomitant immunosuppressive therapy; 80 of 104 on azathioprine/6-mercaptopurine (77%); and 24 of 104 on methotrexate (23%). The mean duration of clinical response was 94 weeks (95% CI 78.8 to 109.2). The proportion of patients who maintained response at 30 weeks was 83.2%, at 54 weeks was 63.6% and at 108 weeks was 44.9%. Adverse events occurred for 15 of 117 patients (12.8%), consisting of nine infusion reactions, four serum sickness-like reactions, one rash and one infection.
Patients treated with infliximab therapy for luminal Crohn’s disease in our outpatient clinic achieved excellent induction and maintenance of response rates, confirming the real-life efficacy of maintenance infliximab established in clinical trials.
Clinical practice; Crohn’s disease; Immunosuppression; Infliximab
Infliximab is a monoclonal antibody against tumour necrosis factor-alpha. Recent studies have shown that it is effective in treating patients with refractory Crohn's disease and in those with Crohn's fistulae. Though this drug is found to be safe in clinical trials, sporadic reports of serious complications have been recorded in the literature. The case of a patient who developed profuse genital warts after infliximab treatment is reported. The literature is reviewed and information is presented on side effects and complications as a result of infliximab therapy.
Background: Several placebo controlled studies have demonstrated the efficacy of infliximab in inflammatory bowel disease (IBD) but the potential toxicity of this new biological compound has been less studied.
Aim: To assess the use of infliximab in IBD in a population based cohort, with special emphasis on the occurrence of severe adverse events and mortality.
Patients: All patients with IBD treated with infliximab between 1999 and 2001 in Stockholm County were evaluated.
Methods: Prospective registration of clinical data was carried out. Retrospective analyses were made of possible adverse events occurring in relation to infliximab treatment. Adverse events requiring pharmacological treatment or hospitalisation were defined as severe. Clinical response was assessed as remission, response, or failure.
Results: A cohort comprising 217 patients was assembled: 191 patients had Crohn’s disease (CD), and infliximab was used off label for ulcerative colitis (UC) in 22 patients. Four patients were treated for indeterminate colitis (IC). Mean age was 37.6 (0.9) years (range 8–79). The mean number of infliximab infusions was 2.6 (0.1) (range 1–11). Forty two severe adverse events were registered in 41 patients (CD, n = 35). Eleven of the severe adverse events occurred postoperatively (CD, n = 6). Three patients with CD developed lymphoma (of which two were fatal), opportunistic infections occurred in two patients (one with UC, fatal), and two patients with severe attacks of IBD died due to sepsis (one with CD, one postoperatively with UC). One additional patient with UC died from pulmonary embolism after colectomy. Mean age in the group with fatal outcome was 62.7 years (range 25–79). The overall response rate was 75% and did not differ between the patient groups.
Conclusions: Infliximab was efficacious as an anti-inflammatory treatment when assessed in a population based cohort of patients with IBD. However, there appear to be a significant risk of deleterious and fatal adverse events, particularly in elderly patients with severe attacks of IBD. Off label use of infliximab in UC and IC should be avoided until efficacy is proven in randomised controlled trials. The underlying risk of developing malignancies among patients with severe or chronically active CD in need of infliximab treatment is not known but the finding of a 1.5% annual incidence of lymphoma emphasises the need for vigilant surveillance with respect to this malignant complication.
Crohn’s disease; inflammatory bowel disease; infliximab; lymphoma; mortality; ulcerative colitis