Randomised, Double-blind, Placebo-controlled Trial of CCR9-targeted Leukapheresis Treatment of Ulcerative Colitis Patients.

BACKGROUND AND AIMS: Ulcerative colitis patients display increased numbers of circulating pro-inflammatory monocyte human leukocyte antigen-DR [HLA-DRhi] monocytes expressing high levels of the gut-homing C-C chemokine receptor 9 [CCR9] and tumour necrosis factor [TNF]-α. The aim of this first-in-human, double-blind, randomised, placebo-controlled trial was to evaluate selective removal of circulating CCR9-expressing monocytes by leukapheresis in patients with moderate to severe ulcerative colitis, with regards to safety, tolerability, and immunological response. METHODS: Patients with ulcerative colitis were treated every second day with leukapheresis during five sessions with a C-C chemokine ligand 25 [CCL25; CCR9 ligand] column or a placebo column. RESULTS: No major safety concerns were raised and the procedure was well tolerated. Pro-inflammatory HLA-DRhi cells decreased significantly in the active treatment group [p = 0.0391] whereas no statistically significant change was seen in the placebo group [p = 0.4688]. There was a significant decrease of HLA-DRhi monocytes in the active group compared with the placebo group when corrected for the imbalance in weight between the groups [p = 0.0105]. Mayo score decreased in the active group [p = 0.0156] whereas the change in the placebo group was not significant [p = 0.1250]. Mayo score ≤ 3 was observed in five out of 14 patients [35.7%] in the active group compared with one out of eight [12.5%] receiving placebo. The number of responders in the active treatment group was eight out of 14 patients [57.1%], whereas in the corresponding placebo group three out of eight patients [37.5%] responded to placebo. A dose-response correlation was observed between the blood volume processed and clinical outcome. CONCLUSION: This clinical induction trial using CCL25-tailored leukapheresis demonstrates a safe and effective removal of activated monocytes with a clinical effect in patients with ulcerative colitis.

Use of complementary and alternative medicine in Swedish patients with inflammatory bowel disease: a controlled study.

BACKGROUND: There is an increasing interest in complementary and alternative medicine (CAM) in patients with chronic diseases, including those with inflammatory bowel disease (IBD). Patients may turn to CAM when conventional therapies are inadequate or associated with side effects for symptomatic relief or to regain control over their disease. The objectives were to explore CAM use and perceived effects in IBD patients in comparison with a control group. METHODS: A cross-sectional, multicenter, controlled study was carried out. IBD patients were invited from 12 IBD clinics in Sweden. Controls were selected randomly from a residence registry. A study-specific questionnaire was used for data collection. RESULTS: Overall, 48.3% of patients with IBD had used some kind of CAM during the past year compared with 53.5% in controls (P=0.025, adjusted for age, sex, geographic residence, and diet). The most frequently used CAM among IBD patients was massage (21.3%), versus controls (31.4%) (adjusted P=0.0003). The second most used CAM was natural products, 18.7% in IBD patients versus 22.3% of the controls (unadjusted P=0.018). In all, 83.1% of the patients experienced positive effects from CAM and 14.4% experienced negative effects. CONCLUSION: Overall, 48.3% of Swedish IBD patients used some kind of CAM and controls used CAM significantly more. Natural products were used by one-fifth of the patients and even more by controls. This is notable from a patient safety perspective considering the possible risks of interactions with conventional medication. In all, 40% of the patients reported adverse events from conventional medicine. Patients experienced predominantly positive effects from CAM, and so did controls.

Experiences of complementary and alternative medicine in patients with inflammatory bowel disease - a qualitative study.

BACKGROUND: The use of Complementary and Alternative Medicine (CAM) in Inflammatory Bowel Disease (IBD) is increasing. Although CAM often improves patients' well-being, it can also lead to side-effects and interactions with conventional medications. Research on patients with IBD in Sweden who have experiences of CAM is sparse. More studies are needed to enhance awareness of and improve communication about CAM. The aim of this study was to describe experiences of CAM in the healthcare context reported by patients with IBD. METHODS: Fifteen patients with IBD, eight with Crohn's disease (CD) and seven with ulcerative colitis (UC), were recruited. Semi-structured qualitative interviews were conducted and qualitative content analysis was performed. RESULTS: The analysis revealed the theme Knowledge and communication lead to participation in the area of CAM based on three categories; CAM use, Communication and Self-care. Patients with IBD wanted to be asked about CAM to be able to start a dialogue, as some perceived being treated in a disparaging manner and not taken seriously when raising the subject. Healthcare professionals (HCPs) need to be aware of this in order to meet and understand patient needs. Patients with IBD found it easier to communicate about CAM with the IBD nurses than physicians and dietary changes was one important CAM treatment. CONCLUSIONS: The finding that it was easier to discuss CAM with nurses than physicians emphasizes the important role of the IBD nurse in communication and monitoring patients' CAM use. Patients wanted to be asked about CAM to be able to start a dialogue, as some perceived not taken seriously when raising the subject. Furthermore, HCPs need to understand that many patients with IBD regard dietary changes as an important part of CAM treatment. Further research in these areas is needed.

Inflammatory bowel disease professionals' attitudes to and experiences of complementary and alternative medicine.

BACKGROUND: Complementary and alternative medicine (CAM) use in patients with IBD is on the increase. Patients report they use CAM when their condition is unresponsive to conventional medication or when they suffer from side-effects, negative stress and disease-related concerns. CAM use may improve patients' well-being but it can also lead to side-effects and interactions with conventional medications. Research on attitudes to and experiences of CAM among healthcare professionals working with IBD patients is not well studied. Studies in this area could lead to enhanced awareness of and improved communication about CAM between care staff and IBD patients. The aim of this study was to explore IBD professionals' attitudes to and experience of CAM. METHODS: Sixteen physicians and nurses, 26-70 years old, who had worked with IBD patients for 1-42 years, were recruited. Semi-structured qualitative interviews were conducted. Qualitative content analysis was performed. RESULTS: Participants stated patients used CAM to improve their well-being generally and there conditions specifically. Participants had a positive attitude towards CAM and respected their patients' decision to use it, but reported a lack of CAM knowledge. They required education about CAM to be able to meet patients' needs and provide adequate information. The result of this study indicates that there is a need for CAM education to be implemented in nursing and medical school. CONCLUSIONS: All participants had experience of IBD patients who had used CAM in an attempt to achieve improvement and well-being. Attitudes to CAM were mainly positive, although a problematic aspect was lack of knowledge and evidence in relation to CAM. Implementing CAM education in nursing and medical school will allow healthcare professionals to gain an understanding of therapies widely used by patients with IBD. In clinical practice, using a standard questionnaire regarding CAM use allow healthcare professionals to better understand their patients' wishes and current CAM use.

HLA-DR(hi) and CCR9 Define a Pro-Inflammatory Monocyte Subset in IBD.

OBJECTIVES: It has been demonstrated that circulating monocytes relocate to the intestinal mucosa during intestinal inflammation, but the phenotype and inflammatory mechanisms of these monocytes remain poorly understood. Here, we have investigated blood monocytes expressing high levels of HLA-DR and CCR9 in patients with inflammatory bowel disease (IBD). METHODS: Fifty-one patients with mild to severe ulcerative colitis (UC; n=31; UC-DAI 3-12) or Crohn's disease (CD; n=20; Harvey-Bradshaw indices (HBI) 2-16) were included together with 14 controls, during IBD therapy for four consecutive weeks. The frequency of CD14(+)HLA-DR(hi) monocytes was monitored weekly in peripheral blood, using flow cytometry. The surface phenotype and cytokine profile of these monocytes were established using flow cytometry and real-time PCR. Clinical parameters were assessed weekly in all patients. RESULTS: The frequency of circulating CD14(+)HLA-DR(hi) monocytes was significantly higher in IBD patients with moderate to severe disease compared with healthy controls (P<0.001). During treatment with corticosteroids and granulocyte/monocyte apheresis, the proportion of circulating CD14(+)HLA-DR(hi) monocytes was significantly reduced. CD14(+)HLA-DR(hi) monocytes produced high levels of inflammatory mediators, such as tumor necrosis factor (TNF)-α, and expressed the gut-homing receptor CCR9. Furthermore, we found that the CCR9 ligand, CCL25/TECK, was expressed at high levels in the colonic mucosa in IBD patients with active disease. CONCLUSIONS: CD14(+)HLA-DR(hi) blood monocytes were increased in patients with active IBD. These monocytes exhibit a pro-inflammatory, gut-homing phenotype with regard to their TNF-α production and expression of CCR9. Our results suggest that these monocytes are important in mediating intestinal inflammation, and provide potential therapeutic targets in IBD.

Long-term follow-up with Granulocyte and Monocyte Apheresis re-treatment in patients with chronically active inflammatory bowel disease.

BACKGROUND: Patients with IBD and chronic inflammation refractory to conventional therapy often demonstrate higher risk of serious complications. Combinations of immunosuppression and biological treatment as well as surgical intervention are often used in this patient group. Hence, there is need for additional treatment options. In this observational study, focused on re-treatment and long-term results, Granulocyte/Monocyte Adsorption (GMA, Adacolumn) treatment has been investigated to study efficacy, safety and quality of life in IBD-patients with chronic activity. METHODS: Fifteen patients with ulcerative colitis and 25 patients with Crohn's disease, both groups with chronically active inflammation refractory to conventional medication were included in this observational study. The patients received 5-10 GMA sessions, and the clinical activity was assessed at baseline, after each completed course, and at week 10 and 20 by disease activity index, endoscopy and quality of life evaluation. Relapsed patients were re-treated by GMA in this follow-up study up to 58 months. RESULTS: Clinical response was seen in 85% and complete remission in 65% of the patients. Ten patients in the UC-group (66%) and 16 patients in the CD-group (64%) maintained clinical and endoscopic remission for an average of 14 months. Fourteen patients who relapsed after showing initial remission were re-treated with GMA and 13 (93%) went into a second remission. Following further relapses, all of seven patients were successfully re-treated for the third time, all of three patients for the fourth time and one for a fifth time. CONCLUSIONS: IBD-patients with chronic inflammation despite conventional therapy seem to benefit from GMA. Re-treatment of relapsing remission patients seems to be effective.