Efficacy and safety of granulocyte and monocyte adsorption apheresis for ulcerative colitis: A meta-analysis

BackgroundSafe and effective treatments are required for patients with ulcerative colitis. It was suggested that granulocyte and monocyte adsorption apheresis might play an important role for ulcerative colitis. Therefore, a meta-analysis was performed.MethodsMedline and the Cochrane controlled trials register were used to identify randomized controlled trials comparing granulocyte and monocyte adsorption apheresis with corticosteroids, and comparing intensive with conventional apheresis in patients with ulcerative colitis.ResultsNine randomized trials were eligible for inclusion criteria. According to pooled data, granulocyte and monocyte adsorption apheresis is effective for inducing clinical remission in patients with ulcerative colitis compared with corticosteroids (odds ratio, 2.23; 95% confidence interval: 1.38–3.60). However, the efficacy of granulocyte and monocyte adsorption apheresis was not dependent on the number of apheresis sessions. The intensive apheresis (≥2 sessions per week) is more effective for inducing clinical remission than weekly apheresis (odds ratio, 2.10; 95% confidence interval: 1.12–3.93). The rate of adverse events by apheresis was significantly lower than that by corticosteroids (odds ratio, 0.24; 95% confidence interval: 0.15–0.37).ConclusionOur meta-analysis reveals that intensive granulocyte and monocyte adsorption apheresis is a safe and effective treatment with higher rates of clinical remission and response for ulcerative colitis compared with corticosteroids.     

Granulocyte, monocyte/macrophage apheresis for inflammatory bowel disease: the first 100 patients treated in Scandinavia

OBJECTIVE: Selective leukocyte apheresis is a new type of non-pharmacological treatment for patients with active ulcerative colitis and Crohn's disease. Preliminary data have indicated that this type of therapy is safe and efficacious, and large sham-controlled studies are currently in progress. In Scandinavia, a substantial number of patients with chronic inflammatory bowel disease have already received leukocyte apheresis on a compassionate use basis and the aim of this study was to report the clinical outcome and adverse events in the first patients treated. MATERIAL AND METHODS: Clinical details of the first consecutive 100 patients with inflammatory bowel disease treated with granulocyte, monocyte/macrophage (Adacolumn) apheresis in Scandinavia were prospectively registered. Median length of follow-up was 17 months, (range 5-30). RESULTS: The study population comprised 52 patients with ulcerative colitis, 44 patients with Crohn's disease and 4 patients with indeterminate colitis. In 97 patients the indication for Adacolumn treatment was steroid-refractory or steroid-dependent disease. Clinical remission was attained in 48% of the patients with ulcerative colitis, and an additional 27% had a clinical response to the apheresis treatment. The corresponding figures for patients with Crohn's disease were 41% and 23%, respectively. Complete steroid withdrawal was achieved in 27 out of the 50 patients taking corticosteroids at baseline. Adverse events were reported in 15 patients and headache was most frequently reported (n=7). CONCLUSIONS: Granulocyte, monocyte/macrophage apheresis treatment seems to be a valuable adjuvant therapy in selected patients with refractory inflammatory bowel disease. The risk for toxicity or severe adverse events appears to be low.     

Single‐Needle Intensive Granulocyte and Monocyte Adsorptive Apheresis Is Suitable for Elderly Patients With Active Ulcerative Colitis Taking no Corticosteroids or Biologics

Twice‐weekly intensive granulocyte/monocyte adsorptive apheresis is effective and safe for ulcerative colitis, but maintaining two blood access routes is problematic. We previously reported that intensive granulocyte/monocyte adsorptive apheresis using a single needle in ulcerative colitis is effective and safe. We hypothesized that the efficacy and safety of single‐needle intensive granulocyte/monocyte adsorptive apheresis for ulcerative colitis would especially benefit the elderly. We enrolled 17 elderly ulcerative colitis patients to receive single‐needle intensive granulocyte/monocyte adsorptive apheresis, 27 elderly ulcerative colitis patients to receive double‐needle intensive granulocyte/monocyte adsorptive apheresis, and 52 nonelderly ulcerative colitis patients to receive single‐needle intensive granulocyte/monocyte adsorptive apheresis. Remission and mucosal healing rates after treatment did not differ significantly between elderly ulcerative colitis patients receiving single‐needle apheresis and the other two groups. In addition, no serious adverse effects, including blood clots, were observed in single‐needle intensive granulocyte/monocyte adsorptive apheresis patients. Single‐needle intensive granulocyte/monocyte adsorptive apheresis might be a novel alternative therapeutic option for elderly ulcerative colitis patients before considering corticosteroids.     

Leukocyte Apheresis Using a Centrifugal Cell Separator in Refractory Ulcerative Colitis: A Multicenter Open Label Trial

Abstract: Recently, successful results of ulcerative colitis (UC) treatments with leukocyte apheresis have been reported by several institutes. To certify the efficacy of leukocyte apheresis in refractory UC patients, a multicenter open label trial was conducted, and results were analyzed. Fifty patients diagnosed with active steroid‐resistant UC were enrolled in this study from 14 medical centers. Using a centrifugal cell separator (Component Collection System, Haemonetics), leukocyte apheresis was performed once a week for 5 weeks. General conditions and abdominal symptoms were recorded daily, and laboratory tests were followed weekly. Changes of colonoscopic and histological manifestations of luminal activity through the study period were evaluated. At the end of the study period, stool frequency was decreased to less than 4 times a day in 68.4% (26 of 38) and serum C‐reactive protein (CRP) concentration was normalized in 56.7% (17 of 30) of the patients. Colonoscopic remission was achieved in 57.7% (26 of 45), and histological improvement was noted in 54.1% (20 of 37) of the patients tested. Improved disease activity was demonstrated in 74% (37 of 50) of the patients by general assessment criteria. Analysis of the trial data confirmed the valid clinical efficacy of leukocyte apheresis by centrifugal cell separator in refractory UC patients.     

Stool decay-accelerating factor as a marker for monitoring the disease activity during leukocyte apheresis therapy in patients with refractory ulcerative colitis

BACKGROUND AND AIMS: We have shown previously that concentrations of stool decay-accelerating factor (DAF; CD55), a complement regulatory protein, in patients with ulcerative colitis (UC) are increased in relation to the severity of the colonic mucosal inflammation. In the present study, we evaluated the usefulness of stool DAF as a marker for monitoring disease activity in patients with steroid-resistant active UC being treated with leukocyte apheresis performed with a centrifugal cell separator. METHODS: Twenty-one patients with active and steroid-resistant UC were treated with leukocyte apheresis once a week for 4 weeks, and stool DAF concentrations were determined weekly by immunoassay. RESULTS: After treatment, 11 (52%) of the 21 UC patients went into remission. Stool DAF concentrations decreased promptly and steadily in the responsive group. The difference reached statistical significance as soon as after the second apheresis session (P < 0.003), compared with values before the therapy and corresponding values in the non-responsive group (P = 0.024). The reduction in stool DAF concentrations after the second apheresis session was significantly greater in the responsive group (median 90%, range 22-90%) than in the non-responsive group (median -13%, range -307-94%) (P = 0.008). Hematological tests, that is, white blood cell (WBC) count and C-reactive protein, declined significantly during the apheresis therapy, but not in relation to therapeutic response. CONCLUSION: Stool DAF concentration is a useful marker in the clinical response of UC patients to treatment with leukocyte apheresis.     

Leukocytapheresis Therapy for Severe Ulcerative Colitis

Abstract: Severe attacks of ulcerative colitis are medical emergencies, and surgical treatment is indicated when glucocorticoid therapy is not effective. We have carried out an open clinical study of patients with severe attacks of ulcerative colitis to find out whether leukocytapheresis (LCAP) therapy can improve their outcomes. Nine patients were enrolled in this study. Seven of the nine patients had failed to respond to an intensive intravenous regimen before LCAP. LCAP was performed once a week for 4–5 weeks as intensive therapy using a leukocyte apheresis filter. Six of the 9 patients had an overall improvement after intensive therapy. Three patients reached the remission stage. The percentages of HLA-DR+, HLA-DR+ CD3+, HLA-DR+ CD4+, and HLA-DR+ CD8+ cells in the peripheral blood were higher in the responders than in the nonresponders, but there were no significant differences. In conclusion, LCAP therapy is useful for patients with severe attacks of ulcerative colitis, even those patients who failed to respond to glucocorticoid therapy.     

选择性白细胞分离法联合药物治疗对溃疡性结肠炎诱导缓解和维持治疗的荟萃分析

不同研究显示选择性白细胞分离法对溃疡性结肠炎（UC）的疗效差异很大.目的：系统性评价选择性白细胞分离法联合药物治疗对UC诱导缓解和维持治疗的作用.方法：检索PubMed、EMBASE、Cochrane Central Register of Controlled Trials、Science Citation Index和中文科技期刊数据库.纳入所有比较选择性白细胞分离法联合药物治疗与传统药物治疗对UC诱导缓解和维持治疗疗效的随机对照试验（RCTs）.采用RevMan 5.0软件分析两者的诱导缓解率、维持缓解率和不良反应发生率.结果：共9项RCTs、685例患者符合人选标准,7项评估诱导缓解率,2项评估维持缓解率.选择性白细胞分离法联合药物治疗组的诱导缓解率显著高于传统药物治疗组（40.7%对29.1%,OR值为2.19,P〈0.0001）,维持缓解率亦显著高于传统药物治疗组（70.4%对25.0%,OR值为8.14,P=0.002）.选择性白细胞分离法联合药物治疗组的轻中度不良反应发生率明显低于传统药物治疗组（44.7%对65.3%,OR值为0.16,P=0.003）.结论：与传统药物治疗相比,选择性白细胞分离法联合药物治疗能明显提高UC患者的诱导缓解率和维持缓解率,并能降低不良反应发生率.     

Granulocyte,monocyte/macrophage apheresis for inflammatory bowel disease: The first 100 patients treated in Scandinavia

Objective. Selective leukocyte apheresis is a new type of non-pharmacological treatment for patients with active ulcerative colitis and Crohn's disease. Preliminary data have indicated that this type of therapy is safe and efficacious, and large sham-controlled studies are currently in progress. In Scandinavia, a substantial number of patients with chronic inflammatory bowel disease have already received leukocyte apheresis on a compassionate use basis and the aim of this study was to report the clinical outcome and adverse events in the first patients treated. Material and methods. Clinical details of the first consecutive 100 patients with inflammatory bowel disease treated with granulocyte, monocyte/macrophage (Adacolumn) apheresis in Scandinavia were prospectively registered. Median length of follow-up was 17 months, (range 5–30). Results. The study population comprised 52 patients with ulcerative colitis, 44 patients with Crohn's disease and 4 patients with indeterminate colitis. In 97 patients the indication for Adacolumn treatment was steroid-refractory or steroid-dependent disease. Clinical remission was attained in 48% of the patients with ulcerative colitis, and an additional 27% had a clinical response to the apheresis treatment. The corresponding figures for patients with Crohn's disease were 41% and 23%, respectively. Complete steroid withdrawal was achieved in 27 out of the 50 patients taking corticosteroids at baseline. Adverse events were reported in 15 patients and headache was most frequently reported (n=7). Conclusions. Granulocyte, monocyte/macrophage apheresis treatment seems to be a valuable adjuvant therapy in selected patients with refractory inflammatory bowel disease. The risk for toxicity or severe adverse events appears to be low.     

A prospective,open-label trial assessing dexamethasone pulse therapy in moderate to severe ulcerative colitis

BACKGROUND: Severe ulcerative colitis is conventionally treated with parenteral corticosteroids followed by oral corticosteroids. Regular use of corticosteroids is associated with side effects. Corticosteroid pulse therapy, i.e., use of supraphysiologic dose followed by complete withdrawal, which is likely to have fewer side effects, was tried in the current study. STUDY: Dexamethasone pulse therapy, i.e., 100-mg/d infusion in 5% dextrose, was used for 3 consecutive days in 14 patients with severe ulcerative colitis. Ulcerative colitis disease activity was assessed on days 7, 15, 30, and 60. The primary end point was defined as the number of patients who achieved clinical remission and an activity index less than 150 at day 15. The second end point was the number of patients who remained in remission and had an activity index less than 150 at 30 and 60 days. None of the patients enrolled got subsequent oral corticosteroids after their 3 days of megadose corticosteroid infusion. RESULTS: Clinical remission was achieved in 93% patients (13 of 14 patients) by day 15. Two of these 13 patients suffered relapse during follow-up, and hence, the clinical remission was sustained in 79% patients at 30 and 60 days. CONCLUSIONS: Dexamethasone pulse therapy is highly effective in inducing remission in patients with ulcerative colitis, but randomized controlled trials are needed to compare dexamethasone pulse therapy with standard oral continuous corticosteroid regimens.     

Stool decay-accelerating factor as a marker for monitoring the disease activity during leukocyte apheresis therapy in patients with refractory ulcerative colitis

Background and Aims:  We have shown previously that concentrations of stool decay-accelerating factor (DAF; CD55), a complement regulatory protein, in patients with ulcerative colitis (UC) are increased in relation to the severity of the colonic mucosal inflammation. In the present study, we evaluated the usefulness of stool DAF as a marker for monitoring disease activity in patients with steroid-resistant active UC being treated with leukocyte apheresis performed with a centrifugal cell separator.
Methods:  Twenty-one patients with active and steroid-resistant UC were treated with leukocyte apheresis once a week for 4 weeks, and stool DAF concentrations were determined weekly by immunoassay.
Results:  After treatment, 11 (52%) of the 21 UC patients went into remission. Stool DAF concentrations decreased promptly and steadily in the responsive group. The difference reached statistical significance as soon as after the second apheresis session ( P <  0.003), compared with values before the therapy and corresponding values in the non-responsive group ( P =  0.024). The reduction in stool DAF concentrations after the second apheresis session was significantly greater in the responsive group (median 90%, range 22–90%) than in the non-responsive group (median −13%, range −307–94%) ( P =  0.008). Hematological tests, that is, white blood cell (WBC) count and C-reactive protein, declined significantly during the apheresis therapy, but not in relation to therapeutic response.
Conclusion:  Stool DAF concentration is a useful marker in the clinical response of UC patients to treatment with leukocyte apheresis.     

Successful treatment of ulcerative colitis with leukocytapheresis using non-woven polyester filter

Ulcerative colitis is a chronic inflammatory disease of the rectum and colon. Although the pathogenesis of ulcerative colitis is not fully elucidated, cell-mediated immunity plays an important role in disease pathogenesis. Leukocytapheresis is a newly emerging therapy to eliminate activated leukocyte from systemic circulation. We have studied the effects of leukocytapheresis on patients with ulcerative colitis who had failed to respond to conventional therapy. A total of 51 patients with ulcerative colitis were treated with apheresis using a non-woven polyester fiber filter (Finecell, Asahi Medical Co.,Tokyo, Japan) originally developed as a microcoagulation elimination filter for massive transfusion. Of the 51 patients, 33 (64.7%) achieved clinical remission manifested by clinical activity and colonoscopic findings without any adverse effects. This result suggested that leukocytapheresis using Finecell might serve as an alternative therapy for ulcerative colitis as other leukocytapheresis using centrifugation or column.     

Clinical Effectiveness of Selective Granulocyte,Monocyte Adsorptive Apheresis with the Adacolumn<Superscript>®</Superscript> Device in Ulcerative Colitis

The purpose of this meta-analysis was to determine whether selective adsorptive granulocyte and monocyte apheresis (GMA apheresis) using the Adacolumn^® device can effectively reduce clinical symptoms and endoscopic signs of inflammation in patients with ulcerative colitis (UC). A comprehensive search for randomized controlled trials (RCTs) published up to May 2008 was performed. Each study’s quality was evaluated, and the data reported in the results were abstracted. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using the fixed-effects model. Heterogeneity was quantified statistically and explained by the variation in the trial design. Seven RCTs including 594 patients were found, and six RCTs on active UC contributed to the main analyses. In half of the trials, GMA apheresis was compared to steroids. Only one trial was fully blinded. A response or remission after 6 weeks was achieved more often in patients treated with GMA apheresis (RR 1.42; CI 1.15–1.75). Also, after 12 weeks, GMA apheresis produced significantly higher remission rates (RR 1.41; CI 1.08–1.83), but long-term data were sparse. In the trials that compared GMA apheresis and steroids (n = 220 patients), side effects were much less frequent in the GMA apheresis groups (RR 0.19; CI 0.11–0.34). Homogeneous evidence from seven RCTs shows that GMA apheresis induces a clinical remission in a higher proportion of UC patients as compared to conventional medical therapy.     

Clinical evaluation of granulocyte/monocyte apheresis therapy for active ulcerative colitis

BACKGROUND: Recent evidence suggests that peripheral blood granulocytes and monocytes/macrophages have a major role in the exacerbation of ulcerative colitis. AIMS: Our objective was to investigate if selective granulocyte and monocyte adsorptive apheresis with Adacolumn promotes remission of active ulcerative colitis and spares corticosteroid. SUBJECTS: Sixty patients with active ulcerative colitis were studied, of whom 39 had relapsing-remitting ulcerative colitis, 15 had chronic continuous and 6 had their first episode of ulcerative colitis. METHODS: Granulocytapheresis was done with an Adacolumn filled with cellulose acetate beads as apheresis carriers that adsorb FcgammaR and complement receptors bearing leucocytes (granulocytes, monocytes and a small fraction of lymphocytes). Patients received up to 10 Adacolumn sessions over 12 weeks, one session was 60-90 min at 30 mL/min. No additional medication was given. Efficacy was assessed with Seo's activity index (AI) [Seo M, Okada M, Yao T. An index of disease activity in patients with ulcerative colitis. Am J Gastroenterol 1992;87:971-6]. The mean AL was 197.5 and range 154.4-277.7. AI < 150 was considered significant improvement and AI < 100 was considered clinical remission. RESULTS: Of 60 patients, 50 (83.3 %) improved, 14 achieved remission, granulocytapheresis was most effective in steroid-dependent patients. At entry, the mean dose of prednisolone was 15.3 mg/day per patient and was reduced to 3.6 mg/day after 10 sessions. Granulocytapheresis was well tolerated and no serious side-effects were observed. CONCLUSION: Based on our experience in patients with diverse ulcerative colitis disease expression and long-term exposure to conventional drug therapy, we believe that granulocytapheresis is an effective adjunct to conventional medication for promoting remission and sparing steroids in patients with active ulcerative colitis.     

Factors affecting clinical and endoscopic efficacies of selective leucocytapheresis for ulcerative colitis

BackgroundGranulocyte, monocyte/macrophage adsorptive apheresis is a novel treatment for active ulcerative colitis. However, as yet no study has reported on a subset of patients who might respond well to granulocyte, monocyte/macrophage adsorptive apheresis therapy.AimTo identify factors affecting clinical and endoscopic efficacies of granulocyte, monocyte/macrophage in patients with ulcerative colitis.MethodsFifty consecutive patients with active ulcerative colitis initially received five granulocyte, monocyte/macrophage adsorptive apheresis sessions with the Adacolumn over five consecutive weeks. Patients who improved without achieving remission received five additional granulocyte, monocyte/macrophage adsorptive apheresis sessions.ResultsOne week after the last granulocyte, monocyte/macrophage adsorptive apheresis session, 26 (52%) and 17 patients (34%) achieved clinical and endoscopic remission, respectively. In the multivariate analysis, the dose of prednisolone administered at entry and the cumulative dose of prednisolone administered before entry were independent significant factors for both clinical and endoscopic remission, negatively impacted the efficacy of granulocyte, monocyte/macrophage adsorptive apheresis. Age, gender, duration of ulcerative colitis, number of prior relapses, duration of current exacerbation, extent and severity of ulcerative colitis, extra-intestinal manifestations, entry haematology values and C-reactive protein did not affect the outcome.ConclusionsBased on the outcomes of this study, it appears that steroid-naïve patients and patients on low dose steroid and short duration of exposure respond to granulocyte, monocyte/macrophage adsorptive apheresis. Further studies in larger cohorts of patients should strengthen our findings.     

Treatment of Ulcerative Colitis with Oral 5-Aminosalicylic Acid Including Patients with Adverse Reactions to Sulfasalazine

Sulfasalazine is an effective drug for maintaining remission in ulcerative colitis, but its use may be precluded by side effects. Eighty-five patients with active ulcerative colitis participated in a prospective open trial to examine the tolerance of the active constituent 5-aminosalicylic acid (5-ASA), coated with an acrylic resin, and its efficacy in inducing and subsequently maintaining a remission. Fifty-one of the patients had previously developed adverse reactions to sulfasalazine. After 4 wk of treatment with 3.2 g 5-ASA daily, a remission was achieved in 23 of 36 patients (64%) with mild or moderate disease, but in none of 43 patients with severe disease. Six patients were withdrawn because of side effects to 5-ASA, but only two of these patients had similar reactions on sulfasalazine. Supplementary corticosteroids for 6 wk or less induced a remission in 27 of the patients who had failed on 5-ASA alone. Fifty patients were therefore eligible for the maintenance phase of the trial, and 39 (78%) had a sustained clinical and endoscopic remission upon 1-yr follow-up. 5-ASA appears to be an effective drug for inducing remission in mild or moderate ulcerative colitis and for the maintenance of remission. It thus represents a valuable addition to the management of patients intolerant to sulfasalazine.     

Ratio of Platelet Reduction is an Early Predictive Factor for the Effectiveness of Leukocytapheresis for Ulcerative Colitis Patients

Abstract: Leukocytapheresis is effective for ulcerative colitis (UC), and both peripheral leukocyte and platelet counts decrease during apheresis. While leukocyte counts increase and overshoot after finishing the apheresis procedure, platelet reduction continues even after apheresis. The aim of this study is to elucidate the impact of the overshoot of leukocyte and continuous platelet reduction on the efficacy of leukocytapheresis for UC. Leukocyte and platelet counts before and one hour after each leukocytapheresis session of 43 UC cases were examined (31 entered remission, but 12 did not). The correlation between the efficacy of leukocytapheresis and leukocyte overshoot or platelet reduction was examined. The average increase ratio of leukocytes in the initial five sessions of the responders was not significantly different from that of the non-responders (95% vs. 92%, P = 0.28). In contrast, the average decrease ratio of platelets in the initial five sessions of the responders was significantly higher than that of the non-responders (34% vs. 27%, P = 0.0041). Moreover, the platelet reduction at the third and fourth apheresis sessions in the responders was remarkably greater than that in the non-responders (33% vs. 20%, P = 0.0018). The efficiency of platelet reduction could be a predictive factor for the efficacy of leukocytapheresis.     

Medical approaches and future options in chronic active ulcerative colitis

Background Immunosuppressive therapy employing purine analogues is the therapeutic mainstay in patients with chronic active ulcerative colitis. However, despite therapeutic optimization according to thiopurine-methyltransferase activity or red blood cell 6-thioguanine levels, a substantial proportion of patients does not tolerate azathioprine or 6-mercaptopurine or relapses during this treatment. In the latter multiple therapeutic regimens comprising 6-thioguanine, cyclosporin or tacrolimus, methotrexate, cyclophosphamide, infliximab, interferons, heparin, leukocyte apheresis, and various other regimens might be considered aiming at long-term remission. Many of these treatment forms have only been evaluated in small mostly uncontrolled trials.Objective In this review existing treatment modalities and future options for patients with chronic active ulcerative colitis will be discussed focusing on immunomodulating approaches.     

Open label trial of granulocyte apheresis suggests therapeutic efficacy in chronically active steroid refractory ulcerative colitis

AIM: To study the efficacy, safety, and feasibility of a granulocyte adsorptive type apheresis system for the treatment of patients with chronically active ulcerative colitis despite standard therapy. METHODS: An open label multicenter study was carried out in 39 patients with active ulcerative colitis (CAI 6-8) despite continuous use of steroids (a minimum total dose of 400 mg prednisone within the last 4 wk). Patients received a total of five aphereses using a granulocyte adsorptive technique (Adacolumn, Otsuka Pharmaceutical Europe, UK). Assessments at wk 6 and during follow-up until 4 mo comprised clinical (CAI) and endoscopic (EI) activity index, histology, quality of life (IBDQ), and laboratory tests. RESULTS: Thirty-five out of thirty-nine patients were qualified for intent-to-treat analysis. After the apheresis treatment at wk 6, 13/35 (37.1%) patients achieved clinical remission and 10/35 (28.6%) patients had endoscopic remission (CAK4, EI<4). Quality of life (IBDQ) increased significantly (24 points, P<0.01) at wk 6. Apheresis could be performed in all but one patient. Aphereses were well tolerated, only one patient experienced anemia. CONCLUSION: In patients with steroid refractory ulcerative colitis, five aphereses with a granulocyte/ monocyte depleting filter show potential short-term efficacy. Tolerability and technical feasibility of the procedure are excellent.     

Mucosal features and granulocyte–monocyte-apheresis in steroid-dependent/refractory ulcerative colitis

BACKGROUND: Mucosa-infiltrated granulocyte neutrophils are an early characteristic of inflammation and the main histological feature of active ulcerative colitis. Mucosal healing has recently been indicated as an important tool in the evaluation of response to treatment. While several studies have stressed the efficacy of granulocyte-monocyte-apheresis in inducing clinical remission in active ulcerative colitis, few data are available on mucosal features. AIM: Aim of this study was to assess the effects of granulocyte-monocyte-apheresis on clinical and mucosal features in patients with ulcerative colitis, dependent upon or refractory to steroids. MATERIAL AND METHODS: From April 2004 to April 2005, 12 patients (5 females, 7 males, mean age 49 years, range 33-71 years), with mild-moderate ulcerative colitis (six left colitis, six pancolitis) dependent/refractory upon steroids were enrolled. Each patient was treated for a 5-week period with five cycles of granulocyte-monocyte-apheresis. Patients were evaluated at baseline and 1 week after the last apheresis by means of Global Physician Assessment, quality of life features, laboratory tests (erythrocyte sedimentation rate, CRP, full blood count, faecal calprotectine), endoscopy and histology. RESULTS: At week 6 of follow-up, complete mucosal healing was observed in 3 out of 12 patients, partial mucosal healing in 8 patients and no change in 1 patient. Clinical response was complete in 8 out of 12 patients. CONCLUSIONS: These data suggest that granulocyte-monocyte-apheresis induces an improvement both in clinical and mucosal lesions in steroid-dependent/refractory ulcerative colitis. Of note, the reduction in granulocyte infiltration and the improvement in mucosal lesions are accompanied by a reduction in faecal calprotectine.     

Compared azathioprine efficacy in ulcerative colitis and in Crohn's disease

AIM: To compare the 6-month efficacy and tolerance of azathioprine in 68 patients with steroid-resistant or steroid-dependent chronic ulcerative colitis (n=30) or Crohn's disease (n=38).METHODS: Clinical remission was defined as a Crohn's Disease Activity Index<150 for Crohn's disease and number of non-bloody stools<=3/day for ulcerative colitis, associated with prednisone requirement<=10 mg/day.RESULTS: Seventy-three per cent of patients with ulcerative colitis had distal or left-sided colitis and 84% of patients with Crohn's disease had pancolitis. Azathioprine was discontinued early for side-effect in 8 (26.7%) patients with ulcerative colitis and in 8 (21.1%) patients with Crohn's disease (NS). In patients treated at least 6 months by azathioprine, clinical remission rates were 77.3% and 70% for chronic ulcerative colitis and Crohn's disease (NS). Complete corticosteroids weaning was obtained significantly more often in ulcerative colitis patients than in Crohn's disease patients (59.1% vs 30%; P<0.05).CONCLUSION: Azathioprine seems to be at least as effective and equally tolerated in steroid-resistant or steroid-dependent chronic ulcerative colitis or Crohn's disease patients.