Efficacy of cytapheresis in patients with ulcerative colitis showing insufficient or lost response to biologic therapy.

For the optimal management of refractory ulcerative colitis (UC), secondary loss of response (LOR) and primary non-response to biologics is a critical issue. This article aimed to summarize the current literature on the use of cytapheresis (CAP) in patients with UC showing a poor response or LOR to biologics and discuss its advantages and limitations. Further, we summarized the efficacy of CAP in patients with UC showing insufficient response to thiopurines or immunomodulators (IM). Eight studies evaluated the efficacy of CAP in patients with UC with inadequate responses to thiopurines or IM. There were no significant differences in the rate of remission and steroid-free remission between patients exposed or not exposed to thiopurines or IM. Three studies evaluated the efficacy of CAP in patients with UC showing an insufficient response to biologic therapies. Mean remission rates of biologics exposed or unexposed patients were 29.4 % and 44.2%, respectively. Fourteen studies evaluated the efficacy of CAP in combination with biologics in patients with inflammatory bowel disease showing a poor response or LOR to biologics. The rates of remission/response and steroid-free remission in patients with UC ranged 32%-69% (mean: 48.0%, median: 42.9%) and 9%-75% (mean: 40.7%, median: 38%), respectively. CAP had the same effectiveness for remission induction with or without prior failure on thiopurines or IM but showed little benefit in patients with UC refractory to biologics. Although heterogeneity existed in the efficacy of the combination therapy with CAP and biologics, these combination therapies induced clinical remission/response and steroid-free remission in more than 40% of patients with UC refractory to biologics on average. Given the excellent safety profile of CAP, this combination therapy can be an alternative therapeutic strategy for UC refractory to biologics. Extensive prospective studies are needed to understand the efficacy of combination therapy with CAP and biologics.

Cytapheresis re-induces high-rate steroid-free remission in patients with steroid-dependent and steroid-refractory ulcerative colitis.

BACKGROUND: It is a crucial issue for patients with refractory ulcerative colitis (UC), including steroid-dependent and steroid-refractory patients, to achieve and maintain steroid-free remission. However, clinical studies focused on the achievement of steroid-free remission in refractory UC patients are insufficient. Cytapheresis (CAP) is a non-pharmacological extracorporeal therapy that is effective for active UC with fewer adverse effects. This study comprised UC patients treated with CAP and suggested the efficacy of CAP for refractory UC patients. AIM: To clarify the efficacy of CAP in achieving steroid-free remission in refractory UC patients. METHODS: We retrospectively reviewed the collected data from 55 patients with refractory UC treated with CAP. We analyzed the following points: (1) Efficacy of the first course of CAP; (2) Efficacy of the second, third, and fourth courses of CAP in patients who experienced relapses during the observation period; (3) Efficacy of CAP in colonic mucosa; and (4) Long-term efficacy of CAP. Clinical efficacy was evaluated using Lichtiger's clinical activity index or Sutherland index (disease activity index). Mucosal healing was evaluated using Mayo endoscopic subscore. The primary and secondary endpoints were the rate of achievement of steroid-free remission and the rate of sustained steroid-free remission, respectively. Statistical analysis was performed using the paired t-test and chi-squared test. RESULTS: The rates of clinical remission, steroid-free remission, and poor effectiveness after CAP were 69.1%, 45.5%, and 30.9%, respectively. There were no significant differences in rate of steroid-free remission between patients with steroid-dependent and steroid-refractory UC. The mean disease activity index and Lichtiger's clinical activity index scores were significantly decreased after CAP (P < 0.0001). The rates of steroid-free remission after the second, third, and fourth courses of CAP in patients who achieved steroid-free remission after the first course of CAP were 83.3%, 83.3%, and 60%, respectively. Mucosal healing was observed in all patients who achieved steroid-free remission after the first course of CAP. The rates of sustained steroid-free remission were 68.0%, 60.0%, and 56.0% at 12, 24, and 36 mo after the CAP. Nine patients (36%) had maintained steroid-free remission throughout the observation period. CONCLUSION: Our results suggest that CAP effectively induces and maintains steroid-free remission in refractory UC and re-induces steroid-free remission in patients achieving steroid-free remission after the first course of CAP.

Long-interval Cytapheresis as a Novel Therapeutic Strategy Leading to Dosage Reduction and Discontinuation of Steroids in Steroid-dependent Ulcerative Colitis.

Objective This study was performed to confirm the efficacy of long-interval cytapheresis on steroid-dependent ulcerative colitis (UC). Methods To discontinue steroids in patients with steroid-dependent UC, we previously designed a novel regimen of cytapheresis (CAP), which we termed "long-interval cytapheresis (LI-CAP)", in which CAP was performed as one session every two or three weeks and continued during the whole period of tapering steroid dosage. In this study, we performed LI-CAP therapy 20 times (11 male and 9 female; mean age 41.8 years) between April 2010 and April 2015 for 14 patients with steroid-dependent UC. We evaluated the effectiveness of LI-CAP by examining the improvement in Lichtiger's clinical activity index (CAI), the rate of clinical remission, and the rate of steroid discontinuation. We further examined the rate of sustained steroid-free clinical remission at 6 and 12 months after LI-CAP in patients who successfully discontinued steroid-use after LI-CAP. The primary endpoint was the rate of discontinuation of steroids after LI-CAP. Results The mean CAI score before LI-CAP (7.550) significantly decreased to 1.65 after LI-CAP (p<0.0001). The rate of clinical remission after LI-CAP was 80%. The rate of steroid discontinuation after LI-CAP was 60.0%. The mean dose of daily prednisolone was significantly decreased after LI-CAP (2.30 mg) compared with that before therapy (17.30 mg) (p=0.0003). The rate of sustained steroid-free clinical remission after LI-CAP was 66.7% at 6 months and 66.7% at 12 months. Conclusion We confirmed that LI-CAP has therapeutic effects on reducing the dosage and discontinuing steroids in patients with steroid-dependent UC.

One year of infliximab therapy successfully improved a case of refractory pouchitis without the use of antibiotics.

A 29-year-old woman with ulcerative colitis underwent total colectomy with ileal-pouch-anal canal anastomosis in 1999. After the surgery, she developed refractory pouchitis. We administered metronidazole, mesalamine and ciprofloxacin; however, her clinical symptoms improved only very slightly. We initiated treatment with infliximab in June 2011 and discontinued the antibiotics. Thereafter, the patient's abdominal symptoms quickly improved. We discontinued the infliximab therapy in June 2012, after which time, the patient's abdominal symptoms remained in remission for 40 weeks, without the use of antibiotics. This report suggests that infliximab is useful not only for improving the clinical symptoms of refractory pouchitis, but also discontinuing antibiotic therapy in such patients.

Ulcerative colitis accompanied by idiopathic thrombocytopenic purpura and Helicobacter pylori infection.

The coexistence of idiopathic thrombocytopenic purpura (ITP) and active ulcerative colitis (UC) has been reported. We herein report a rare case of UC accompanied by ITP and Helicobacter pylori (H. pylori) infection. A female UC patient was diagnosed with ITP. At that time, the UC was almost in remission and we suspected that the ITP was caused by some factor other than UC. Accordingly, we found H. pylori infection and administered H. pylori eradication therapy. Consequently, the patient's serum platelet count recovered dramatically. Our report demonstrates the importance of conducting examinations for H. pylori infection in ITP patients, even those with UC.

Molecular cloning reveals nearly half of patients with Crohn's disease have an antibody to peroxiredoxin 6-like protein.

BACKGROUND AND AIM: Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) of unknown etiology. We aimed to identify the etiological agent of CD using a molecular cloning strategy that was particularly focused on identifying agents causing immune abnormalities and infectious agents. METHODS: We constructed a cDNA library derived from the inflamed intestinal tissue of a CD patient, and screened 1.5 million clones in this library with the serum from another typical CD patient. The expressed cDNA clones that positively reacted with the serum were then expressed as fusion proteins with glutathione S-transferase, and western blotting was performed using the sera of 22 CD, 13 ulcerative colitis (UC), and 16 non-IBD patients. RESULTS: We identified nine positive clones that did not contain any viral or bacterial genomic DNA. Of these, we selected one clone (clone 50) with which the typical CD patient's serum most strongly reacted. Clone 50 is highly homologous to the antioxidant protein peroxiredoxin 6. In western blotting, the sera of 47.6% CD patients (small intestine type 80%, large and small intestine type 43%, large intestine type 0%) showed strong reactivity to clone 50, none of the UC patients were reactive to clone 50, and 18.8% of non-IBD patients were very weakly reactive to it. We also found that the expression of peroxiredoxin 6 was significantly increased in inflamed intestinal epithelia of CD. CONCLUSION: The present study first showed that some CD patients have an antibody against peroxiredoxin 6-like protein, which may be involved in the pathogenesis of CD.

Typical gastroduodenal endoscopic findings in a Crohn's disease patient in remission stage.

A 39-year-old patient with Crohn's disease (CD) was referred to our hospital for maintenance treatment of CD. He was diagnosed as having CD of the small and large intestines at 32 years old. He underwent partial resection of the ileum at 35 years old because of ileal perforation. He had received enteral nutritional supplement (1200 kcal/d) and metronidazole preparation (500 mg/d), and was in remission Crohn's disease activity index 73. We performed a routine gastroduodenal endoscopic examination, which revealed the representative endoscopic findings of gastroduodenal lesions in CD, namely, bamboo-joint-like appearance of the gastric body and cardia and a notched sign in the duodenum. These findings were clearly observed by using indigo carmine dye spraying. In our patient, typical gastroduodenal findings were observed even in the remission stage, suggesting that these findings would contribute to the early diagnosis of CD not only in the active stage but also during remission.

Acute respiratory distress syndrome associated with severe ulcerative colitis.

Various extraintestinal manifestations including pulmonary abnormalities have been reported in patients with ulcerative colitis. Acute respiratory distress syndrome (ARDS) is a serious and fatal pulmonary manifestation. We have experienced a 67-year-old male patient with ARDS associated with a severe type of ulcerative colitis (UC). Severe dyspnea symptoms occurred during the treatment of UC in a previous hospital and the patient was transferred to our hospital on June 27, 2007. Both blood and sputa cultures for bacteria and fungi were negative. Cytomegalovirus antigenemia was also not detected. From the clinical and radiological [Chest X-ray, computed tomography (CT)] findings, the patient was diagnosed with ARDS on the basis of the definition of ARDS developed by the European-American Consensus Conference on ARDS. Both colonic inflammations and ARDS symptoms of the patient were resistant to any medical treatment including corticosteroids and antibiotics. However, ARDS symptoms were dramatically improved after surgical colectomy. We believe that severe colonic inflammation from UC was closely associated with the onset of ARDS of the patient. Our case report suggests that a severe type of ulcerative colitis might be taken into consideration as one of the predisposing factors of ARDS.