Cytapheresis for pyoderma gangrenosum associated with inflammatory bowel disease:A review of current status

Pyoderma gangrenosum(PG)is a neutrophilic dermatosis clinically characterized by the presence of painful skin ulcerations with erythematous.As it is frequently associated with inflammatory bowel diseases,including ulcerative colitis,gastroenterologists should be familiar with the disease including therapeutic options.Therefore,we have conducted a review focusing on the cytapheresis for PG in cases of inflammatory bowel diseases.A literature search was conducted to extract studies published in the last 20 years,with information on demographics,clinical symptoms,treatment,and the clinical course from a total of 22 cases reported and our recent case.In most patients,cytapheresis was associated with improvement or resolution of PG after failure of conventional therapeutic options such as corticosteroids,antibiotics,immunosuppressive agents and immunoglobulin.Based on the information summarized,cytapheresis is helpful in the majority of patients with PG refractory to medical treatment associated with inflammatory bowel diseases and could be further studied in a multicenter,randomized trial.

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 steroidfree 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 steroiddependent 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.

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.

Efficacy of low-dose thiopurine therapy for the induction of remission in steroid-dependent ulcerative colitis: Comparison with cytapheresis

Background: The role of azathioprine (AZA) and 6-mercaptopurine (6-MP) in the induction of remission in patients with ulcerative colitis (UC) remains unclear. Aims: To compare the efficacy and safety of low-dose thiopurine (AZA/6-MP) and cytapheresis (CAP) for the induction of remission in patients with steroid- dependent UC. Patients and Methods: We reviewed the clinical course of 65 patients with steroid-dependent UC with moderate activity, who were treated with either low-dose AZA/6-MP (T-group, n = 38) or with CAP (C-group, n = 27). The efficacy and safety for the first 10 weeks after the start of the therapies were compared between the two groups. The cumulative probability curves of treatment failure were estimated by the Kaplan-Meier method. Clinical remission was defined as an ulcerative colitis activity index value of less than 150 without any other treatments. Results: Neither clinical characteristics, concomitant therapies, nor laboratory data (except for serum albumin levels) were different between the two groups. The remission rate at 10 weeks was not different between the two groups (55.3% in the T-group and 70.4% in the C-group, p = 0.22 in the intention-to-treat analysis). The frequencies of adverse events did not differ be- tween the two groups (p = 0.12). The cumulative pro- bability of treatment failure at 10 weeks was 44.7% for the T-group and 29.6% for the C-group (p = 0.23). Conclusions: Low-dose thiopurine therapy is an alter- native candidate for the induction of remission in pa- tients with steroid-dependent, moderate UC.