Takumi Fukuchi , Kousaku Kawashima , Hideaki Koga , Ran Utsunomiya, Kohei Sugiyama , Keiji Shimazu , Takaaki Eguchi , Shunji Ishihara J Clin Biochem Nutr. 2022 Mar;70(2):197-204. doi: 10.3164/jcbn.21-112. Epub 2021 Dec 25.
Induction of mucosal healing by intensive granulocyte/monocyte adsorptive apheresis (GMA) without use of corticosteroids in patients with ulcerative colitis: long-term remission maintenance after induction by GMA and efficacy of GMA re-treatment upon relapse
This study examined the long-term maintenance rate after inducing remission by intensive granulocyte/monocyte adsorptive apheresis (GMA) without use of corticosteroids (CS) and GMA re-treatment efficacy in the same patients upon relapse with ulcerative colitis. Patients who achieved clinical remission and mucosal healing (MH) by first-time intensive GMA (first GMA) without CS were enrolled. The cumulative non-relapse survival rate up to week 156 was calculated. Patients with relapse during the maintenance period underwent second-time intensive GMA (second GMA) without CS. Clinical remission and MH rates following second GMA were compared to those following first GMA in the same patients. Of the 84 patients enrolled, 78 were followed until week 156 and 34 demonstrated relapse. The cumulative non-relapse survival rate by week 156 was 56.4%. Clinical remission and MH rates after second GMA did not differ from those after first GMA in the same patients (week 6: clinical remission, 100% vs 88.4%, p = 0.134; MH, 100% vs 84.8%, p = 0.074). In conclusion, MH induction by intensive GMA without use of CS in ulcerative colitis patients contributes to subsequent long-term clinical remission maintenance. GMA re-treatment efficacy was comparable to that of first GMA in the same patients who had relapse.
Factors associated with the outcomes in ulcerative colitis patients undergoing granulocyte and monocyte adsorptive apheresis as remission induction therapy: A multicenter cohort study
GMA was an effective treatment for corticosteroid-naïve patients and the efficacy sustained longer in those not receiving immunomodulators during GMA. GMA fulfills the notion that apheresis is to induce disease remission by removing from the body factors known to perpetuate disease. In therapeutic settings, these findings should help better decision making and avoid futile use of medical resources.
SY3-04 Real-world experiences of cytapheresis therapy for ulcerative colitis; results from large-scale multicenter observational studies
poster at ISFA 2019 pag 53
There are two types of extracorporeal therapy for treating active ulcerative colitis (UC), granulocyte and monocyte adsorption (GMA) and leukocytapheresis (LCAP). Although Sawada et al reported the efficacy of LCAP by the randomized controlled trial (Sawada K et al. Am J Gastroenterol 2005), the larger sham-controlled multicenter trial of GMA failed to prove its efficacy (Sands BE et al. Gastroenterol 2008). Therefore, evidence to show their efficacy relies more on the real-world data, including the post-marketing surveillance (PMS). The large-scale PMS for LCAP was named as REFINE study, involving 847 patients from 116 medical facilities in Japan (Yokoyama Y, Kobayashi T et al. J Crohn Colitis 2014). Adverse events were seen only in 10.3% and the vast majority were mild. The overall clinical remission rate was 68.9%, and the mucosal healing rate was 62.5%. These results were very consistent with the results from PMS of 697 patients treated with GMA, which also demonstrated its real-world effectiveness and safety (Hibi T et al. Dig Liver Dis 2008). In addition, a retrospective observational study aimed to evaluate the clinical outcome at 1 year and identify risk factors for relapse after LCAP was recently conducted among patients who had achieved remission in the PMS (Kobayashi T et al. J Gastroenterol 2018). The 1-year cumulative relapse free rate was 63.6%. Following LCAP, a high clinical activity and a high leukocyte count were associated with a greater risk of relapse. Intensive LCAP was associated with favorable long-term outcomes in corticosteroidrefractory patients. The response rate of re-treatment upon relapse was as high as 85%. These results on the risks of relapse as well as effectiveness of re-treatment may help to overcome the weakness of cytapheresis therapy in maintaining remission. Results from the clinical trial evaluating the clinical efficacy of intermittent maintenance cytapheresis therapy are also warranted.
Combination Therapy With Adalimumab Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis in Patients With Refractory Ulcerative Colitis.
It was concluded that combination therapy with ADA plus intensive GMA is useful for induction of clinical remission in refractory UC patients, and is well tolerated.
First Case Report of De Novo Ulcerative Colitis Developing After Orthotopic Liver Transplantation Successfully Treated by Granulocyte and Monocyte Apheresis.
Background: Immunosuppressants such as tacrolimus and cyclosporine are prescribed long-term after orthotopic liver transplantation (OLT) to prevent allograft rejection. Although these immunosuppressants are known to effectively control ulcerative colitis (UC), some post-OLT patients develop exacerbation of preexisting UC or de novo UC. Although aminosalicylates and corticosteroid courses are usually effective to treat such UC, several patients have developed uncontrollable disease and required colectomies. Case report: We have reported a patient who developed de novo UC after OLT to treat liver cirrhosis and hepatocellular carcinoma associated with hepatitis B virus (HBV) infection. Existence of the HBV infection made us avoid to increase the corticosteroid dose or to use other immunosuppressants such as azathioprine or infliximab. Conclusions: In this patient, granulocyte and monocyte apheresis was highly effective in terms of inducing remission of de novo UC. No adverse event was noted.
Treating Inflammatory Bowel Disease by Adsorptive Leucocytapheresis: A Desire to Treat without Drugs
Ulcerative colitis and Crohn’s disease are the major phenotypes of the idiopathic inflammatory bowel disease (IBD), which afflicts millions of individuals throughout the world with debilitating symptoms, impairing function and quality of life. Current medications are aimed at reducing the symptoms or suppressing exacerbations. However, patients require life-long medications, and this can lead to drug dependency, loss of response together with adverse side effects. Indeed, drug side effects become additional morbidity factor in many patients on long-term medications. Nonetheless, the efficacy of anti-tumour necrosis factors (TNF)-α biologics has validated the role of inflammatory cytokines notably TNF-α in the exacerbation of IBD. However, inflammatory cytokines are released by patients’ own cellular elements including myeloid lineage leucocytes, which in patients with IBD are elevated with activation behaviour and prolonged survival. Accordingly, these leucocytes appear logical targets of therapy and can be depleted by adsorptive granulocyte/monocyte apheresis (GMA) with an Adacolumn. Based on this background, recently GMA has been applied to treat patients with IBD in Japan and in the European Union countries. Efficacy rates have been impressive as well as disappointing. In fact the clinical response to GMA seems to define the patients’ disease course, response to medications, duration of active disease, and severity at entry. The best responders have been first episode cases (up to 100%) followed by steroid naïve and patients with a short duration of active disease prior to GMA. Patients with deep ulcers together with extensive loss of the mucosal tissue and cases with a long duration of IBD refractory to existing medications are not likely to benefit from GMA. It is clinically interesting that patients who respond to GMA have a good long-term disease course by avoiding drugs including corticosteroids in the early stage of their IBD. Additionally, GMA is very much favoured by patients for its good safety profile. GMA in 21st century reminds us of phlebotomy as a major medical practice at the time of Hippocrates. However, in patients with IBD, there is a scope for removing from the body the sources of pro-inflammatory cytokines and achieve disease remission. The bottom line is that by introducing GMA at an early stage following the onset of IBD or before patients develop extensive mucosal damage and become refractory to medications, many patients should respond to GMA and avoid pharmacologics. This should fulfill the desire to treat without drugs.
OC.11.4 LONG TERM EFFICACY OF GRANULOCYTE-MONOCYTE-APHERESIS IN ULCERATIVE COLITIS. THE ITALIAN REGISTRY OF THERAPEUTIC APHERESIS
Background and aim: Granulocyte-monocyte-apheresis (GMA) is effective in the treatment of ulcerative colitis (UC). However, all published studies evaluated a low number of patients, with an overall limited follow-up. This observational study investigates the long-term efficacy of GMA in a large number of patients included in the Italian Registry of Therapeutic Apheresis. Material and methods: Data of patients with mild/moderate UC treated with a standard protocol of GMA (5 sessions in 5 weeks) were evaluated. All patients had failed to respond to mesalamine or sulphasalazine, and were under steroid treatment. Clinical evaluations were performed at 3, 12 and 24 months since the end of GMA session. The following parameters were assessed: incidence of clinical remission (CAI [Colits Active Index] <4); CAI; erythrocyte sedimentation rate (ESR); c-reactive protein (CRP); white cells blood count (WBC). Endoscopical evaluations were performed at a 3- month follow-up: the incidence of endoscopical remission (EAI [endoscopical activity index] 0/1) was assessed. Results: Data for 347 patients (214 males, age 46.3 years; CAI 7.47) were available; 288 patients were either steroid-resistant or steroid-dependent. The proportion of patients with remission of disease was 66% at 3 months, 77% at 12 months and 78% at 24 months. At 24 months, all other efficacy parameters had improved from baseline: CAI (7.47 vs 3.47), ESR (35.87 vs 24.1 mm/h), CRP (4.31 vs 2.75 mg/dl) and WBC (8.61 vs 7.19) (p<0.001 for all comparisons). Endoscopic data were available for 107 patients. The incidence of mucosal healing was 47% and all patients with mucosal healing presented a clinical remission over the entire follow-up period. No major adverse events were reported during GMA sessions. Conclusions: Data collected on a large sample of steroid-resistant or steroidrefractory patients included in the Italian Registry of Therapeutic Apheresis show that GMA is a safe and effective procedure over a long-term follow-up. Mucosal healing appears strongly associated with clinical remission.
Successful treatment of three cases of generalized pustular psoriasis with granulocyte and monocyte adsorption apheresis.
Akiko Suzuki 1, Kunitaka Haruna, Yuki Mizuno, Yoshiyuki Kuwae, Yuka Ono, Kazuko Okumura, Osamu Negi, Yasuko Kon, Kaori Takeuchi, Kenji Takamori, Shigaku Ikeda, Yasushi Suga,Ther Apher Dial. 2012 Oct;16(5):445-8.
Generalized pustular psoriasis (GPP) is a rare form of psoriasis characterized by the presence of variable numbers of sterile pustules appearing in erythematous and scaly lesions, which are associated with moderate to severe constitutional symptoms. It can be life-threatening especially in the elderly; therefore, medical care must be performed in rapid succession of treatment especially in refractory cases. We have performed granulocyte and monocyte adsorption apheresis (GCAP) on three GPP cases associated with several systemic and laboratory findings. As a result, the edema, erythema and numbers of sterile pustules on the skin lesions were reduced dramatically in all three patients after the first sessions of GCAP therapy. The sizes of the psoriatic lesions were reduced in all three patients following a weekly GCAP treatment for 5 consecutive weeks. Psoriasis area and severity index on discharge had improved in all three patients. No serious adverse effects were observed for up to at least 8 months after treatment. We therefore considered GCAP as one effective alternative to currently existing therapies, especially for recalcitrant cases of GPP.
Long-term clinical impact of early introduction of granulocyte and monocyte adsorptive apheresis in new onset, moderately active, extensive ulcerative colitis
in patients with the first UC episode, GMA therapy at an early stage significantly reduces steroid administration and steroid-dependency in the long-term clinical course.
Predictive factors of clinical response in steroid-refractory ulcerative colitis treated with granulocyte-monocyte apheresis
GMA may be a valid therapeutic option for steroid-dependent ulcerative colitis patients with mild-moderate disease and its clinical efficacy seems to persist for 12 months.
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