Scientific corner

Granulocytapheresis in ulcerative colitis (in Spanish)

Gerardo Prieto Bozano an. pedatr. contin.2012;10(5):286-9

  • Existen 2 dispositivos de granulocitoféresis: Cellsorba® (fibras de poliéster no tejidas), que fija granulocitos y linfocitos, y Adacolumn® (acetato de celulosa) que fija selectivamente granulocitos y monocitos.
  • Además de retirar leucocitos activados, la aféresis produce incremento del número de granulocitos CD10-negativos (inmaduros), disminución de citocinas proinflamatorias (factor de necrosis tumoral alfa [TNF-α], interleucina [IL-6],IL-8 e IL-1β) e incremento de citocinas inhibitorias (IL-1, IL-10)
  • La granulocitoféresis es un método razonablemente eficaz y seguro para obtener la remisión en niños con colitis ulcerosa corticodependiente o resistente, sobre todo en pacientes en el primer episodio, en enfermedad de corta evolución y en aquellos que no han recibido esteroides
  • El procedimiento requiere 2 accesos venosos de buen flujo. La pauta más habitual de tratamiento consiste en 1–2 sesiones semanales de 60min a un flujo de 30ml/min, hasta un total de 5–10 sesiones

https://www.elsevier.es/es-revista-anales-pediatria-continuada-51-articulo-granulocitoferesis-colitis-ulcerosa-S1696281812701002

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EO5-01 A case of pustular psoriasis deteriorated during the second pregnancy was successfully treated with intensive GMA and certolizumab pegol

Asumi Fujii, Yuki Hattori, Miho Kawamura, Yoko Mizutani, En Shu, Mariko Seishima

poster at ISFA 2019 pag 141-142

A 31-year-old woman with the IL36RN gene mutation developed psoriasis at 3 years old. As she had pustular psoriasis at 16 years old, she was treated with cyclosporine (Cys), resulting in remission at 20 years old. Afterwards, she had been maintained by topical treatment for long years.During the first pregnancy at the age of 29, she developed pustular psoriasis at 29 weeks
of gestation. She received one course of granulocyte / monocyte adsorption apheresis (GMA) with Cys and prednisolone (PSL), and gave birth to a girl at 33 weeks of gestation. The baby was a low birth weight child, but is healthy and has no problems in growth and development until now. However, the patient did not sufficiently improve symptoms after delivery. We thus started the treatment with infliximab (IFX) BS at 2 months postpartum. During the second pregnancy at the age of 30, we continued the IFX-BS administration. She had erythema and pustules rapidly enlarged from 23 weeks of pregnancy. Oral administration of PSL and GMA were started. However, we switched the therapy to intensive GMA (twice in a week), because the effect was insufficient. Initially, administration of IFX-BS was scheduled to end at 30 weeks of gestation, but due to unstable symptoms, we considered it was necessary to use another biologics even after 30 weeks of gestation. We switched to non-placental certolizumab pegol (CTZ) from 26 weeks of gestation and continued the administration until delivery, and she gave birth to a girl at 35 weeks of gestation. Although the baby was a low birth weight child, there was no physical abnormality and the baby was discharged after gaining weight. After delivery, administration of CTZ was discontinued and the PSL dose was gradually reduced. However,reintroduction of biologics is under consideration, because erythema and pustules still remain.

http://www.atalacia.com/isfa/data/abstract.pdf

Scientific corner

SY4-03 The efficacy of combination therapy of intensive GMA with biologics or a JAK inhibitor for refractory inflammatory bowel disease

Satoshi Tanida

poster at ISFA 2019 pag 56

Background and Aim: A monotherapy with intensive GMA, biologics or a JAK inhibitor are limited in patients with intractable Crohn’s disease (CD) or ulcerative colitis (UC). We retrospectively evaluated the 10- and 52-week efficacy and safety of combination therapy of intensive GMA with biologics or a JAK inhibitor for intractable UC or CD.
Method: A combination of intensive GMA (2 sessions a week, total 10 times) with tofacitinib (TOF) for active UC was performed and that of intensive GMA with ustekinumab (UST) for active CD was done. Results: Of 6 consecutive UC patients receiving a combination therapy of TOF (20 mg daily for 8 weeks as induction therapy and subsequently 10 mg daily) plus intensive GMA for moderately-to-severely active UC and loss of response to corticosteroids, azathioprine, and/ or biologic therapies, 67% (4 cases) displayed clinical remission according to Mayo score and 100% displayed mucosal healing at 10 weeks. A temporary increase in CPK were seen. Of 5 consecutive CD patients receiving a combination therapy of ustekinumab (every 8 weeks) plus intensive GMA for moderately-to-severely active CD and loss of response to corticosteroids, azathioprine, and/or biologic therapies, 75% displayed cumulative steroid-free clinical remission at 10 weeks and did such remission over 52 weeks under subsequent maintenance monotherapy of UST. The mean CDAI at baseline were 257. Its values at 10 and 52 weeks after the combination therapy with UST plus intensive GMA were 48 and 68, respectively. One case showed mucosal healing at 52 weeks according to SES-CD. No adverse events were observed. Conclusions: Combination therapy of intensive GMA with biologics or a JAK inhibitor appeared to be effective and safe for refractory UC or CD.

http://www.atalacia.com/isfa/data/abstract.pdf

Scientific corner

SY3-04 Real-world experiences of cytapheresis therapy for ulcerative colitis; results from large-scale multicenter observational studies

Taku Kobayashi

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.

http://www.atalacia.com/isfa/data/abstract.pdf

Scientific corner

Efficacy and usefulness of new single-needle Intensive granulocyte and monocyte adsorptive apheresis in active ulcerative colitis patients without corticosteroids and biologics

Keiji Shimazu 1Takumi Fukuchi 2Insung Kim 3Yuki Noguchi 3Megumi Iwata 1Shintaro Koyama 2 4Satoshi Ubukata 2Atsuo Tanaka 1 , Ther Apher Dial 2016 Aug;20(4):383-9.

Intensive granulocyte and monocyte adsorptive apheresis (GMA) twice weekly is effective and safe for patients with active ulcerative colitis (UC), but the requirement for maintaining two blood access routes is problematic. Here we compared the efficacy and safety of one-route blood access intensive GMA using a single-needle (SN) and conventional two-route blood access intensive GMA using a double-needle (DN) in patients with active UC not undergoing corticosteroid therapy. Among 80 active UC patients, 38 patients received SN intensive GMA and 42 patients received DN intensive GMA. The clinical remission ratio and mucosal healing ratio at 6 weeks, and the cumulative non-relapse ratio at 52 weeks did not differ significantly between groups. In addition, no serious or mild adverse effects were observed in SN intensive GMA. SN intensive GMA may be an adequate and novel therapeutic option for active UC as an alternative therapy before using corticosteroids.

https://pubmed.ncbi.nlm.nih.gov/27523079/

Scientific corner

Current status and future perspectives of leukocytapheresis for inflammatory bowel disease.

Ken Fukunaga 1Takayuki Matsumoto, J Gastroenterol Hepatol. 2012 Jun;27(6):997-1003.

Ulcerative colitis (UC) and Crohn’s disease (CD) comprise the idiopathic inflammatory bowel diseases (IBD) of the gut. The etiology of IBD is poorly understood, but an autoimmune disturbance has been suggested to play an important role in this incurable disease. Extracorporeal leukocytapheresis (CAP) is an additional adjunct for IBD patients refractory to other conventional therapies, including steroids. The primary aim of CAP should be to suppress such unwanted immunological response by removing circulating inflammatory cells from the blood stream. The first decade has been passed since CAP was approved by Japanese social health insurance policy. It is therefore now an appropriate opportunity to upgrade and summarize our current understandings and/or future perspectives of this unique non-pharmacological and non-surgical strategy for IBD patients. According to several clinical and basic research reports, an early introduction of CAP should produce higher efficacy as compared with CAP applied sometime after a clinical relapse. Likewise, CAP therapy adjusted to patients’ body-weight as well as two treatment sessions per week (intensive regimen) should benefit the efficacy rate. The etiology of IBD is not fully elucidated yet. As a result, the major therapeutic strategies in the Western world have been immunosuppressive therapy, including biologics. CAP is an unusual treatment modality for IBD because it seems to have both effectiveness and safety, which should generally be balanced in this type of illness. We now have to develop future strategies with and without combining biologics to improve the quality of life of IBD patients.

https://pubmed.ncbi.nlm.nih.gov/22414250/

Scientific corner

The efficacy of intensive granulocyte and monocyte adsorption apheresis in a patient with Crohn’s disease complicated by extensive subcutaneous aseptic neutrophilic abscesses.

Shingo Kato 1Eriko HosomiFumi AmanoTaisuke KobayashiKazuhito KaniRyuichi YamamotoTomonari OgawaAkihiko MatsudaYoshiki SatoSeiichi IzakiTetsuya MitaraiKoji Yakabi, J Crohns Colitis. 2012 Aug;6(7):787-91.

Background and aims: Subcutaneous aseptic abscess is one phenotype of neutrophilic dermatitis. We were interested to see if a case of steroid refractory Crohn’s disease (CD) complicated by subcutaneous aseptic neutrophilic abscesses responds to intensive granulocyte/monocyte adsorptive apheresis (GMA). Methods: The patient was a 21-year-old male with worsening severe CD while on oral prednisolone (30 mg/day). His symptoms included fever, bloody diarrhoea and multiple painful subcutaneous nodules throughout his body. Skin biopsy showed chronic panniculitis with neutrophilic infiltrates. Further, colonoscopy showed oedematous sigmoid colon, while colonic biopsy showed non-caseous granuloma. Because biologics were feared to increase the risk of bacteraemia as the result of germ culture on his pus was not known at the time, we decided to treat this case with GMA. Five GMA sessions with the Adacolumn over 5 consecutive days (daily GMA) were initiated. Results: On admission, his CD activity index (CDAI) was 355, C-reactive protein (CRP) 11.2 mg/dL. After 5 GMA sessions, CDAI decreased to 170, and CRP fell to 5.0 mg/dL, with no fever. GMA was restarted at 2 sessions/week (total 10 sessions). The patient’s CDAI fell to <150, and the skin lesions re-epithelialized. Conclusions: In this CD case complicated by subcutaneous aseptic neutrophilic abscesses, GMA appeared to be effective. Our impression is that when biopsy reveals neutrophil infiltrate is a major feature of the lesions, GMA should be considered. As GMA appears to have no safety concerns, a frequent GMA protocol, like daily followed by 2 to 3 times/week should be preferred over the routine weekly GMA.

https://pubmed.ncbi.nlm.nih.gov/22386738/

Scientific corner

Current and emerging drugs for the treatment of inflammatory bowel disease

John K TriantafillidisEmmanuel Merikas, and Filippos Georgopoulos Drug Des Devel Ther. 2011; 5: 185–210. doi: 10.2147/DDDT.S11290

During the last decade a large number of biological agents against tumor necrosis factor-α (TNF-α), as well as many biochemical substances and molecules specifically for the medical treatment of patients with inflammatory bowel disease (IBD), have been developed. This enormous progress was a consequence of the significant advances in biotechnology along with the increased knowledge of the underlying pathophysiological mechanisms involved in the pathogenesis of IBD. However, conventional therapies remain the cornerstone of treatment for most patients. During recent years conventional and biologic IBD therapies have been optimized. Newer mesalazine formulations with a reduced pill size and only one dose per day demonstrate similar efficacy to older formulations. New corticosteroids retain the efficacy of older corticosteroids while exhibiting a higher safety profile. The role of antibiotics and probiotics has been further clarified. Significant progress in understanding thiopurine metabolism has improved the effective dose along with adjunctive therapies. Quite a large number of substances and therapies, including biologic agents other than TNF-α inhibitors, unfractionated or low-molecular-weight heparin, omega-3 polyunsaturated fatty acids, microbes and microbial products, leukocytapheresis, and other substances under investigation, could offer important benefits to our patients. In this paper we review the established and emerging therapeutic strategies in patients with Crohn’s disease and ulcerative colitis.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084301/

Scientific corner

An open-label prospective randomized multicenter study shows very rapid remission of ulcerative colitis by intensive granulocyte and monocyte adsorptive apheresis as compared with routine weekly treatment

Atsushi Sakuraba 1Satoshi MotoyaKenji WatanabeMasakazu NishishitaKazunari KankeToshiyuki MatsuiYasuo SuzukiTadayuki OshimaReiko KunisakiTakayuki MatsumotoHiroyuki HanaiKen FukunagaNaoki YoshimuraToshimi ChibaShinsuke FunakoshiNobuo AoyamaAkira AndohHiroshi NakaseYohei MizutaRyoichi SuzukiTaiji AkamatsuMasahiro IizukaToshifumi AshidaToshifumi Hibi

Intensive GMA in patients with active UC seems to be more efficacious than weekly treatment, and significantly reduced the patients’ morbidity time without increasing the incidence of side effects.

)https://pubmed.ncbi.nlm.nih.gov/19724269/

Scientific corner

Leukocytapheresis in a girl with severe ulcerative colitis refractory to corticosteroids, infliximab, and cyclosporine A

Katalin DittrichMarkus RichterWolfgang RascherHenrik Köhler Inflamm Bowel Dis 2008 Oct;14(10):1466-7. doi: 10.1002/ibd.20464.

Although medical therapy remains the first-line treatment for UC, colectomy may be required for patients with severe medically refractory disease. Leukocytapheresis (LCAP) has been reported as a new line of therapy in
patients with UC. Only 2 pediatric case series, not including patients on immunosuppressive therapy or biologicals, treated with granulocytapheresis have been reported. The patient reported by us is the youngest to the best of our knowledge in which this LCAP technique was used . She had severe colitis refractory to corticosteroids, infliximab and yclosporine A. We were able to avoid colectomy and the procedure was well tolerated.

https://pubmed.ncbi.nlm.nih.gov/18421764/

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