Scientific corner

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.

Scientific corner

Efficacy and Safety of Adsorptive Granulocyte and Monocyte Apheresis in Elderly and Pregnant Patients With Ulcerative Colitis

Kazuki Yanagisawa 1Minoru Murakami 2Yuya Kondo 1Shun Oguma 1Shun Kobayashi 1Hiroshi Miyasaka 1Tomoaki Shinohara 3Akihisa Tomori 3Yui Nakano 2Shunichi Furuhata 2Masaya Ikezoe 2 , Ther Apher Dial 2019 Jun;23(3):217-223.

In patients with active ulcerative colitis (UC), adsorptive granulocyte/monocyte apheresis (GMA) is expected to promote remission. We conducted a retrospective cohort study to evaluate the efficacy and safety of GMA in patients with active UC. Twenty‐one UC patients including five pregnant or lactating mothers and four elderly patients (aged >60 years) received up to 10 GMA sessions. UC severity was evaluated at baseline and after GMA therapy according to Lichtiger’s Clinical Activity Index (CAI). We defined clinical remission as CAI ≤4. Overall, the median CAI score after GMA therapy had decreased from 9 to 4 (P < 0.001). The clinical remission rate was 62%, but in the elderly and pregnant or lactating mothers, the remission rates were 100% and 60%, respectively. No severe adverse effects were seen in this study. Our results may support GMA as an effective and safe treatment for active UC patients, including elderly patients and pregnant cases.

Scientific corner

Successful remission of ulcerative colitis flare-up during pregnancy with adsorptive granulomonocytapheresis plus tacrolimus

Tomoyoshi Shibuya 1Keiichi Haga 1Masato Kamei 1Koki Okahara 1Shoko Ito 1Masahito Takahashi 1Osamu Nomura 1Takashi Murakami 1Masae Makino 1Tomohiro Kodani 1Dai Ishikawa 1Naoto Sakamoto 1Taro Osada 1Tatsuo Ogihara 1Sumio Watanabe 1Akihito Nagahara 1 , Intest Res. 2018 Jul;16(3):484-488.

Our experience indicates that GMA, as a non-drug therapeutic intervention with a favorable safety profile, plus tacrolimus might be a relevant treatment option for patients with active IBD during pregnancy. A future study of a large cohort of pregnant patients should strengthen our findings.

Scientific corner

Changes in Treatment with Granulocyte and Monocyte Adsorptive Apheresis from the Past to Future in Patients with Inflammatory Bowel Disease

Shingo KatoAkira IshibashiKaori SugiuraKazuhito KaniTomonari OgawaHajime HasegawaKoji Yakabi, Contrib Nephrol 2018;196:200-208.

GMA decreases inflammatory cytokines and upregulates regulatory T cells. Intensive GMA is significantly more effective than weekly GMA in patients with IBD. The frequency of GMA sessions per week positively correlates with treatment effects. GMA can be safely used in pregnant women and children because of its low adverse event rates. Maintenance therapy and rescue therapy for loss of response of anti-tumor necrosis factor (TNF)-α antibodies are effective. Optimal patients who responded to combination therapy with infliximab and GMA showed aggravation characteristics against infliximab treatment at week 4. Key Message: Prospective randomized blinded studies using a sham column should be performed for the loss of response against anti-TNF-α antibodies.

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Therapeutic Apheresis in Pregnancy: Three Differential Indications With Positive Maternal and Fetal Outcome

Giuseppina Perrone 1Roberto Brunelli 1Eleonora Marcoccia 1Ilaria Zannini 1Miriam Candelieri 1Maria Gozzer 2Claudia Stefanutti 3

When approaching TA in pregnancy, clinicians have to consider the severity of disease, the strength of the indications, and the gestational age. Each case must be evaluated individually on the basis of existing evidence since, despite the increasing use, specific guidelines for apheresis in pregnancy are still lacking.

Scientific corner

Ulcerative colitis and granulocyte-monocyte-apheresis: Safety and efficacy of maintenance therapy during pregnancy.

Valeria D’Ovidio 1Donatella MeoMaria GozerMarco E BazuroPiero Vernia, J Clin Apher. 2015 Feb;30(1):55-7.

To minimize symptoms and the risk of severe clinical relapse, a maintenance GMA treatment was performed throughout pregnancy. The course of pregnancy was uneventful with no side effects; the mother and the baby were all healthy and well at the delivery.

Scientific corner

Flare up of ulcerative colitis during pregnancy treated by adsorptive granulocyte and monocyte apheresis: therapeutic outcomes in three pregnant patients.

Hiroki Takahashi 1Kaori SugawaraMikako SugimuraMasahiro IwabuchiYutaka ManoKatsuaki UkaiKeiichi Tadokoro, Arch Gynecol Obstet. 2013 Aug;288(2):341-7.

In these three cases with active ulcerative colitis during pregnancy, granulocytapheresis as a non-pharmacologic treatment was effective and safe. In case 3 that did not respond well to the initial granulocytapheresis sessions, a moderate dose of prednisolone enhanced the efficacy of granulocytapheresis and tapering of prednisolone shortly after administration was not associated with relapse.

Scientific corner

Granulocyte and monocyte adsorption apheresis for Behçet’s disease in a pregnant woman.

Yuko Higashi 1Mitsuyoshi ShimokawaKazuhiro KawaiTakuro Kanekura, J Dermatol. 2013 Dec;40(12):1042-4.

We present a 39-year-old pregnant woman with Behçet’s disease who was treated successfully with granulocyte and monocyte adsorption apheresis (GMA). There were no complications or adverse effects during her pregnancy and delivery. The neonate manifested no abnormalities.

Scientific corner

Therapeutic efficacy of leukocytapheresis in a pregnant woman with severe active ulcerative colitis

H Okada 1C MakidonoR TakenakaS HiraokaA FujiwaraJ KatoY KawaharaH KawamotoM MizunoY Shiratori

Digestion 2006;74(1):15-8. doi: 10.1159/000095478. Epub 2006 Aug 29.

Leukocytapheresis has recently been used to induce remission in patients with ulcerative colitis (UC) who fail to respond to corticosteroids. We could not find a report in the literature on leukocytapheresis for UC with gestational exacerbation. We have recently encountered this unique condition and report the details here. A 30-year-old Japanese woman with left-sided severe UC was corticosteroid-dependent and had recurrence of the active disease during tapering of corticosteroid. She declined any dose increase and the use of any immunosuppressive agent because she was in the 13th week of pregnancy. Then, concomitant leukocytapheresis was performed without increasing the corticosteroid dose. Recovery was rapid and dramatic. Mucous and bloody stool decreased after the first session, and she had remission 2 weeks later. She underwent a total of four sessions without complications. After 6 weeks, she was discharged from our hospital and underwent maintenance treatment as an outpatient with mesalazine and corticosteroid tapering. Subsequently, she gave birth to a healthy baby girl by an uncomplicated vaginal delivery while keeping the remitted stage of UC.

Scientific corner

The present status and the recent development of the treatment for inflammatory bowel diseases: desirable effect of extracorporeal immunomodulation

Masakazu Takazoe 1Torao TanakaKenji KondoToshiki IchimoriToshio Shinoda Ther Apher 2002 Aug;6(4):305-11. doi: 10.1046/j.1526-0968.2002.00445.x.

The immunological and genetic pathogeneses of inflammatory bowel disease (IBD) have been well elucidated in the recent years. The pharmacologic treatment of IBDs accordingly becomes to focus upon the individual pathologic step (targeting therapy), whereas the therapeutic action is not yet a pinpoint one. It has been known recently that new drugs such as biological immunomodulating agents and anti-inflammatory cytokines have better short-term effects in some respects than the conventional drugs, and they might alter the treatment strategy of IBDs in the near future. The limitation of pharmacologic treatments mainly results from adverse effects of the drugs, i.e. infection susceptibility, oncogenesis, teratogenesis and so forth. The extracorporeal therapy such as leukocytapheresis and photopheresis is reportedly effective for IBDs probably through immunomodulation such as decrease in circulating activated T-lymphocytes and activated granulocytes that play a central role in the pathogenesis of IBD. It can be said that these extracorporeal treatment methods have advantage of rapid action and lack of serious adverse effects to drug therapy.

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