Journal of Clinical Apheresis 00:00–00 (2014)
Case Report Ulcerative Colitis and Granulocyte-Monocyte-Apheresis: Safety and Efficacy of Maintenance Therapy During Pregnancy Valeria D’Ovidio,1* Donatella Meo,2 Maria Gozer,2 Marco E. Bazuro,3 and Piero Vernia1 1
GI Unit, Department of Internal Medicine and Medical Specialties, Policlinico Umberto I, University of Rome “ La Sapienza” , Sapienza, University of Rome, Italy 2 Transfusional Unit, Policlinico Umberto I, University of Rome “ La Sapienza” , Rome, Italy 3 GI Unit, S Eugenio Hospital, Rome, Italy Inflammatory bowel disease characteristically affects young adults in their reproductive ages. Thus the medication used for the treatment of active disease should not compromise fertility and, also, should not have teratogenic effect on baby. A lot of data are available about effects of steroids, antibiotics, and mesalazine but no data are available about safety and efficacy of granulocyte-monocyte-apheresis (GMA) during pregnancy. In this case report, the 37 year-old pregnant woman with chronically active and steroid dependent ulcerative colitis (UC), at risk of abortion, refused more aggressive pharmacological therapeutic options and gave the informed consent to GMA. 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. J. Clin. Apheresis 00:000–000, 2014. C 2014 Wiley Periodicals, Inc. V
Key words: pregnancy; ulcerative colitis; granulocyte-monocyte-apheresis
INTRODUCTION
It is generally accepted that pregnancy has no direct effect on the course/ progression of ulcerative colitis (UC) [1], some evidence suggests that pregnancy may have a favorable effect on UC, with a median period of 10 months of remission. Conversely, it is widely accepted that disease activity at the moment of conception may unfavorably influence the course of pregnancy and that the risk of flare up after birth is related to the activity of the disease at term [1,2]. The safety of all therapeutic options used for the treatment of active UC during pregnancy is reasonably well documented for steroids, antibiotics, mesalazine azathioprine, and biologics [2]. Nonetheless, pregnant women, often prefer avoiding pharmacological therapies as much as possible. Granulocyte-monocyte-apheresis (GMA), a nonpharmacological treatment of UC characterized by minimal adverse effects [3], could represent an attractive approach, but information concerning GMA during pregnancy is minimal and based on few case-reports [4,5]. CASE REPORT
A 36 years old woman first presented with bloody diarrhea in 2009 and moderate-severe pancolitis was C 2014 Wiley Periodicals, Inc. V
diagnosed on the base of endoscopical and histological findings. A two weeks course of oral and topical mesalazine therapy (2,4 g and 1 g/day, respectively) led to partial clinical response and oral steroids were instituted. In the following 6 months, the disease showed a chronic relapsing, steroid-dependent pattern and the patient underwent cycles of oral steroids followed by symptom relapse during tapering. The patient refused more aggressive therapeutic options as she was planning for pregnancy, which occurred in November 2009. She decided to discontinue all drugs with the exception of oral mesalazine. During the 10th week of pregnancy the patient presented with severe abdominal pain, bowel urgency, and bloody diarrohea (4–6/day with liquid stool). Mesalazine and steroid enemas proved ineffective. One week later, she had spontaneous abortion and was admitted to our GI Unit. A further full-dose of oral steroid treatment (prednisone *Correspondence to: Valeria D’Ovidio; GI Unit, Department of Internal Medicine and Medical Specialties, Sapienza, University of Rome, Rome, Italy. E-mail: [email protected]. Received 9 October 2013; Accepted 11 July 2014 Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jca.21349
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D’Ovidio et al.
50 mg/day) once more led to clinical improvement, but not remission. Despite our indication, she refused to undergo more aggressive pharmacological treatment regimens, consisting of immunosuppressive drugs (azathioprine) or biologics fearing for possible negative effects on the pregnancy, she was still planning in the next future. Thus, a nonpharmacological therapeutic optionGMA- was selected as the treatment of choice. GMA was performed with Adacolumn (Adacolumn@,JimroOtsuka Production, Milan). The apheresis column is filled with specially designed cellulose acetate beads which selectively adsorb most activated granulocytes, monocytes/macrophages, and significant fraction of platelets but not of red blood cells and lymphocytes [3]. The duration of one GMA procedure is 60 min at a flow rate of 30 ml/min. The patient received a cycle of five standard GMA treatments (one treatment/week), while tapering off steroid, with partial response (improvement of abdominal pain and diarrhea, from 6–8/day to 1–2/day but blood in the stools was still present). A further five weekly GMA treatments were performed and bowel urgency, abdominal pain and bloody diarrhea completely disappeared. Oral steroids were discontinued. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were in the reference range (
Case Report Ulcerative Colitis and Granulocyte-Monocyte-Apheresis: Safety and Efficacy of Maintenance Therapy During Pregnancy Valeria D’Ovidio,1* Donatella Meo,2 Maria Gozer,2 Marco E. Bazuro,3 and Piero Vernia1 1
GI Unit, Department of Internal Medicine and Medical Specialties, Policlinico Umberto I, University of Rome “ La Sapienza” , Sapienza, University of Rome, Italy 2 Transfusional Unit, Policlinico Umberto I, University of Rome “ La Sapienza” , Rome, Italy 3 GI Unit, S Eugenio Hospital, Rome, Italy Inflammatory bowel disease characteristically affects young adults in their reproductive ages. Thus the medication used for the treatment of active disease should not compromise fertility and, also, should not have teratogenic effect on baby. A lot of data are available about effects of steroids, antibiotics, and mesalazine but no data are available about safety and efficacy of granulocyte-monocyte-apheresis (GMA) during pregnancy. In this case report, the 37 year-old pregnant woman with chronically active and steroid dependent ulcerative colitis (UC), at risk of abortion, refused more aggressive pharmacological therapeutic options and gave the informed consent to GMA. 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. J. Clin. Apheresis 00:000–000, 2014. C 2014 Wiley Periodicals, Inc. V
Key words: pregnancy; ulcerative colitis; granulocyte-monocyte-apheresis
INTRODUCTION
It is generally accepted that pregnancy has no direct effect on the course/ progression of ulcerative colitis (UC) [1], some evidence suggests that pregnancy may have a favorable effect on UC, with a median period of 10 months of remission. Conversely, it is widely accepted that disease activity at the moment of conception may unfavorably influence the course of pregnancy and that the risk of flare up after birth is related to the activity of the disease at term [1,2]. The safety of all therapeutic options used for the treatment of active UC during pregnancy is reasonably well documented for steroids, antibiotics, mesalazine azathioprine, and biologics [2]. Nonetheless, pregnant women, often prefer avoiding pharmacological therapies as much as possible. Granulocyte-monocyte-apheresis (GMA), a nonpharmacological treatment of UC characterized by minimal adverse effects [3], could represent an attractive approach, but information concerning GMA during pregnancy is minimal and based on few case-reports [4,5]. CASE REPORT
A 36 years old woman first presented with bloody diarrhea in 2009 and moderate-severe pancolitis was C 2014 Wiley Periodicals, Inc. V
diagnosed on the base of endoscopical and histological findings. A two weeks course of oral and topical mesalazine therapy (2,4 g and 1 g/day, respectively) led to partial clinical response and oral steroids were instituted. In the following 6 months, the disease showed a chronic relapsing, steroid-dependent pattern and the patient underwent cycles of oral steroids followed by symptom relapse during tapering. The patient refused more aggressive therapeutic options as she was planning for pregnancy, which occurred in November 2009. She decided to discontinue all drugs with the exception of oral mesalazine. During the 10th week of pregnancy the patient presented with severe abdominal pain, bowel urgency, and bloody diarrohea (4–6/day with liquid stool). Mesalazine and steroid enemas proved ineffective. One week later, she had spontaneous abortion and was admitted to our GI Unit. A further full-dose of oral steroid treatment (prednisone *Correspondence to: Valeria D’Ovidio; GI Unit, Department of Internal Medicine and Medical Specialties, Sapienza, University of Rome, Rome, Italy. E-mail: [email protected]. Received 9 October 2013; Accepted 11 July 2014 Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jca.21349
2
D’Ovidio et al.
50 mg/day) once more led to clinical improvement, but not remission. Despite our indication, she refused to undergo more aggressive pharmacological treatment regimens, consisting of immunosuppressive drugs (azathioprine) or biologics fearing for possible negative effects on the pregnancy, she was still planning in the next future. Thus, a nonpharmacological therapeutic optionGMA- was selected as the treatment of choice. GMA was performed with Adacolumn (Adacolumn@,JimroOtsuka Production, Milan). The apheresis column is filled with specially designed cellulose acetate beads which selectively adsorb most activated granulocytes, monocytes/macrophages, and significant fraction of platelets but not of red blood cells and lymphocytes [3]. The duration of one GMA procedure is 60 min at a flow rate of 30 ml/min. The patient received a cycle of five standard GMA treatments (one treatment/week), while tapering off steroid, with partial response (improvement of abdominal pain and diarrhea, from 6–8/day to 1–2/day but blood in the stools was still present). A further five weekly GMA treatments were performed and bowel urgency, abdominal pain and bloody diarrhea completely disappeared. Oral steroids were discontinued. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were in the reference range (
