scholarly journals Pregnancy Outcomes in Patients Treated with Bosutinib

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1729-1729 ◽  
Author(s):  
Jorge E. Cortes ◽  
Carlo Gambacorti-Passerini ◽  
Michael W. Deininger ◽  
Elisabetta Abruzzese ◽  
Liza DeAnnuntis ◽  
...  

Abstract Introduction: Studies in animals have shown reproductive toxicity with bosutinib exposure, with teratogenic events in maternal exposure, but little is known about its effect during conception or pregnancy in humans. Methods: Here we describe pregnancy outcomes in bosutinib-treated patients from the Pfizer safety database, which includes cases from both clinical trials and spontaneous reports. Pregnancy cases reported up to February 28, 2018 were identified by searching the database using the Standardized MedDRA Query Pregnancy and Neonatal Topics in patients receiving bosutinib. Results: The database search identified 33 relevant pregnancy reports, including 17 cases of exposure via the father and 16 cases of maternal exposure. Among the 16 cases of maternal exposure, 5 vaginal deliveries of healthy babies, 2 patient-requested induced abortions, 1 spontaneous abortion, and 1 partial molar pregnancy requiring a dilation and curettage were reported. In 1 case, the patient was reported to have delivered a baby, but the details of the status of the baby was not provided. Outcomes in 6 cases are unknown. Of the healthy deliveries, 4 pregnancies went to full term (≥39 weeks) and 1 was of unknown duration; bosutinib was discontinued during the first trimester of pregnancy in all 5 cases. The reported spontaneous abortion was due to a suspected ectopic pregnancy in a 34-year-old patient who began taking bosutinib 500 mg once daily while pregnant and was thought to be unrelated to bosutinib exposure. Of the 17 cases of exposure via father, 8 vaginal deliveries of healthy babies, 1 Caesarean section delivery of a healthy baby, 4 induced abortions, and 1 spontaneous abortion were reported. The remaining 3 cases had unknown outcomes. Of the 4 induced abortions, 1 was elective due to an unintended pregnancy, and 2 were due to unknown reasons. In the last case, it was reported that the fetus was not growing properly and that the pregnancy would subsequently be terminated; no confirmation of congenital abnormality or further information is available. The reported spontaneous abortion was thought to be unrelated to bosutinib; fetal biopsy revealed basal deciduitis with necrosis loci and bleeding. Conclusions: Overall, a review of the available experience with bosutinib in pregnancy did not identify any safety signals. However, adverse effects of bosutinib exposure at conception or during pregnancy in humans cannot be ruled out, particularly if therapy is not interrupted upon recognition of pregnancy. Bosutinib is not recommended for use during pregnancy, and patients on bosutinib treatment should use effective contraception. Disclosures Cortes: Astellas Pharma: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Arog: Research Funding. Gambacorti-Passerini:BMS: Consultancy; Pfizer: Consultancy, Honoraria, Research Funding. Deininger:Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Blueprint: Consultancy. Abruzzese:Novartis: Consultancy; Ariad: Consultancy; BMS: Consultancy; Pfizer: Consultancy. DeAnnuntis:Pfizer Inc: Employment, Equity Ownership. Brümmendorf:Janssen: Consultancy; Merck: Consultancy; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Takeda: Consultancy.

2015 ◽  
Vol 42 (12) ◽  
pp. 2270-2278 ◽  
Author(s):  
Megan E.B. Clowse ◽  
Douglas C. Wolf ◽  
Frauke Förger ◽  
John J. Cush ◽  
Amanda Golembesky ◽  
...  

Objective.To provide information on pregnancy outcomes in women receiving certolizumab pegol (CZP).Methods.The UCB Pharma safety database was searched for pregnancies through to September 1, 2014. Reports for maternal and paternal CZP exposure were included and outcomes examined, and data on CZP exposure, pregnancy, comorbidities, and infant events were extracted by 2 independent reviewers. Concomitant medications and disease activity were reviewed for clinical trial patients.Results.Of 625 reported pregnancies, 372 (59.5%) had known outcomes. Paternal exposure pregnancies (n = 33) reported 27 live births, 4 miscarriages, 1 induced abortion, and 1 stillbirth. Maternal exposure pregnancies (n = 339) reported 254 live births, 52 miscarriages, 32 induced abortions, and 1 stillbirth. Almost all reported pregnancies had exposure to CZP in the first trimester, when organogenesis takes place, and a third of them continued the drug into the second and/or third trimesters. The most frequent indications for maternal CZP use were Crohn disease (192/339) and rheumatic diseases (118/339). Twelve cases of congenital malformation and a single neonatal death were reported.Conclusion.Analysis of pregnancy outcomes after exposure to CZP supports previous reports, suggesting a lack of harmful effect of maternal CZP exposure on pregnancy outcomes. However, additional data from a larger number of outcomes after exposure and studies including an unexposed comparison group are required to fully evaluate CZP safety and tolerability in pregnancy.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S20-S21
Author(s):  
Hala Shamsuddin ◽  
Casey Raudenbush ◽  
Brittany Sciba ◽  
Erica N Gooch ◽  
Wayne Greaves ◽  
...  

Abstract Background Safety data are needed regarding HIV treatment in women of reproductive potential and during pregnancy. This review is to evaluate pregnancy outcomes following prospective exposures (exposure report prior to knowledge of pregnancy outcome) to raltegravir during pregnancy. Methods Exposures to raltegravir during pregnancy reported cumulatively through March 26, 2019 to the internal safety database at Merck & Co., Inc. were reviewed. This database includes all reports of pregnancy from clinical trials sponsored by the company, spontaneous post-marketing reports, and noninterventional data sources. Prospective pregnancy reports were evaluated to determine rates of spontaneous abortion, stillbirth, and congenital anomalies, including neural tube defects. Data from two ongoing cohorts of pregnant women with HIV-1 infection, not included in the internal safety database, were also reviewed. Results A total of 2,508 prospective pregnancy reports with reported outcomes were identified among women exposed to raltegravir: 919 from the internal safety database (Table 1) and 1,589 from the UK/Ireland and French pregnancy cohorts. Among the 2,508 prospective pregnancy exposures, 945 were in the first trimester, of which 757 were within the periconception period (within 28 days of conception). Of the 471 documented first trimester exposures identified in the internal safety database, the rates of spontaneous abortion (6.9%), stillbirth (1%), and congenital anomalies (1.5% per live births) were similar to the rates observed in the background populations of the United States Among outcomes following any exposure, the rate of congenital anomalies was 3.4% per live births. There were no reports of neural tube defects identified within the internal safety database or among the cohort data. Conclusion Prospectively collected pregnancy outcome data do not suggest an association between raltegravir exposure and spontaneous abortion, stillbirth, or congenital anomalies, including neural tube defects. These data support the current HIV treatment recommendations for the use of raltegravir 400 mg twice daily in women of reproductive potential and during pregnancy. Disclosures All Authors: No reported Disclosures.


Author(s):  
Ümit Görkem ◽  
Özgür Kan ◽  
Mehmet Ömer Bostancı ◽  
Deniz Taşkıran ◽  
Hasan Ali İnal

Objective: Spontaneous abortion is the most common complication of early pregnancy, affecting up to 20% of recognized pregnancies. Kisspeptin is predominantly released by placental syncytiotrophoblasts, and regulates their placental invasion into the uterine matrices. We aimed to establish an association of serum kisspeptin levels with pregnancy outcomes during the early gestational stage of the first trimester. Method: In this prospective study, 90 pregnant women in their 7 to 8 6/7 gestational weeks were classified into three groups: (i) The control group, consisting of healthy pregnant women (n=30), (ii) the threatened abortion group (n=30), and (iii) the spontaneous abortion group (n=30). The maternal serum samples were analyzed for complete blood count parameters and kisspeptin levels. Results: There was no statistical difference regarding body mass index (BMI) and gestational age (p=0.370). Regarding detailed obstetric notations, including gravida, parity, abortion, and living children, socioeconomic levels, and employment rates, all study groups were comparable (p>0.05, for all). No significant association was found regarding the biochemical parameters of complete blood count, including neutrophil, lymphocyte, and platelet concentrations, as well as neutrophil-to-lymphocyte ratios (NLR) and platelet-to-lymphocyte ratios (PLR) (p>0.05, for all). The median serum kisspeptin levels of the study groups did not differ between the groups (p=0.153). Correlation analysis revealed no significant relationship between serum kisspeptin levels and other study parameters in any study groups (p>0.05, for all) Conclusions: We found no statistically significant relationship between serum kisspeptin concentrations and pregnancy outcomes in the early gestational stage of the first trimester, and serum kisspeptin concentrations did not seem to be a reliable marker to distinguish abortion status from viable pregnancy


2021 ◽  
Vol 2021 ◽  
pp. 1-4
Author(s):  
Kristen E. Park ◽  
Nicole L. Vestal ◽  
Michael S. Awadalla ◽  
Sharon A. Winer

Septate uteri have been associated with adverse pregnancy outcomes including spontaneous abortion, preterm delivery, and malpresentation. It is unclear if uterine septa are associated with infertility. Although some studies have shown improved pregnancy outcomes after septum resection, indications for resection are not well established. We describe a case of a woman with a large partial uterine septum diagnosed during workup for infertility who conceived without septum resection. Both of her subsequent pregnancies were initially breech presentations for which the patient underwent external cephalic version followed by full-term vaginal deliveries. This case adds evidence that an unresected uterine septum should not be considered a contraindication to external cephalic version.


2014 ◽  
Vol 58 (8) ◽  
pp. 4392-4398 ◽  
Author(s):  
Stephanie Padberg ◽  
Evelin Wacker ◽  
Reinhard Meister ◽  
Mary Panse ◽  
Corinna Weber-Schoendorfer ◽  
...  

ABSTRACTFluoroquinolones are avoided during pregnancy due to developmental toxicity in animals. The aim of this study was to assess the fetal risk after intrauterine fluoroquinolone exposure. We performed an observational study of a prospectively ascertained cohort of pregnant women exposed to a fluoroquinolone during the first trimester. Pregnancy outcomes were compared to those of a cohort exposed to neither fluoroquinolones nor teratogenic or fetotoxic drugs. The outcomes evaluated were major birth defects (structural abnormalities of medical, surgical, or cosmetic relevance), spontaneous abortion, and elective termination of pregnancy. Pregnancy outcomes of 949 women with fluoroquinolone treatment were compared with those of 3,796 nonexposed controls. Neither the rate of major birth defects (2.4%; adjusted odds ratio [ORadj], 0.91; 95% confidence interval [CI], 0.6 to 1.5) nor the risk of spontaneous abortion (adjusted hazard ratio [HRadj], 1.01; 95% CI, 0.8 to 1.3) was increased. However, there was a nonsignificant increase in major birth defects after exposure to moxifloxacin (6/93, 6.5%; crude odds ratio [ORcrude], 2.40; 95% CI, 0.8 to 5.6). Neither a critical exposure time window within the first trimester nor a specific pattern of birth defects was demonstrated for any of the fluoroquinolones. The rate of electively terminated pregnancies was increased among the fluoroquinolone-exposed women (HRadj, 1.32; 95% CI, 1.03 to 1.7). The gestational ages at delivery and birth weights did not differ between groups. Our study did not detect an increased risk of spontaneous abortion or major birth defects. These reassuring findings support the recommendation to allow fluoroquinolone use in early pregnancy in selected cases. After the use of moxifloxacin, a detailed fetal ultrasound examination should be considered.


2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Jing Yang ◽  
Yan Wang ◽  
Xiao-ye Wang ◽  
Yan-yu Zhao ◽  
Jing Wang ◽  
...  

Although a history of first-trimester recurrent spontaneous abortion (FRSA) is regarded as a risk factor in antenatal care, the characteristic of subsequent pregnancy outcome is not clearly elucidated. Here, a retrospective analysis was performed on the clinical data of 492 singleton pregnant women. 164 of them with the history of FRSA were enrolled in study group, compared to 328 deliveries without the history of FRSA. For maternal outcomes, patients in the study group delivered earlier with mean gestational age and the incidences of cesarean section and postpartum hemorrhage were higher compared to the control group. For placental outcomes, the incidence of placenta-mediated pregnancy complications (PMPC) in the study group increased in terms of late-onset preeclampsia, oligohydramnios, early-onset fetal growth restriction, and second-trimester abortion. Patients in the study group were more likely to suffer from placenta accreta, placenta increta, and placenta percreta. For perinatal outcomes, the proportion of birth defects of newborns in the study group was greater. At last, logistic regression analyses showed that the history of FRSA was an independent risk factor for cesarean section and pregnancy complications. In conclusion, women with the history of FRSA are often exposed to an elevated incidence of maternal-placental-perinatal adverse pregnancy outcomes.


2018 ◽  
Vol 37 (2) ◽  
pp. 123-130 ◽  
Author(s):  
Yumi Kawai ◽  
Tsuyoshi Tsuchiya ◽  
Shigeru Aoki

Background: This is the first retrospective report of pregnancy outcomes after exposure to adalimumab treatment in Japan. Methods: Using the AbbVie safety database, we analyzed pregnancy outcome data from patients who received adalimumab treatment from April 16, 2008, to May 15, 2017. Results: Data were extracted retrospectively for 74 pregnancies in 73 patients. More than half of the patients included in the study received adalimumab for the treatment of Crohn’s disease (37.8%) or ulcerative colitis (20.3%), while 9.5% received adalimumab for rheumatoid arthritis. Of the 53 pregnancies with available outcome data, 45 newborns (45/53 [84.9%]) were delivered. Of these births, 30 were full-term, 2 were preterm, and 13 were unknown. Apgar scores were available for 11 of the 16 newborns whose mothers were exposed to adalimumab in the third trimester; all scores were within the normal range. Low birth weight was observed in 5 infants out of the 30 full-term deliveries. There were also 5 miscarriages (5/53 [9.4%]), 2 induced abortions (2/53 [3.8%]), and 1 stillbirth (1/53 [1.9%]). Eight maternal adverse events were observed in 5 pregnancies; no serious adverse events occurred. Conclusion: Although safety concerns were inconclusive, these data do not report additional risk to pregnancy outcomes with adalimumab exposure.


2020 ◽  
Vol 9 (2) ◽  
pp. IJH26 ◽  
Author(s):  
Jorge E Cortes ◽  
Carlo Gambacorti-Passerini ◽  
Michael Deininger ◽  
Elisabetta Abruzzese ◽  
Liza DeAnnuntis ◽  
...  

Aim: Preclinical studies have shown reproductive toxicity with bosutinib, but little is known about its effects during conception or pregnancy in humans. Methods: Pregnancy cases in patients receiving bosutinib were identified from the Pfizer safety database. Results: Thirty-three pregnancy reports were identified. Sixteen cases of maternal exposure: six live births, four abortions and six with unknown outcomes. Seventeen instances of paternal exposure: nine live births, five abortions and three with unknown outcomes. Conclusion: Adverse effects of bosutinib exposure at conception or during pregnancy in humans cannot be excluded, particularly if therapy is not interrupted upon recognition of pregnancy. Contraceptive use is recommended for female patients receiving bosutinib, and patients should be made aware of the potential risks associated with bosutinib use during pregnancy.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 213.2-213
Author(s):  
M. Clowse ◽  
R. Fischer-Betz ◽  
C. Nelson-Piercy ◽  
A. Scheuerle ◽  
T. Kumke ◽  
...  

Background:Chronic inflammatory diseases (CID) in women of reproductive age are increasingly being treated with tumour necrosis factor inhibitors (TNFi), in line with recent guidelines.1 However, data on TNFi-exposed pregnancy outcomes are still limited. Certolizumab pegol (CZP), a PEGylated, Fc-free TNFi, has no/minimal placental transfer from mother to infant during the third trimester.2Objectives:To assess pregnancy outcomes from the UCB Pharmacovigilance safety database from over 1,300 prospectively reported pregnancies with maternal CZP exposure.Methods:Details of CZP-exposed pregnancies from the UCB Pharmacovigilance safety database were reviewed up to November 1, 2020. Analysis was limited to prospectively reported cases with known pregnancy outcomes to avoid potential reporting bias. Confounders (specific CID, non-biologic medications and maternal infection) were evaluated using a multivariate stepwise regression model; results from the confounders analysis are reported as odds ratios (OR) with 95% confidence intervals (CI). Patients with missing information about presence or absence of confounders were excluded from the model.Results:1,392 prospective pregnancies (1,425 fetuses) with maternal CZP exposure and known outcomes were reported (Figure 1). Mean (SD) maternal age was 31.9 (5.1) years. Of these, 1,021/1,392 (73.3%) pregnancies had at least first-trimester CZP exposure and 547/1,392 (39.3%) were exposed during all trimesters. Overall, there were 1,259/1,425 (88.4%) live births, 150/1,425 (10.5%) abortions (miscarriages and terminations), 11/1,425 (0.8%) stillbirths, and 5/1,425 (0.4%) ectopic pregnancies. Congenital malformations were reported in 35/1,425 fetuses (2.5%) and in 30/1,259 live-born infants (2.4%); 26 (2.1%) congenital malformations were major according to the Metropolitan Atlanta Congenital Defects Program criteria. There was no pattern of specific congenital malformations. Preterm births occurred in 124/1,259 (9.8%) live births, and 101/1,259 (8.0%) of infants had low birth weight (<2.5 kg). In the confounders analysis, reported corticosteroid use was independently associated with increased odds of preterm birth (OR [95% CI]: 2.1 [1.3–3.4]; p<0.005) and low birth weight (OR [95% CI]: 1.7 [1.0–2.9]; p<0.05), but decreased odds of abortion (OR [95% CI]: 0.5 [0.3–0.9]; p<0.05). Reported NSAID use was associated with increased odds of abortion (OR [95% CI]: 2.2 [1.2–4.0]; p<0.05), as was methotrexate/leflunomide use (OR [95% CI]: 3.2 [1.7–6.2]; p<0.0005). Maternal infections were associated with increased odds of preterm birth (OR [95% CI]: 1.9 (1.1–3.5; p<0.05). Finally, there was an association between a diagnosis of Crohn’s disease and odds of abortion (OR [95% CI]: 2.5 [1.5–4.1]; p=0.0005), and between rheumatoid arthritis and low birth weight (OR [95% CI]: 1.9 [1.1–3.3]; p<0.05).Conclusion:This prospective analysis, including more than 1,000 pregnancies with CZP exposure in at least the first trimester, represents one of the largest cohorts of pregnancies with known outcomes in patients with CID. Our data confirm the impact of specific CID, concomitant drugs or comorbidities on pregnancy outcomes. In particular, additional use of corticosteroids was highlighted as a risk factor for preterm birth and low birth weight in our cohort of CZP-treated patients. No increase in adverse pregnancy outcomes or specific congenital malformations was observed in CZP-exposed pregnancies, compared to the general population,3,4 which offers further reassurance for women of childbearing age considering CZP treatment.References:[1]Sammaritano LR. Arthritis Rheum 2020;72:529–56;[2]Mariette X. Ann Rheum Dis 2018;77:228–33;[3]Ventura SJ. Natl Vital Stat Rep 2012;60:1–21;[4]Lee H. BMC Pregnancy Childbirth 2020;20:33.Acknowledgements:This study was funded by UCB Pharma. Editorial services were provided by Costello Medical.Disclosure of Interests:Megan Clowse Consultant of: UCB Pharma, Grant/research support from: Janssen, Pfizer, Rebecca Fischer-Betz Consultant of: AbbVie, BMS, Celgene, Chugai, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi, UCB Pharma, Catherine Nelson-Piercy Consultant of: Alliance Pharma, UCB Pharma, Angela Scheuerle Consultant of: Antiretroviral Pregnancy Registry, Harmony Biosciences, IQVIA, ICON, NovoNordisk, PPD, Roche, Sanofi-Genzyme, Syneos, UCB Pharma, ViiV, Thomas Kumke Shareholder of: UCB Pharma, Employee of: UCB Pharma, Bernard Lauwerys Employee of: UCB Pharma, Rachna Kasliwal Employee of: UCB Pharma, Frauke Förger Speakers bureau: Mepha, Roche, UCB Pharma, Grant/research support from: UCB Pharma.


2021 ◽  
pp. 1-12
Author(s):  
Xueluo Zhang ◽  
Junmei Fan ◽  
Yanhua Chen ◽  
Jun Wang ◽  
Zhijiao Song ◽  
...  

In the present study, we retrospectively recruited 340 patients who underwent spontaneous abortions to investigate chromosomal abnormalities of the conception products in the first trimester. We also performed a relevant analysis of clinical factors. Of these patients, 165 had conception products with chromosomal abnormalities, including 135 aneuploidies, 11 triploidies, 10 complex abnormalities, and 9 segmental aneuploidies. The most common abnormal chromosomes were chromosome 16 in the embryo-transfer group and sex chromosomes in the natural-conception group. The most common abnormal chromosomes in all analyzed maternal age groups were sex chromosomes, 16, and 22. The chromosomal abnormality incidence was related to age and number of spontaneous abortions (both <i>p</i> &#x3c; 0.05), but not to number of pregnancies, deliveries, induced abortions, or methods of conception (all <i>p</i> &#x3e; 0.05). The rates of abnormality for chromosomes 12, 15, 20, and 22 increased with age, while the rates for chromosomes 6, 7, 13, and X decreased. In all age groups, aneuploidy was by far the most common abnormality; however, the low-incidence distributions of chromosomal abnormalities were entirely different. Overall, chromosomal aneuploidy was the primary cause of pregnancy loss in the first trimester, and low-frequency abnormalities differed across age subgroups. Chromosomal aberrations were found to be related to maternal age and spontaneous abortion, but not all chromosomal abnormalities increased with age.


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