Effects of natalizumab, an α4 integrin inhibitor, on fertility in male and female guinea pigs

Wehner, Nancy; Skov, Michael J.; Shopp, George M.; Rocca, Meredith S.; Clarke, Jessica L.

doi:10.1002/bdrb.20191

Cited by 33 publications

(19 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, reproductive and/or fetal development processes may be affected by inhibition of α4 integrins; of particular note are the processes of fertilization, placental development, embryo implantation, hematopoiesis, and cardiac development [30–35]. Natalizumab has been categorized as a pregnancy category C medication based on animal studies showing transplacental crossing and potential for offspring effects, such as reduced pup survival in guinea pigs and mild anemia or reduced platelet count in the fetus of monkeys [6, 12, 13]. However, no treatment-related teratogenic effects were observed, including no cardiac abnormalities observed in any natalizumab study, in contrast to the published role of α4 in the formation of the epicardium and consequent cardiac abnormalities in α4 null mice [12, 16, 34].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of pregnancy outcomes from the Tysabri® (natalizumab) pregnancy exposure registry: a global, observational, follow-up study

et al. 2016

View full text Add to dashboard Cite

BackgroundPatients with multiple sclerosis (MS) or Crohn’s disease (CD) being treated with natalizumab (Tysabri®, Biogen) who are planning to become pregnant or discover they are pregnant after exposure to natalizumab are currently advised to balance the potential benefits and potential risks of exposure when considering treatment options. This study was undertaken to evaluate pregnancy outcomes of women with MS or CD who were exposed to natalizumab at any time within 3 months prior to conception or during pregnancy. A pregnancy registry was created to better understand the effect of natalizumab exposure on pregnancy outcomes.MethodsThe Tysabri Pregnancy Exposure Registry was a global, observational exposure registration and follow-up study. Evaluations included spontaneous abortions (<22 weeks gestational age), fetal losses (≥22 weeks gestational age), ectopic pregnancies, elective or therapeutic terminations, stillbirths, birth defects, and live births. Birth defects were reviewed and coded in accordance with the Metropolitan Atlanta Congenital Defects Program (MACDP) classification of birth defects.ResultsA total of 369 patients with MS and 7 patients with CD were enrolled prospectively, of whom 355 patients (99.4 %; 349 MS and 6 CD) had known pregnancy outcomes (including 8 twin sets). The spontaneous abortion rate was 9.0 % (n = 32; 95 % confidence interval [C. I.], 6.3–12.5 %). An independent advisory committee review determined the major birth defect rate to be 5.05 % (16 of 316 live births + 1 elective abortion; 95 % C. I., 2.9–8.1 %). The mean gestational age of the live-born infants was 38.3 weeks, and the mean birth weight was 3158.3 g.ConclusionsAlthough the overall rate of birth defects was higher than that observed by the MACDP, these registry outcomes showed no specific pattern of malformations that would suggest a drug effect, and the spontaneous abortion rate was consistent with that of the general population.Trial registrationClinicalTrials.gov NCT00472992 (11 May 2007).

show abstract

Section: Discussionmentioning

confidence: 99%

Evaluation of pregnancy outcomes from the Tysabri® (natalizumab) pregnancy exposure registry: a global, observational, follow-up study

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Both of these criteria were used to evaluate the effects of drugs on developmental and reproductive function (Jacquet et al, 1997;Adriaens et al, 1999;Wehner et al, 2009). Therefore, our findings could help to clarify mechanisms involved in human embryonic ovarian development and folliculogenesis.…”

Section: Discussionmentioning

confidence: 99%

Cell proliferation and apoptosis in the fetal and neonatal ovary of guinea pigs

et al. 2014

View full text Add to dashboard Cite

ABSTRACT. The guinea pig is an excellent animal model for studying reproductive biology of adult humans and most domestic animals. Yet, whether this animal might serve as a good model for embryonic stage investigations and determinations of signals affecting or directing ovary development remains unknown. These questions were addressed by examining morphological evolution and the expression of biomarkers of cell proliferation and apoptosis in the ovaries of fetal and neonatal guinea pigs in the present study. Embryonic and neonatal guinea pigs at 30, 40, 50, 60, and 68 days postcoitum (dpc) and at 1 day postpartum (dpp) were evaluated, and the dynamic changes in follicles between 30 dpc and 1 dpp were observed. Results also showed that a critical period of follicular development in guinea pig embryos occurred at 40 to 50 dpc. Moreover, the proliferating-cell nuclear antigen, a cell proliferation marker, immunohistochemically stained healthy follicles, while caspase-3, an apoptosis marker, was mainly observed in atretic follicles. Together, these results demonstrate that cell proliferation and apoptosis contribute to follicular formation, development, and atresia in fetal and neonatal guinea pig ovaries. Furthermore, this study Cell proliferation and apoptosis in the ovary of guinea pigs confirmed that the guinea pig is also an excellent animal model for studying reproductive biology in human and domestic animal embryos.

show abstract

“…A study in guinea pigs failed to show any differences in reproductive capacity as compared to the untreated group. 164 Still, some recommend withholding the medication two months prior to conception. 165 …”

Section: Biologicsmentioning

confidence: 99%

Understanding the Cautions and Contraindications of Immunomodulator and Biologic Therapies for Use in Inflammatory Bowel Disease

Cohn

Dave

Loftus

2017

Inflammatory Bowel Diseases

View full text Add to dashboard Cite

Ulcerative colitis and Crohn’s disease are chronic inflammatory bowel diseases for which there are no cures. These diseases are immunopathogenic, and medical treatment is centered on the temperance of a dysregulated immune response to allow mucosal healing and prevent the sequelae of fistulation and stenosis. Accordingly, the armamentarium of medications, which has expanded immensely in recent history, is not without significant infectious and neoplastic risks. Many of these untoward effects can be mitigated by screening and avoidance of contraindicated medications. This review seeks to highlight the cautions for use of immunomodulators, anticytokine and α4-integrin antagonists. The potential adverse events are further complicated by substantial heterogeneity in disease phenotype in the IBD population. Large patient registries and databases provide considerable experience and knowledge to calculate the incidence of safety outcomes. To identify rarer outcomes after prolonged therapy, more prospective studies and continued adverse event reporting will aid safe application and minimize potential harms.

show abstract

Effects of natalizumab, an α4 integrin inhibitor, on fertility in male and female guinea pigs

Abstract: Natalizumab had no effects on male fertility, but did result in a reduction in pregnancy rates in females treated with the high dose of 30 mg/kg.

Cited by 33 publications

References 36 publications

Evaluation of pregnancy outcomes from the Tysabri® (natalizumab) pregnancy exposure registry: a global, observational, follow-up study

Evaluation of pregnancy outcomes from the Tysabri® (natalizumab) pregnancy exposure registry: a global, observational, follow-up study

Cell proliferation and apoptosis in the fetal and neonatal ovary of guinea pigs

Understanding the Cautions and Contraindications of Immunomodulator and Biologic Therapies for Use in Inflammatory Bowel Disease

Contact Info

Product

Resources

About