Final results from the ribavirin pregnancy registry, 2004-2020.

INTRODUCTION: Significant teratogenic effects have been demonstrated for ribavirin in animal studies. Ribavirin is prescribed for chronic hepatitis C and is contraindicated in pregnant women and their male sexual partners. Both are advised to avoid pregnancy for 6 months after exposure. The registry monitored pregnancy exposures to oral formulations of ribavirin for hepatitis C for signals of possible human teratogenicity from 2004 to 2020. METHODS: Pregnant women were voluntarily enrolled following direct exposure (ribavirin use during pregnancy or the 6 months prior) or indirect exposure (through sexual contact during pregnancy or 6 months prior, with a man who has taken ribavirin within 6 months). Women were followed until the end of pregnancy. Infants were followed until 1 year of age. Birth defect rates were compared with the published rate of 2.67 per 100 live births from the Metropolitan Atlanta Congenital Defects Program (MACDP). RESULTS: The registry enrolled 280 pregnancies resulting in 186 live births: eight birth defect cases among 88 directly exposed [9.09% (8/88, 95% CI: 4.01, 17.13)], and six birth defect cases among 98 indirectly exposed [6.12% (6/98, 95% CI: 2.28, 12.85)]. The 95% CI around the birth defect rate among directly exposed pregnancies exceeds the MACDP rate; however, no patterns suggestive of a teratogenic mechanism or safety signal were detected. CONCLUSION: Based on the patterns of birth defects reported, the final results from this registry do not suggest a clear signal of human teratogenicity for ribavirin. The registry did not meet sample size requirements; therefore, caution should be exercised when interpreting the results.

An Innovative Online Qualitative Study to Explore the Symptom Experience of Patients with Primary Sjögren's Syndrome.

INTRODUCTION: Primary Sjögren's syndrome (pSS) is a complex, heterogenous autoimmune disease; no immunomodulatory drug has demonstrated efficacy, and no current treatments target the underlying cause. This study aimed to explore the disease and treatment experiences of patients with pSS. METHODS: This qualitative study (208399) comprised moderated online forum discussions and online one-to-one questions conducted in the USA over a 2-week period. Participants were self-reported patients with pSS; physician confirmation of diagnosis was sought. Participants described disease and symptom severity and satisfaction with current pSS treatments. Qualitative data analysis was performed using inductive coding analysis via open coding. RESULTS: Fifty-two participants entered the study, of whom 48 provided analysable data. Symptoms were described as highly unpredictable and variable, with fatigue rated as the most severe and burdensome. Participants discussed how their pSS symptoms and the frequent need for regular treatment impacted their daily activities, social life, career and finances. Many participants perceived a poor understanding of pSS amongst physicians, leading to emotional distress and difficulties obtaining a diagnosis. All participants stated that an ideal medication would address the cause of pSS and not just treat symptoms. CONCLUSION: New insights into patients' perspectives of pSS were generated from online discussion forums, revealing the additional impact of unpredictable symptoms and multiple symptomatic treatments to the high disease burden. Improving physician education of pSS may help to alleviate frustrations and delays associated with diagnosis; the advent of novel effective treatments would be welcomed by patients with pSS.

The Ribavirin Pregnancy Registry: An Interim Analysis of Potential Teratogenicity at the Mid-Point of Enrollment.

INTRODUCTION: Significant teratogenic effects have been demonstrated in all animal species exposed to ribavirin. Ribavirin is prescribed for chronic hepatitis C and is contraindicated in women who are pregnant and in the male sexual partners of women who are pregnant. Both sexes are advised to avoid pregnancy for 6 months after exposure. The Ribavirin Pregnancy Registry was established in 2003 to monitor pregnancy exposures to ribavirin for signals of possible human teratogenicity. METHODS: This voluntary registry enrolls pregnant women with prenatal exposure to ribavirin. Exposure is classified as direct-women taking ribavirin during pregnancy or the 6 months prior to conception-or indirect-women exposed through sexual contact, 6 months prior to or during pregnancy, with a man who is taking or has taken ribavirin in the past 6 months. Women are followed until delivery and infants for 1 year. When enrollment is complete, birth defect rates will be compared with the Metropolitan Atlanta Congenital Defects Program's published rate of 2.67. Using data collected since inception in 2003 through February 2016, preliminary rates were calculated. RESULTS: The registry has enrolled 272 pregnant women, with 180 live births: there were seven birth defect cases among 85 directly exposed women [7/85 (8.2%) (95% confidence interval (CI) 3.4-16.2)] and four birth defect cases among 95 indirectly exposed women [4/95 (4.2%) (95% CI 1.2-10.4)]. Of the 11 infants, nine had structural defects and two had chromosomal anomalies. Patterns suggesting a common etiology or relationship with ribavirin exposure are not seen. CONCLUSION: Based on the patterns of birth defects reported, preliminary findings do not suggest a clear signal of human teratogenicity for ribavirin. However, the current sample size is insufficient for definitive conclusions, and ribavirin exposure should be avoided during pregnancy and during the 6 months prior to pregnancy, in accordance with prescribing information. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00114712.

Medication Safety During Pregnancy: Improving Evidence-Based Practice.

Nearly 90% of women in the United States have taken medications during pregnancy. Medication exposures during pregnancy can result in adverse pregnancy and neonatal outcomes including birth defects, fetal loss, intrauterine growth restriction, prematurity, and longer-term neurodevelopmental outcomes. Advising pregnant women about the safety of medication use during pregnancy is complicated by a lack of data necessary to engage the woman in an informed discussion. Routinely, health care providers turn to the package insert, yet this information can be incomplete and can be based entirely on animal studies. Often, adequate safety data are not available. In a busy clinical setting, health care providers need to be able to quickly locate the most up-to-date information in order to counsel pregnant women concerned about medication exposure. Deciding where to locate the best available information is difficult, particularly when the needed information does not exist. Pregnancy registries are initiated to obtain more data about the safety of specific medication exposures during pregnancy; however, these studies are slow to produce meaningful information, and when they do, the information may not be readily available in a published form. Health care providers have valuable data in their everyday practice that can expand the knowledge base about medication safety during pregnancy. This review aims to discuss the limitations of the package insert regarding medication safety during pregnancy, highlight additional resources available to health care providers to inform practice, and communicate the importance of pregnancy registries for expanding knowledge about medication safety during pregnancy.

Final results from the 16-year sumatriptan, naratriptan, and treximet pregnancy registry.

OBJECTIVES: To monitor for a signal of major teratogenicity by determining the risk of all birth major defects following in utero exposure to sumatriptan, naratriptan, and the sumatriptan/naproxen sodium combination product (tablets marketed in the United States as Treximet [GlaxoSmithKline, Research Triangle Park, NC, USA]), and to monitor for unusual patterns of defects that might suggest teratogenicity. BACKGROUND: The prevalence of migraine is highest in women of childbearing age. Coupled with the recurrent nature of migraine attacks and the high proportion of unplanned pregnancies, intentional and inadvertent exposure to anti-migraine drugs in pregnancy is likely. The Sumatriptan, Naratriptan, and Treximet Pregnancy Registry captured data on women exposed to those drugs during pregnancy to monitor for evidence of major teratogenicity. METHODS: In this primarily prospective, observational study, health care professionals from anywhere in the world enrolled, on a voluntary basis, women exposed to sumatriptan, naratriptan, or the sumatriptan/naproxen sodium combination product during their pregnancies. Only pregnancies with unknown outcomes at the time of enrollment were included in the analysis. The proportion of infants or fetuses with major birth defects was calculated as the total number of infants/fetuses with major birth defects divided by the sum of the number of infants/fetuses with major birth defects + the number of live births without defects. The risk of major birth defects was further stratified by earliest trimester of pregnancy exposure. RESULTS: The registry enrolled 680 evaluable exposed pregnant women, which resulted in 689 infants and fetuses (outcomes). Of these outcomes, 626 were exposed to sumatriptan, 57 were exposed to naratriptan (seven were exposed to both sumatriptan and naratriptan), and six were exposed to the sumatriptan/naproxen sodium combination product. Twenty outcomes with major birth defects were reported among 528 outcomes exposed in the first trimester to sumatriptan. The estimated risk of major birth defects following first-trimester sumatriptan exposure is 4.2% (20/478 [95% confidence interval [CI] 2.6%-6.5%]). Among 52 first-trimester exposures to naratriptan, major birth defects were reported in one outcome, an infant with exposure to both sumatriptan and naratriptan [birth defect risk of 2.2% (1/46 [95% CI 0.1%-13.0%]). No major defects were reported among the five outcomes with first-trimester exposure to the sumatriptan/naproxen sodium combination products. CONCLUSIONS: The Sumatriptan, Naratriptan, and Treximet Pregnancy Registry detected no signal of teratogenicity associated with major birth defects for sumatriptan. This finding is consistent with results from other observational studies using a variety of control groups. Enrollment in the registry was insufficient to permit definitive conclusions of the risks associated with naratriptan or sumatriptan/naproxen sodium tablets, or to assess the risk of individual birth defects in any of the products studied. Low enrollment and high rates of loss to follow up within the registry over an extended period of time led the registry's scientific advisory committee to conclude that continuation of the registry beyond its 16 years would offer little additional power to rule out more moderate increases in the risk of birth defects. Data from the other ongoing surveillance sources constitute an important element of post-marketing surveillance of these medications. The lack of a signal of major teratogenicity with sumatriptan across these several sources of data is encouraging.