Tofacitinib in Pregnancy: Assessing Pregnancy and Infant Outcomes, Cord Blood, and Breast Milk Concentrations.

Janus kinase (JAK) inhibitors are effective anti-inflammatory agents for treatment of ulcerative colitis (UC).1 According to drug regulatory agencies and international guidelines, JAK inhibitors should be avoided during pregnancy and lactation.2-4 The existing evidence on safety of JAK inhibitors during pregnancy is scarce and almost exclusively limited to tofacitinib.4-7.

Real-World Experience With Tofacitinib Dose De-Escalation in Patients With Moderate and Severe Ulcerative Colitis.

BACKGROUND & AIMS: Tofacitinib is associated with sustained steroid-free remission in patients with ulcerative colitis (UC), with the lowest effective dose recommended for maintenance therapy. However, there are limited real-world data to guide decisions on the optimal maintenance regimen. We aimed to evaluate predictors and outcomes of disease activity after tofacitinib dose de-escalation in this population. METHODS: Included were adults with moderate-severe UC treated with tofacitinib between June 2012 and January 2022. The primary outcome was evidence of UC disease activity-related events: hospitalization/surgery, corticosteroid initiation, tofacitinib dose increase, or therapy switch. RESULTS: Among 162 patients, 52% continued 10 mg twice daily while 48% underwent dose de-escalation to 5 mg twice daily. Cumulative incidence rates of UC events at 12 months were similar in patients with and without dose de-escalation (56% vs 58%; P = .81). In univariable Cox regression among patients with dose de-escalation, an induction course with 10 mg twice daily for more than 16 weeks was protective of UC events (hazard ratio [HR], 0.37; 95% CI, 0.16-0.85) while ongoing severe disease (Mayo 3) was associated with UC events (HR, 6.41; 95% 95% CI, 2.23-18.44), which remained significant after adjusting for age, sex, duration of induction course, and corticosteroid use at dose de-escalation (HR, 6.05; 95% CI, 2.00-18.35). Twenty-nine percent of patients with UC events had their dose re-escalated to 10 mg twice daily, with only 63% able to recapture clinical response at 12 months. CONCLUSIONS: In this real-world cohort, we observed a 56% cumulative incidence of UC events at 12 months in patients with tofacitinib dose de-escalation. Observed factors associated with UC events after dose de-escalation included induction course for fewer than 16 weeks and active endoscopic disease 6 months after initiation.

Effectiveness and Safety of Biologic Therapy in Hispanic Vs Non-Hispanic Patients With Inflammatory Bowel Diseases: A CA-IBD Cohort Study.

BACKGROUND & AIMS: There are limited data on outcomes of biologic therapy in Hispanic patients with inflammatory bowel diseases (IBDs). We compared risk of hospitalization, surgery, and serious infections in Hispanic vs non-Hispanic patients with IBD in a multicenter, electronic health record-based cohort of biologic-treated patients. METHODS: We identified adult patients with IBD who were new users of biologic agents (tumor necrosis factor α [TNF-α] antagonists, ustekinumab, vedolizumab) from 5 academic institutions in California between 2010 and 2017. We compared the risk of all-cause hospitalization, IBD-related surgery, and serious infections in Hispanic vs non-Hispanic patients using 1:4 propensity score matching and survival analysis. RESULTS: We compared 240 Hispanic patients (53% male; 45% with ulcerative colitis; 73% TNF-α antagonist-treated; 20% with prior biologic exposure) with 960 non-Hispanic patients (51% male; 44% with ulcerative colitis; 67% TNF-α antagonist-treated; 27% with prior biologic exposure). After propensity score matching, Hispanic patients were younger (37 ± 15 vs 40 ± 16 y; P = .02) and had a higher burden of comorbidities (Elixhauser index, >0; 37% vs 26%; P < .01), without any differences in patterns of medication use, burden of inflammation, and hospitalizations. Within 1 year of biologic initiation, Hispanic patients had higher rates of hospitalizations (31% vs 23%; adjusted hazard ratio [aHR], 1.32; 95% CI, 1.01-1.74) and IBD-related surgery (7.1% vs 4.6%; aHR, 2.00; 95% CI, 1.07-3.72), with a trend toward higher risk of serious infections (8.8% vs 4.9%; aHR, 1.74; 95% CI, 0.99-3.05). CONCLUSIONS: In a multicenter, propensity score-matched cohort of biologic-treated patients with IBD, Hispanic patients experienced higher rates of hospitalization, surgery, and serious infections. Future studies are needed to investigate the biological, social, and environmental drivers of these differences.

Comparative Safety and Effectiveness of Biologic Therapy for Crohn's Disease: A CA-IBD Cohort Study.

BACKGROUND & AIMS: We compared the safety and effectiveness of tumor necrosis factor α (TNF-α) antagonists vs vedolizumab vs ustekinumab in patients with Crohn's disease (CD) in a multicenter cohort (CA-IBD). METHODS: We created an electronic health record-based cohort of adult patients with CD who were initiating a new biologic agent (TNF-α antagonists, ustekinumab, vedolizumab) from 5 health systems in California between 2010 and 2017. We compared the risk of serious infections (safety) and all-cause hospitalization and inflammatory bowel disease-related surgery (effectiveness) between different biologic classes using propensity score (PS) matching. RESULTS: As compared with TNF-α antagonists (n = 1030), 2:1 PS-matched, ustekinumab-treated patients with CD (n = 515) experienced a lower risk of serious infections (hazard ratio [HR], 0.36; 95% CI, 0.20-0.64), without any difference in the risk of hospitalization (HR, 0.99; 95% CI, 0.89-1.21) or surgery (HR, 1.08; 95% CI, 0.69-1.70). Compared with vedolizumab (n = 221), 1:1 PS-matched, ustekinumab-treated patients with CD (n = 221) experienced a lower risk of serious infections (HR, 0.20; 95% CI, 0.07-0.60), without significant differences in risk of hospitalization (HR, 0.76; 95% CI, 0.54-1.07) or surgery (HR, 1.42; 95% CI, 0.54-3.72). Compared with TNF-α antagonists (n = 442), 2:1 PS-matched, vedolizumab-treated patients with CD (n = 221) had a similar risk of serious infections (HR, 1.53; 95% CI, 0.84-2.78), hospitalization (HR, 1.32; 95% CI, 0.98-1.77), and surgery (HR, 0.63; 95% CI, 0.27-1.47). High comorbidity burden, concomitant opiate use, and prior hospitalization were associated with serious infections and hospitalization in biologic-treated patients with CD. CONCLUSION: In a multicenter cohort of biologic-treated patients with CD, ustekinumab was associated with a lower risk of serious infections compared with TNF-α antagonists and vedolizumab, without any differences in risk of hospitalization or surgery. The risk of serious infections was similar for TNF-α antagonists vs vedolizumab.

Maternal and Neonatal Outcomes in Vedolizumab and Ustekinumab Exposed Pregnancies: Results from the PIANO registry.

BACKGROUND: Pregnancy outcomes in inflammatory bowel disease (IBD) patients with quiescent disease are similar to the general population. Data from the Pregnancy Inflammatory bowel disease And Neonatal Outcomes (PIANO) registry have demonstrated the safety of anti-tumor necrosis factor alpha (TNFs) agents and thiopurines in pregnancy. The objective of this study was to provide information from the PIANO registry on maternal and fetal outcomes in patients exposed to the newer biologics ustekinumab (UST) and vedolizumab (VDZ). METHODS: In this multicenter prospective observational study, we included pregnant women with singleton pregnancies and a diagnosis of IBD. Questionnaires were administered to women at study intake, each subsequent trimester, delivery, and at 4, 9, and 12 months after birth. Bivariate analyses were utilized to determine the independent effects of specific drug classes on outcomes. The exposure cohorts were VDZ, UST, anti-TNFs, immunomodulators, and combination with anti-TNFs and immunomodulators. All were compared to no exposure and to biologics/immunomodulators. RESULTS: There were 1669 completed pregnancies with 1610 live births. Maternal mean age was 32.1 (SD 4.6) years at delivery with 66 VDZ and 47 UST exposed. Women on UST were more likely to have Crohn's disease. There was no increased risk of spontaneous abortion, small for gestational age, low birth weight, neonatal intensive care unit stay, congenital malformations, or intrauterine growth restriction with in utero VDZ or UST exposure. The rate of preterm birth was lower (0.0%) for UST-exposed as compared to other groups including VDZ (13.8%), anti-TNF (8.2%), combination therapy (14.2%), immunomodulator (12.3%), and unexposed (9.7%)(p = 0.03). Rates of serious infections at birth, 4 months, and within the first 12 months of life were comparable among all groups. Nonserious infections were lower at 12 months in UST exposed pregnancies. There was no increased risk signal for placental complications in the VDZ cohort. UST infant concentrations at birth were increased whereas VDZ concentrations were overall decreased compared to maternal serum drug concentration. CONCLUSION: This analysis of UST and VDZ exposure during pregnancy suggests no increase in complications compared to TNFs, immunomodulators and combination TNFs/immunomodulators. No signal was found for increased placental events with either therapy. Continuation of UST and VDZ throughout pregnancy is recommended.

Exposure to corticosteroids in pregnancy is associated with adverse perinatal outcomes among infants of mothers with inflammatory bowel disease: results from the PIANO registry.

OBJECTIVE: Active inflammatory bowel disease (IBD) during pregnancy may require the use of corticosteroids. The aim of this study was to investigate the impact of in utero corticosteroid exposure on adverse pregnancy outcomes, congenital malformations, infections and neurocognitive development among offspring of mothers with IBD. DESIGN: Using the prospective Pregnancy in Inflammatory Bowel Disease and Neonatal Outcomes registry, data were collected at each trimester, delivery; and in the 12 months post partum. Bivariate statistics and multivariate logistic regression models compared pregnancy outcomes by corticosteroid exposure. RESULTS: A total of 1490 mothers with IBD were enrolled, with 1431 live births recorded. Corticosteroid use was associated with increased risk of preterm birth, small for gestational age, low birth weight (LBW), intrauterine growth restriction and neonatal intensive care unit (NICU) admission. On adjusted multivariate models, corticosteroid use was associated with preterm birth (OR 1.79, 95% CI 1.18 to 2.73), LBW (OR 1.76, 95% CI 1.07 to 2.88) and NICU admission (OR 1.54, 95% CI 1.03 to 2.30). Late corticosteroid use (second and/or third trimester) was associated with serious infections at 9 and 12 months (4% vs 2% and 5% vs 2%, respectively, p=0.03 and p=0.001). There were five newborns with in utero corticosteroid exposure born with orofacial clefts versus one without corticosteroid exposure. Developmental milestones were similar across corticosteroid exposure groups. CONCLUSION: In this prospective pregnancy registry, offspring of women exposed to corticosteroids during pregnancy were more likely to have adverse pregnancy outcomes. This emphasises the importance of controlling disease activity before and during pregnancy with steroid-sparing therapy.

Day Care Attendance and Infectious Complications in Children Born to Mothers With Inflammatory Bowel Disease.

Active inflammation during pregnancy in women with inflammatory bowel disease (IBD) is a risk factor for clinical relapse.1,2 In utero exposure to biologics is not associated with adverse pregnancy outcomes3 or infections in infants born to mothers with IBD.1,2,4 However, prior studies did not account for day care exposure in the first year of life, which is an established risk factor for infection in the general population. We aimed to determine whether children born to mothers with IBD have an increased rate of infection when attending day care in the first year after exposure to biologic therapy in utero.

Pregnancy and Neonatal Outcomes After Fetal Exposure to Biologics and Thiopurines Among Women With Inflammatory Bowel Disease.

BACKGROUND & AIMS: Pregnant women with inflammatory bowel disease (IBD) may require biologic or thiopurine therapy to control disease activity. Lack of safety data has led to therapy discontinuation during pregnancy, with health repercussions to mother and child. METHODS: Between 2007 and 2019, pregnant women with IBD were enrolled in a prospective, observational, multicenter study across the United States. The primary analysis was a comparison of 5 outcomes (congenital malformations, spontaneous abortions, preterm birth, low birth weight, and infant infections) among pregnancies exposed vs unexposed in utero to biologics, thiopurines, or a combination. Bivariate analyses followed by logistic regression models adjusted for relevant confounders were used to determine the independent effects of specific drug classes on outcomes of interest. RESULTS: Among 1490 completed pregnancies, there were 1431 live births. One-year infant outcomes were available in 1010. Exposure was to thiopurines (n = 242), biologics (n = 642), or both (n = 227) vs unexposed (n = 379). Drug exposure did not increase the rate of congenital malformations, spontaneous abortions, preterm birth, low birth weight, and infections during the first year of life. Higher disease activity was associated with risk of spontaneous abortion (hazard ratio, 3.41; 95% confidence interval, 1.51-7.69) and preterm birth with increased infant infection (odds ratio, 1.73; 95% confidence interval, 1.19-2.51). CONCLUSIONS: Biologic, thiopurine, or combination therapy exposure during pregnancy was not associated with increased adverse maternal or fetal outcomes at birth or in the first year of life. Therapy with these agents can be continued throughout pregnancy in women with IBD to maintain disease control and reduce pregnancy-related adverse events. ClinicalTrials.gov, Number: NCT00904878.

Paternal Exposure to Immunosuppressive and/or Biologic Agents and Birth Outcomes in Patients With Immune-Mediated Inflammatory Diseases.

BACKGROUND & AIMS: We conducted a retrospective cohort study to inform the safety of exposure to immunosuppressive and/or biologic agents around conception in expectant fathers with immune-mediated inflammatory diseases (IMIDs) on birth outcomes. METHODS: Using a deidentified administrative claims database (OptumLabs Data Warehouse), we identified 7453 expectant fathers with IMIDs (inflammatory bowel diseases, rheumatoid arthritis, psoriasis/psoriatic arthritis, and ankylosing spondylitis) linked to newborns with periconception medication exposure between 38 and 60 weeks before the newborn birth date (34-58 weeks prior for preterm newborns) and neonatal follow-up for 3 months after the birth date. Through logistic regression adjusting for paternal age and race (and, in a subset, for maternal age, race, presence of IMIDs, and nonsingleton births), we compared the risk of major congenital malformations (primary outcome) and preterm birth and low birth weight in fathers exposed to thiopurines (n = 461), methotrexate (n = 171), tumor necrosis factor (TNF) α antagonists (n = 1082), or non-TNF-targeting biologic agents (n = 132) vs fathers not exposed to any of these medications (n = 5607). RESULTS: As compared to unexposed fathers (3.4% prevalence of major congenital malformations), exposure to thiopurines (relative risk [RR], 1.12; 95% confidence interval [CI], 0.66-1.76), methotrexate (RR, 0.67; 95% CI, 0.21-1.55), TNF-α antagonists (RR, 1.14; 95% CI, 0.81-1.57), and non-TNF-targeting biologic agents (RR, 1.75; 95% CI, 0.80-3.24) was not associated with increased risk of major congenital malformations. No association was observed between paternal medication exposure and risk of preterm birth or low birth weight. Results were stable on subanalyses of linked father-mother-newborn triads. CONCLUSIONS: In a large cohort study of 7453 expectant fathers with IMIDs, exposure to immunosuppressive or biologic agents around conception was not associated with increased risk of adverse birth outcomes.

Effect of Obesity on Risk of Hospitalization, Surgery, and Serious Infection in Biologic-Treated Patients With Inflammatory Bowel Diseases: A CA-IBD Cohort Study.

INTRODUCTION: Obesity is variably associated with treatment response in biologic-treated patients with inflammatory bowel diseases (IBD). We evaluated the association between obesity and risk of hospitalization, surgery, or serious infections in patients with IBD in new users of biologic agents in a large, multicenter, electronic health record (EHR)-based cohort (CA-IBD). METHODS: We created an EHR-based cohort of adult patients with IBD who were new users of biologic agents (tumor necrosis factor [TNF-α] antagonists, ustekinumab, and vedolizumab) between January 1, 2010, and June 30, 2017, from 5 health systems in California. Patients were classified as those with normal body mass index (BMI), overweight, or obese based on the World Health Organization classification. We compared the risk of all-cause hospitalization, IBD-related surgery, or serious infections among patients with obesity vs those overweight vs those with normal BMI, using Cox proportional hazard analyses, adjusting for baseline demographic, disease, and treatment characteristics. RESULTS: Of 3,038 biologic-treated patients with IBD (69% with Crohn's disease and 76% on TNF-α antagonists), 28.2% (n = 858) were overweight, and 13.7% (n = 416) were obese. On a follow-up after biologic initiation, obesity was not associated with an increased risk of hospitalization (adjusted hazard ratio [aHR] vs normal BMI, 0.90; [95% confidence interval, 0.72-1.13]); IBD-related surgery (aHR, 0.62 [0.31-1.22]); or serious infection (aHR, 1.11 [0.73-1.71]). Similar results were observed on stratified analysis by disease phenotype (Crohn's disease vs ulcerative colitis) and index biologic therapy (TNF-α antagonists vs non-TNF-α antagonists). DISCUSSION: In a multicenter, EHR-based cohort of biologic-treated patients with IBD, obesity was not associated with hospitalization, surgery, or serious infections. Further studies examining the effect of visceral obesity on patient-reported and endoscopic outcomes are needed.

Delayed Initiation of Rescue Therapy Associated with Increased Length of Stay in Acute Severe Ulcerative Colitis.

BACKGROUND: Reducing hospitalization length of stay (LOS) for acute severe ulcerative colitis (ASUC) will reduce healthcare costs, mitigate hospitalization-associated risks (e.g., venous thromboembolism), and improve quality of life. METHODS: A chart review was performed of all adult ASUC-related hospitalizations at University of California, San Francisco, from July 1, 2014, to December 31, 2017. Univariate and multivariate analyses were performed to identify factors associated with LOS < 7 days versus ≥ 7 days. A subgroup analysis was performed excluding patients who underwent colectomy during hospitalization. RESULTS: A total of 95 ASUC-related hospitalizations were identified. The initial univariable analysis identified the following factors associated with LOS ≥ 7 days (P < 0.05): higher maximum heart rate in the first 24 h, higher C-reactive protein, being biologic therapy naïve, and a later hospital day of biologic therapy initiation. On mixed model multivariable analysis, later hospital day of biologic initiation was associated with increased LOS ≥ 7 days (OR 3.1 95% CI 1.2-7.56, p = 0.012). CONCLUSIONS: We identified multiple predictors for longer hospital LOS, including factors related to disease severity (non-modifiable) and treatment (potentially modifiable). Importantly, this study identified biologic naïve treatment status and delayed inpatient biologic therapy initiation as predictors of longer LOS (≥ 7 days) in patients who did not ultimately require colectomy during their hospital stay. Potentially modifiable strategies to reduce LOS may include early communication and patient education about biologic therapy in both the inpatient and outpatient setting.

Treat-to-target approach in the management of inflammatory Bowel disease.

With the advent of biologic and small molecule therapies, there has been a substantial change in the treatment of inflammatory bowel disease. These advances have had a great impact in preventing disease progression, intestinal damage and, therefore, have contributed to a better quality of life. Discordance between symptom control and mucosal healing has been demonstrated. This has led to the search for new disease control targets. The treat to target strategy, based on expert recommendations and now a randomized controlled trial, has determined that clinical and endoscopic remission should be the goal of therapy. Biomarkers (fecal calprotectin) can be a surrogate target. Although histological healing has shown benefits, there is inadequate evidence and inadequate therapy for that to be a fixed goal at this time. This review will focus on therapeutic goals, according to the evidence currently available, and evaluate strategies to achieve them.

Dietary Guidance From the International Organization for the Study of Inflammatory Bowel Diseases.

Recent evidence points to a plausible role of diet and the microbiome in the pathogenesis of both Crohn's disease (CD) and Ulcerative Colitis (UC). Dietary therapies based on exclusion of table foods and replacement with nutritional formulas and/or a combination of nutritional formulas and specific table foods may induce remission in CD. In UC, specific dietary components have also been associated with flare of disease. While evidence of varying quality has identified potential harmful or beneficial dietary components, physicians and patients at the present time do not have guidance as to which foods are safe, may be protective or deleterious for these diseases. The current document has been compiled by the nutrition cluster of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) based on the best current evidence to provide expert opinion regarding specific dietary components, food groups and food additives that may be prudent to increase or decrease in the diet of patients with inflammatory bowel diseases to control and prevent relapse of inflammatory bowel diseases.

Men With Inflammatory Bowel Disease: Sexual Function, Fertility, Medication Safety, and Prostate Cancer.

Half of patients with inflammatory bowel disease (IBD) are men, yet less attention has been focused on their sexual issues despite higher rates of sexual dysfunction and infertility than the general population. Depression and IBD disease activity are the most consistently reported risk factor for sexual dysfunction among men with IBD. Methotrexate and sulfasalazine have been rarely associated with impotence. Sulfasalazine reversibly reduces male fertility. No other medications used in IBD significantly affect fertility in humans. There is no increase in adverse fetal outcomes among offspring of fathers with IBD. Patients with IBD seem to be at a higher risk for prostate cancer; therefore, screening as recommended for high-risk patients should be considered.

Safety of Flexible Sigmoidoscopy in Pregnant Patients with Known or Suspected Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Lower gastrointestinal endoscopy is crucial in the diagnosis and staging of inflammatory bowel disease (IBD). However, there are limited safety data in pregnant populations, resulting in conservative society guidelines and practice patterns favoring diagnostic delay. We studied whether performance of flexible sigmoidoscopy is associated with adverse events in pregnant patients with known or suspected IBD. METHODS: A retrospective cohort study was conducted at the University of California San Francisco (UCSF) between April 2008 and April 2019. Female patients aged between 18 and 48 years who were pregnant at the time of endoscopy were identified. All patient records were reviewed to determine disease, pregnancy outcomes, and lifestyle factors. Two independent reviewers performed the data abstraction. Adverse events were assessed for temporal relation with endoscopy. RESULTS: We report the outcomes of 48 pregnant patients across all trimesters who underwent lower endoscopy for suspected or established IBD. There were no hospitalizations or adverse obstetric events temporally associated with sigmoidoscopy. 78% (38/50) of lower endoscopies performed in the patients resulted in a change in treatment following sigmoidoscopy. 12% (5/43) of the lower endoscopies performed in patients with known IBD showed no endoscopic evidence of disease activity despite symptoms. CONCLUSIONS: Lower endoscopy in the pregnant patient with known or suspected IBD is low risk and affects therapeutic decision making. It should not be delayed in patients with appropriate indications.

Exposure Concentrations of Infants Breastfed by Women Receiving Biologic Therapies for Inflammatory Bowel Diseases and Effects of Breastfeeding on Infections and Development.

BACKGROUND & AIMS: Exposure to biologic and immunosuppressant agents during breastfeeding is controversial, and there are limited data on safety. We investigated whether biologics are detectable in breast milk from women receiving treatment for inflammatory bowel diseases (IBDs) and whether breastfeeding while receiving treatment is associated with infections or developmental delays. METHODS: We performed a multicenter prospective study of women with IBD and their infants, collecting breast milk samples (n = 72) from patients receiving biologic therapy from October 2013 to November 2015. Drug concentrations were measured in all breast milk samples at several time points within 48 hours of collection and within 168 hours for some samples. Child development was assessed using the Ages and Stages Questionnaire 3, completed by 824 women with IBD (treated or untreated) during pregnancy (620 breastfed, and 204 did not). Data on children's health and development were obtained from mothers and pediatricians, along with information on mothers' medication exposure, IBD history, activity, pregnancy, and postpartum complications. We used chi-squared method or Fisher exact test to determine associations between categorical values and compared differences in continuous outcomes between groups using analysis of variance models. The primary outcome was drug concentration of biologic agents in breast milk (from 72 women) at 1, 12, 24, and 48 hours after dosing and also at 72, 96, 120, and 168 hours for available samples. Secondary outcomes were a range of infant infections and Ages and Stages Questionnaire 3-defined developmental delays among all breastfed infants. RESULTS: We detected infliximab in breast milk samples from 19 of 29 treated women (maximum, 0.74 µg/mL), adalimumab in 2 of 21 treated women (maximum, 0.71 µg/mL), certolizumab in 3 of 13 treated women (maximum, 0.29 µg/mL), natalizumab in 1 of 2 treated women (maximum, 0.46 µg/mL), and ustekinumab in 4 of 6 treated women (maximum, 1.57 µg/mL); we did not detect golimumab in breast milk from the 1 woman receiving this drug. Rates of infection and developmental milestones at 12 months were similar in breastfed vs non-breastfed infants: any infection, 39% vs 39% in control individuals (P > .99) and milestone score, 87 vs 86 in control individuals (P = .9992). Rates of infection and developmental milestones did not differ among infants whose mothers received treatment with biologics, immunomodulators, or combination therapy compared with unexposed infants (whose mothers received treatment with mesalamines or steroids or no medication). CONCLUSIONS: In a study of women receiving treatment for IBD and their infants, we detected low concentrations of infliximab, adalimumab, certolizumab, natalizumab, and ustekinumab in breast milk samples. We found breastfed infants of mothers on biologics, immunomodulators, or combination therapies to have similar risks of infection and rates of milestone achievement compared with non-breastfed infants or infants unexposed to these drugs. Maternal use of biologic therapy appears compatible with breastfeeding. Clinicaltrials.gov no.: NCT00904878.