Minimal to no transfer of certolizumab pegol into breast milk: Results from CRADLE, a prospective, postmarketing, multicentre, pharmacokinetic study

Background Women with chronic inflammatory diseases face uncertainty regarding the safety of biologics during breast feeding. CRADLE was the first industry-sponsored study to evaluate certolizumab pegol (CZP) concentrations in human breast milk and estimate average daily infant dose (ADID) of maternal CZP. Methods CRADLE (NCT02154425) was a pharmacokinetic study of lactating mothers receiving CZP. After ≥3 CZP doses, breast milk samples were collected across one dosing period (14 days for 200 mg every 2 weeks [Q2W]; 28 days for 400 mg every 4 weeks [Q4W]). Optimal analytical methods were developed to determine CZP and polyethylene glycol (PEG) levels in breast milk. ADID and relative infant dose (RID) were estimated. Safety events in mothers and infants were assessed. Results 19 CZP-Treated mothers were screened; 17 entered the sampling period: 16 on 200 mg Q2W, 1 on 400 mg Q4W. 77/137 (56%) breast milk samples had no measurable CZP. For 4/17 mothers, all samples were below the lower limit of quantification (LLOQ). Estimated ADID was 0-0.0104 mg/kg/day; median RID: 0.15%. PEG was undetectable in 134/137 samples (results could not be determined in three samples). Infants of CZP-exposed mothers had a safety profile consistent with that of unexposed similar-Age infants. Conclusion When quantifiable, CZP concentrations were <3× LLOQ (<1% plasma concentration observed with therapeutic dose), indicating no/minimal CZP transfer from plasma to breast milk. RID was 0.15% of maternal dose; <10% is considered unlikely to be of clinical concern. No PEG transfer was observed. CZP absorption by infants via breast milk is unlikely due to its low oral bioavailability and Fc-Â-free molecular structure. These findings are reassuring and support continuation of CZP treatment during breast feeding. Trial registration number NCT02154425; Results

Patterns of Prednisone Use During Pregnancy: Daily and Cumulative Dose

Background: Descriptions of oral corticosteroid use during pregnancy are usually limited to trimester prevalence estimates. We sought to better characterize the use during pregnancy. Methods: Data were collected from MotherToBaby Pregnancy Studies (2005–2014) that enrolled pregnant women with asthma and autoimmune diseases before gestational week 20. Information on medication use and pregnancy outcomes was collected by telephone interview at enrollment, 24 and 32 weeks gestation, and after delivery, plus by medical record review. Women were included if they had a live or still birth and reported dates of oral prednisone use and dose during pregnancy. Women were classified by diagnosis: asthma (n = 15), rheumatoid arthritis (n = 254), Crohn’s disease (n = 39), ankylosing spondylitis (n = 15), and \u3e 1 autoimmune disease (n = 29). Prednisone daily dose and cumulative dose by gestational day were plotted using a heatmap for each individual and stratified by disease. To summarize the many observations for rheumatoid arthritis, we used k-means clustering method to identify and plot group trajectories for prednisone dose. The associations between trajectory group and maternal age, race/ethnicity, socioeconomic status, obesity, rheumatoid arthritis severity as measured by the Health Assessment Questionnaire-Disability Index (HAQ) (range: 0–3) before gestational week 20, and gestational age at delivery were evaluated. Results: Women used prednisone on 1 to 292 days total during pregnancy. Daily doses ranged from 2 to 60 mg for asthma; \u3c 1 to 60 mg for rheumatoid arthritis, ankylosing spondylitis and \u3e 1 autoimmune disease; and \u3c 1 to 70 mg for Crohn’s disease. Total cumulative dose ranged from 15 to 1,325 mg for asthma, 8 to 6,225 mg for rheumatoid arthritis, 10 to 9,105 mg for Crohn’s disease, 60 to 2,720 mg for ankylosing spondylitis, and 20 to 5,120 mg for \u3e 1 autoimmune disease. High-dose prednisone for a short duration was more common for asthma, whereas lower doses for longer was more common for rheumatoid arthritis. For women with rheumatoid arthritis, the highest versus lowest cumulative dose trajectory groups had significantly different disease severity (median HAQ: 0.7 vs 0.0) and gestational length (gestational weeks: 35.9 vs 39.0). Conclusion: The individual-level plots illustrate variability in prednisone dosage (amount and pattern), which may impact pregnancy outcomes. Group trajectories, used to summarize these factors, provide an alternative to the typical trimester exposure approach when studying risks of corticosteroids and other medications during pregnancy

The Impact of US Abortion Policy on Rheumatology Clinical Practice: A Cross-Sectional Survey of Rheumatologists

In June of 2022, the US Supreme Court\u27s decision in Dobbs v Jackson Women’s Health overturned Roe v Wade, finding that there was no federal constitutional right to abortion. Subsequently, almost one third of states have near-total abortion bans in effect. Our team distributed a confidential web-based survey to a sample of US-based rheumatologists to assess how the Dobbs decision is affecting the clinical care of reproductive-age females with rheumatic diseases (RMDs), including teratogen prescribing, pregnancy termination referrals, and rheumatologists’ perceived vulnerability to criminalization