Ustekinumab Exposure in Pregnant Women From Inflammatory Bowel Disease Clinical Trials: Pregnancy Outcomes Through Up To 5 Years in Crohn's Disease and 2 Years in Ulcerative Colitis.

Background: While no adverse developmental outcomes were observed in preclinical animal studies, limited data exist regarding effects of ustekinumab on human pregnancies. Previously, no data have been reported for women treated with ustekinumab in inflammatory bowel disease (IBD) clinical trials and corresponding pregnancy outcomes. Here, we present pregnancy outcomes from IBD clinical trials, incorporating 5 years of treatment in Crohn's disease (CD) and 2 in ulcerative colitis (UC). Methods: All patients in the clinical trials agreed to use adequate birth control and were discontinued from treatment upon pregnancy confirmation. Nonetheless, 39 pregnancies occurred with maternal ustekinumab exposure from 4 CD and 1 UC study. Maternal and neonatal outcomes and data are presented with summary statistics, where available. Results: Of 1289 women who received ≥1 dose of ustekinumab, 39 maternal pregnancies with outcomes were reported (pregnancy cohort). Median maternal age was 28.0 years and median duration of ustekinumab treatment before pregnancy was 63.7 weeks with the last dose of ustekinumab administered prior to or during the first trimester (terminal half-life of ~3 weeks). Outcomes for the 39 pregnancies were: 26 live births (all normal newborns), 8 spontaneous abortions, and 5 elective abortions. No congenital anomalies were reported among normal newborns and no safety signals emerged with neonatal outcomes. Conclusions: Based on this series of 39 pregnancies with outcomes from IBD clinical trials, mothers treated with ustekinumab (limited to up to the first trimester) did not demonstrate a risk of negative outcomes. More data are needed to characterize the safety profile of ustekinumab use during pregnancy.

First rib resection and scalenectomy for chronically occluded subclavian veins: what does it really do?

First rib resection and scalenectomy is an acceptable therapy for those with axillosubclavian vein thrombosis who have responded to lytic therapy and demonstrated subclavian vein patency. However, the treatment for those patients who present with a chronically occluded subclavian vein is controversial. We present four such patients who underwent first rib resection and scalenectomy and whose subclavian vein spontaneously opened within the first year following surgery while anticoagulated, as well as the ultrasound protocol we employ at our institution to identify such reopening. The average age of these patients was 20 (range 17-23) years; three were male and one was female. The average time interval prior to surgery when the initial thrombosis occurred was 25 (12-34) weeks. All patients were symptomatic and underwent a transaxillary first rib resection and scalenectomy with attention to incise the subclavius tendon. All were maintained on warfarin postoperatively and surveilled by duplex scan. In all four patients the subclavian vein subsequently opened after an average of 7 (2-11) months and anticoagulation was stopped. The resultant patent subclavian vein correlated with improvement in symptoms in all four patients. All patients were asymptomatic in the postoperative follow-up period at an average of 14 (2-33 months). In conclusion, selective symptomatic patients with subclavian vein occlusion can be aggressively treated with first rib resection and scalenectomy along with anticoagulation that will lead to recanalization and opening of vein over time. This treatment correlates with improvement of their symptoms.

Multiple treatment algorithms for successful outcomes in venous thoracic outlet syndrome.

BACKGROUND: We sought to determine the outcomes in patients presenting with venous thoracic outlet syndrome. METHODS: Prospectively collected data from 67 patients between October 2003 and December 2007. The average age was 31 years (range, 16-54); the 37 males and 30 females presented on average 9.2 months (range, 1 month-6 years) after acute thrombosis. Four treatment algorithms were utilized. RESULTS: In group 1, 3 patients presented with acute occlusion and received tissue plasminogen activator (tPA) and immediate first rib resection with scalenectomy (FRRS). One vein rethrombosed and was treated by intravenous tPA postoperatively. In group 2, 39 patients presented with stenotic subclavian veins an average of 22 weeks after their initial thrombosis, all of whom underwent FRRS followed by a venogram 2 weeks postoperatively: 25 had a tight stenosis and underwent venoplasty with anticoagulation; 13 had patent, nonstenotic subclavian veins, and 1 patient required tPA and venoplasty owing to rethrombosis. Two patients had their subclavian vein thrombose after venoplasty and were treated with anticoagulation, tPA, and venoplasty. In group 3, 11 patients presented with intermittent venous obstruction without thrombosis and underwent FRRS; 3 underwent venograms because of concerns of residual stenosis, 2 of whom required venoplasty postoperatively. Finally, in group 4, 14 patients presented with occluded subclavian veins and underwent FRRS with long-term anticoagulation. Eleven have recanalized at an average of 6 months (range, 2-12). CONCLUSION: Overall, 64 of 67 patients have patent subclavian veins after a median follow-up of 10 months, and all patients are asymptomatic for a success rate of 96%. Tailored treatment algorithms including FRRS, postoperative venograms with or without intervention, and the use of long-term anticoagulation seems to be required in this complicated group of young patients to achieve optimal results.