Background:There is very limited information about the passage of biologics into breast milk and into the peripheral blood of breastfed infants. However, based on pharmacological properties of biologic DMARDs (bDMARDs) lactation may not be discouraged in patients with chronic inflammatory rheumatic disease to treat or prevent postpartum relapses. We here report two cases treated with bDMARDs during lactation: one woman with Muckle-Wells syndrome (MWS) treated with canakinumab and one woman with microscopic polyangiitis (MPA) treated with rituximab.Objectives:To determine the level of rituximab and canakinumab in breast milk, in sera of breastfed infants as well as in sera of the mother and to calculate the average daily infant dose and the relative infant dose.Methods:Serum and milk levels of Rituximab were measured by ELISA using commercially available coating and detection antibodies. For Canakinumab an ELISA was established by coating of plates with recombinant human IL-1beta and detection of Canakinumab in samples by a polyclonal anti-human IgG coupled to HRP. In both cases separate standard curves for serum and milk were established. Serum samples and milk samples of unexposed healthy controls were used to determine the lower limit of quantification.Results:One patient with MWS received canakinumab 150 mg s.c. to treat a worsening of her disease ten days postpartum. She continued to breastfeed her child. The average concentration of canakinumab in milk samples collected on 10 consecutive days was 15.8 ng/ml. The average daily infant dose was 0.002 mg/kg/day. The relative infant dose, which refers infant to maternal exposure on a dose/weight basis, was 0.11%. There was no detectable canakinumab in the serum of the infant.One patient with MPA received rituximab 500 mg i.v. as a remission maintenance therapy four months postpartum. She continued to breastfeed her child. The average concentration of rituximab in milk samples collected on 4 consecutive days was 3.71 ng/ml. The average daily infant dose was 0.001 mg/kg/day. The relative infant dose was 0.01%. There was no detectable rituximab in the serum of the infant.Conclusion:Only minimal concentrations of canakinumab and rituximab can be detected in breastmilk. For both bDMARDs, the relative infant dose was below 1% of the maternal dose, which is considered unlikely to be of clinical concern. The lack of detectable levels of canakinumab and rituximab in the infants’ sera supports the notion of low oral bioavailability of large monoclonal antibodies. Together, the results are similar to those seen in TNF inhibitors which are regarded to be compatible with breastfeeding, yet more data are needed (1, 2, 3).References:[1]Götestam Skorpen C, Hoeltzenbein M, Tincani A, Fischer-Betz R, Elefant E, Chambers C, da Silva J, Nelson-Piercy C, Cetin I, Costedoat-Chalumeau N, Dolhain R, Förger F, Khamashta M, Ruiz-Irastorza G, Zink A, Vencovsky J, Cutolo M, Caeyers N, Zumbühl C, Østensen M. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis. 2016 May;75(5):795-810. doi: 10.1136/annrheumdis-2015-208840. Epub 2016 Feb 17.[2]Clowse ME, Förger F, Hwang C, Thorp J, Dolhain RJ, van Tubergen A, Shaughnessy L, Simpson J, Teil M, Toublanc N, Wang M, Hale TW. Minimal to no transfer of certolizumab pegol into breast milk: results from CRADLE, a prospective, postmarketing, multicentre, pharmacokinetic study. Ann Rheum Dis. 2017 Nov;76(11):1890-1896. doi: 10.1136/annrheumdis-2017-211384. Epub 2017 Aug 16.[3]Matro R, Martin CF, Wolf D, Shah SA, Mahadevan U. Exposure Concentrations of Infants Breastfed by Women Receiving Biologic Therapies for Inflammatory Bowel Diseases and Effects of Breastfeeding on Infections and Development.Gastroenterology. 2018;155(3):696–704. doi:10.1053/j.gastro.2018.05.040Disclosure of Interests:Astrid Zbinden: None declared, Klara Eriksson: None declared, Frauke Förger Grant/research support from: Unrestricted grant from UCB, Consultant of: UCB, GSK, Roche, Speakers bureau: UCB, GSK
Salicylic acid in the serum of subjects not taking aspirin. Comparison of salicylic acid concentrations in the serum of vegetarians, non-vegetarians, and patients taking low dose aspirin
