van den Brandt Stephanie, Zbinden Astrid, Baeten Dominique, Villiger Peter M, Østensen Monika, Förger Frauke
Department of Rheumatology, Immunology and Allergology, University Hospital, University of Bern, Freiburgstrasse 8, 3010, Bern, Switzerland.
Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Meibergdreef 9, 1105, AZ, Amsterdam, The Netherlands.
Arthritis Res Ther. 2017 Mar 20;19(1):64. doi: 10.1186/s13075-017-1269-1.
During pregnancy, patients with rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA) can experience active disease, which might be influenced by adjustment of treatment around conception. The aim of this study was to identify possible risk factors of disease flares during pregnancy and to evaluate the effect of treatment in pregnant patients experiencing a flare.
Pregnant patients with RA and axSpA were prospectively followed before, during, and after pregnancy. Disease activity and flares of disease activity were analyzed in regard to medication.
Among 136 pregnant patients, disease flares during pregnancy occurred in 29% of patients with RA and in 25% of patients with axSpA. In both diseases, active disease and tumor necrosis factor inhibitor (TNFi) discontinuation in early pregnancy were identified as risk factors for disease flares during pregnancy. Of 75 patients with RA, 15 patients were on TNFi and discontinued the treatment at the time of the positive pregnancy test. After stopping TNFi, disease activity increased, which was reflected by peaking C-reactive protein levels at the first trimester. The relative risk of flare in patients with RA stopping TNFi was 3.33 (95% CI 1.8-6.1). Initiation of TNFi or glucocorticosteroid (GC) treatment in 60% of these patients resulted in disease improvement at the second and third trimesters. In comparison, patients with RA without TNFi in the preconception period, most of whom had used pregnancy-compatible antirheumatic drugs, showed mild and stable disease activity before and during pregnancy. Of 61 patients with axSpA, 24 patients were on TNFi and discontinued the treatment at the time of the positive pregnancy test. In patients with axSpA stopping TNFi, a disease aggravation at the second trimester could be observed. The relative risk of flare in this group was 3.08 (95% CI 1.2-7.9). In spite of initiated TNFi or GC treatment in 62.5% of these patients, disease activity remained elevated throughout pregnancy. Patients with axSpA without TNFi in the preconception period showed persistent high disease activity from prepregnancy until the postpartum period.
On the basis of a risk-benefit analysis, to stabilize disease activity and to prevent a flare during pregnancy in patients with RA and axSpA, tailored medication including TNF inhibitors should be considered beyond conception.
在孕期,类风湿关节炎(RA)和轴性脊柱关节炎(axSpA)患者可能会出现疾病活动,这可能受受孕前后治疗调整的影响。本研究的目的是确定孕期疾病复发的可能危险因素,并评估治疗对孕期疾病复发患者的效果。
对患有RA和axSpA的孕妇在孕前、孕期和产后进行前瞻性随访。分析疾病活动及疾病活动复发与用药的关系。
在136例孕妇中,29%的RA患者和25%的axSpA患者在孕期出现疾病复发。在这两种疾病中,孕期疾病活动及孕早期停用肿瘤坏死因子抑制剂(TNFi)均被确定为孕期疾病复发的危险因素。在75例RA患者中,15例患者正在使用TNFi,在妊娠试验阳性时停用了该治疗。停用TNFi后,疾病活动增加,这在孕早期C反应蛋白水平达到峰值时得到体现。停用TNFi的RA患者疾病复发的相对风险为3.33(95%可信区间1.8 - 6.1)。这些患者中有60%开始使用TNFi或糖皮质激素(GC)治疗,在孕中期和孕晚期疾病得到改善。相比之下,孕前未使用TNFi的RA患者,其中大多数使用了与妊娠兼容的抗风湿药物,在孕前和孕期疾病活动轻度且稳定。在61例axSpA患者中,24例患者正在使用TNFi,在妊娠试验阳性时停用了该治疗。在停用TNFi的axSpA患者中,可观察到孕中期疾病加重。该组疾病复发的相对风险为3.08(95%可信区间1.2 - 7.9)。尽管这些患者中有62.5%开始使用TNFi或GC治疗,但整个孕期疾病活动仍持续升高。孕前未使用TNFi的axSpA患者从孕前到产后疾病活动持续处于高水平。
基于风险效益分析,为稳定RA和axSpA患者孕期的疾病活动并预防疾病复发,应在受孕后考虑使用包括TNF抑制剂在内的个体化药物治疗。