Tumour necrosis factor inhibitor combined with intravenous immunoglobulin and heparin for treatment of recurrent spontaneous abortion: A two‐centre, retrospective, cohort study

Immune disorder is a key trigger of recurrent spontaneous abortion (RSA); meanwhile, tumour necrosis factor inhibitor (TNFi) is a fundamental therapeutic for multiple immune and inflammatory diseases. Hence, this real-world study aimed to explore the efficacy and safety of TNFi combined with intravenous immunoglobin (IVIG) and heparin therapy in RSA patients.A total of 105 RSA patients who received TNFi+IVIG+Heparin (enoxaparin) (n = 48) or IVIG+Heparin (enoxaparin) (n = 57) were retrospectively included in this two-centre cohort study.The live birth rate of RSA patients in the TNFi+IVIG+heparin group was 72.9% (95% confidence interval [CI]: 69.6%-85.9%). Besides, the live birth rate in the IVIG+heparin group was 52.6% (95% CI: 42.8%-62.4%). By comparison, the live birth rate was higher in the TNFi+IVIG+heparin group compared to the IVIG+heparin group (p = 0.033). After adjustment by the multivariate logistic regression model using the enter method, TNFi+IVIG+Heparin was also superior to IVIG+Heparin regarding increased live birth rate (odds ratio [OR] = 2.941, p = 0.015). Moreover, TNFi+IVIG+Heparin (vs. IVIG+Heparin) also served as an independent factor for increased live birth rate (OR = 2.423, p = 0.035) by the forward stepwise method in the multivariate analysis. Gestational weeks at delivery (38.3 ± 1.3 vs. 37.7 ± 2.0 weeks, p = 0.155), newborn weight (3123.9 ± 332.1 vs. 3056.6 ± 287.4 g, p = 0.390), Apgar score of newborns (9.8 ± 0.5 vs. 9.7 ± 0.7, p = 0.271) were of no difference between TNFi+IVIG+Heparin and IVIG+Heparin groups. In terms of safety profile, the adverse events were of no difference between the TNFi+IVIG+Heparin and the IVIG+Heparin groups (all p > 0.05), either.TNFi combined with IVIG and heparin therapy improves the live birth rate but does not elevate the adverse events compared to IVIG and heparin therapy in RSA patients.