Adding caplacizumab to standard of care in thrombotic thrombocytopenic purpura: A systematic review and meta-analysis
Djulbegovic M, Tong J, Xu A, Yang J, Chen Y, Cuker A, Pishko A
Blood advances. 2022
Introduction Immune thrombotic thrombocytopenic purpura (iTTP) is an acquired, fatal microangiopathy if untreated. Randomized controlled trials (RCT's) demonstrated faster time-to-response with adding caplacizumab to standard of care (SOC). However, concerns about RCT selection bias and the high cost of caplacizumab warrant examination of all evidence, including real-world observational studies. Methods In this systematic review and meta-analysis, we searched the literature for comparative studies evaluating SOC with or without caplacizumab for the treatment of iTTP. We assessed risk-of-bias using the Cochrane RoB-2 tool (RCT's) and Newcastle-Ottawa Scale (observational studies). The primary efficacy outcome was all-cause mortality, and the primary safety outcome was treatment-emergent bleeding. Secondary outcomes included exacerbation and relapse, refractory iTTP, and time-to-response. Results We included two high-quality RCT's and three observational studies at high-risk-of-bias comprising 632 participants. Compared with SOC, caplacizumab was associated with a non-significant reduction in the RR (0.21 [CI 0.05-1.74]) of death in RCT's and observational studies (RR 0.62 [CI 0.07, 4.41]). Compared with SOC, caplacizumab was associated with an increased risk of bleeding in RCT's (RR 1.37 [CI 1.06, 1.77]). In observational studies, the risk of bleeding was not significantly increased (RR 7.10 [CI 0.90, 56.14]). Addition of caplacizumab was also associated with a significant reduction in refractory iTTP and exacerbation, increased risk of relapse, and shortened response time. Conclusion Frontline addition of caplacizumab does not significantly reduce all-cause mortality compared with SOC alone, although it reduces refractory disease risk, shortens time-to-response, and improves exacerbation rates, at the expense of increased relapse and bleeding risk.
[Effect of convalescent plasma and immunoglobulin on patients with severe acute respiratory syndrome: a systematic review]
Zhu T, Xu A, Bai X, He Y, Zhang H
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2020;32(4):435-438
OBJECTIVE To systematically review evidence for the effect of convalescent plasma and immunoglobulin on treatment of severe acute respiratory syndrome (SARS), and further provide advice on the treatment of coronavirus disease 2019 (COVID-19). METHODS Clinical studies of convalescent plasma and immunoglobulin in the treatment of SARS were collected from a variety of databases such as PubMed, Cochrane Library, Web of Science, Embase, CNKI, VIP, Wanfang, and CBM from November 2002 to March 2020. Two researchers independently screened the literature, extracted the data, and assessed the risk of bias based on the national institute for health and clinical excellence case series quality scale, and systematically evaluated the results. RESULTS A total of 10 clinical studies, including 212 patients, were eventually included. There were 4 case series studies, 5 case reports and 1 case-control study. Most studies were with low or very low quality. The systematic analysis showed that 107 patients administered convalescent plasma and 16 patients used immunoglobulin during the treatment of SARS. Forty-nine patients were definitely not treated with the above two methods, and the remaining 40 patients were not reported clearly. The treatment of convalescent plasma and immunoglobulin could both improve the symptoms and reduce the mortality (12 died), and most SARS patients got better, while 11 SARS patients who did not receive the above therapies died. CONCLUSIONS Convalescent plasma and immunoglobulin were effective on relieving symptoms of SARS patients. However, due to low quality and lacking of control group, convalescent plasma and immunoglobulin should be used with caution to treat COVID-19 patients.
Antepartum immunoprophylaxis of three doses of hepatitis B immunoglobulin is not effective: a single-centre randomized study
Yuan J, Lin J, Xu A, Li H, Hu B, Chen J, Yao J, Dong H, Jiang M
Journal of Viral Hepatitis. 2006;13((9):):597-604.
To investigate the efficacy of antepartum administration of three doses of hepatitis B immunoglobulin (HBIg), currently being used in China, 250 pregnant women who were seropositive for hepatitis B e antigen (HBeAg) were randomly divided into study (117 cases) and control groups (133 cases). Subjects in the study group received HBIg 400 IU intramuscularly once a month at the third, second and first month before delivery; subjects in the control group received no antepartum treatment. All neonates received passive-active immunization after birth. The maternal hepatitis B virus (HBV) markers, hepatitis B surface antigen (HBsAg) titres and HBV deoxyribonucleic acid (DNA) levels were measured at week 28 of gestation (before the antepartum treatment) and at labour; the neonatal serum HBV markers were detected at birth and at 12 months after birth. No side-effects were found in any of the women or their neonates. No statistical differences were seen between the maternal HBsAg and HBV DNA levels of the study and control groups at labour nor the protective efficacy rates of postnatal immunoprophylaxis at 12 months after birth (P > 0. 05, respectively). To conclude, antepartum administration of three doses of HBIg for the HBeAg-positive women is inefficacious.