Risk of bleeding associated with antiangiogenic monoclonal antibodies bevacizumab and ramucirumab: a meta-analysis of 85 randomized controlled trials

Abstract Background In recent years, there were many clinical trials assessed the efficacy and safety of monoclonal antibodies (MAbs) in combination with proteasome inhibitors or immunomodulators plus dexamethasone/prednisoneare for the treatment of multiple myeloma (MM). The treatment outcomes of comparing different MAbs in combination with above-mentioned agents remain unknown. We conducted this meta-analysis to compare indirectly the efficacy and safety of MAbs targeting CD38, SLAMF7 and PD-1/PD-L1 in combination with bortezomib/immunomodulators plus dexamethasone/ prednisone in patients with MM. Methods We electronically searched for randomized controlled trials (RCTs) in which at least one of the three MAbs was included among multiple arms. We included eleven eligible RCTs with 5367 patients in the meta-analysis. Statistical analysis used StataMP14 and Indirect Treatment Comparisons software. Results We synthesized hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS), relative risk (RR) for overall response rate, complete response (CR) or better, very good partial response (VGPR) or better, VGPR, partial response, stable disease and grade 3 or higher adverse events among the three groups. The HR for PFS of the CD38 group vs SLAMF7 group, CD38 group vs PD-1/PD-L1 group and SLAMF7 group vs PD-1/PD-L1 group were 0.662(95CI0.543-0.806), 0.317(95CI 0.221–0.454) and 0.479(95CI0.328-0.699) respectively. The HR for OS of the CD38 group vs SLAMF7 group was 0.812(0.584–1.127). The RR for CR or better in the CD38 group versus SLAMF7 group was 2.253(95CI1.284-3.955). The RR for neutropenia of the CD38 group versus SLAMF7 group was 1.818(95CI1.41-2.344). Conclusions Treatment with the CD38 group resulted in longer PFS and better treatment response than the SLAMF7 and PD-1/PD-L1 group. In addition, the SLAMF7 group prolonged PFS compared with the PD-1/PD-L1 group, and had a lower incidence of grade 3 or higher neutropenia than the CD38 and PD-1/PD-L1 group. In

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Different Targets of Monoclonal Antibodies in Neuromyelitis Optica Spectrum Disorders: A Meta-Analysis Evidenced From Randomized Controlled Trials

Frontiers in Neurology ◽

10.3389/fneur.2020.604445 ◽

2020 ◽

Vol 11 ◽

Author(s):

Tao Xue ◽

Jiahao Yu ◽

Shujun Chen ◽

Zilan Wang ◽

Yanbo Yang ◽

...

Keyword(s):

Monoclonal Antibody ◽

Monoclonal Antibodies ◽

Adverse Events ◽

Randomized Controlled Trials ◽

Neuromyelitis Optica ◽

Meta Analysis ◽

Antibody Therapy ◽

Controlled Trials ◽

Monoclonal Antibody Therapy ◽

Randomized Controlled

Background: Neuromyelitis optica spectrum disorder (NMOSD), an autoimmune inflammatory disorder of the central nervous system, often leads to vision loss or paralysis. This meta-analysis focused on the assessment of the monoclonal antibody therapy in NMOSD and compared different targets of monoclonal antibodies with each other in terms of efficacy and safety outcomes.Method: We searched through the databases of MEDLINE, EMBASE, Central Register of Controlled Trials (CENTRAL), and clinicaltrials.gov for randomized controlled trials (RCTs) evaluating monoclonal antibody therapy in NMOSD up to April 2020.Results: We identified seven randomized controlled trials (RCTs), including 775 patients (monoclonal antibody group, n = 485 and placebo group, n = 290). Monoclonal antibody therapy decreased relapse risk (RR 0.33, 95% CI 0.21–0.52, P < 0.00001), annualized relapse rate (ARR) (mean −0.28, 95% CI −0.35−0.20, P < 0.00001), expanded disability status scale score (EDSS) (mean −0.19, 95% CI −0.32−0.07, P = 0.002) and serious adverse events (RR 0.78, 95% CI 0.61–1.00, P = 0.05). However, we did not observe any significant difference in terms of adverse events or mortality. Further, the subgroup analysis demonstrated that the anti-complement protein C5 monoclonal antibody (eculizumab) might have a lower relapse risk (RR 0.07, 95% CI 0.02–0.23, P < 0.0001) in the AQP4 seropositive patients, and anti-interleukin-6 receptor monoclonal antibodies (satralizumab and tocilizumab) showed decreased EDSS score (mean −0.17, 95% CI −0.31−0.02, P = 0.02) more effectively than other monoclonal antibodies.Conclusions: Monoclonal antibodies were effective and safe in NMOSD. Different targets of monoclonal antibodies might have their own advantages.

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