A methodological review with meta-epidemiological analysis of preclinical systematic reviews with meta-analyses.

Systematic reviews and meta-analyses have been proposed as an approach to synthesize the literature and counteract the lack of power of small preclinical studies. We aimed to evaluate (1) the methodology of these reviews, (2) the methodological quality of the studies they included and (3) whether study methodological characteristics affect effect size. We searched MEDLINE to retrieve 212 systematic reviews with meta-analyses of preclinical studies published from January, 2018 to March, 2020. Less than 15% explored the grey literature. Selection, data extraction and risk of bias assessment were performed in duplicate in less than two thirds of reviews. Most of them assessed the methodological quality of included studies and reported the meta-analysis model. The risk of bias of included studies was mostly rated unclear. In meta-epidemiological analysis, none of the study methodological characteristics was associated with effect size. The methodological characteristics of systematic reviews with meta-analyses of recently published preclinical studies seem to have improved as compared with previous assessments, but the methodological quality of included studies remains poor, thus limiting the validity of their results. Our meta-epidemiological analysis did not show any evidence of a potential association between methodological characteristics of included studies and effect size.

Efficacy and safety of steroid-sparing treatments in giant cell arteritis according to the glucocorticoids tapering regimen: A systematic review and meta-analysis.

OBJECTIVES: To assess the efficacy and safety of adjuvant therapies in newly diagnosed or relapsing giant cell arteritis (GCA) in terms of relapse rate at week 52 (primary outcome) and to assess the impact of GC tapering regimen on adjuvant effectiveness. METHODS: For this systematic review and meta-analysis, we searched PubMed, EMBASE, CENTRAL, trial registries, from inception to November 2020. We included all randomized controlled trials (RCTs) and controlled prospective studies evaluating adjuvant treatments in GCA, without date or language restriction. Two reviewers independently selected studies, extracted data and assessed risk of bias. Quality of evidence was summarised with GRADE. RESULTS: Of the 680 records identified, 16 studies were included (1,068 participants) evaluating various adjuvant therapies compared to GC only. No study compared adjuvants with each other. Risk of bias was high in 5/7 trials evaluating our primary outcome. Risk of relapse at week 52 was reduced for only the anti-IL6 and IL6-receptor drug class versus the control (RR=0.45, 95%CI 0.30-0.66, I2=38%), particularly tocilizumab (RR=0.38, 95%CI 0.23-0.63, I2=42%) with a moderate quality of evidence. We found no significant interaction according to GC tapering regimen. Our meta-analysis did not show a significant benefit for methotrexate. Except for dapsone, ciclosporine and hydroxychloroquine, other adjuvants did not seem to show increased risk of adverse events. CONCLUSIONS: Tocilizumab seems to reduce the relapse rate in GCA at week 52 but the quality of evidence was moderate. No other molecule has shown efficacy. No significant interaction on relapse rate by GC tapering regimen was found. STUDY REGISTRATION: PROSPERO CRD42020172011.

Serum IgG2 levels predict long-term protection following pneumococcal vaccination in systemic lupus erythematosus (SLE).

Systemic lupus erythematosus (SLE) patients are at risk for pneumococcal infection. Twenty-one consecutive SLE patients (40[25-75] years) received the sequential PCV13/PPSV23 vaccine and factors associated with long-term protection were analyzed. Immune protection, defined by an antigen-specific IgG concentration ≥1.3 µg/mL for at least 70% of 7 pneumococcal serotypes was assessed at baseline, 2, 6, 12 and 36 months defining long-term protection. Only 10 patients showed pneumococcal immune protection 36 months after vaccination. Eleven (52.4%) patients had no long-term protection with a seroconversion that never or only transiently occurred. SLE disease features, treatment received and immunological characteristics did not differ between protected and unprotected patients except for the pre-vaccination IgG2 serum levels. Serum IgG2 level >2.125 µg/ml showed a sensitivity of 100% and a specificity of 90.9% for long-term protection. Sequential pneumococcal vaccination conferred poor immune protection in SLE. Baseline IgG2 serum level identified patients able to benefit from pneumococcal vaccination.