Biologic drugs in adult onset Still’s disease: a systematic review and meta-analysis of observational studies

<p><b>Background</b>: Biological drugs, mainly interleukin (IL)-1 and IL-6 antagonists, but also tumor necrosis factor (TNF) inhibitors, have been used in the treatment of adult onset Still’s disease patients (AOSD).</p> <p><b>Methods</b>: We summarised the available evidence for the effectiveness of biologic drugs in AOSD. A systematic review of the literature was performed in order to identify all the available data concerning the effectiveness of biologic drugs in AOSD. The proportion of patients achieving complete remission or any clinical response was calculated. The meta-analysis was thus performed using a random-effects model accounting for the expected high level of heterogeneity.</p> <p><b>Results</b>: Nineteen observational published studies were included in the meta-analysis. The pooled analysis under a random-effects model showed an overall rate of clinical response of 0.85 (95% CI: 0.77–0.91, p < 0.0001) and an overall rate of complete remission of 0.66 (95% CI: 0.54–0.77, p = 0.01). The heterogeneity across studies was high (Q = 59.82 with df = 19.0, p < 0.0001, I² = 68.23%).</p> <p><b>Conclusions</b>: Our meta-analysis suggests that AOSD patients may experience a clinical response and/or a complete remission when treated with biologic drugs. Specifically designed and powered studies are needed to fully investigate the role of such medications in the management of AOSD patients.</p

Receiver operator characteristic (ROC) curve of mean value DAS28(ESR) in predicting the development of type 2 diabetes (T2D).

<p>Receiver operator characteristic (ROC) curve of mean value DAS28(ESR) in predicting the development of type 2 diabetes (T2D).</p

Study design.

<p>* In the pre-recruitment screening phase, patients were excluded if presented: 1) past diagnosis of T2D previously performed by a physician <i>or</i> 2) current or past treatment with antidiabetic medications (including oral antidiabetic drugs and insulin); 3) fasting plasma glucose (FPG) ≥ 126 mg/dL in at least two separate occasions. ** In the recruitment screening phase patients were excluded if fasting plasma glucose (FPG) ≥ 126 mg/dL.</p

Logistic regression analysis for prediction of new-onset impaired fasting glucose.

<p>Logistic regression analysis for prediction of new-onset impaired fasting glucose.</p

Logistic regression analysis for prediction of new-onset type 2 diabetes.

<p>Logistic regression analysis for prediction of new-onset type 2 diabetes.</p

Demographic and clinical characteristics of the study cohort.

<p>Demographic and clinical characteristics of the study cohort.</p

Receiver operator characteristic (ROC) curve of mean value DAS28(ESR) in predicting the development of type 2 diabetes (T2D).

<p>Receiver operator characteristic (ROC) curve of mean value DAS28(ESR) in predicting the development of type 2 diabetes (T2D).</p

Baseline clinical characteristics.

<p>Baseline clinical characteristics.</p

Predictive factors of new CVEs onset.

<p>Predictive factors of new CVEs onset.</p

Effectiveness and disease activity evaluation in the enrolled patients.

<p>This Figure shows: A) and B) the progressive reduction of both DAS28 and SDAI values; C) the disease activity at the first observation and after 12 months of follow up, respectively; E) the EULAR response criteria after 12 months of follow up.</p