Systematic review with meta-analysis: Efficacy and safety of biological treatment on salivary gland function in primary Sjögren's syndrome

Abstract

Objective: The study aimed to assess the efficacy and safety of clinical trials of biologics in improving the salivary gland (SG) function in primary Sjögren's syndrome (pSS), which has not been analyzed critically and systematically. Methods: PubMed, Web of Science, ClinicalTrials.gov, the EU Clinical Trials Register, and the Cochrane Library were searched for clinical trials that reported effects of biological treatment on the SG function and safety in pSS patients. Inclusion criteria were defined following participants, interventions, comparisons, outcome, and study design (PICOS) recommendations. The objective index (the change of unstimulated whole saliva (UWS) flow) and the serious adverse event (SAE) were assessed as main outcome measures. A meta-analysis of the efficacy and safety of the treatment was conducted. Quality assessment, sensitivity analysis, and publication bias were assessed. The effect size together with a 95% confidence interval was used to estimate the efficacy and safety of biological treatment and was plotted as a forest plot. Results: The literature search yielded 6,678 studies, nine of which fulfilled the inclusion criteria, with seven randomized controlled trials (RCTs) and two non-RCT clinical studies. Generally, biologics do not significantly increase UWS from the baseline of pSS patients compared to the control group at a matched time point (p = 0.55; standard mean difference, SMD = 0.05; 95% confidence interval, CI: -0.11 and 0.21). However, pSS patients with shorter disease duration (≤3 years; SMD = 0.46; 95% CI: 0.06 and 0.85) were prone to have a better response to biological treatment by showing higher increased UWS than patients with longer disease duration (> 3 years; SMD = -0.03; 95% CI: -0.21 and 0.15) (p = 0.03). For the meta-analysis of the safety of biological treatment, the SAEs in the biologics group were significantly higher than those of the control group (p = 0.0021; log odds ratio, OR = 1.03; 95% CI: 0.37 and 1.69). Conclusion: Biological intervention during the early course of the disease may benefit pSS patients better than that during the late course. Significantly, more SAEs in the biologics group indicate that the safety of biologics needs to be addressed for future biological clinical trials and treatment.

Keywords: biologics; efficacy; meta-analysis; primary Sjögren’s syndrome; safety; salivary gland function.