Is Chinese herbal formula (nourishing Yin therapy) effective and well tolerated as an adjunct medication to hydroxychloroquine in the treatment of primary Sjögren’s syndrome? A meta-analysis of randomised controlled trials

BACKGROUND: Previously, data mining methodology was used to identify 71 patented prescriptions in Chinese patent databases, indicating that Yin-nourishing therapy (YNT) may be an adjunct medication to hydroxychloroquine in the treatment of primary Sjögren’s syndrome (pSS). The purpose of this study was to investigate effects of the addition of YNT, which includes tonifying liver and kidney therapy (TLKT) and replenishing Qi and nourishing Yin therapy (RQNYT), in the treatment of pSS. METHODS: Fourteen databases (including Chinese, English, Japanese, Korean and Latin databases) were searched to identify randomised controlled trials (RCTs) of YNT plus hydroxychloroquine (YNTPH) versus hydroxychloroquine alone in patients with pSS. Relevant publications up to June 2021 were selected. A meta-analysis and trial sequential analysis (TSA) were performed using Review Manager 5.3, Stata 14.0 and TSA 0.9 software. The quality of identified studies was assessed based on the Cochrane risk of bias tool and GRADE (grading of recommendations, assessment, development and evaluation) criteria. RESULTS: We included five RCTs with a total of 345 participants. Pooled results indicated significant differences in short-term outcomes, which were assessed via European League Against Rheumatism (EULAR) Sjögren’s Syndrome Patient Reported Index (ESSPRI), EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI), tear production, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and immunoglobulin G (IgG) results when YNTPH was compared with hydroxychloroquine use alone (p < 0.05). No significant difference in salivary flow rate was reported. The most common side effect reported for both groups was gastrointestinal reaction. Sensitivity analyses suggested that heterogeneity might be ascribed to clinical methodology. Subgroup analyses revealed heterogeneities regarding salivary flow rate were eliminated. TLKT appeared to be better than RQNYT for improving salivary flow rate. TSA only supported changes in ESSPRI, ESSDAI and ESR values. For all studies, the quality of evidence was low. CONCLUSION: YNTPH may be an effective complementary therapy. Current evidence, however, is insufficient for determining whether YNTPH is more effective than hydroxychloroquine alone. Well-designed RCTs are needed to determine the role of YNT in pSS treatment.