The Effectiveness and Safety of Total Glucosides of Paeony in Primary Sjögren's Syndrome: A Systematic Review and Meta-Analysis

Abstract

Objective: To assess the effectiveness and safety of the total glucosides of paeony (TGP) on the treatment of primary Sjögren's syndrome (pSS) by conducting a meta-analysis. Methods: Eight databases were searched from their inception to December 10, 2018 for randomized controlled trials (RCTs). The Revman 5.3 software was used for this meta-analysis. Results: Nine RCTs which included 770 participants were identified. Pooled results showed that significant difference in Schirmer's test ( P < 0.00001) comparing TGP with placebo (PBO). However, the pooled results displayed significant differences in salivary flow rate, Schirmer's test, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), serum γ-globulin, immunoglobulin G (IgG), IgA, IgM, and effective rate ( P ≤ 0.01) in the co-administration of TGP with immunosuppressant (IS) compared with IS alone. Subgroup analyses revealed both heterogeneities in ESR and serum γ-globulin were eliminated, showing combined intervention of TGP + IS being more advantageous than single usage of IS ( P < 0.00001). However, the advantage varied among three subgroups and showed a gradual weakening over time. Furthermore, our results showed statistical significance in Schirmer's test ( P = 0.0006), when hydroxychloroquine (HCQ) was jointly applied, but not in the case of combined TGP with methotrexate (MTX) ( P = 0.41). For the safety analysis, the most common adverse events (AEs) were diarrhea or gastrointestinal discomfort, and no severe AEs were reported in TGP group. Meanwhile, six trials showed statistically insignificant differences between TGP + IS and IS in AEs ( P = 0.76). Conclusions: Improving the lacrimal gland secretion (Schirmer's test) is the prominent function of TGP compared with PBO. TGP + IS can improve the clinical symptoms, such as lacrimal and salivary gland secretion function (Schirmer's test, salivary flow rate), inflammatory indices (ESR, CRP, and RF) and immunoglobulins (γ-globulin, IgG, IgA, and IgM) on the basis of IS monotherapy. In addition, TGP has an acceptable safety profile and AEs were not increased when TGP combined with IS in pSS. Therefore, TGP can be considered to be a potentially valid and safe drug for the treatment of pSS in the clinic. In view of the limitations of the included trials, the potential beneficial effectiveness and safety of TGP need additional high-quality, multi-center, and large-scale RCTs to assess its use in pSS treatment.

Efficacy and safety of Tripterygium glycosides in Sjögren’s syndrome treatment: evidence from 12 randomized controlled trials

“…Therefore, combination therapy including TGs with other therapies may be more effective than single treatment interventions. The present meta-analysis demonstrated that TGs combined with TGP significantly reduced the levels of CRP and immunoglobulins (IgG, IgM, and IgA) to an extent greater than TGs alone, which may be related to the synergistic effect of TGP on reducing immunoglobulins (43) or regulating immune homeostasis by modulating the Th17/Treg ratio (28). Despite the promising therapeutic potential of TGs for patients with SS, the incidence of adverse events is worthy of discussion.…”

Effectiveness and Safety of Iguratimod in Treating Primary Sjögren’s Syndrome: A Systematic Review and Meta-Analysis

“…Our meta-analysis suggested that the IGU group showed lower ESR than the non-IGU group, which was also observed in Shao’s study of 24 weeks ( Shao et al, 2020 ). Previous research studies have shown that HCQ or TGP can reduce ESR ( Feng et al, 2019 ; Bodewes et al, 2020 ); thus, IGU might enhance the anti-inflammatory activity of HCQ or TGP through a synergistic effect or independent pathways. In patients treated with IGU along with HCQ and GC, the RF level significantly decreased compared to that in patients treated with HCQ and GC.…”

Update on disease pathogenesis, diagnosis, and management of primary Sjögren’s syndrome

“…Total glucosides of paeony (TGP) is a common Chinese medicine, which has been recorded with analgesic, anti‐inflammatory, immunomodulatory effects, and few side effects. Decreasing the substantial damage of glands and improving the secretion of lacrimal glands (Schirmer's test), are the significant functions of TGP 26 . At the same time, studies have shown that TGP can enhance the negative co‐stimulation pathway programmed cell death protein 1 (PD‐1)/PD‐L1 expression by reducing the expression of soluble PD‐1, further regulating Th17/Treg balance and reducing the production of autoantibodies.…”