Efficacy and Safety of Iguratimod Combined with Methylprednisolone for Primary Sjögren's Syndrome: a Meta-analysis and Trial Sequential Analysis

Objective: The purpose of this study is to evaluate the combination of iguratimod (IGU) and methylprednisolone (MP) for the efficacy and safety of primary Sjögren's syndrome (pSS) by a meta-analysis and a trial sequential analysis (TSA).

Materials And Methods: Clinical studies of IGU combined with MP for pSS were searched through eight databases. Revman 5.3 and TSA 0.9.5.10 Beta were used for the meta-analysis and TSA.

Results: In terms of efficacy endpoints, compared with "HCQ+MP" group, "IGU+MP" group decreased erythrocyte sedimentation rate (ESR) [mean difference (MD)=-5.15, 95% confidence interval (CI)=(-7.37, -2.93), p<0.0001], immunoglobulin G (IgG) [MD=-3.38, 95% CI=(-4.13, -2.64), p<0.00001], immunoglobulin M (IgM) [MD=-0.64, 95% CI=(-1.19, -0.09), p=0.02], Immunoglobulin A (IgA) [MD=-1.16, 95% CI=(-1.92, -0.39), p=0.003], EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) [MD=-1.62, 95% CI=(-2.07, -1.17), p<0.0001], EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) [MD=-2.07, 95% CI=(-2.54, -1.59), p<0.0001], increase platelet (PLT) [MD=13.21, 95% CI=(9.77,16.65), p<0.00001], and improve Schirmer I test (SIT) [MD=1.86, 95% CI=(1.40, 2.32), p<0.0001]. TSA presented that these benefits observed with the current information volume were all conclusive, except for IgM. In terms of safety endpoints, the total adverse event rates (AEs), leucopenia, gastrointestinal (GI) AEs, skin diseases, and liver dysfunction of the "IGU+MP" group and the "HCQ+MP" group were comparable. And TSA indicated that the results need to be confirmed by additional studies. Harbord regression showed no publication bias (p=0.986).

Conclusions: IGU combined with MP effectively attenuates autoimmune responses (IgG, IgM, IgA), reduces clinical symptoms and disease activity (ESR, PLT, ESSPRI, ESSDAI), and improves the exocrine gland functional status (SIT) in patients with pSS. IGU combined with MP does not increase the risk of adverse events, which means that IGU combined with MP may be a safe and effective strategy for the treatment of pSS and has value for further research exploration.