Efficacy Of Ultra-low Dose Rituximab Combined With Low-dose Hormone In Moderate Pemphigus

BackgroundPemphigus is a fatal and rare chronic relapsing inflammatory bullous disease.The main clinical manifestations were blisters and bullae on the basis of erythema.As an autoimmune disease,pemphigus has been mainly treated with high-dose glucocorticoids since the 1950 s.Although the use of high-dose glucocorticoids has reduced the mortality rate of pemphigus patients from 75% to 30%,the side effects it brings to patients should not be underestimated,including femoral head necrosis,infection,obesity,atrophic striae,skin telangiectasia,metabolic disorders,electrolyte imbalance,etc,and these side effects seriously affect the quality of life of patients.In order to reduce the side effects caused by hormones and better control the condition of pemphigus patients,numerous researchers are committed to exploring a better pemphigus treatment regimen.With the application of targeted biologics in autoimmune diseases,B cells as a cell that plays a key role in autoimmune diseases,the application of B cell-targeted drugs in autoimmune diseases has received increasing attention.Rituximab(RTX),a B-cell targeted drug,has been gradually tried in autoimmune diseases,including rheumatoid arthritis,systemic lupus erythematosus,and pemphigus.As more and more clinical studies have been conducted,the efficacy of rituximab in the treatment of pemphigus has been well documented.Objective1.To investigate the efficacy and safety of low-dose and half-dose rituximab combined with glucocorticoids and glucocorticoids combined with immunosuppressive agents in the treatment of moderate pemphigus.MethodIn this study,36 patients with pemphigus who visited the Dermatology Hospital of Southern Medical University from January 2021 to December 2021 were included,and finally 30 patients completed the follow-up.All patients met the inclusion criteria and voluntarily signed the informed consent form.Subjects were divided into three groups:low-dose rituximab group(ULRTX),half-dose rituximab group(LRTX),and no rituximab group(NRTX).In the low-dose rituximab group,one 200 mg rituximab infusion was administered on Day 1,Week 2,and Months 6-9.In the half-dose rituximab group,one infusion of 500 mg rituximab was administered on day 1,week 2,and months 6 –9.The hormone combined with immunosuppressive agent group was treated with10-20 mg MTX combined with glucocorticoid.After treatment,follow-up at day 1,2weeks,3 months,6 months,9 months and 12 months included the following indicators:time to achieve disease control,time to complete remission after treatment,pemphigus disease area index score,monthly average dosage of prednisone,12-month cumulative dose of prednisone,recurrence rate,treatment-emergent adverse reactions,anti-Dsg1 antibody titer,anti-Dsg3 antibody titer and peripheral blood B lymphocyte percentage.The differences in the efficacy among the three groups were compared and observed.Results1.All patients treated with rituximab in this experimental study achieved complete remission after treatment,and a total of 7 patients achieved complete remission during the follow-up period in the NRTX group.The median time to complete remission after treatment was 139.5(30-227)days,120(62-228)days and 268(126-360)days in ULRTX group,LRTX group and NRTX group,respectively.2.Compared with the PDAI scores of the three groups,there was no statistical difference between the ULRTX group and the LRTX group(P = 0.096 > 0.05),there was statistical difference between the NRTX group and the ULRTX group(P < 0.001),and there was statistical difference between the NRTX group and the LRTX group(P <0.001).The PDAI score showed statistical difference from the third month among the three groups(P < 0.05).3.Compared with the average dosage of prednisone per month,there was no statistical difference between ULRTX and LRTX groups(P = 0.969 > 0.05),between ULRTX and NRTX groups(P = 0.005 < 0.05),and between LRTX and NRTX groups(P =0.004 < 0.05).4.Disease control was achieved in all three groups during the 12-month follow-up period in this study.The mean time to disease control was 20.4 ± 6.55 days in the ULRTX group,16.1 ± 14.15 days in the LRTX group,and 21.9 ± 15.16 days in the NRTX group.There was no statistical difference in the time to achieve disease control among the three groups(P > 0.05).5.In this study,there was a statistically significant difference in the percentage of patients achieving complete remission after treatment among the three groups(P =0.024 < 0.05).6.All patients treated with rituximab in this study did not experience relapse during the 12-month follow-up period,whereas a total of 7 patients experienced relapse during the 12-month follow-up period in the NRTX group,3 of whom had relapsed twice during the 12-month follow-up period.ConclusionsRituximab combined with glucocorticoids has better clinical advantages compared with traditional treatment of glucocorticoids combined with immunosuppressive agents,which can reduce the cumulative dosage of glucocorticoids,reduce the number of disease relapses,and prolong remission time.Compared with half-dose rituximab,low-dose rituximab has no statistical difference in the clinical efficacy in the treatment of pemphigus,and can rapidly reduce the percentage of peripheral blood B cells within two weeks and has the same therapeutic effect,so it has more clinical application value for moderate pemphigus.