| Objective(s):B-cell activator(BAFF)is an important signaling molecule for B cell survival and development,and its increased expression may be related to the pathogenesis of immune thrombocytopenia(ITP).At present,ITP is considered as a heterogeneous autoimmune disease involving B lymphocytes and T lymphocytes.To evaluate the efficacy and safety of BAFF-targeting belimumab combined with T-cell-targeting cyclosporine in the treatment of glucocorticoid-refractory ITP,we initiated a single-center,small-sample exploratory study,hoping to provide a new approach for the treatment of glucocorticoid-refractory ITP.Methods:Included patients met the diagnostic criteria of Chinese ITP guidelines or were diagnosed as connective tissue disease secondary ITP;And platelet count≤30×10~9/L or platelet count<50×10~9/L accompanied by bleeding symptoms;And did not respond to glucocorticoid therapy or relapse after glucocorticoid;And the course of the disease was longer than 3 months.They were treated with Belimumab,10mg/kg/time,intravenously infusion at week 0,2,and 4,then every 4 weeks until week 24;Meanwhile,cyclosporine was taken orally 2.5-3mg/kg/day for 24 weeks.The primary endpoint was assessed at week 52 and was set as the overall response rate.Secondary endpoints included response rate at other time points,duration of response,adverse events,and lymphocyte subsets.Results:At present,a total of 11 patients were included,among which 8 patients were available for efficacy analysis,with a male to female ratio of 1:7,aged 42-61,and an average age of 52.50±7.8 years,the median duration of thrombocytopenia was12.5 years(1.75-22.50).Immune thrombocytopenia secondary to systemic lupus erythematosus or Sjogren’s syndrome was present in 3 of the 8 patients(37.5%).As of January 31,2023,the median follow-up time was 7 months(4.00-10.75),and none of the eight patients reached the evaluation time for the primary endpoint.At present,4patients were evaluated for efficacy at 6 months,with a response rate of 50%(2/4),and a sustained response rate of 25%(1/4)over 6 months,showing a complete response.This patient with sustained response was diagnosed as secondary ITP(secondary to Sjogren’s syndrome),recurrent after splenectomy,defined as refractory ITP,and platelet sustained response time has reached 10 months.Another patient with Sjogren’s syndrome achieved a complete response at week 2 and has maintained it since,with platelet response lasting 4.5 months.In general,platelet response in the first 12 weeks was better in patients with a shorter course of disease than in patients with a longer course of disease(P<0.05);Whereas there was no significant difference in platelet response between patients with primary ITP and secondary ITP in the first12 weeks(P>0.05).Four patients were tested for platelet antibodies,three positive and one negative.Platelet response in the first 12 weeks was better in platelet-antibody positive patients than in platelet-antibody negative patients(all platelet-antibody positive patients were in the shorter course group,while platelet-antibody negative patients were in the longer course group).Similar to other studies of Belimumab,transitional B cells,naive B cells,and plasmablasts/plasma cells all declined after treatment,while memory B cells temporarily increased.The combination treatment was well tolerated,and no serious adverse reactions,severe hypogammaglobulinemia,or severe infection were observed.Conclusion(s):Belimumab in combination with cyclosporine may be an effective ITP treatment regimen with an acceptable safety.Preliminary results from our exploratory study suggest that patients with shorter duration of glucocorticoid-refractory ITP may benefit more from this combination therapy,and combination therapy may have some application prospect in patients with connective tissue disease secondary ITP.The present results provide a preliminary basis for future efficacy and safety validation in larger sample size randomized controlled trials. |
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