Meet the Expert Therapy

ABATACEPT AS A LONG-TERM TARGETED THERAPY FOR LRBA DEFICIENCY

Lecture Time
15:25 - 15:35
Presenter
  • Safa Baris, Turkey
Room
Gold
Date
18.09.2019, Wednesday
Session Time
14:35 - 15:35
Presentation Topic
Therapy

Abstract

Background and Aims

LRBA deficiency presents with susceptibility to infections,autoimmunity and lymphoproliferation.Long-term efficacy of CTLA4-Ig as targeted therapy for its immune dysregulatory features remains to be established.We sought to determine the clinical and immunological features of LRBA-deficiency and long-term efficacy of abatacept treatment in controlling the different disease manifestations.

Methods

22 LRBA-deficient patients were recruited from different immunology centers and followed prospectively.Patients on abatacept were evaluated every 3 months for clinical and immunological responses.LRBA expression,lymphocyte subpopulations and circulating T follicular helper cells were determined.

Results

The mean age of the patients was 13.4±7.9years and the follow up period was 3.4±2.3years.Recurrent infections(n:19,86.4%),immune dysregulation(ID,n:18,81.8%) and lymphoproliferation(LP,n:16,72.7%) were common clinical features.The long-term benefits of abatacept in 16 patients were demonstrated by complete control of LP and chronic diarrhea followed by ID,most notably autoimmune cytopenias.Weekly or every other week administration of abatacept gave better disease control compared to every 4-weeks.There were no serious side effects related to the abatacept therapy.cTFH cell frequencies were found to be a reliable biomarker of disease activity,which decreased on abatacept therapy in the majority of subjects.However,high cTFH cell frequencies persisted in two patients who had a more severe disease phenotype that was relatively resistant to abatacept therapy.

Conclusions

The targeted therapy was able to effectively control the different immune dysregulatory disease manifestations in most patients,and more favorable responses were achieved in patients who received abatacept at weekly intervals without serious side effects.Monitoring cTFH cells during abatacept therapy provides a useful measure of disease activity,and may uncover cases of relative therapy resistance that require alternative treatment approaches.

*This work was supported by grant from the Scientific and Technological Research Council of Turkey (217S847)

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