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Randomized controlled trial of intravenous immunoglobulin for autoimmune postural orthostatic tachycardia syndrome (iSTAND)

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Abstract

Objective

This study assesses response to intravenous immunoglobulin (IVIG) in presumed autoimmune postural orthostatic tachycardia syndrome (POTS).

Background

POTS may be associated with autoimmune disorders, serum autoantibodies, or recent infection. Uncontrolled case studies suggest that IVIG is beneficial for treating autoimmune POTS. No previous randomized controlled trials have been conducted.

Methods

This single-site randomized controlled trial compared IVIG with intravenous albumin infusions. Albumin comparator ensured blinding and control for effects of volume expansion. Eligible patients with POTS had COMPASS-31 total weighted score ≥ 40 and met predetermined criteria suggesting autoimmunity. Over 12 weeks, participants received eight infusions (0.4 gm/kg each). Four infusions were given weekly followed by four infusions every other week. Primary outcome measure was improvement in COMPASS-31 2 weeks after final infusion.

Results

A total of 50 participants consented; 30 met inclusion criteria and received study drug (16 IVIG and 14 albumin; 29 female). Group baseline characteristics were well matched; 27 participants completed treatment protocol. Change in COMPASS-31 did not differ between groups (median change [IQR]; IVIG: −5.5 [−23.3, 2.5] versus albumin: −10.6 [−14.1, −4.7]; p-value = 0.629). The IVIG group had a higher response rate (46.7% versus 38.5%), but this was not statistically significant. Adverse events were common but usually mild and did not differ between treatment groups.

Conclusions

This small randomized controlled trial of IVIG in POTS found no statistical difference in response compared with albumin infusion. Both groups showed improvement possibly related to volume expansion or other effects obscuring group differences. These findings inform development of future immunomodulatory clinical trials in POTS.

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Data availability

Primary study data is available on request.

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Acknowledgements

This study was supported by grants from Dysautonomia International and the Sjogren’s Foundation. Study drugs were provided by Grifols (Research Triangle Park, NC, USA). Additional funding was provided by a generous gift from Roy and Janis Coffee.

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Authors and Affiliations

  1. Department of Neurology, UT Southwestern Medical Center, Dallas, TX, USA

    Steven Vernino, Steve Hopkins, Meredith Bryarly, Roberto S. Hernandez & Amber Salter

Authors
  1. Steven Vernino
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  2. Steve Hopkins
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  3. Meredith Bryarly
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  4. Roberto S. Hernandez
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  5. Amber Salter
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Contributions

SV serves as a consultant for argenx, Antag, and CSL Behring; on a Data Safety Monitoring Board for Alterity; and receives research funding from Takeda and NIH; SH has served as a consultant for Theravance; MB receives research funding from Theravance; RH has nothing to disclose; AS receives research funding from Multiple Sclerosis Society of Canada, National Multiple Sclerosis Society, Consortium of MS Centers, and the Department of Defense Congressionally Directed Medical Research Program; is a member of the editorial board for Neurology; serves as a consultant for Gryphon Bio, LLC, and Abata Therapeutics; is a member of the Data and Safety Monitoring Board for Premature Infants Receiving Milking or Delayed Cord Clamping (PREMOD2), Central Vein Sign: A Diagnostic Biomarker in Multiple Sclerosis (CAVS-MS), and Methotrexate treatment of Arthritis caused by Chikungunya virus (MARCH); and holds the Kenney Marie Dixon‐Pickens Distinguished Professorship in Multiple Sclerosis Research.

Corresponding author

Correspondence to Steven Vernino.

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Vernino, S., Hopkins, S., Bryarly, M. et al. Randomized controlled trial of intravenous immunoglobulin for autoimmune postural orthostatic tachycardia syndrome (iSTAND). Clin Auton Res 34, 153–163 (2024). https://doi.org/10.1007/s10286-024-01020-9

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  • DOI: https://doi.org/10.1007/s10286-024-01020-9

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