Assess symptomatic response to intravenous immunoblobulin (IVIG) in presumed autoimmune postural orthostatic tachycardia syndrome (POTS)

This was a single site randomized controlled clinical trial comparing IVIG to intravenous albumin infusions. Albumin comparator group ensured blinding and control for effects of volume expansion. Eligible POTS patients had COMPASS-31 score ≥ 40 and met pre-determined clinical criteria suggesting an autoimmune etiology. Over 12 weeks, participants received 8 infusions (0.4gm/kg per infusion). The first four infusion were given weekly followed by four infusion given every other week. The primary outcome measure was improvement in autonomic symptom severity 2 weeks after final infusion compared to baseline.

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; symptom improvement was seen in 46% in both groups. There was no difference between groups in response rate or change in COMPASS-31 score. Adverse events were common but usually mild and did not differ between treatment groups.

This pilot study (first randomized double-blinded controlled trial) of IVIG in POTS found no difference in symptom response between IVIG and matched intravenous albumin infusion. Both treatments were associated with improvement which may represent the effects of volume expansion obscuring specific benefits of immunomodulation. Future clinical trials may benefit from the use of POTS-specific clinical outcome measures or biomarkers that are more sensitive to symptoms other than orthostatic intolerance.