Benefits of IVIG in Pediatric Acute-Onset Neuropsychiatric Syndrome
Melamed I, Kobayashi RH, O’Connor M, Kobayashi AL, Schechterman A, Heffron M, Canterberry Preview Changes (opens in a new tab)S, Miranda H, Rashid N. Evaluation of Intravenous Immunoglobulin in Pediatric Acute-Onset Neuropsychiatric Syndrome. J Child Adolesc Psychopharmacol. 2021 Feb 18. doi: 10.1089/cap.2020.0100. Epub ahead of print. PMID: 33601937.
Although this is an open-label pilot study with a small sample size and lack of a control group, there was a statistically significant decrease in PANS symptoms after six infusions of IVIG, and the duration of response is significant as most of the PANS symptoms were controlled at the late follow-up visits at up to 46 weeks.
Psychometric assessments were taken at three points: baseline, end of treatment and early/late follow-up visits (Figs. 1–4 and Tables 2and 3). The PRPQ parent questionnaire also provided data on the efficacy of IVIG in between those three data points. It elucidated that symptoms were significantly reduced by the third IVIG infusion (Fig. 4 and Table 3) but not before. It was noted in patients that participated in the late follow-up visit (n=12), their tics had returned but below baseline level (Fig. 3 and Table 2).
This IVIG study was the first to assess the efficacy of a total of six infusions. Although it was an open-label pilot study with a small sample size, it substantiates earlier randomized, controlled clinical trials demonstrating the benefits of IVIG for alleviating PANS symptoms (Perlmutter et al. 1999; Williams et al. 2016). The significant difference is this study’s extended dosing strategy demonstrates the “durability of effects up to 46 weeks following the final infusion.”
Previous studies infused 1 g/kg administered over 2 consecutive days (2 g/kg total) of IVIG (Perlmutter et al.1999; Williams et al. 2016). This study used a total dose of 1g/kg every 3 weeks for a total of six infusions. In the adult population, a dose of 2 g/kg of IVIG for immunomodulation is typical but for the pediatric population, this is a very large dose and must be administered over 2–4 days.
“The results of this study demonstrated that in PANS, which maybe associated with an underlying immune dysregulation, sequential infusions of IVIG [Octagam 5%] successfully ameliorated psychological symptoms and dysfunction, with sustained benefits for at least 8 weeks, and up to 46 weeks in a subset of subjects, following the final infusion. In addition, baseline immune and auto-immune profiles demonstrated significant elevations in a majority of subjects, which requires further evaluation, characterization, and study to clarify the potential immune dysfunction by which PANS manifests and progresses….These positive results warrant a randomized, placebo-controlled trial to definitively evaluate the impact of multiple, sequential IVIG infusions on PANS symptoms. The durability of response is also noteworthy. Although the majority of PANS symptoms were still under control at the late follow-up visit (up to 46 weeks), it is of interest that tics returned in a subset of subjects following wash out of IVIG. For these patients, additional infusions may be required to ameliorate recurrent symptoms.”
Immunodeficiencies Biennial Meeting in Gothenburg Poster Session 2021
The results of a research collaboration between the IMMUNOe Research Center, Stanford and Octapharma on the efficacy of IVIg treatment for PANS was published as a poster at the European Society for Immunodeficiencies Biennial Meeting in Gothenburg.
From Maeve O’Connor, MD’s poster session at the 2019 AAP Conference
Dr. O’Connor held an informative poster session at the AAP 2019 National Conference in advance of the publication of this research paper. ASPIRE thanks Dr. O’Connor for spending time at the ASPIRE Booth at the AAP 2019 National Conference answering questions from pediatricians and doing a Question and Answer session with ASPIRE. Please see ASPIRE’s Question and Answer Sessions: AAP Evolving Views on IVIG & PANS and Preparing for an Immunology Appointment.
Results demonstrated statistically significant reductions in symptoms from baseline to end of treatment (infusion 6) in all 6 assessments measured. CY-BOCS results demonstrated statistically significant reductions in obsessive compulsive symptoms, resulting in > 50% improvement sustained for at least 8 weeks after the final infusion and up to 46 weeks in a subset of subjects.
This study looked at 21 PANS patients, male and female, between the ages of 4 and 16. It was a multi-site, open label pilot study; 7 patients per site.
- Statistically significant reductions in all 6 assessments done measuring from baseline to final treatment (6 infusions).
- Significant reduction in symptoms after the 3rd round of IVIG compared to baseline as per Parent-Related Symptoms Survey
- Significant reductions from baseline to Visit 7 and then continued reduction of symptoms in visits 8 and 9 as per CGI Severity of Illness Scale
- 100% of patients had out of range results on the Cunningham Panel and 71% had out of range results on the Neural Zoomer.
In PANS patients, all pyschometric endpoints studied exhibited statistically significant decreases following 6 cycles (infusions) of IVIG as well as durability of response for up to 46 weeks in a subset of subjects.
Patients with PANS can benefit from a 6-cycle course of IVIG. Provisional data demonstrate durability of the positive impact of IVG treatment. PANS is an autoimmune disease; innate immunity and the complement system may play a role in the pathogenesis of PANS.