Repeat IVIG Dosing Common in Guillain-Barré Syndrome, Suggesting Harm in Non-Responders

In a study exploring the frequency of repeat intravenous immunoglobulin (IVIG) dosing and combination therapy of plasma exchange (PLEX) followed by IVIG in patients with Guillain-Barré syndrome (GBS), investigators found that repeat IVIG dosing was common before newer trials, suggesting potential harm for those unresponsive to IVIG, according to results published in Muscle & Nerve.¹

Guillain-Barré syndrome can cause weakness and numbness in the legs. | Image Credit: © Bangkok Click Studio | stock.adobe.com

In a pivotal 2021 trial, investigators found no therapeutic value to repeat IVIG dosing in patients with poor prognosis due to GBS. These results built on findings from a randomized controlled clinical trial in 1997 that conclusively demonstrated both the therapeutic equivalency of IVIG and PLEX while indicating no additive benefit with combination therapy.^2,3

Current guidelines strongly advocate against utilizing repeat IVIG dosing or combination therapy in non-responders due to the risk that each therapy poses through an increase in adverse events (AEs). In the 2021 trial, patients who received a second IVIG dose had more serious AEs compared with those who did not, including thromboembolic events.^1,2

Another outcome of clinical importance is the transition from GBS to acute onset chronic inflammatory demyelinating polyneuropathy (CIDP). Treatment-related fluctuation (TRF) can occur within the first 8 weeks after treatment with IVIG or PLEX; one retrospective study found that nearly 1-in-4 patients with CIDP are initially characterized as having GBS.¹

The current trial sought to address these gaps in knowledge by analyzing the frequency of repeat IVIG dosing and combination therapy, in addition to the incidence of initial GBS diagnoses transitioning to a diagnosis of CIDP. Investigators identified 2325 patients with only a diagnosis of GBS who had received at least 1 prior immunotherapy, while 1092 individuals with an initial diagnosis of GBS and later diagnosis of CIDP were also found.¹

In patients with a sole diagnosis of GBS, 66.0% received only IVIG, 28.0% received only PLEX, and 141 (6.1%) received combination therapy. In 923 patients with GBS (39.7%), repeat IVIG dosing was observed; of these, 345 (37.4%) received 2 doses of IVIG and 578 (62.6%) received 3 or more doses.¹

Notably, among individuals with only a GBS diagnosis, female patients had reduced odds of repeat IVIG dosing (OR 0.79; 95% CI, 0.65-0.96), in addition to those with a high-medium net worth—considered between $250,000 and $499,000—compared with patients with a low net worth (less than $25,000) (OR 0.64; 95% CI, 0.45-0.90).¹

Among patients who were initially classified as GBS, 1092 (32.0%) later re-classified as CIDP, with the proportion of these patients remaining stable over time. According to an adjusted logistic regression, older age (OR 1.01; 95% CI, 1.01-1.02) and Asian ethnicity had heightened odds of being re-classified as CIDP (reference group = White, OR 1.77; 95% CI, 1.09-2.86), the investigators found.¹

Though repeat IVIG dosing was much more prevalent than combination therapy, the investigators found that both practices persisted without change over the last 2 decades. Furthermore, the incidence of diagnostic re-classification from GBS to CIDP occurred at a much higher rate than the investigators expected.¹

These results are especially significant considering the 2021 trial that conclusively found no added benefit associated with repeat IVIG dosing in those with a poor prognosis at presentation. A lack of significant patient-level factors indicates that health care system- or provider-level factors may be the drivers of high repeat IVIG treatment in this population that was privately insured.^1,2

“Patient characteristics were not consistently associated with these outcomes; therefore, provider and/or health care system-facing interventions are likely needed to reduce unnecessary treatment of GBS non-responders,” the investigators concluded.¹

REFERENCES

1. Stino AM, Reynolds EL, Watanabe M, Callaghan BC. Intravenous immunoglobulin and plasma exchange prescribing patterns for Guillain-Barre syndrome in the United States—2001 to 2018. Muscle & Nerve. 2024. doi:10.1002/mus.28265

2. Walgaard C, Jacobs BC, Lingsma HF, et al. Second intravenous immunoglobulin dose in patients with Guillain-Barré syndrome with poor prognosis (SID-GBS): a double-blind, randomized, placebo-controlled trial. Lancet Neuro. 2021;20(4):275-283. doi:10.1016/S1474-4422(20)30494-4

3. Plasma Exchange/Sandoglobulin Guillain-Barré Syndrome Trial Group. Randomized trial of plasma exchange, intravenous immunoglobulin, and combined treatments in Guillain-Barré syndrome. 1997;349(9047):225-230. doi:10.1016/S0140-6736(96)09095-2