Professor of Clinical Neurology, Weill Cornell Medical College

Dr. Rubin reports he is a consultant for Merck Sharp & Dohme Corp.

SYNOPSIS: In an open-label, non-randomized clinical trial using a second course of intravenous immunoglobulin (IVIg) to treat patients with Guillain-Barré syndrome, no benefit was observed. A single course of 2 g/kg of IVIg should be administered. No additional treatment is helpful.

SOURCE: Verboon C, van den Berg B, Cornblath DR, et al. Second IVIg course in Guillain-Barré syndrome with poor prognosis: The non-randomised ISID study. J Neurol Neurosurg Psychiatry 2019; Oct 5. doi:10.1136/jnnp-2019-321496. [Epub ahead of print].

Despite current treatment, Guillain-Barré syndrome (GBS) remains a severe disease. Artificial ventilation will be required for days to months in 25% of patients, about 20% will be unable to walk after six months, 5-10% will have incomplete recovery, and 3-10% will die. Depending on preferences, availability, contraindications, and risk factors, intravenous immunoglobulin (IVIg) or plasma exchange are equally efficacious and of proven benefit for GBS when administered within weeks of disease onset. However, sequential treatment using plasma exchange followed by IVIg offers no additional benefit. Corticosteroids, either alone or in combination with IVIg, are to be avoided. For severe GBS patients unlikely to regain independent ambulation as identified by the modified Erasmus GBS Outcome Score (mEGOS), does a second course of IVIg have benefit in the treatment of severe GBS, if no significant response was obtained after an initial round?

Using the database of the prospective, observational, International Guillain-Barré Syndrome Outcome Study (IGOS), which included GBS patients within the first two weeks of onset, a comparison was made, with respect to disease course, of patients treated with one course of IVIg, 2 g/kg IVIg over two to five consecutive days, vs. two courses. Exclusionary criteria included patients who died or were lost to follow-up within the first week of study entry, those who received a second course of IVIg as a result of a reported treatment-related fluctuation observed by the local physician, and children younger than 6 years of age, for whom mEGOS is not validated. Patient data were collected at entry, and at weeks 1, 2, and 26, and included GBS disability score, Medical Research Council (MRC) sum score, and the presence of sensory deficits, facial weakness, and prior diarrhea. Improved functional outcome on the GBS disability scale after four weeks was the primary endpoint. Secondary endpoints included improvement of ≥ 1 score on the GBS disability scale at four and 26 weeks, GBS disability score at 26 weeks, median change in the MRC sum score at four and 26 weeks, ability to walk independently at 26 weeks, ventilation need at any time during follow-up, time admitted to the intensive care unit, time on a ventilator, and GBS-related mortality at six months. Statistical analysis comprised the Mann-Whitney U test, and one-way ANOVA or Kruskal-Wallis tests, with a two-sided
P value < 0.05 considered significant.

Among 1,300 patients enrolled in IGOS, 831 initially received IVIg. Poor prognosis (mEGOS 6-12) was predicted in 260, of which 237 satisfied inclusionary criteria. Among these, 199 received a single course of IVIg, while 20 received a second course within one to two weeks, and 18 within two to four weeks after start of initial IVIg. Those receiving two courses were more disabled at baseline and week 1 compared to those receiving one course, and a second course of IVIg did not significantly affect the primary endpoint GBS score four weeks after study entry. GBS disability score at 26 weeks, a secondary endpoint, also was unaffected. No serious complications from the second IVIg course were reported, but no benefit accrued.

COMMENTARY

Weakness, sensory loss, fatigue, and pain are the most common residual deficits in GBS, requiring patients to modify their work, lifestyle, and social activities. Often overlooked, prolonged and intensive physical rehabilitation can improve prognosis. In a retrospective analysis of 51 GBS patients seen between 2003 and 2017 at the Neurological Unit of Sant’Andrea Hospital, La Spezia, Italy, 40 patients underwent intensive physical rehabilitation for an average of two months while inpatients, of which 31 continued for an additional three months as outpatients. Mean MRC sum score and GBS-Disability scale improved significantly in the intensive physical rehabilitation group, compared to the medical therapy. Intensive physical rehabilitation should be performed in patients with severe GBS.¹

REFERENCE

1. Prada V, Massa F, Salerno A, et al. Importance of intensive and prolonged rehabilitative treatment on the Guillain-Barré syndrome long-term outcome: A retrospective study. Neurol Sci 2019; Oct 4. doi: 10.1007/s10072-019-04077-x.