Disease profile of Guillain-Barré syndrome among Indian patients receiving intravenous immunoglobulin: a real-world observational study

INTRODUCTION

Guillain‐Barré syndrome (GBS), an acute, immune-mediated paralysing, inflammatory peripheral nerve disease, is an uncommon disease of the nerves outside the brain and spinal cord.^1,2 It is characterized by weakness and numbness of the limbs, facial and respiratory muscles. The common pathogenesis includes multifocal inflammation of spinal roots and peripheral nerves, especially their myelin sheaths.^2-4

GBS has a global median annual incidence of 1.11 (range: 0.81–1.89) cases per 100,000 persons.⁵

The GBS has been traditionally used interchangeably with acute inflammatory demyelinating polyradiculo-neuropathy (AIDP) for several years, until the recent evidence suggested that AIDP is a subtype of GBS among others. The GBS is considered as group of several immune polyneuropathies that leads to generalized weakness with different etiopathogenesis. Among these, the axonal subtypes of GBS include acute motor axonal neuropathy (AMAN) and acute motor-sensory axonal neuropathy (AMSAN). Furthermore, several other subtypes of GBS, have been reported.⁶ The AIDP subtype of GBS is predominantly observed in Europe and North America whereas in Asian countries, AMAN is the most common subtype.⁷

Management with immunomodulatory drugs is recommended in GBS when patients are unable to walk independently for 10 metres.⁸ In up to 30% patients with GBS diagnosis, mechanical ventilation and intensive care unit (ICU) admission are warranted.⁹ Pharmacological treatments are effective in reducing the time to recovery and improving the clinical outcomes in patients with GBS.¹⁰ Patients with GBS are commonly treated with intravenous immunoglobulins (IVIg), plasma exchange (PE) and experimental drugs such as eculizumab.^9,10

The current study was conducted to evaluate the real-world usage patterns of IVIg for the treatment of patients with GBS, and to understand the disease characteristics and demographic pattern of patients with GBS receiving IVIg treatment.

METHODS

Study design

In this retrospective, observational study, data were collected from multiple centres across India including hospitals, clinics and health care institutes. The study inclusion criteria were the patients with GBS who received IVIg treatment at the study centers. Data were collected retrospectively by the neurologists in the GBS IVIg study data collection form. Data of patients with GBS, who received treatments other than IVIg were excluded. The choice of patient selection was purely based on treating physician’s discretion. There were no new interventions or evaluations performed in this study.

The data was collected between April 2021 and March 2022. The data collected included demographic details (age, sex, height, weight etc), disease characteristics, medical history, details of treatment. The study endpoints included the descriptive analysis of patient demographic profile and disease characteristics, and the proportion of patients receiving various IVIg regimens.

Statistical analysis

There was no formal sample size calculation in this study, and the observations from patient’s records only were analyzed. In this real-world study, patients’ data was collected retrospectively. Demographic and baseline characteristics were summarized using descriptive statistics. Categorical variables were summarized with frequency and percentage. Continuous variables were summarized with count, mean, standard deviation, etc. Graphical presentation of data was done using bar chart as appropriate. Statistical analyses were performed using SAS^® version 9.4 (SAS Institute Inc., USA).

Ethics statement

The study protocol was approved by the ACEAS independent ethics committee, Ahmedabad, India. This study was performed in accordance with Good Clinical Practice and the ethical principles of the Declaration of Helsinki. As this study involved data retrieval from patient records only, an informed consent of patients was not obtained.

RESULTS

Overall, data of 3064 patients with GBS who received IVIg treatment at 364 centres were analysed. The baseline characteristics of patients are summarized in Table 1. The mean age of the patients was 48.97 years. The gender distribution showed 68.8% men and 31.2% women in this study. Hypertension (41.1%) and diabetes (33.9%) were the most common comorbid conditions.

Cm-centimetre, kg-kilogram, SD-standard deviation.

Disease characteristics

Bilateral and flaccid weakness was the most common presentation (65.3%) followed by decreased/absent reflexes (58.7%) (Figure 1).

Among antecedent conditions within the last 2 months, fever (37.2%) was most commonly reported followed by cough (28.5%) (Figure 2).

Subtypes of GBS

As per electrophysiological studies, acute inflammatory demyelinating polyneuropathy (AIDP) was found to be the most common subtype of GBS (60.5%), followed by acute motor axonal neuropathy (AMAN; 11.6%), and acute motor sensory axonal neuropathy (AMSAN; 3%) (Table 2).

Details of the therapy

The majority (>94%) of patients received IVIg therapy as first-line treatment (Table 3). Among patients receiving IVIg as later line of therapy, steroids were generally given in their earlier lines of therapy and very few patients had undergone plasmapheresis. A total of 2402 (78.4%) patients were given the standard dose of 2 g/kg bodyweight (given over 5 days); and 97.1% (n=2974) of the total study population received IVIg regimen over 5 days as per the standard protocol.

AIDP-acute inflammatory demyelinating polyneuropathy; AMAN-acute motor axonal neuropathy; AMSAN-acute motor and sensory axonal neuropathy.

DISCUSSION

This retrospective study in 3064 patients with GBS showed that the real-world usage pattern of IVIg was largely aligned with the published literature. AIDP was the most common subtype of GBS. The dosing and duration of IVIg were in line with the recommended treatment protocol.

In this study, the mean age of the patients was 48.97 years, with a male preponderance (male: female, 2.2:1). Dhadke et al reported similar findings with a male preponderance (male: female, 1.5:1) and commonest age group affected was 13-40 years in a real-world study.¹¹ Rath et al reported a male: female ratio of 1.5:1 and that median age of 48 years in GBS patients in a real-world study.¹²

In our study, bilateral and flaccid weakness was the most common presentation followed by decreased/absent reflexes, which is generally consistent with previous reports.^1,8 Fever and cough were the most common antecedent conditions within the last 2 months in our study, similar to that observed by Koga et al.¹³

Our study reported that AIDP (60.5%) was the most common subtype of GBS followed by AMAN (11.6%) and AMSAN (3%) types. In India, Sriwastava et al reported that AIDP was the most common GBS subtype reported in 66% of the patients; AMSAN (4%) and AMAN (2%) were also reported.¹⁴ Kalita et al reported that 73.8% patients had AIDP, 13.4% had AMAN, and 4.6% had AMSAN subtypes.¹⁵

IVIg is a proven effective treatment for GBS. The exact mechanism of IVIg in GBS remains unclear, however, it is thought to have immune-modulating action. Rath et al reported that IVIg was given over 5 days in majority of the courses (81%) in GBS patients.¹² In our study majority of the patients received the standard dose of 0.4 g/kg body weight daily for 5 days, and mostly patients were on 5-day regimen. The current study findings interpretation require consideration in view of certain limitations which include missing data, and potential inconsistency in data entry as multiple study centres were involved. Future prospective studies are warranted to elicit efficacy and safety results of IVIg in patients with GBS.

CONCLUSION

This retrospective, observational study reports the real-world usage patterns of IVIg in GBS patients in India. In the clinical spectrum of GBS, AIDP was the most common subtype. IVIg was used at generally recommended dose and duration in Indian patients with GBS.

ACKNOWLEDGEMENTS

Authors would like to thank the study investigators for their contribution.

Funding: The study was funded by Intas Pharmaceuticals Limited

Conflict of interest: Dr. Anil Rajani, Dr. Lav Patel, and Mr. Shreekant Sharma are employees of Intas Pharmaceuticals Limited, Ahmedabad, Gujarat, India

Ethical approval: The study was approved by the ACEAS Independent Ethics Committee, Ahmedabad, India

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