Clinical characteristics and prognosis of amyotrophic lateral sclerosis with autoimmune diseases

Abstract

Introduction: The occurrence of autoimmune diseases (AIDs) in amyotrophic lateral sclerosis (ALS) patients is widely reported, but little is known about the associated clinical phenotype. This study aims to evaluate the clinical features and prognosis of ALS patients with AID.

Methods: This retrospective study was based on the ALS Registry dataset of Peking Union Medical College Hospital from 2013 to 2020. Clinical features and inflammatory biomarkers at registration were compared between ALS patients with coexisting AIDs and those without (controls). The medical records of immunotherapy were also collected. The Kaplan-Meier method and Cox proportional hazard model were used to study the survival of ALS patients.

Results: There are 26 (1.6%) ALS patients with AIDs in our database. The ALS patients with AIDs had older ages at onset and poorer respiratory function than controls (p<0.05). After propensity score matching by sex, onset age, and disease duration, the difference in respiratory function remained significant between groups. We found no differences in overall survival between ALS patients with and without AIDs before and after matching (p = 0.836; p = 0.395). Older age at onset, rapid disease progression, and lower erythrocyte sedimentation rate (ESR) were associated with shorter survival (p<0.05). Among ALS patients with AIDs, 8 (30.8%) had a history of immunotherapy and showed slightly prolonged survival compared with those without immunotherapy, but the results did not reach statistical significance (p = 0.355).

Conclusions: Patients with coexisting ALS and AIDs had older onset age and poorer respiratory function but similar overall survival than those with pure ALS.

Fig 1. The effect of clinical parameters and immunotherapy on survival.

Survival curves of ALS patients categorized by predominant involvement of UMN or LMN (A), site of onset (B), DPR (C), NLR (D), ESR (E), hs-CRP (F), coexisting AID (G), and immunotherapy (H-I). Patients with bulbar onset and rapid disease progression had worse survival when the relationship between clinical features and survival was analyzed (A-C). No significant difference in survival was found in patients grouped by serum inflammatory biomarkers. Coexisting autoimmune diseases do not influence the survival in ALS patients before and after propensity score matching (G-H). The patients with coexisting ALS and AIDs who had a history of immunotherapy presented a trend of longer survival. UMN, upper motor neuron; LMN, lower motor neuron; DPR, disease progression rate; NLR, neutrophil-lymphocyte ratio; ESR, erythrocyte sedimentation rate; hs-CRP, hypersensitive C-reactive protein; AID, autoimmune disease; IMT, immunotherapy.

Fig 2. Variation in the ALSFRS-R score among ALS patients with coexisting Sjögren syndrome.

In patients who received immunotherapy (blank line), the ALSFRS-R score increased in 1 patient and declined at a slower rate after treatment in 2 patients. The slope of decreased ALSFRS-R score increased in patients not treated with immunotherapy (gray line). ALSFRS-R, revised ALS functional rating scale; IMT, immunotherapy.