Impact of autoimmune comorbidity on inflammatory activity and disability accumulation in multiple sclerosis

Autoimmune comorbidities occur more frequently in patients with multiple sclerosis (MS) and have been proposed to exacerbate disease through a putative increase in immune burden. Whether the coexistence of autoimmune disease translates into greater inflammatory activity or accelerated disability progression in relapsing MS remains uncertain.

We performed a large retrospective matched cohort study using the international MSBase registry, including patients with relapsing - remitting MS or clinically isolated syndrome. Autoimmune comorbidity was defined by documented diagnoses present before or at baseline. Patients with and without autoimmune comorbidity were matched 1:2 using propensity scores. Clinical and radiological outcomes included annualized relapse rate, time to first relapse, MRI inflammatory activity, and 6-month confirmed disability worsening (6M-CDW), analyzed using negative binomial and Cox proportional hazards models.

The matched cohort comprised 1773 patients, of whom 591 had at least one autoimmune comorbidity. Autoimmune comorbidity was not associated with higher relapse rates, shorter time to first relapse, or increased MRI inflammatory activity. In contrast, patients with autoimmune comorbidity had a significantly higher risk of confirmed disability worsening over time (hazard ratio 1.21, 95% CI 1.04-1.41).

In relapsing multiple sclerosis, autoimmune comorbidity is not associated with increased relapse activity or inflammatory MRI findings. However, patients with autoimmune comorbidity experience a higher risk of disability worsening over time. This pattern suggests that autoimmune comorbidity does not intensify acute inflammatory disease activity, but may increase susceptibility to chronic, relapse-independent mechanisms of disability accumulation.