Results of Population-Based Study Show That Ankylosing Spondylitis May Increase Risk for Amyloidosis

Document with diagnosis amyloidosis
Document with diagnosis amyloidosis
Researchers aimed to evaluate the risk, predictors, and prognostic outcomes of amyloidosis among patients with ankylosing spondylitis.

Patients with ankylosing spondylitis (AS) have a higher risk of developing amyloidosis, which is associated with an increased risk for end-stage kidney disease (ESKD) and dialysis use, according to study results published in Rheumatology (Oxford)

Studies exploring the association between AS and amyloidosis are limited, and there is an unmet need to address the clinical burden of disease in this patient population.

In the current study, the researchers sought to investigate the risk for amyloidosis among patients with AS and identify its predictors and prognostic outcomes.

Researchers conducted a retrospective, population-based cohort study using data from the Clalit Health Services database, Israel. To investigate the risk for amyloidosis, patients with AS and age-, sex, and ethnicity-matched control participants were evaluated longitudinally. The median follow-up time was estimated at 7.8 years for both groups.

Data from the incident cases of AS between 2003 and 2018 were retrieved, and 5911 patients with AS and 29,007 control participants were included in the study. The mean age of the study population was 49.4±17.2 years; 36.4% of the participants were women; and 79.8% had Jewish ancestry.

Results of the study showed that the incidence of amyloidosis was 2.15 (95% CI, 1.09-2.82) and 0.35 (95% CI, 0.16-0.66) per 10,000 person-years among patients with AS and control individuals, respectively. The risk of developing incident amyloidosis was more than 6-folds higher among patients with AS (adjusted hazard ratio [HR], 6.16; 95% CI, 2.43-15.60; P <.001).

In a sex-stratified analysis, the risk for new-onset amyloidosis was prominent among women (HR, 19.69; 95% CI, 2.20-176.13; P =.008) but was also significant among men with AS (HR, 4.22; 95% CI, 1.42-12.56; P =.010). In an age-stratified analysis, patients with AS aged older than 48.8 years had a significantly increased risk for amyloidosis (HR, 8.55; 95% CI, 2.50-29.20; P=.001) compared with patients aged younger than 48.8 years at presentation (HR, 3.74; 95% CI, 0.84-16.69; P =.084).

Patients with AS and comorbid amyloidosis had a 14-fold higher risk for ESKD and were dependent on dialysis, compared with the remaining patients with AS (HR, 14.7; 95% CI, 2.0-107.2; P =.008). The all-cause mortality was comparable between the 2 groups (HR, 2.16; 95% CI, 0.69-6.71; P =.1740).

The risk for amyloidosis among patients with AS was predicted by a high comorbidity burden (odds ratio [OR], 1.36; 95% CI, 1.08-1.73; P =.010) and elevated C-reactive protein levels among patients with AS and comorbid amyloidosis compared with the remaining patients with AS (36.1 [2.8%] vs 2.6 [0.4%], respectively; P <.001).

Study limitations included lack of data on the severity of AS and amyloidosis; the improper classification of amyloidosis, which may have underestimated the association between AS and amyloidosis; and the low number of patients with AS-related amyloidosis restricted the identification of accurate predictors and outcomes of the condition.

Researchers concluded, “AS increases the risk of amyloidosis by 6-folds. The presence of amyloidosis in patients with AS increases the risk of end-stage renal disease necessitating dialysis but not the risk of all-cause mortality. Awareness of this association is of great value to physicians treating patients with AS.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Kridin M, Kridin K, Cohen A, Amital H, Watad A. The risk, predictors, and outcomes of amyloidosis in ankylosing spondylitis: a longitudinal population-based cohort study. Rheumatology (Oxford). Published online August 9, 2021. doi:10.1093/rheumatology/keab633