Comorbidity Clusters in Ankylosing Spondylitis and Their Association with Disease Activity and Functional Impairment: Data from the PSOAS Cohort

Background Comorbidities in ankylosing spondylitis (AS) occur more frequently than in the general population and are associated with higher morbidity and mortality. Some comorbidities may occur together, making one more likely in the presence of another, and different combinations of comorbidities may have differential considerations for AS management and outcomes. Objectives To examine the association of baseline comorbidities with disease activity and functional status in AS. Methods We used baseline data from the Prospective Study Of Ankylosing Spondylitis (PSOAS) cohort, a multicenter, prospective cohort from five centers (4 in the US, 1 in Australia). AS patients ≥ 18 years fulfilling mNY criteria for AS (2002-20) were included. Patient-reported AS comorbidities (N=28) and extra-musculoskeletal manifestations (EMMs, N=2) within 3 years of enrollment (prespecified on the baseline case-report form) and only those occurring in ≥1% were included. Undocumented comorbidities were assumed to be absent if missing in <15% of patients, and those missing in >50% of patients were excluded. Comorbidity clusters were identified using K-median clustering. The optimal number of clusters was determined using scree plot of the sum of squared errors and “elbow” on the graph line. Baseline characteristics of the clusters were compared, and associations of with disease activity and functional status measures (primary outcomes: ASDAS-CRP and BASFI) were examined using linear regression adjusted for age and sex. Results There were 1,270 AS patients included with a mean age of 44.6 ±14.3 years, 74.4% males, and 81.2% whites. Mean AS symptom duration was 20.6±5.6 years, 81.6% HLA-B27 positive, and CRP elevated in 27.5% of patients at baseline. Depression was the most prevalent comorbidity (31.4%) followed by hypertension (26.1%); uveitis was the most common EMM (30.4%). The five clusters identified included depression (27%), no comorbidities (22%), hypertension (21%), uveitis (20%), and asthma/low bone mass (10%) (Figure 1). The cluster with no comorbidities was significantly younger, with lower symptom duration (p<0.001). Females had higher odds of being in the depression (OR=2.00, 95% CI 1.38- 2.90) and uveitis (OR=2.09, 95% CI 1.41-3.11) clusters compared to the cluster with no comorbidities. The number of comorbidities and clusters with depression and hypertension were significantly associated with worse disease activity and functional status (Table 1). Table 1. Age and sex adjusted associations between comorbidity clusters, compared to cluster 3, and baseline disease activity/ functional status measures in ankylosing spondylitis based on Linear regression models. Cluster 1 (depression ) Cluster 3 (hypertension ) Cluster 4 (uveitis ) Cluster 5 (asthma, low bone mass ) Outcomes Coef (95% CI) Coef (95% CI) Coef (95% CI) Coef (95% CI) ASDAS-CRP 0.98 (0.78-1.18) 0.43 (0.18-0.68) 0.04 (-0.19-0.27) 0.16 (-0.12-0.44) BASFI (0-10) 1.92 (1.51-2.34) 1.00 (0.53-1.48) -0.03 (-0.49-0.42) 0.64 (0.076-1.20) Enthesitis count 1.17 (0.73-1.61) 0.73 (0.19-1.26) 0.18 (-0.32-0.68) 0.48 (-0.13-1.08) Swollen joint count (0-44) 0.27 (-0.08-0.62) 0.43 (-0.01-0.86) 0.31 (-0.09-0.71) -0.95 (-0.58-0.39) Tender joint count (0-46) 1.24 (0.59-1.88) 0.44 (-0.34-1.23) 0.56 (-0.18-1.29) 0.34 (-0.55-1.23) BASDAI (0-10) 2.30 (1.88-2.71) 0.88 (0.36-1.40) 0.30 (-0.17-0.78) 0.61 (0.03-1.19) Patient Global (0-10) 2.25 (1.82-2.68) 0.76 (0.21-1.30) -0.22 (-0.71-0.27) 0.29 (-0.31-0.89) Patient Pain (0-10) 2.45 (1.95-2.94) 1.00 (0.37-1.62) 0.19 (-0.38-0.75) 0.16 (-0.54-0.85) Spinal pain (0-10) 2.40 (1.89-2.91) 1.05 (0.41-1.70) 0.43 (-0.16-1.01) 0.76 (0.04-1.47) Figure 1. Comorbidity clusters in PSOAS cohort at baseline Conclusion Distinct comorbidity clusters were identified in AS patients in the PSOAS cohort. In addition to the number of comorbidities, the type of comorbidity seems to be important. Depression and hypertension clusters seem to be associated with worse disease activity and function. Disclosure of Interests Paras Karmacharya: None declared, Cynthia S. Crowson: None declared, Dilli Poudel: None declared, John M Davis III Consultant of: Dr. Davis has received consulting fees and/or honoraria from AbbVie and Sanofi-Genzyme (less than $10,000 each), Grant/research support from: Dr. Davis has received research support from Pfizer., Alexis Ogdie Consultant of: Dr. Ogdie has served as a consultant for AbbVie, Amgen, BMS, Celgene, Corrona, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB (less than 10,000 each), Grant/research support from: Dr. Ogdie has received grants from Novartis and Pfizer to Penn and from Amgen to Forward (grants more than 10,000)., Jean Liew Grant/research support from: Dr. Liew received grant/research support from Pfizer (> $10,000), Michael Ward: None declared, Mariko Ishimori: None declared, Michael Weisman Consultant of: Dr. Weisman received consulting fees for Novartis, UCB, Gilead, and GSK (< $10,000)., Matthew Brown: None declared, Mohammad Rahbar: None declared, Mark Hwang: None declared, John D Reveille Consultant of: JDR received consulting fees for UCB (< $10,000), Grant/research support from: Dr. Reveille received research support from Lilly and Janssen unrelated to this work., Lianne S. Gensler Consultant of: Dr. Gensler has received consulting fees for AbbVie, Eli Lilly, GSK, Gilead, Pfizer (< $10,000)., Grant/research support from: Dr. Gensler received grant/research support from UCB and Novartis (> $10,000).