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ORIGINAL ARTICLE
Ahead of print publication  

Comorbidity burden in psoriatic arthritis and its impact on disease measures


1 Departments of Clinical Immunology and Rheumatology, St. John's Medical College Hospital, Bangalore, Karnataka, India
2 Chanre Rheumatology and Immunology Research Centre, Bangalore, Karnataka, India
3 Department of Rheumatology, Columbia Asia Hospital, Bangalore, Karnataka, India
4 Arthritis Specialty Clinic, Hubli, Karnataka, India
5 Department of Rheumatology, Manipal Hospitals, Bangalore, Karnataka, India
6 Department of Rheumatology, Vikram Hospital, Bangalore, Karnataka, India
7 Department of Clinical immunology and Rheumatology, Narayana Health City, Bangalore, Karnataka, India
8 Department of Rheumatology, Sakra Hospital, Bengaluru, Karnataka, India
9 Department of Rheumatology and Clinical Immunology, SDM Medical College, Dharwad, Karnataka, India
10 Department of Rheumatology and Immunology, JSS Medical College, Mysore, Karnataka, India
11 Department of Rheumatology, Yenepoya Specialty Hospital, Mangalore, Karnataka, India
12 Department of Rheumatology, Apollo Hospital, Bengaluru, Karnataka, India
13 Departments of Clinical Immunology and Rheumatology, Mahaveer Jain Hospital, Bengaluru, Karnataka, India
14 Department of Rheumatology, Aster CMI Hospital, Bengaluru, Karnataka, India
15 Apollo BGS Hospital, Mysore, Karnataka, India
16 Department of Rheumatology, Fortis Hospital, Bengaluru, Karnataka, India
17 Department of Rheumatology, Sparsh Hospital, Bengaluru, Karnataka, India
18 Samarpan Health Centre, Bengaluru, Karnataka, India

Date of Submission09-Feb-2022
Date of Acceptance22-Apr-2022
Date of Web Publication25-Oct-2022

Correspondence Address:
Vineeta Shobha,
Department of Clinical Immunology and Rheumatology, St John's Medical College Hospital, Sarjapur Road, Bengaluru - 560 034, Karnataka
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/injr.injr_29_22

  Abstract 


Introduction: Comorbidities frequently accompany psoriasis and psoriatic arthritis (PsA) and add to the disease burden. We aimed to identify the comorbidity burden in patients with PsA and evaluate its impact on the disease activity measures in our geographic region.
Methods: This was a multicenter, cross-sectional study involving consecutive PsA patients from 17 rheumatology centers. Their disease variables and comorbidities were recorded.
Results: In 549 enrolled patients, the mean age was 39.2 (14.9) years, with male predominance (6:5). The mean duration of PsA was 63.1 (76.3) months and 232 (42.3%) patients had one or more comorbidities. Dyslipidemia was the most prevalent comorbidity, followed by hypertension (HTN) (19.8%) and diabetes (16.6%). About 39% of patients were overweight and 18% were obese. Smoking, ischemic heart disease, hypothyroidism, osteoarthritis, depression, anxiety, and fractures were seen in <5% of the cohort. Increasing age, longer duration of psoriasis, a family history of cardiovascular disease (CVD) or stroke, smoking, alcohol consumption, and higher waist circumference were associated with the presence of one or more comorbidities. Overall, 104 (18.9%) patients needed hospitalization for various comorbidities. Infections accounted for 59 (10.8%), of which skin (23) was the most common site, followed by urinary tract (6) and lung (4).
Conclusions: More than 40% of PsA patients have comorbidities. Dyslipidemia, HTN, diabetes, and obesity were most prevalent, putting these patients at risk for CVDs. Active screening for these comorbidities is crucial for providing comprehensive care to these patients.

Keywords: Diabetes mellitus, dyslipidemia, hypertension, metabolic syndrome, obesity, psoriatic arthritis comorbidity index



How to cite this URL:
Chanakya K, Shobha V, Chandrashekara S, Kumar S, Haridas V, Rao V, Jois R, Daware M, Singh Y, Singhai S, Dharmanad BG, Chebbi P, Ramaswamy S, Kamath A, Karjiigi U, Jain VK, Dharmaplaiah C, Prasad S, Srinivas C, Janardana R, Pinto B, Nazir B, Harshini A S, Mahendranath. Comorbidity burden in psoriatic arthritis and its impact on disease measures. Indian J Rheumatol [Epub ahead of print] [cited 2022 Nov 29]. Available from: https://www.indianjrheumatol.com/preprintarticle.asp?id=359464




  Introduction Top


Psoriatic arthritis (PsA) is a chronic progressive disease, which may lead to joint destruction. It is being increasingly recognized that PsA is not limited to the joint and enthesis but has far-reaching systemic effects. It has been noted in the literature that comorbidities complicate patients with PsA significantly more than patients with psoriasis without joint disease.[1] Over a half of patients with PsA have a comorbidity which is likely to affect their physical function, quality of life, and are associated with a significant economic burden.[2],[3] Many comorbidities remain unrecognized for a long if the consulting rheumatologist or dermatologist is not sensitized to the burden of this problem.[4] Similar to the incidence and prevalence of PsA which vary across different ethnic groups across the world, comorbidities associated with PsA vary too. Han et al. in their large database review of rheumatoid arthritis (RA), PsA, and ankylosing spondylitis patients found that cardiovascular diseases (CVD) and their risk factors were more common in these patients compared to matched controls.[5] Another large population-based study from the USA showed that the risk of major cardiovascular events is higher in patients of PsA who were not treated with disease-modifying antirheumatic drug (DMARD)-linking inflammation with cardiovascular risk.[6] Studies reporting mortality in PsA have identified that patients with PsA have increased risk of dying from cardiovascular (36.2%) and respiratory comorbidities (21.3%) as compared to the general population.[7] It has been noted that active PsA requiring disease-modifying therapy, elevated inflammatory markers, and radiographic changes were prognostic indicators of death.[8]

Although the disease burden of PsA in the Indian subcontinent is comparable to other Asian and Western countries, the comorbidity burden has been scarcely reported in studies. We conducted this study to identify the comorbidity burden in patients with PsA and evaluate its impact on the disease activity measures.

Methods

This study was conducted in the South Indian state of Karnataka with a multicenter, cross-sectional design. Seventeen dedicated rheumatology centers recruited consecutive PsA patients defined by the Classification Criteria for Psoriatic Arthritis from February to December 2019. At enrollment, using a structured case record form, demographic and clinical parameters and disease-related assessments were recorded. Skin disease was assessed using Psoriasis Area and Severity Index (PASI),[9] while joint disease was measured by Disease Activity in PsA (DAPSA),[10] which comprised tender joint count (TJC-68), swollen joint count (SJC-66), patient global assessment (PtGA) and physician global assessment, patient pain Visual Analog Scale (VAS), and C-reactive protein. Disability was assessed using the Health Assessment Questionnaire-Disability Index (HAQ-DI Indian version).[11] Minimal disease activity (MDA) was considered when five of the six criteria were met:[12] PtGA ≤20, Pt pain VAS ≤15, HAQ-DIu0.5, TJC ≤1, SJC ≤1, PASI or body surface area ≤1 or ≤3, respectively, and Leeds Enthesitis Index ≤1. PsA comorbidity index (PsACI) was used to record all comorbidities.[13] Current and past medical records were reviewed to retrieve comorbidities based on a physician diagnosis or use of medication for that particular comorbidity. Dyslipidemia was defined as per the National Cholesterol Education Program guidelines.[14] Obesity was defined based on the National Institutes of Health body mass index (BMI)-based definition.[15] Information about smoking and alcohol consumption was as declared by self and was interpreted as per the standard recommendations DEL (REF).[16],[17] The data were collected on paper case record forms at each center and were fed into a common Excel sheet which was then used for analysis. All the participating rheumatologists underwent training and harmonization sessions on relevant measures before the data collection. The harmonization exercise was led by an expert with hands-on scoring. Written consent was obtained from all participating subjects, and respective institutional ethical clearances were obtained (Institutional Ethics Committee, St. John's Medical College, IEC No. 10/2019, dated February, 10 2019).

Statistical analysis

Normally distributed continuous variables were expressed as mean standard deviation or median interquartile range for nonnormally distributed variables. Categorical variables were depicted as percentages. Means between the two groups were compared using independent Student's t-test for normally distributed variables and Mann–Whitney U-test for non-Gaussian variables. Chi-square test or Fisher's exact test was used to show the association between categorical variables. Unadjusted and adjusted odds ratio (OR) and 95% confidence interval (CI) were computed using logistic regression analysis. Variables that were significant in the bivariate analysis were subjected to multivariate analysis. P <0.05 was considered statistically significant, and all calculations were done using GraphPad prism (GraphPad Software 2365 Northside Dr. Suite 560 San Diego, CA 92108) for Windows 10 software and SPSS version 25.0 All statistical analyses were performed using IBM Corp. Released 2017. IBM SPSS Statistics for Windows, Version 25.0. Armonk, New York: IBM Corp.United States.


  Results Top


The study population consisted of 549 patients with PsA. The mean age of the cohort was 39.1 (14) years, with a slight male preponderance (6:5). Demographic details and disease characteristics of the study population are depicted in [Table 1]. One or more comorbidities were noted in 232 (42.3%) PsA patients. Dyslipidemia (51.3%) was the most frequent comorbidity, followed by hypertension (HTN) (19.8%) and diabetes mellitus (DM) (16.6%). Comorbidity frequencies in the study population are represented in [Figure 1]. A family history of a CVD or stroke was present in 72 (15.1%) patients. The mean BMI of the cohort was 26 kg/m2;[4] 39.2% were overweight and 18.1% were obese. Obesity was not associated with high joint DAPSA or high disability (HAQ-DI), and there was no difference in achieving MDA-5 compared to nonobese patients. Elder age (OR: 1.029, CI: 1.01–1.04), longer duration of psoriasis (OR: 1.003, CI: 1.00–1.005), a family history of CVD or stroke, smoking (OR: 1.908, CI: 1.15–3.16), alcohol consumption (OR: 1.686, CI: 1.08–2.62), and higher waist circumference (OR: 1.021, CI: 1.00–1.04) were associated with comorbidities in PsA patients [Table 1]. Skin scores, HAQ disability, and rates of hospitalization were numerically higher in patients with comorbidities. The mean PsACI was 0.98 (1.6). Multivariate regression showed that age (OR: 1.04, CI: 1.019–1.07) and smoking (OR: 3.22, CI: 1.45–7.11) were independent risk factors for the presence of one or more comorbidities.
Figure 1: Observed frequency (%) of comorbidities in KPsAC

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Table 1: Baseline characteristics and comparison between patients with and without comorbidities

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Overall, 104 (18.9%) patients required hospitalization for various comorbidities. Infection as a comorbidity (in the period of PsO/PsA diagnosis and at any time during treatment) was seen in 59 (10.8%) patients; skin (23) was the most common site, followed by urinary tract (6) and lung (4) infections. Eighteen patients were hospitalized due to infections.

Overall, the presence of one or more comorbidities increased with increasing age (P < 0.01); the prevalence of DM, HTN, and CVD also increased with higher age [Table 2]. It was also noted that with a longer duration of arthritis, a greater proportion of PsA patients accumulated comorbidities (P < 0.01) such as HTN (P = 0.04). No difference in comorbidity burden was noted among those on the varying duration of DMARD therapy (<6 and >6 months).
Table 2: Prevalence of comorbidities in relation to age, duration of psoriatic arthritis, disease activity, and therapy

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  Discussion Top


In the present study, we have identified the comorbidity burden using PsACI in a large cohort of PsA from South India and identified their disease associations and correlation. Over 40% of the cohort had one or more comorbidities complicating their PsA, dyslipidemia (51.3%) being the most frequent comorbidity, followed by HTN (19.8%) and DM (16.6%). Smoking, anxiety, ischemic heart disease, hypothyroidism, osteoarthritis, depression, and fractures were seen in 5% or less in the cohort.

Several previous studies have reported dyslipidemia, HTN, and DM to be the most prevalent comorbidities in patients with PsA.[5],[18],[19],[20] The reported prevalence of dyslipidemia, HTN, and DM varies in different cohorts of PsA in the literature and is presumably influenced by the different ethnic factors driving the development of these comorbidities as well as differences in the psoriatic disease itself.

It has been delineated previously that PsA patients accumulated more comorbidities than patients with RA.[21] In our prior study assessing comorbidities in RA from the same ethnic and geographic population as the current study, noted that 40.3% patients had one or more comorbidities; HTN, dyslipidemia, and DM were seen in 20.7%, 18.9%, and 14.3%, respectively. Dyslipidemia seems to be more prevalent in PsA than in RA when comparing these two studies.[22] Dyslipidemia and DM prevalence in our PsA cohort is higher compared to that in the general population in our country, which is 15%–30% and 7.5%, respectively. However, the prevalence of HTN (25.3%) among the general population seems to be comparable.[23],[24]

Nearly 40% and 20% of our cohort were overweight and obese, respectively. Obesity has been consistently reported in PsA cohorts across the world,[25],[26],[27] and it has been observed that PsA patients tend to get more obese compared to those with RA.[21],[26] Previous studies have suggested a link between obesity and severity of PsA, likely due to additional inflammatory milieu contributed by obesity.[28],[29] di Minno et al. from Italy compared 135 normal weight PsA patients to 135 obese PsA patients and found that a lesser proportion of obese patients achieved MDA, and at 24-month follow-up, obesity was a negative predictor of MDA achievement and maintenance.[30] However, in our study, there were no significant differences in achieving MDA by obese and nonobese PsA patients. Furthermore, the disease activity and disability indices were not different among these groups in our cohort. Ethnic differences could explain these findings; however, larger studies on the Indian population would be needed to study the impact of obesity on the severity of PsA.

The mean BMI of our PsA cohort was 26 kg/m2. A study from a comparable population in a similar geographic location as our study in RA patients showed a mean BMI of 23.4 kg/m2.[31] Similar findings have been reported by Bhole et al., who found that BMI in PsA was 2.3 kg/m2 higher than a comparable RA cohort and by another large registry data from the USA (PsA 32.1 vs. RA 29.8 kg/m2, P < 0.001).[21],[32] This difference hints toward the metabolic differences between these two diseases.

The general population prevalence of obesity in the country was reported by a recent cross-sectional representative study, which found that the mean BMI of Indian adult women to be 21.9 kg/m2 and 20% were overweight or obese, while the mean BMI among adult men was 21.9 kg/m2 and 26.6% were overweight or obese.Compared to the general population, patients with PsA in our cohort had a higher BMI (26 kg/m2 ), and nearly 60% were overweight or obese. This high burden of overweight or obesity in PsA patients puts them at an escalated risk for cardiovascular events compared to the general population.

Persistent or chronic inflammation is a known risk factor for CVDs. It is understood from the above discussion that PsA patients have an increased prevalence of comorbidities which contribute to CVD than the general population across various ethnic groups. Our study confirms the same in the Indian population. Similar to RA, the PsA patients are at increased risk of mortality due to CVDs.[7],[34],[35],[36],[37] A trend toward reduction in the standardized mortality rates has been observed in PsA patients over years with early and improved treatment and increased recognition of comorbidities.[35] Given the risk which these comorbidities pose to a PsA patient toward a CVD, it is of paramount importance that these comorbidities are actively identified and addressed in parallel to the treatment of PsA.

Self-reported depression and anxiety were noted in about 5% of our cohort. McDonough et al. in their study to screen PsA patients for anxiety and depression reported a high prevalence of 36.6% and 22.2%, respectively. They further reported that both depression and anxiety were associated with unemployment, female gender, high joint activity, disability, pain, and fatigue.[38] It is remarkable to note such a high prevalence of anxiety and depression in PsA and its associations, and hence, it is imperative to screen for these comorbidities in PsA patients.

The following limitations must be considered when interpreting our study. This being a cross-sectional study, all the assessments are based on the one-time assessment at enrollment and that there is no comparator control group. Referral bias could confound our findings as severe PsA subsets are more likely to be referred to a rheumatologist, and, therefore, we may be missing capturing comorbidities in milder PsA subsets. Some comorbidities such as anxiety and depression were self-reported and likely do not reflect the actual burden of these in our PsA cohort. Similarly, the prevalence of metabolic syndrome could not be assessed due to noninterventional design of our study. Some demographic data such as age were not captured in a small subset of patients.

Strengths of our study are a large sample size with a multicentric design in real-life setting using a validated comorbidity assessment tool. To our knowledge, this is the first study reporting prevalent comorbidities in PsA patients in the Indian population.


  Conclusions Top


Over 40% of patients with PsA have one or more additional comorbidities complicating their disease. Components of metabolic syndrome, namely dyslipidemia, HTN, diabetes, and obesity, are prevalent in PsA predisposing them to high risk for CVD. Awareness among physicians and patients about the comorbidities is of paramount importance for early detection. The importance of active screening and treatment of these comorbidities cannot be overemphasized for providing holistic care to these patients.

Acknowledgment

We thank Dr. Ashish Jacob Mathew, Department of Clinical Immunology and Rheumatology, Christian Medical College, Vellore, Tamil Nadu, India, for conducting the training program for outcome measures.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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