Abstract
Objective This study aimed to assess the prevalence of comorbidities among patients with rheumatoid arthritis (RA) and identify factors associated with it.
Methods A cross-sectional study was conducted at 2 tertiary care hospitals among 653 patients with RA. Data on demographics, poor prognostic factors (high erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], rheumatoid factor, anticyclic citrullinated peptide antibody titers, and Disease Activity Score in 28 joints [DAS28] > 5.1), and comorbidities were collected through a structured questionnaire and medical record review. Comorbidities were quantified by the Charlson Comorbidity Index (CCI). Logistic regression analyses were used to identify associated factors.
Results A total of 646 (98.9%) patients had ≥ 1 comorbidity. The most prevalent were dyslipidemia (75.8%), obesity (58.7%), hypertension (42.7%), type 2 diabetes mellitus (30.3%), and osteoporosis (OP; 15.6%). Age ≥ 45 years was independently associated with coronary artery disease (odds ratio [OR] 9.71, 95% CI 1.91-178.00), OP (OR 19.60, 95% CI 5.96-121.00) and infectious diseases (OR 1.60, 95% CI 1.03-2.54). Female sex was associated with lower cardiovascular risk (OR 0.27, 95% CI 0.11-0.62), whereas female sex was associated with increased odds of OP (OR 3.55, 95% CI 1.71-8.37) and gastrointestinal (GI) disorders (OR 2.18, 95% CI 1.37-3.56). The use of targeted synthetic and biologic disease-modifying antirheumatic drugs increased the risk of infection (OR 14.80 and 4.11, respectively). High DAS28-CRP and ESR values were linked to GI comorbidities. The CCI survival index was significantly lower in older patients (≥ 45 years; mean 68.7 [SD 26.7]) than in younger patients (mean 93.3 [SD 6.7], P < 0.001).
Conclusion The prevalence of multimorbidity is high among patients with RA in Bangladesh, particularly early cardiovascular disease risk.
Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disorder clinically characterized by persistent inflammation of the synovial membrane that gradually results in joint damage, structural deformities, and functional impairment.1,2 Beyond the musculoskeletal (MSK) system, RA has significant extraarticular manifestations (EAMs) that affect multiple organ systems, including the cardiovascular (CV), respiratory, and gastrointestinal (GI) systems.2
RA is a globally prevalent condition. The prevalence varies between 0.5% and 1% worldwide.3 Although studies have reported a relatively high prevalence of RA in high-income countries, the true burden in low- and middle-income countries (LMICs) might be underestimated due to limited diagnostic resources and underreporting.4 In Bangladesh, the prevalence of RA is approximately 1.6%, which is greater than that in India (0.5%), Pakistan (0.6%), Thailand (0.1%), and Malaysia (0.2%).5
RA is associated with an increased risk of mortality and morbidity.4,6 Additionally, patients with RA exhibit a higher prevalence of comorbid conditions, further exacerbating disease outcomes.7 A previous metaanalysis reported that more than two-thirds of patients with RA had at least 1 comorbidity, with anxiety, depression, and hypertension being the most common.8 In addition, CV diseases (CVDs), such as myocardial infarction (MI) and stroke, are among the most prevalent comorbidities in individuals with RA, with an estimated prevalence ranging from 8.5% to 22%, significantly contributing to the increased risk of mortality in these patients.9 Moreover, osteoporosis (OP) is another common comorbidity in patients with RA, affecting 27% of patients, and is often exacerbated by chronic inflammation, prolonged glucocorticoid (GC) use, and physical inactivity.10 GI disorders, including peptic ulcer disease (PUD) and GI bleeding, are also common and are often attributed to nonsteroidal antiinflammatory drug (NSAID) use and GC therapy.11 Further, these patients have increased susceptibility to infections due to underlying immune dysregulation and immunosuppressive treatment.12 Hence, effective management of RA in these patients extends beyond merely controlling joint inflammation and pain, as comorbidities significantly contribute to increased healthcare utilization, compromised quality of life, and an overall greater disease burden.13
Like other LMICs, Bangladesh is experiencing a rapid increase in noncommunicable diseases, including hypertension, diabetes, and CVD, all of which may exacerbate RA-related morbidity and mortality.14 South Asian populations also exhibit a distinct RA genetic profile. Although RA susceptibility genes, such as HLA-DRB1 shared epitope alleles, are present across ethnic groups, their frequencies and subtypes differ from those in White populations.15 In addition, the non-HLA risk variant protein tyrosine phosphatase, nonreceptor type 22 (PTPN22) is rare in the Asian population.16 These genetic differences may influence autoantibody production, systemic inflammation, and EAMs, thereby affecting the comorbidity burden. Further, widespread exposure to air pollution and tobacco smoke may induce epigenetic modifications that modulate immune regulation in this population.17
There is a significant gap in data on RA-related comorbidities from Bangladesh and other LMICs. Most studies in Bangladesh have focused on the clinical presentation of RA, with limited emphasis on the burden of comorbidities. The scarcity of comprehensive data hinders the development of targeted interventions for the early detection and management of these conditions. Importantly, rheumatology care in Bangladesh is concentrated in tertiary centers, with limited routine comorbidity screening, fragmented referral pathways, and constrained access to multidisciplinary care. Given this background, the present study aimed to determine the prevalence of comorbidities and their associated factors in patients with RA in Bangladesh.
METHODS
Study design and setting. This cross-sectional study was conducted at the Rheumatology Clinics of Bangladesh Medical University (BMU) and Ibn Sina Hospital (ISH), Dhaka, Bangladesh, from January 2024 to December 2024. As tertiary care centers, these hospitals serve as referral facilities for patients with rheumatic diseases across the country, thereby ensuring a diverse patient population.
Study participants. The study population consisted of all patients diagnosed with RA who attended the rheumatology clinics at BMU and ISH during the study period. The inclusion criterion was participants aged > 18 years who met the 2010 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for RA.18 A total of 653 patients were included in the study through a consecutive sampling method.
Data collection procedure. Patients were interviewed face-to-face by rheumatologists using a structured case record form (CRF). Age, sex, disease characteristics, treatment history, and selected comorbidities were included in the CRF. A BMI (calculated as weight in kilograms divided by height in meters squared) of ≥ 25 was considered obese.19 The rheumatoid factor (RF) cutoff value was 15 IU/mL, with values below this cutoff considered as RF negative, 15-44 IU/mL indicating low-titer positivity, and ≥ 45 IU/mL indicating high-titer positivity. The laboratory value for anticyclic citrullinated peptide (anti-CCP) antibodies was 5 U/mL; a titer of 5-14.99 U/mL was considered low positive, and a titer of ≥ 15 U/mL was considered high positive. Data on selected poor prognostic factors (PPF) were collected in accordance with the 2023 recommendations of the Bangladesh Rheumatology Society (BRS) for RA management.20 These were erythrocyte sedimentation rate (ESR) ≥ 52 mm/h, C-reactive protein (CRP) ≥ 10 mg/L, RF and anti-CCP antibody at high titers (≥ 3 times the upper limit of normal), and high disease activity (Disease Activity Score in 28 joints based on CRP [DAS28-CRP] > 5.1) during the initial visit. Baseline comorbidity data were gathered during patient registration. Further assessment for comorbidities was prospectively conducted, up to 12 months, based on patient self-reports and clinical and laboratory evaluations, as well as Charlson Comorbidity Index (CCI) scores. All the patients underwent several routine investigations (complete blood count, alanine aminotransferase [ALT], creatinine), lipid profile, and oral glucose tolerance test (if they had risk factors). Dyslipidemia was defined according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) guidelines and characterized by the presence of ≥ 1 of the following conditions: total cholesterol ≥ 200 mg/dL (≥ 5.2 mmol/L); low-density lipoprotein cholesterol ≥ 130 mg/dL (≥ 3.4 mmol/L); high-density lipoprotein cholesterol < 40 mg/dL (< 1.0 mmol/L); or triglycerides ≥ 150 mg/dL (≥ 1.7 mmol/L).21
The CCI, comprising 17 categories of comorbid conditions, was used to classify comorbidities and estimate 10-year survival.22 According to the CCI, severe CCI was defined as having a score ≥ 5. A weighting of 1 for RA was not applied in this study. Information on comorbidities was collected for the following systems: diseases of the circulatory system; endocrine and metabolic diseases; and diseases of the GI, respiratory, MSK, nervous, and renal systems. CVDs include ischemic heart disease (IHD), which consists of stable or unstable angina, MI, stroke, and peripheral arterial disease. The QRISK3 calculator was used to predict 10-year CVD risk. Any patient with a 10-year CVD risk ≥ 10% according to the QRISK3 calculator was considered at high risk for CVD.23 Latent tuberculosis (TB) infection (LTBI) was screened by an interferon-gamma release assay (QuantiFERON-TB Gold plus assay), the Mantoux test, and chest radiograph following the BRS RA management recommendation before the initiation of either targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) or biologic DMARDs (bDMARDs).20 EAMs of RA were assessed during the study period. Due to the lack of validated criteria for EAMs, we included all broad EAM features, as well as those identified in previous studies.24
Statistical analysis. The sociodemographic and clinical characteristics of the study participants are presented by descriptive statistics. Continuous variables were examined for normality by the Kolmogorov-Smirnov test. Normally distributed continuous variables were summarized using means and SDs, whereas nonnormally distributed variables were reported as medians and IQRs. Categorical variables are presented as proportions and percentages. The overall prevalence of comorbidities was calculated and stratified by age and sex.
To identify factors associated with major comorbidities, including CVD, OP, GI disorders, and infectious diseases, multivariable logistic regression analyses were performed. Because the independent variables included in the regression model were selected a priori on the basis of their clinical relevance, no bivariate analysis was performed. The independent variables were age, sex, disease duration, inflammatory markers (ESR and CRP), seropositivity for RF and anti-CCP antibody, and medication history (GCs, methotrexate, tsDMARDs, and bDMARDs). Multicollinearity was assessed using the variance inflation factor, which was < 5 for all predictor variables in the logistic regression model. The regression model results are presented as odds ratios (ORs) with corresponding 95% CIs. Statistical significance was defined as a P value of < 0.05 for all tests and regression models. All the statistical analyses were conducted using SPSS version 29.0 (IBM).
RESULTS
Sociodemographic and clinical characteristics. A total of 653 patients with RA were included in this study. The mean age was 51.3 years, and 506 (77.5%) were women. The mean disease duration was 7.22 years. The mean age of patients without comorbidities was lower (39.1 years) than that of patients with multiple comorbidities, with age increasing progressively as the number of comorbidities increased. The mean BMI of patients was 26.2, with lower BMI in those without comorbidities (20.9) and higher BMI in those with ≥ 4 comorbidities (27.4). Regarding treatment, tsDMARDs and bDMARDs were used more frequently in patients with ≥ 4 comorbidities.
RF was positive in 560 (85.76%) patients, whereas anti-CCP antibody was positive in 550 (84.23%) patients. High titers of RF and anti-CCP antibodies were present in 68.9% and 80.1% of patients, respectively. Both ESR and CRP levels were elevated in > 61% of patients. The majority (70.2%) had high disease activity as measured by DAS28-CRP. Approximately 97% of patients had ≥ 1 PPF, and 74% had ≥ 3 PPFs. The proportion of patients with multiple PPFs increased with increasing comorbidity burden (Table 1).
Demographic, clinical, and laboratory features of patients with RA (N = 653) by number of comorbidities.
Prevalence of comorbidities. Overall, 98.9% of patients with RA had ≥ 1 comorbid condition (9.2% had 1, 17.5% had 2, 24% had 3, and 48.2% had ≥ 4; Table 1). Among the comorbidities, dyslipidemia, obesity, hypertension, and type 2 diabetes mellitus (T2DM) were the most prevalent, affecting 75.8%, 58.7%, 42.7%, and 30.3% of participants, respectively (Table 2).
Prevalence of comorbidities in patients with RA (N = 653).
Diseases of the circulatory system were more prevalent in men, particularly IHD (8.2% vs 2.6%, P = 0.004) and stroke (2.7% vs 0.2%, P = 0.01), whereas hypertension was more common in women (45.1% vs 34.7%, P = 0.03). Older participants (≥ 45 years) had a significantly greater prevalence of IHD (5.1% vs 0.5%, P = 0.01) and hypertension (53.5% vs 15.6%, P = 0.001) than those < 45 years. The prevalence of dyslipidemia was high across groups, with no significant differences according to sex or age. A QRISK3 score ≥ 10% was notably higher in men (72.2% vs 49%, P < 0.001) and in participants aged ≥ 45 years (73% vs 8.6%, P < 0.001; Table 2 and Figure 1).
Prevalence of cardiovascular risk factors in patients with rheumatoid arthritis (N = 653).
Among endocrine and metabolic diseases, T2DM was present in 30.3% of patients and was significantly more common in those aged ≥ 45 years (37.3% vs 12.9%, P = 0.001), with no difference according to sex (male 29.3% vs female 30.6%, P = 0.83). Obesity affected 58.7% of participants overall, with a significantly greater prevalence in women than in men (63% vs 43.5%, P = 0.001), but there was no difference across age groups (Table 2).
Overall, infectious diseases were reported in 29% of patients. Pulmonary and extrapulmonary TB affected 2.8% of the patients, whereas LTBI was present in 7.7%. Among the extrapulmonary TB cases, tubercular lymphadenitis was the most common (3 cases), followed by spondylitis (Pott disease; 2 cases), with 1 case each of abdominal TB, disseminated TB, tubercular osteomyelitis, and hip TB. Other infections accounted for 18.7% of cases, with no significant difference between the sexes. However, infections were significantly more common in older individuals than in younger individuals (21.2% vs 12.4%, P = 0.01). The most common sites of infection were the skin (6.6%), the urinary tract (6.3%), and the respiratory tract (5.4%). Among skin infections, fungal infections predominated (27 cases), followed by cellulitis (6 cases) and herpes zoster virus infections (4 cases). Urinary tract infections are caused primarily by organisms such as Escherichia coli, Klebsiella, and Streptococcus species. Respiratory tract infections (RTIs) included 19 cases of upper RTIs and 16 cases of pneumonia, with common pathogens identified as Klebsiella, Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas, Haemophilus influenzae, E. coli, and Moraxella species. Additionally, 2 cases each of chronic hepatitis B virus infection and septic arthritis were reported among the other infections. Among MSK disorders, OP was most prevalent, present in 15.6% of the participants. Finally, carcinoma was present in 3 patients (1 with follicular carcinoma of the thyroid, 1 with breast carcinoma, and 1 with bronchial carcinoma).
The mean overall CCI was 1.6. Younger patients (< 45 years) had significantly lower CCI scores (mean 0.3 [SD 0.6]) than older patients (≥ 45 years), who had a mean score of 2.1 (SD 1.3; P = 0.001). The CCI survival index was significantly lower in patients aged ≥ 45 years (mean 68.7 [SD 26.7]) than in younger patients (mean 93.3 [SD 6.7], P = 0.001). Although men had a lower mean survival index (71.9 [SD 27.1]) than women (76.4 [SD 25.5]), this difference was not statistically significant (P = 0.08; Table 2).
Factors associated with major comorbidities. In the multivariable logistic regression analysis, for CVD, age ≥ 45 years was a strong independent predictor, with nearly 10 times greater odds than patients aged < 45 years (OR 9.71, 95% CI 1.91-178.00; P = 0.03). Compared with male patients, female patients had significantly lower odds of developing CVD (OR 0.27, 95% CI 0.11-0.62; P = 0.002; Table 3).
Factors associated with major comorbidities in patients with RA (multiple logistic regression model).
For OP, older age remained a major risk factor, with patients aged ≥ 45 years having higher odds than younger individuals (OR 19.60, 95% CI 5.96-121.00, P < 0.001). Female sex was also independently associated with increased odds of OP (OR 3.55, 95% CI 1.71-8.37; P = 0.002). Further, female patients had a higher risk of GI disorders (OR 2.18, 95% CI 1.37-3.56). Additionally, a longer duration of RA was associated with an increased risk of OP (OR 1.05, 95% CI 1.02-1.08; P = 0.004; Table 3).
Among those with PPFs, having 2 (OR 3.60, 95% CI 1.20-21.50, P = 0.046) or 3 (OR 2.59, 95% CI 1.18-8.72, P = 0.04) such factors were significantly associated with an increased risk of GI diseases. For infectious diseases, advanced age (≥ 45 years) was significantly associated with increased risk (OR 1.60, 95% CI 1.03-2.54; P = 0.04). Further, the use of tsDMARDs (OR 14.80, 95% CI 2.17-300.00, P = 0.02) and bDMARDs (OR 4.11, 95% CI 1.56-11.70, P = 0.005) was associated with increased odds of contracting infectious diseases (Table 3).
EAMs and complications of RA treatment. Overall, EAMs were present in 104 (15.9%) patients. Among these, carpal tunnel syndrome (6.13%) and secondary Sjögren disease (SjD; 4.90%) were the most common, with their prevalence increasing alongside the number of comorbidities. Interstitial lung disease (ILD) and rheumatic nodules were also observed in approximately 2.50% of the patients. The other EAMs and complications of RA treatment are listed in Table 4.
EAMs of RA and complications of RA treatment (N = 653).
DISCUSSION
Patients with RA in our study had a high prevalence of comorbidities. Nearly all patients had at least 1 comorbidity, with more than half having 4 or more comorbid conditions. Dyslipidemia, obesity, and hypertension were the most prevalent comorbidities. Other common comorbidities included T2DM, infections, iron deficiency anemia, and OP. In addition, we found that carpal tunnel syndrome and secondary SjD were the most common EAMs of RA. To our knowledge, this is the first study from Bangladesh to assess the burden of comorbidities, determine the prevalence of PPFs, and measure EAMs.
The high burden of metabolic and CV comorbidities observed in our study aligns with prior reports. Hypertension was among the most prevalent comorbidities (42.7%), exceeding rates in the general population of Bangladesh.25 This prevalence is consistent with the Comorbidities in Rheumatoid Arthritis (COMORA) and Consortium of Rheumatology Researchers of North America (CORRONA, now CorEvitas) studies, which reported hypertension in nearly half of patients.9,26 Obesity was observed in 58.7% of patients in our cohort, higher than the global prevalence reported in the CorEvitas study (50.7%).26 Rapid urbanization, increased consumption of fast food and/or junk foods, and sociodemographic changes have contributed to rising obesity in Bangladesh. Additionally, high GC use, physical inactivity, and the application of World Health Organization (WHO)–recommended lower BMI thresholds for Asians19 may have further elevated obesity prevalence. T2DM affected 30.3% of patients in our present study, exceeding rates in the general population of Bangladesh (13.2%),27 the US (8.4%), Europe (12.4%), India (13.5%), and South Korea (9.6%).9,28 Dyslipidemia was highly prevalent (75.8%) in our cohort, surpassing that in reports from Latin America (18.6%), Europe (28%), India (5.3%), and the US (7.2%).9 Baseline CVD prevalence (4.6%; Table 2) was lower than in India (5.6%), the US and Latin America (8.5%), and Europe (21%),9 but higher than in China (2.2%)29 and similar to Korea (4%).28
Iron deficiency anemia affected 20.7% of patients, consistent with a metaanalysis reporting 27% prevalence among patients with RA.30 Chronic inflammation in RA contributes to anemia via functional iron deficiency, impaired erythropoiesis, and elevated hepcidin levels, disrupting iron metabolism.31 PUD, along with NSAID and GC use, likely contributed to the prevalence of high iron deficiency anemia. OP was observed in 15.6% of patients, lower than the 27% reported in a metaanalysis.10 Widespread calcium and vitamin D supplementation in Bangladesh may partially explain this lower prevalence, although dual-energy x-ray absorptiometry scans could not be performed for all at-risk patients due to financial constraints. PUD was present in 13% of participants, comparable to the 14% reported in the COMORA study.26 High PUD prevalence is likely driven by NSAID and GC use, as well as Helicobacter pylori infection (81.2% in this study). Infections were reported in 29% of patients, with TB being most common, reflecting immune dysregulation and immunosuppressive therapy.12
We observed sex- and age-related differences in comorbidity prevalence. Men had a higher prevalence of circulatory system disorders, particularly IHD and stroke, consistent with the Chinese Registry of Rheumatoid Arthritis (CREDIT) study.29 In Bangladesh, higher smoking rates among men32 likely contribute to this disproportionate CV burden in men.29 Conversely, women had higher rates of obesity, hypertension, hypothyroidism, and OP. Patients aged ≥ 45 years demonstrated significantly elevated prevalence of CVD, hypertension, T2DM, and OP. Notably, our findings suggest earlier onset of cardiometabolic comorbidities compared with other populations; for example, the prevalence of CVD in a Chinese cohort was 5% among patients > 60 years,29 whereas we observed a similar prevalence (5.6%) in patients aged ≥ 45 years. Early-onset metabolic comorbidities are also reported in the Indian REAL YOUNG study, with hypertension and DM affecting 42.4% of patients aged 35-45 years.33 These disparities may reflect differences in genetic susceptibility, lifestyle, healthcare access, and RA severity or management across populations.
We identified several risk factors for major comorbidities in patients with RA. Advanced age (≥ 45 years) was a strong predictor of CVD, OP, and infectious diseases. Aging is an established risk factor for these diseases.34 In addition, in our study, male patients were significantly more likely to develop CVD, whereas female patients were more prone to OP and GI disorders. Men generally have a higher incidence of CVD than women do, particularly before menopause.35 The prolonged disease duration of RA was associated with OP and GI comorbidities, likely due to the prolonged use of NSAIDs and GCs.11
In our study, GCs and tsDMARDs were associated with a lower likelihood of CVD. This contrasts with prior findings suggesting that higher-dose or chronic GC use may increase CVD risk.36 However, evidence indicates that low-dose or bolus GC therapy for inflammatory conditions such as RA may confer a protective effect.36,37 For example, the Glucocorticoid Low-Dose in Rheumatoid Arthritis (GLORIA) trial found no significant increase in CVD incidence with 5 mg/day prednisolone over 2 years in patients aged > 65 years.38 The lower CVD risk in the tsDMARD group likely reflects cautious avoidance of tofacitinib in patients with existing CVD (used in only 7 of 25 patients), considering the caution raised in the ORAL Surveillance trial.39 Reassuringly, Safety of Tofacitinib in Routine Care Patients With Rheumatoid Arthritis (STAR-RA; N = 102,263), the Anti-Rheumatic Therapies in Sweden (ARTIS) trial, and the German Rheumatoid Arthritis: Observation of Biologic Therapy (RABBIT) registry reported no difference in CVD frequency between tsDMARDs and other DMARDs.40,41 Nevertheless, both tsDMARDs and bDMARDs were associated with increased infection risk, consistent with their immunomodulatory effects in long-standing, refractory RA.42
Finally, among patients with RA in our study, the high prevalence of PPFs—defined as elevated ESR and CRP levels, high titers of RF and anti-CCP antibodies, and high disease activity—indicates a substantial disease burden and its association with comorbid conditions. Nearly all patients exhibited at least 1 PPF, with a significant proportion having 3 or more, suggesting a heightened risk of severe disease progression. Notably, the accumulation of multiple PPFs strongly correlated with an increasing comorbidity burden. These findings align with those of previous studies, indicating that comorbidities such as CVD, T2DM, and OP contribute to worse RA outcomes by exacerbating systemic inflammation and limiting treatment efficacy.7
In our patients, EAMs were present in 15.9% of patients. The overall prevalence of EAMs in the literature ranges from 8% to 40%, and their occurrence has decreased over time.43 Carpal tunnel syndrome (6.13%) and secondary SjD (4.90%) were the most common EAMs. Carpal tunnel syndrome is one of the most common neurological EAMs of RA, and a metaanalysis revealed that the prevalence of carpal tunnel syndrome in patients with RA was 5.5%, which is consistent with the findings of this study.44 ILD and rheumatic nodules are less common but comparable in prevalence to those reported in the UK Early Rheumatoid Arthritis Study (ERAS).24 The complication rates in our study, such as Cushing syndrome and adrenal insufficiency, were lower than those reported in ERAS.24
The extremely high comorbidity burden observed in our study has important clinical implications. Patients with RA require a comprehensive assessment beyond joint inflammation, including regular screening for CV, metabolic, MSK, infection, and GI comorbidities. Early identification and management of these conditions can mitigate morbidity, optimize treatment outcomes, and reduce long-term complications. Multidisciplinary care involving rheumatologists, cardiologists, endocrinologists, and other specialists including physiotherapists and nurse practitioners, among others, may be required for the holistic care of patients with RA. Additionally, integrating comorbidity monitoring into routine follow-up can guide individualized therapy and improve overall patient quality of life.
However, our study has several limitations that should be considered when interpreting the findings. First, as a cross-sectional study, causal relationships between RA and comorbidities could not be established, and the observed associations may reflect reverse causation or residual confounding rather than true etiologic effects. Second, the absence of an age- and sex-matched control group limits direct comparisons with the population without RA, which may result in an overestimation of the relative burden of comorbidities among patients with RA. Third, the extremely high prevalence of comorbidities (98.9%) may reflect hospital-based sampling of patients with established, long-standing RA, who are more likely to accumulate comorbid conditions, indicating potential selection bias. Additionally, the inclusion of obesity as a comorbidity using the lower WHO-recommended Asian BMI cutoff, using the NCEP-ATP III guideline to define dyslipidemia, and the high infection prevalence potentially contributed to the high prevalence of comorbidities. Unmeasured confounders, including genetic predisposition, lifestyle factors, and socioeconomic status, may have influenced the observed associations, potentially biasing prevalence estimates and risk factor associations. Some ORs had wide CIs, particularly for less common comorbidities, reflecting limited events and necessitating cautious interpretation. Finally, the study did not evaluate the effect of comorbidities on disease activity, treatment outcomes, or quality of life, thereby limiting the assessment of their clinical significance and their prioritization in management strategies.
Overall, we found a high burden of comorbidities among patients with RA, with circulatory and metabolic disorders, including obesity, dyslipidemia, hypertension, and T2DM, being the most prevalent. Advanced age, male sex, elevated inflammatory markers, and longer disease duration were significant risk factors for major comorbidities. We recommend a comprehensive, individualized approach to managing RA, emphasizing early screening, targeted interventions, and multidisciplinary care to mitigate comorbidity-related complications and to improve long-term clinical outcomes in these patients.
ACKNOWLEDGMENT
The authors would like to express their sincere gratitude to Dr. Latifur Rahman for assisting with data collection and to Pi Research & Development Centre, Dhaka, Bangladesh (www.pirdc.org), for their assistance with manuscript revision and editing.
Footnotes
CONTRIBUTIONS
Conceptualization: MSMM, RB, SAH, MTN; formal analysis: MSMM, MJH, MTN; investigation: MSMM, MJH, MRC; methodology: MSMM, RB, MJH, SAH; resources: MSMM, MRC; supervision: MSMM, MJH; writing – original draft: MSMM, RB, MJH, MRC; writing – review & editing: MSMM, MJH, SAH, MTN. All authors have read and agreed to the published version of the manuscript.
FUNDING
The study was partially supported by the BMU (grant no. BSMMU/2023/13052).
CONFLICTS OF INTEREST
The authors declare that they have no competing interests relevant to this article.
ETHIC AND PATIENT CONSENT
The study protocol was reviewed and approved by the Institutional Review Board of Bangladesh Medical University (formerly Bangabandhu Sheikh Mujib Medical University; registration ID 723, date: December 1, 2022). All the authors declare that no human subjects were harmed and that the procedures followed were in accordance with the ethical standards and regulations established by the Declaration of Helsinki of the World Medical Association. Informed written consent was obtained from the participants involved in the study.
DATA AVAILABILITY
Patient-level data will be available upon request from the corresponding author.
- Accepted for publication April 1, 2026.
- Copyright © 2026 by the Journal of Rheumatology
This is an Open Access article, which permits use, distribution, and reproduction, without modification, provided the original article is correctly cited and is not used for commercial purposes.
