Rheumatoid arthritis (RA) is chronic inflammatory arthritis characterized by the inflammation of multiple joints and significant joint destruction and disability. It is the most common form of inflammatory arthritis that affects synovial joints. In early disease, the wrists, proximal interphalangeal, metacarpophalangeal, interphalangeal joints of the thumbs, and metatarsophalangeal are the most commonly affected joints in the body [1]. Additionally, chronic inflammation secondary to RA can result in a tremendous risk of pulmonary and cardiovascular disease and changes in bone density [1]. RA has a significant effect on body composition, the levels of lip­id, adipokine, and insulin sensitivity [2]. RA patients had a higher body fat mass and lowered lean mass than the healthy population [3]. Despite the significant therapeutic advances in the medical treatment of RA, a considerable proportion of RA patients shows an inadequate response to treatments and, therefore, are at high risk of different medical complications, disability, and low quality of life [4-6]. Consequently, it is essential to recognize factors that impact the outcome of RA. Obesity is implicated in this poor outcome, but this fact is still uncertain [7]. Owing to the inflammatory nature of these two conditions, it is hypothesized that obesity and overweight are associated with high disease activity and more disease severity in RA patients [7]. Studies suggest that adipose tissue is not just a store for inert energy, but it is an endocrine organ that interplays with the central nervous and immune system, with a range of essential functions, such as proteins and hormones production that are involved in physiological and pathological processes, including immunity and inflammation [8]. Therefore obesity is implicated in the activation of pro-inflammatory pathways; thus, obese RA patients have more active and severe disease. Adipose tissue is considered a dynamic organ that produces several molecules, including cytokines, adipokines, and interleukin (IL)-6. The pro-inflammatory activities of these molecules are responsible for chronic systemic inflammation. These molecules are abundant in the serum of patients with RA and make the link between obesity and RA [9]. Studies investigating the impact of obesity on RA patients have revealed controversial results. Some studies show poor response to treatment in obese RA patients. These patients did not achieve disease control and were associated with increased structural and functional impairment [10-12]. Some studies showed that obesity is implicated in high disease activity [13,14]. In contrast, obesity was associated with more favorable radiographic outcomes [12,15]. Moreover, studies suggested that obesity may delay the progression of radiographic damage in the early phases of RA [16,17]. However, the mechanism by which obesity may be correlated to RA is still unknown. One mechanism is the association between obesity and chronic inflammation. Fatty tissue increases during weight gain, and adipocytes secret adipocytokines and inflammatory cytokines, including adiponectin, tumor necrosis factor, interleukin-6, CRP, and others [18]. The major adipocytokines have immunomodulatory properties and impact inflammation [19]. This fact offers an active area of research, and adipocytokines and inflammatory cytokines are essential factors in the pathophysiology of rheumatic diseases, such as RA. This study aimed to evaluate the prevalence and the influence of obesity on patients with RA.

This was a cross-sectional study carried out at the Department of Rheumatic outpatients and Basrah biologic center in Basrah Teaching Hospital from May 2021 till May 2022. A sample of 185(38 males and 147 females) patients with RA, diagnosed according to the 2010 ACR/ EULAR criteria for the classification of RA [20], were enrolled for the study. Data collection was done through an interview with the patients using a special questionnaire developed by the researchers. The researchers evaluated the clinical history and physical examination of all patients. The following parameters were recorded in all patients during the first examination; demographic data, clinical findings, disease activity (number of tender/swollen joints among 28 joints), drug history, presence of articular and extra-articular symptoms, presence of concomitant comorbid diseases, laboratory parameters including complete blood count, CRP, ESR, RF, anti-CCP antibody, and radiological changes detected on radiography by a rheumatologist and a radiologist. Patients diagnosed with other connective tissue diseases (overlap syndromes), except for secondary Sjögren syndrome, were excluded. Disease activity was scored using the DAS28 erythrocyte sedimentation rate (ESR) system. Scores was interpreted as follows: <2.6 (clinical remission), 2.6–3.1 (low), 3.2–5.0 (moderate), and ≥ 5.1 (high) [21]. Obesity was determined based on BMI, and the adopted BMI ranges were: normal (18.5–24.9), overweight (25–29.9), and obese (≥ 30) [22]. Normal ranges of laboratory parameters were described as follows: CRP (normal 0–5), ESR (normal 20 mm/h by Westergren method), RF (normal <5 by nephelometry method), and anti-CCP (normal <20 by ELISA method).

Ethical considerations

Written consent was obtained from all participants prior to their involvement. The study was conducted in accordance with the principles of the Declaration of Helsinki.

Statistical analysis

SPSS software version 25.0 was used for data analysis. Percentages and mean were used to present the data in tables. In addition, a comparison of study groups was carried out using a chi-square test for categorical data and Student's t-test for continuous data. A P-value of <0.05 was considered statistically significant.

The demographic distributions of patients are shown in (Table 1). From the total sample of 185 patients with RA, 38 (20.54%) were men, and 147 (79.46%) were women with mean age disease duration and BMI of 55 ± 7.4, 9.7 ± 6.2 years, and 26. 9 ± 7.2 for men respectively and 52 ± 6.4,10.8 ± 5.4 years, and 27. 9 ± 6.4 for women, respectively, the difference was statistically not significant (p>0.05). There were 115 (62.2%)) overweight/obese patients and 70 (37.8%) normal weight patients, the difference was statistically significant (p=0.015). There were no significant differences in structural joint damage, RF, and Anti-CCP between normal weight and overweight/ obese groups, as shown in (Table 2). There were statistically significant differences between normal weight and overweight/obese groups in VAS, ESR, CRP, and DAS28; P-values were 0.022, 0.031, 0.015, and 0.013, respectively, as shown in (Table 2). There were no significant differences in clinical, laboratory, and disease activity between the overweight and obese patients, as shown in (Table 3).

Obesity is medically known as excess body fat that has accumulated to the extent that it may increase morbidity and mortality in obese individuals [23]. Obesity was found to associate with an increased risk of developing RA in a study comparing 349 incident cases of RA and 1457 controls, specifically in women [24]. Similarly, in a prospective case-control study of 165 pairs including both genders, obesity was associated with an almost 4-fold increase in the risk for developing RA; this association was again more pronounced in women [25] and, until recently, some authors still consider obesity as a potential contributor to the development of RA [26]. However, newer studies suggest that obesity is not a predisposing factor for RA [27,28]. The effect of body composition type on patients' clinical state and, more specifically, the degree of disease activity in RA has been examined in several previous studies [29-33], although their conclusions are contradictory. Some reports found a significant association between higher disease activity and the presence of adiposity. Nevertheless, other reports found no proven association between the percentage of fat in body mass and the level of disease activity in RA. A worldwide study identified 18% of RA patients as obese, while a UK-based study found a higher prevalence of 31% [34]. However, in both studies, >60% of RA patients exhibited BMI above the desired levels (>25kg/m²) and were overweight or obese. These results are comparable with those of the general population in the UK, where about 35% are overweight and about 25% obese [35]. Other studies' results indicate that overweight and obesity, even when assessed based on the general (WHO) BMI cut-offs, are at least as prevalent. In this study, overweight/obesity was highly prevalent, as defined by BMI (62.2%) of the study population; of them, 27% were obese. Moreover, it was found to be associated with high disease activity but not with joint erosion or serological positivity. These results are nearly similar to Guimaraes et al. findings [36], who reported that 26.9% of their patients were obese. Moreover, Hammoda et al. demonstrated that 32% of their patients were overweight, and 35% were obese [37]. In agreement with our results, Yacoub et al. [38] demonstrated that 30% of their patients were overweight, but 16.8% of their study population were obese, which is lower than our findings. One explanation of the increased prevalence of overweight and obesity in RA patients may be explained by reduced physical activity and long-term treatment of corticosteroids [39]. We found that overweight and obese patients were significantly older and had longer disease duration with statistically significant female predominance compared to the normal weight group. Voigt et al. [24] reported that obesity was prevalent in RA patients, in particular women. These results disagree with Gharbia et al. [40], who concluded that there was no significant statistical difference between RA patients with normal BMI and overweight RA patients regarding age, disease duration, and sex distribution. In this study, RA patients showed no significant difference in the clinical, laboratory, and activity indexes in terms of DAS-28 and VAS between overweight and obese subgroups. Vidal et al. found a protective effect of obesity against joint damage in their study population. Their results were explained by the association of obesity with seronegativity, which is known to be associated with a better structural prognosis or related to the more intensive therapy because of high DAS28 levels and/or high plasmatic drug concentrations for treatment with dosage adapted to the weight, such as infliximab, abatacept, and tocilizumab [41]. In contrast, we found no significant differences in radiological changes in a term of structural joint damage between overweight/obese and normal weight patients. The result may be related to the lack of optimal treatment regimens, such as the shortage of biological agents in our locality. Our study showed a significant difference in activity indexes regarding DAS-28, VAS of pain, and inflammatory markers such as ESR and CRP. DAS-28, VAS, ESR, and CRP were all higher in overweight/obese patients than those normal-weight patients. This is in agreement with the findings of Stavropoulos-Kalinoglou et al. [14], who evaluated a total of 294 RA patients; based on BMI, patients were divided into four groups (underweight, normal weight, overweight, and obese) and found a significant difference in inflammatory markers and disease activity, between these groups: underweight or obese patients had significantly higher CRP, and poorer DAS-28 than those who had normal weight, which means that obese RA patients have more active disease on clinical, and laboratory levels. Hammoda et al. [37] also reported an increase in inflammatory markers such as (ESR and CRP) and disease activity indexes such as DAS-28 and VAS among overweight/obese compared to normal weight RA patients; results were consistent with ours. The current study found no significant associations between BMI and RF anti- CCP in RA patients. The findings of Gharbia et al. [40] agree with our study's results. However, other studies observed that obesity is significantly associated with increased development of negative anti-CCP [42,43]. In contrast to our finding Hammoda et al. and Yacoub et al. [37,38] studies revealed a statistically significant higher prevalence of RF and anti- CCP seropositivity among overweight and obese patients, and Ellabban et al. [44] reported nearly similar results.

Overweight and obesity were frequent among RA patients and associated with high disease activity. Therefore, weight reduction can help in the improvement of the clinical outcome and disease activity control.

More studies are required to investigate whether weight reduction can decrease the non-remission rate among obese RA patients.

AM: Conceptualization, Methodology, Software, Data curation, Writing- Original draft preparation, approval of the final manuscript. FM: Visualization, Investigation, Software, Validation, approval of the final manuscript. AA: Writing- Reviewing and Editing, approval of the final manuscript.

We kindly appreciate the role of all participants in the study.

No funding was received for this manuscript.

Authors declare that there is no conflict of interest.