Rheumatoid arthritis: thinking and understanding disease through a broader lens

This editorial refers to ‘Is the relationship between deprivation and outcomes in rheumatoid arthritis mediated by body mass index? A longitudinal cohort study’, by Witkam et al. 2023;62:2394–2401. In health and disease, both biological and non-biological factors play an important role. In other words, it is not solely the biological and genetic make-up that define health status. Social factors play a crucial role as shown increasingly by a large body of evidence [1]. In RA, striving for optimal disease outcomes has been a long and unconditional goal among the clinical and research community. We have seen a revolution in drug therapies and treatment strategies over the years, as part of attempts to improve patient care and treatment outcomes. Despite this, a small, yet important proportion of people living with RA have refractory or ‘difficult-to-treat’ disease and suffer poor outcomes. In this context, the potential role of non-biological, socioeconomic factors has been raised, leading to the exploration of new concepts and avenues for research. In this issue, Witkam et al. explore the relationships between deprivation (used as a proxy for socioeconomic status) and obesity with self-reported disability and disease activity in RA [2]. Specifically, they attempt to understand whether BMI is a potential mediator of the relationship between area-level deprivation and these outcomes. Using data from the multicentre, prospective observational cohort Rheumatoid Arthritis Medication Study (RAMS) over 12 months, Witkam et al. have shown that higher deprivation and obesity associate with higher disability and disease activity. BMI mediated 14–17% of the associations of deprivation with disability and disease activity, suggesting that obesity explains at least part of the association between deprivation, disability and disease activity. Area level deprivation was computed by linking the participants’ postcode to the Index of Multiple Deprivation (IMD). In the UK, IMDs are widely used to classify the relative deprivation (essentially a measure of poverty) of small areas or neighbourhoods in England. Multiple components of deprivation (e.g. income, employment rate, education, crime, disability) are weighted and compiled into a single score of deprivation [3]. The finding of an association between obesity and lower socioeconomic status is not new [4]. Associations have also been shown between obesity and worse disability and disease activity. For example, data from RA inception cohorts in the UK show not only that the prevalence of obesity is rising in RA, even in early disease, but that indeed obesity associates with worse disease activity, function and health-related quality of life, reducing significantly the chances of achieving low disease activity [5]. A suggested explanation centres on links between adiposity and inflammation and immunological changes that may drive active disease [6]. However, adiposity (fatness) is not necessarily truly reflected in level of BMI. Therefore, the association between obesity and CRP levels observed by Witkam et al. can be difficult to interpret, especially with other parameters such as waist circumference (which has been shown to more strongly associate with inflammation) missing. A potential explanation, as the authors discuss, is that RA patients who are obese may be less responsive to anti-rheumatic treatment, as supported by existing evidence [7]. Additionally, the higher disease activity scores in obese patients have been shown by Witkam et al. to be driven by the subjective components of this composite index, namely the tender joint count and visual analogue scale general wellbeing, rather than swollen joint counts or CRP levels. Now, with regard to the interesting link between obesity and socioeconomic status, disentangling the various associations described in the literature between lower socioeconomic status, obesity, disability and disease activity helps to shed more light into intricate relationships and pathways implicated in adverse disease outcomes. The study by Witkam et al. suggests that in people living in more deprived areas, obesity further associates with worse disease outcomes. Interestingly, restricting the analyses to samples of either men or women revealed that the mediating effect of BMI was only observed among women for both disability and disease activity. The authors speculate that this observation may be in part explained by a stronger relationship between lower socioeconomic position and obesity in women. However, it is worth noting that the small sample size for men included in the study may in fact be a reason for the lack of effect seen in men, or the presence of unmeasured confounders could be another reason. Observed gender differences can be subject to much speculation, and therefore caution should be exerted when reaching conclusions. Aside from sociodemographic factors (age, gender), this study used only area-level deprivation as a measure of socioeconomic status, with other important socioeconomic factors such as education, type of job or income not explored. Additionally, the use of area-level deprivation as a measure of socioeconomic status would be the same for men and women, without accounting for potential differences between genders in, for example, education level, work status or income. These are limitations and prevent a more comprehensive understanding of the role of individual socioeconomic factors. Nevertheless, the study makes the important point that both deprivation and obesity are associated with worse disease outcomes. Taking the wider perspective, according to the WHO obesity represents a global epidemic, and there is an ongoing and unmet need to tackle this epidemic. However, it is also known that obesity is socially patterned, so targeting those most at risk, including those of lower socioeconomic status through public health campaigns, self-management interventions [8] and other lifestyle changes [9] will likely be of benefit. This should of course be done sensitively, acknowledging the social stigma that comes along with the obesity stigma and that can further threaten health and lead to health disparities [10]. Given the association between obesity and other comorbidities such as cardiovascular disease also increased in patients with RA [11], and the potential impact on treatment choice, it is necessary that obesity is adequately addressed in routine clinical care. However, whereas associations have been shown between weight loss (whether through exercise or nutrition or bariatric surgery [12]) and improvement of disease activity in RA, the effect of these interventions in different socioeconomic groups is not known, calling for more research in this area. As a final reflection, it is important to keep in mind that causality cannot be proven based on these observations, and this is in fact a common problem with observational data, especially with much residual confounding and other biases such as confounding by indication. However, we reiterate the important message here, in that obesity seems to be an important factor in the association between social disparities and adverse disease outcomes in RA. Demonstrating these associations using real-life data comes with important clinical messages, which are worth reinforcing time and time again. The potentially modifiable nature of obesity and its impact not just in RA, but also in many comorbidities, which might in turn further complicate RA treatment, calls for its management to be made central to treatment strategies in RA. This is irrespective of the socioeconomic background of people living with the disease, albeit potentially with a sense of priority in those of lower socioeconomic status. Data are available upon reasonable request by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). All data relevant to the study are included in the article. No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this article. Disclosure statement: The authors have declared no conflicts of interest.