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Surprising Link Between Weight Gain and RA Activity

— Hint: it's not the worsening you probably expected

MedpageToday
Overweight woman suffering from knee pain.

In patients with rheumatoid arthritis (RA) treated with infliximab (Remicade), increases in body mass index (BMI) scores over time were not associated with increased disease activity or faster radiographic progression.

In fact, erosions were less severe in those with rising BMI, according to Theresa Burkard, PhD, of Eidgenössische Technische Hochschule Zürich in Switzerland, and colleagues.

So-called , which quantify erosive joint damage, were negatively associated with increasing BMI in a cohort of 187 RA patients followed for an average of 4.4 years: each 1-point BMI increase correlated with -1.05 Rau points (95% CI -1.92 to -0.19), the researchers .

No significant association was seen in a different cohort between BMI changes and 28-joint Disease Activity Score with erythrocyte sedimentation rate taken into account (DAS28-ESR).

But Burkard and colleagues noted that, in underweight patients (BMI <18.5), there was a hint that weight gain improved disease control. Each 1-point BMI increment was associated with a 0.14-point decrease in DAS28-ESR, though it failed to reach statistical significance (perhaps because only 28 cohort members were underweight).

Infliximab is typically administered with weight-based doses. Burkard's group thus concluded that "BMI increase may not lead to changes in DAS28-ESR in patients receiving infliximab, despite the weight-adapted dose." They also highlighted the apparent protective effect of increasing BMI on radiographic progression, "non-limited to obese patients."

To some extent the findings weren't surprising. Previous studies have found radiographic progression is slower in overweight and obese patients versus those of normal weight. But quantitative measures of disease activity such as DAS28 typically appear worse with higher BMI.

Most of this research, however, has been cross-sectional, examining patients at a single time point. Burkard and colleagues wanted to see whether weight changes over time would show a similar pattern. They decided to focus on patients treated with infliximab so that the study would yield "a homogeneous study population and an analysis independent of [biologic] agent and dose (which may confound or mediate the tested associations)."

For the DAS28-ESR assessment, the researchers analyzed records for 412 RA patients receiving infliximab at some point from 1997 to 2020, followed for a mean of 4.5 years. This group had an average of 6.4 examinations (range 2-27) during which BMI and DAS28-ESR values were recorded. Radiographic progression was evaluated in a different set of 187 patients who had a mean of 6.0 exams (range 2-20) over an average 4.4 years. Both cohorts were drawn from a Swiss registry of RA patients.

In both cohorts, members were typical of patients with established RA: mostly women in their 40s and 50s. In the cohort followed for disease activity, mean DAS28-ESR score at first evaluation was about 4.0, and BMI averaged 25.

Limitations to the study included the reliance on administrative records, the small numbers of patients included, and restricting the analysis to infliximab-treated patients. On the other hand, Burkard and colleagues argued that, since their patients' characteristics were similar to those in studies of other RA therapies based on the Swiss registry, "our results may be [generalizable] to all" patients on disease-modifying agents.

The researchers urged future studies "in bigger cohorts" to investigate further the relationship between body weight and RA disease course and treatment response.

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    John Gever was Managing Editor from 2014 to 2021; he is now a regular contributor.

Disclosures

The study was funded by the ETH Zurich Foundation. Several co-authors reported relationships with numerous pharmaceutical companies involved in rheumatoid arthritis drug development and marketing.

Primary Source

RMD Open

Burkard T, et al "Longitudinal associations between body mass index and changes in disease activity and radiographic progression in rheumatoid arthritis patients treated with infliximab" RMD Open 2023; DOI: 10.1136/rmdopen-2023-003396.