Home Therapeutic relationship Obesity reduces responses to TNF inhibitors and non-TNF biologics

Obesity reduces responses to TNF inhibitors and non-TNF biologics


There does not appear to be any superiority of any type of biologic drug for patients with rheumatoid arthritis in different body mass index (BMI) groups, with obesity and underweight both reducing treatment effects after 6 months of use, according to data registry results on nearly 6,000 individuals.

Dr Joshua Baker

Although interest in the precision use of biologics for RA is growing, few patient characteristics have been identified to inform treatment decisions, Joshua F. Baker, MD, of the Philadelphia Veterans Affairs Medical Center and the University of Pennsylvania, Philadelphia, and colleagues wrote.

Previous studies on the effect of obesity on RA treatments have been inconclusive, and a comparison of RA treatments across BMI categories would provide more definitive insights, they said.

In a study published in Arthritis Care & Research, researchers used the US observational registry CorEvitas (formerly known as Corrona) to identify adults who initiated second- or third-line treatment for RA with tumor necrosis factor inhibitors (n = 2891) or not. -Biological TNFi (n=3010) between 2001 and April 30, 2021.

The study population included adults diagnosed with RA; those with low disease activity or no follow-up visit at 6 months were excluded. BMI was classified as underweight (less than 18.5 kg/m2), normal weight (18.5-25 kg/m2), overweight (25-30 kg/m2), obese (30-35 kg/m2) and severely obese (35 kg/m2 or more). The three measures of response were achievement of low disease activity (LDA), change at least as large as the minimum clinically important difference (MCID), and absolute change in clinical disease activity index. (CDAI) compared to baseline.

A total of 2712 patients were obese or severely obese at the time of treatment initiation.

Overall, patients with severe obesity had significantly lower odds of achieving either LDA or at least as large a change in MCID, as well as less improvement in CDAI score, compared to other categories of ‘BMI. However, in the adjusted models, the differences in these outcomes for patients with severe obesity were no longer statistically significant, whereas underweight was associated with a lower likelihood of achieving ADL (odds ratio , 0.32; P = 0.005) or a change at least as large as the MCID (OR, 0.40; P = .005). The adjusted model also showed less improvement in CDAI in underweight patients, compared to normal weight patients (P = 0.006).

Stratification by TNFi and non-TNFi therapies showed no difference in clinical response rates between BMI categories.

Study represents the first evidence of a similar reduction in therapeutic response with TNFi and non-TNFi in severely obese patients, with estimates for non-TNFi biologics meeting the 95% confidence interval for TNFi biologics, the researchers wrote. “Our current study suggests that a lack of response in obese patients is not specific to TNFi therapies, suggesting that this phenomenon is not biologically specific to the TNF pathway.”

Study results were limited by several factors, including the focus on patients who were not biologic-naïve and the relatively small number of underweight patients (n=57), noted the researchers. Other limitations include unaddressed mediators of the relationship between obesity and disease activity and lack of data on off-label dosing strategies.

However, the results were strengthened by the large sample size, control for a range of confounders, and direct comparison of RA treatments.

The researchers concluded that BMI should not influence the choice of TNF over treatment without TNF in terms of clinical efficacy.

The study was supported by the Corrona Research Foundation. Baker revealed that he received support from a Veterans Clinical Science Research and Development Merit Award and a Rehabilitation Research and Development Merit Award, as well as consultancy fees from Bristol- Myers Squibb, Pfizer, CorEvitas and Burns-White. Two co-authors reported financial ties to CorEvitas.

This story originally appeared on MDedge.com, part of the Medscape Professional Network.