Rheumatoid Arthritis Antibodies Associated With Anti-TNF Therapy Response

TNF cytokine protein molecule
For the first time, researchers have assessed the relationship of antibody interactions with response to anti-TNF therapy in patients with rheumatoid arthritis.

In patients with rheumatoid arthritis (RA), response to antitumor necrosis factor (anti-TNF) therapy is associated with antibody interactions, according to study results published in BMC Musculoskeletal Disorders.

In the current study, the researchers aimed to analyze the association between antibody interactions and response to anti-TNF therapy.

Baseline levels of several antibodies were determined in 80 patients with RA who were initiating an anti-TNF therapy. Clinical response at week 12 was measured using the change in 28- joint Disease Activity Score DAS28 score. The 4 antibody titers measured at baseline were rheumatoid factor (RF), anticyclic citrullinated antibodies (anti-CCP), anticarbamylated protein (anti-CarP), and antipeptidylarginine deiminase type 4 (anti-PAD4).

All 4 autoantibody titers were present in all participants at baseline. Overall, there was an average reduction of 1.96±1.33 points in DAS28 scores. At the single marker level, there were no significant associations between the autoantibodies and improvement in DAS28 scores. A highly significant antibody interaction was observed between anti-CarP and anti-PAD4 (P =.0062), and between anti-CCP and RF (P =.00068) and anti-TNF response. The anti-CarP/anti-PAD4 interaction was associated with a worse therapy response, whereas the anti-CCP/RF was associated with a better response.

The interaction between anti-CCP and RF was replicated in an independent cohort of 199 patients with RA (P =.044), which showed a positive interaction, similar as that in the prospective cohort.

Study limitations included the small sample size and the possibility that small improvements in DAS28 might not translate to clinically meaningful responses. To better define this boundary, more patient data on the 4 antibodies are needed. The lack of comparison of interaction associations between the different anti-TNF drugs was another study limitation.

Researchers concluded, “Our findings also provide an explanation for the lack of consistency observed in previous studies, in which antibodies were analyzed independently. These results leverage the potential of antibodies as biomarkers for anti-TNF response in RA.”


Julià A, López-Lasanta M, Blanco F, et al. Interactions between rheumatoid arthritis antibodies are associated with the response to anti-tumor necrosis factor therapy. BMC Musculoskelet Disord. 2021;22(1):372. doi:10.1186/s12891-021-04248-y