Novel biomarkers enable personalised medicine in early RA

Antibodies against 3 University Hasselt (UH)-rheumatoid arthritis (RA) antigens were predictive of failure to achieve clinical remission, sustained clinical remission, and sustained low-disease activity following first-line therapy with methotrexate and glucocorticoids in patients with RA. These results provide an opportunity for personalised medicine, according to the authors [1].

Methotrexate plus glucocorticoids are the first-line therapy for patients with RA. “However, whether this therapy leads to clinical response is determined by a wait-and-see approach,” said Dr Patrick Vandormael (Hasselt University, Belgium). “If we could predict the effectiveness of methotrexate plus glucocorticoids in individual patients, we may initiate other therapies in case it is unlikely that a particular patient will respond to the standard first-line therapy.” The general hypothesis of the presented study is that autoantibodies can predict a lack of treatment response to first-line therapy in patients with RA. To examine this hypothesis, 179 blood samples were collected from patients who started methotrexate plus step-down glucocorticoids in the CareRA trial. The blood samples of those achieving clinical remission after 8 weeks were compared with those who did not achieve clinical remission at this timepoint.

In total, the investigators reported 6 antibodies against the novel UH-RA antigens that were related to clinical remission after therapy. Those who did not reach clinical remission after 8 weeks of therapy according to Disease Activity Score-28 with C-reactive protein (DAS28-CRP) were more likely to display antibody reactivity against 3 of these antigens at baseline than those who did achieve clinical remission (31% vs 15%; P=0.007). Similar results were seen for remission according to DAS28 with erythrocyte sedimentation rate (DAS28-ESR) (30% vs 14%; P=0.007) and Simplified Disease Activity Index (SDAI) (36% vs 17%; P=0.018), as well as for low-disease activity according to Clinical Disease Activity Index (CDAI) (37% vs 17%; P=0.01). These results were maintained at weeks 16, 40, and 52. Moreover, similar results were obtained for sustained remission and sustained low-disease activity. Finally, the results were consistent in patients with seronegative RA.

“These results may lead the way to personalised therapy for patients with early RA, separating patients who are likely to respond to first-line therapy from those who are not, based on antibody-reactivity at baseline,” argued Dr Vandormael. “We may administer other agents as first-line therapies in patients unlikely to respond to methotrexate plus glucocorticoids, avoiding a prolonged high disease activity.”

1. Vandormael P, et al. Novel antibody biomarkers that predict absence of early and sustained disease remission and low disease activity after intensive first-line therapy in rheumatoid arthritis. Abstract A17, BCR 2022, 21-23 Sep, Mons, Belgium.

 

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Posted on 23 September 202210 October 2022