Clinical Criteria for RA & Early Non-Response to Certolizumab as Predictors of Patient Outcomes

Although anti-tumor necrosis factor (TNF) therapy can be used to effectively treat patients with rheumatoid arthritis (RA), not all patients respond with significant improvements in disease activity. In these cases, because RA treatment guidelines recommend a treat-to-target approach, inadequate response to one treatment should prompt a switch to a different treatment strategy. Thus, rheumatologists look for early clinical markers of response or non-response that can be used to inform treatment decisions.

For RA patients receiving certolizumab treatment, Clinical Disease Activity Index (CDAI) non-response at three months may predict a failure to achieve low disease activity at 12 months, according to a recent French study. The research by Alain Saraux, MD, PhD, professor of rheumatology at CHU de la Cavale-Blanche, France, and colleagues was published in the January issue of RMD Open. The study is the first to be conducted in RA patients treated with certolizumab in a real-world setting, and its findings corroborate published clinical trial data.¹

The investigators began by identifying physicians from an extensive list of French hospital rheumatologists and internal medicine specialists who treat patients with RA. They included 327 rheumatologists and 29 internal medicine specialists practicing in France. Of these 365 physicians, 176 enrolled patients in the study and returned at least one case report form.

The study included 792 patients, and the researchers analyzed data from 730 of them. Patients were 55.0 ± 13.1 years old and predominately female (77.9%). The investigators evaluated three-month data from 574 treated patients and performed predictability analyses on DSAI for 532 patients, Disease Activity Score-28 (DAS28) with erythrocyte sedimentation rate (ESR) for 434 patients and Health Assessment Questionnaire Disability Index (HAQ-DI) for 496 patients.

The researchers used CDAI score of greater than 22 to define non-response. At three months, 16.7% of patients were non-responders. When researchers used DAS28 ESR, 45% of patients were non-responders at three months. And when they used the HAQ-DI score, 46.8% of patients were non-responders at three months. At 12 months, the percentage of patients in treatment failure was 53.4% for CDAI, 54.8% for DAS28 ESR and 66.3% for HAQ-DI.

Of the three indices evaluated, CDAI best predicted non-response. Moreover, the investigators observed high CDAI values both for predictability of long-term treatment failure (89%) and specificity (96%). In other words, approximately 89% of patients identified as non-responders at three months failed to achieve low disease activity at 12 months. Likewise, the specificity of 96% meant that less than 5% of patients who achieved CDAI response at 12 months had not responded at three months. This high level of predictability was maintained regardless of disease severity at baseline or treatment history.

In contrast, the researchers found DAS28 ESR and HAQ-DI could predict response only in patients with high disease activity at baseline and/or those previously treated by a biological disease-modifying anti-rheumatic drug. Both disease severity at baseline and treatment history affected the ability of these two measures to predict long-term treatment failure. The authors conclude CDAI can best be used to identify certolizumab treatment failures at three months and prevent patients from being unnecessarily exposed to ineffective therapy.

Lara C. Pullen, PhD, is a medical writer based in the Chicago area.

Reference

1. Saraux A, Flipo RM, Fagnani F, et al. Early non-response to certolizumab pegol in rheumatoid arthritis predicts failure to achieve low disease activity at 1 year: data from a prospective observational study. RMD Open. 2020 Jan;6(1). pii: e000991.