Using Disease Activity Measures to Guide Tapering and Compare Biologics to Treat RA

While biologics may have improved outcomes in rheumatoid arthritis (RA), they also have higher costs and adverse events, and patients are more likely to request dose reductions or drug holidays.

An abstract presented at the European Congress of Rheumatology of the European League Against Rheumatism sought to identify factors associated with successful long-term tumor necrosis factor (TNF) inhibitor tapering and possible predictive values of different disease activity measures.¹

The researchers observed 91 patients with RA who started their first TNF inhibitor between 2000 and 2014. These patients had tapering applied after they achieved sustained remission or low disease activity (LDA). Disease activity was measured by Disease Activity Score-28 (DAS28), Simple Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI) at the start of de-escalation, as well as at follow-up at 6, 12, 18, and 24 months.

At 12 months, 11 patients (12%) experienced tapering failure, “defined as reinstatement of full dose, escalation to the previous dose level, or discontinuation due to secondary inefficacy.” By 24 months, 18 patients (20%) failed to taper. At 24 months, the researchers identified that a longer time from TNF inhibitor start to achievement of remission was a predictor of tapering failure (odds ratio = 1.64, P = .02). None of the disease activity indices predicted long-term tapering failure.

Another abstract compared RA biologics with each other using DAS28 and CDAI in order to assess whether the scores affect comparative effectiveness studies on biologics used to treat RA.²

The authors compared results by using the corresponding thresholds of LDA, which was <3.2 for DAS28 and £10 for CDAI. They then performed 2 network meta-analyses (NMAs). The researchers found that comparing tocilizumab with other biologics revealed advantages for tocilizumab using DAS28, but that those advantages were not confirmed using CDAI.

Using DAS28, using tocilizumab in methotrexate (MTX)-naïve patients showed a greater benefit than using abatacept, certolizumab pegol, and etanercept, but that benefit was not confirmed by the CDAI. In patients who already tried MTX, DAS28 showed a greater benefit to using tocilizumab compared with abatacept, adalimumab, anakinra, etanercept, golimumab, and infliximab. Again, these advantages were not confirmed by CDAI.

“In comparative effectiveness studies of biologics, the assessment of LDA using the DAS28 (instead of the CDAI) leads to a consistent overestimation of the benefit of tocilizumab versus other biologics in all patient populations, regardless of whether patients were pretreated or received combination therapy with MTX,” the authors concluded.

References

1. Bogas P, Kaneko Y, Takeuchi. Disease activity measures and other potential predictors of successful TNF inhibitors tapering in RA patients. Presented at: EULAR 2020; June 3-6, 2020; Abstract FRI0086. https://ard.bmj.com/content/79/Suppl_1/620.2

2. Janke K, Biester K, Krause D, et al. Measurement of low disease activity using the clinical disease activity index (CDAI) versus the disease activity score 28 (DAS 28): impact of inflammation markers on the comparative effectiveness of biologics for the treatment of rheumatoid arthritis. Presented at: EULAR 2020; June 3-6, 2020; Abstract THU0620-HPR. https://ard.bmj.com/content/79/Suppl_1/553.1