Which RA Patients Have the Greatest Risk of Flares after DMARD Tapering?

A study presented at the ACR/ARP Annual Meeting evaluated whether high levels of calprotectin were indicative of flare after disease-modifying antirheumatic (DMARD) tapering in patients with rheumatoid arthritis (RA).

“Drug-free remission is an increasingly achievable outcome in RA. Up to 25% of patients who taper their medications are able to remain in remission, in a long-term sense, without getting disease flares,” said Emma de Moel, MD, BS, of the Department of Rheumatology at Leiden University Medical Center in the Netherlands, who presented the study’s findings. “However, not all patients are able to do this. Currently, we’re in desperate need of finding a biomarker that’s able to predict which patients are able to taper their medication without experiencing a disease flare.”

Data were collected from two randomized, controlled trials. The IMPROVED2 study evaluated early untreated RA with the goal of achieving disease activity score remission (DAS44 <1.6). Patients who successfully achieved eight-month remission rapidly tapered and terminated methotrexate treatment. The RETRO3 study included long-term RA data on patients in stable remission (DAS44 <2.6). Patients were randomized to either continue, taper by 50%, or terminate biological or conventional DMARDs. For the present study, researchers only evaluated data on the taper and terminate groups. The researchers used a diagnostic calprotectin kit to establish circulating calprotectin at the tapering timepoint. The predictive value of calprotectin for flare during the 12 months following tapering or terminating DMARDs was determined through logistic regression and area under the receiver operating characteristic curves (AUC) analyses.

Final analysis included 104 patients from the IMPROVED and 57 from the RETRO studies. In both studies, there was an association between 12-month flares and higher calprotectin at the time of tapering or terminating DMARDs. In the IMPROVED study, patients with two-fold higher calprotectin at the moment of tapering or stopping DMARDs was correlated with an increased risk of flare (odds ratio [OR], 1.1; 95% CI, 1.0-1.2); the observed risk was even greater in the RETRO study (OR, 3.6; 95% CI, 1.8-7.5). When adjusting for factors including body mass index, gender, anti-cyclic citrullinated peptide 2 (CCP2), and baseline DAS, the OR did not significantly change in the IMPROVED study (OR, 1.1; 95% CI, 1.0-1.2); adjusting for age and anti-CCP2 in RETRO also did not have a significant impact (OR, 4.0; 95% CI, 1.8-8.9). In the IMPROVED study, the AUC for predicting 12-month flare was 0.63 (95% CI, 0.51-0.76) and was 0.80 in the RETRO study (95% CI, 0.69-0.92).

The study’s take-home message, according to Dr. de Moel, was: “Circulating calprotectin levels in [patients with] RA in remission are higher in patients that will flare. However, at the moment, the differences we find between the cohorts preclude definitive conclusions.”