Biomarker Profiles Predictive of RA Relapse During DMARD Taper

In a phase-3 randomized trial, researchers have found that multibiomarker disease activity (MBDA) scores improved prediction of rheumatoid arthritis (RA) disease relapses in patients who were in stable remission and who were in the process of tapering a disease-modifying antirheumatic drug (DMARD).Using a standardized panel of biomarkers, researchers found that residual inflammation was associated with a higher rate of relapse when DMARDs were tapered or stopped.

“Combined with anticitrullinated protein antibody (ACPA) testing, MBDA allowed prediction of relapse in more than 80% of the patients,” wrote Juergen Rech, MD, from the University of Erlangen-Nuremberg and colleagues.

With earlier diagnosis, more efficient DMARD use, and a broader range of drugs available for treatment, increasing numbers of patients with RA are able to achieve remission. A Norwegian study evaluating the effects of DMARD therapy found that remission rates have doubled in the last decade,² and another study found that many patients maintain remission over 2 consecutive visits.³ 

Strategies for managing patients in remission are therefore growing in importance, including ways to taper or stop treatment. The researchers noted that there is a particular need for validated tests that can identify which patients can successfully taper DMARDs without a high risk of relapse.

The researchers randomized 94 patients from the RETRO study (EudraCT number 2009-015740-42), a phase 3, multicenter, randomized, prospective, controlled, parallel-group study, into 3 study arms.

Thirty-five patients were randomized to receive full-dose DMARD treatment for a year, 32 patients were randomized to taper all DMARDs by 50% after 1 year, and 27 patients were randomized to stop all DMARDs after an abbreviated taper period of 6 months. Of the 94 patients, 84% were using methotrexateand 37% were taking biologic DMARDs.

Researchers found that 58% of patients with moderate/high MBDA scores experienced RA disease relapse. This is in comparison to 21% of patients with moderate/high MBDA scores who were able to remain in remission. 

Furthermore, higher baseline MBDA scores were found in relapses RA patients as compared to those in stable remission (P = .0001).  

MBDA scores and ACPA status were subsequently found to be independently predictive of disease relaps after multivariate regression analyses. 

“Our data suggest that markers of inflammation are elevated in a subset of patients with RA in clinical remission, and that these patients are at higher risk for relapse if their anti-inflammatory treatment is reduced,” the authors wrote.

The researchers also found that assessing inflammatory activity allowed them to refine prediction models for relapse during DMARD tapering, and that combined with assessing ACPA status, they were able to predict more than 80% of relapses.

Summary & Clinical Applicability

In a phase-3 randomized trial, researchers found that multibiomarker disease activity score improved prediction of relapses in patients with RA who were in stable remission and who were undergoing DMARD tapering. Combined with ACPA testing, this allowed researchers to predict relapse in more than 80% of patients.

Patients with elevated MBDA scores had an increased prevalence of relapses, which may indicate that their inflammation is suppressed by DMARDs at the clinical level, but that it is not completely resolved. On the other hand, patients with low MBDA scores may be experiencing a true resolution of remission, which would lower their risk of relapse with DMARD tapering.

These findings suggest that MBDA scores are more effective than clinical scores alone in predictive capacity for RA disease relapse. 

Limitations & Disclosures

• The low average DAS28 scores in this cohort may have made it difficult to discriminate patients who did and did not have residual inflammation.

This study was supported by the Deutsche Forschungsgemeinschaft (SPP1468-IMMUNOBONE), the Bundesministerium für Bildung und Forschung,  the Marie Curie project OSTEOIMMUNE, the TEAM and MASTERSWITCH projects of the European Union, and the IMI funded project BTCure.

The authors declared no competing interests.

References

1. Rech J, Hueber AJ, Finzel S, et al. Prediction of disease relapses by multibiomarker disease activity and autoantibody status in patients with rheumatoid arthritis on tapering DMARD treatment. Ann Rheum Dis. 2015. doi:10.1136/annrheumdis-2015-207900.

2. Aga AB, Lie E Uhlig T, et al. Time trends in disease activity, response and remission rates in rheumatoid arthritis during the past decade: results from the NOR-DMARD study 2000–2010. Ann Rheum Dis. 2015;74:381–8. doi:10.1136/annrheumdis-2013-204020.

3. Prince FH Bykerk VP, Shadick NA, et al. Sustained rheumatoid arthritis remission is uncommon in clinical practice. Arthritis Res Ther. 2012;14:R68. doi:10.1186/ar3785.

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