Specific Disease Activity Measures Predict Structural Damage Progression in RA

Routine Assessment of Patient Index Data 3, DAS28 (CRP) and modified DAS28 (CRP) are stronger predictors of structural damage progression than the Simplified or Clinical Disease Activity Indices.

Three measures of disease activity, the Routine Assessment of Patient Index Data 3 (RAPID3), Disease Activity Score in 28 Joints-C-Reactive Protein (DAS28-CRP), modified DAS28-CRP (M-DAS28-CRP), are superior for predicting structural damage in rheumatoid arthritis (RA), according to study results published in Rheumatology.

Researchers conducted post hoc analyses of data from the AMPLE (Abatacept vs Adalimumab Comparison in Biologic-Naïve RA Subjects With Background MTX; ClinicalTrials.gov identifier NCT00929864) and AVERT (Assessing Very Early Rheumatoid Arthritis Treatment; ClinicalTrials.gov identifier NCT01142726) trials to compare the efficacy of different measures of disease activity in predicting structural damage in patient populations with RA. Both AMPLE and AVERT were double-blind, randomized, phase 3 clinical trials.

Data from both trials were analyzed separately. AMPLE included pooled data for all patients who were randomly assigned to either the abatacept plus methotrexate or the adalimumab plus methotrexate treatment arms. The AVERT trial included pooled data from patients randomized to receive abatacept plus methotrexate, abatacept monotherapy, or methotrexate monotherapy. In addition to RAPID3, DAS28-CRP, and M-DAS28-CRP, investigators also assessed the Simplified and Clinical Disease Activity Indices (SDAI, CDAI).

The AMPLE trial included a total of 646 patients (mean symptom duration, 1.7-1.9 years), 318 in the abatacept plus methotrexate arm, and 328 in the adalimumab plus methotrexate arm. Within these arms, 86.2% of patients receiving abatacept and 82% of patients receiving adalimumab completed month 12 of the study, and 79.2% of patients receiving abatacept and 74.7% of patients receiving adalimumab completed month 24.

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The AVERT trial included 351 patients, 119 in the abatacept plus methotrexate cohort (mean age 46.4±13.2 years) and 116 in the methotrexate monotherapy cohort (mean age 49.1±12.4 years). Of these, 86.6% of patients receiving abatacept plus methotrexate and 82.8% of patients receiving methotrexate monotherapy completed the 12-month treatment period.

An adjusted logistic regression analysis demonstrated that RAPID3, DAS28-CRP, and M-DAS28-CRP scores at baseline served as significant predictors of structural progression at months 12 and 24 in AMPLE and months 6 and 12 in AVERT. At baseline, SDAI was a significant predictor of radiographic progression at month 12 but not at month 24 (odds ratio [OR] 1.02; 95% CI, 1.00-1.04, P < 0.05), and of MRI erosion progression at month 12 but not at month 6 in AVERT (OR 1.03; 95% CI, 1.01-1.05, P < 0.01). CDAI was not a significant predictor at any point in either study.

Results of this analysis also demonstrated that the treatment arm did not affect measures of baseline disease activity as predictors of radiographic outcomes in either trial.

Further analysis of receiver operating characteristics curves demonstrated that RAPID3, DAS28-CRP, and M-DAS28-CRP had higher predictive values compared with CDAI and SDAI in terms of radiographic progression at 12 and 24 months in AMPLE and in terms of MRI progression at 6 and 12 months in AVERT. Overall, M-DAS28-CRP was the strongest predictor of radiographic progression in AMPLE and RAPID3 was the strongest predictor of MRI progression in AVERT.

Study limitations included those inherent to post hoc analyses and the relatively small sample sizes in both studies.

“The present post hoc analysis, the first to directly compare five measures of disease activity, demonstrated that the assessment of disease activity at baseline according to RAPID3 had a similar ability to M-DAS28-CRP and DAS28-CRP to predict the risk of progression of structural joint damage in these clinical trial populations, regardless of therapy,” the researchers concluded.

Disclosure: This clinical trial was supported by Bristol-Myers Squibb. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Keystone EC, Ahmad HA, Yazici Y, Bergman MJ. Disease activity measures at baseline predict structural damage progression: Data from the randomized controlled AMPLE and AVERT trials [published online December 9, 2019]. Rheumatology. doi: 10.1093/rheumatology/kez455