Remission Criteria in RA Not Interchangeable


Achieving remission in rheumatoid arthritis may depend on which disease activity measure you use.

Researchers find that remission rates for rheumatoid arthritis patients on tofacitinib are significantly higher when the 28-joint Disease Activity Score using the C-reactive protein level criteria, or DAS28-4(CRP), is used compared with other assessments.

Researchers compared the criteria used to assess rates of remission and low disease activity in five rheumatoid arthritis clinical trials of tofacitinib, an oral janus kinase inhibitor. In the brief report, published online March 8 in Arthritis and Rheumatology, researchers address the inconsistencies they found in rates of remission and low disease activity.

Led by Josef Smolen, M.D., of the Medical University in Austria, the criteria evaluated in this study included the 4-variable DAS28 using the erythrocyte sedimentation rate (DAS28-4[ESR]), 4-variable DAS28 using the C-reactive protein level (DAS28-4[CRP]), the Clinical Disease Activity Index (CDAI), the Simplified Disease Activity Index (SDAI), and Boolean-based assessment.  

Remission is the goal when treating rheumatoid arthritis patients, but when full remission is not possible, the goal is to achieve a state of low disease activity. In past studies of tofacitinib, DAS28-based analyses were used to evaluate remission rates and low disease activity. 

Although traditional definitions of remission have included the DAS28-ESR or DAS28-CRP of less than 2.6, these definitions are not considered valid criteria by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR). A state of low disease activity is typically defined by a higher cutoff point within a composite measure:  SDAI low disease activity is defined as a score of less than or equal to 11.0 and DAS28 low disease activity is defined as a score of less than or equal to 3.2.

In 2011, the ACR and EULAR came up with new provisional definitions of remission: an index-based approach using the SDAI definition or the CDAI definition of remission (less than or equal to 3.3 and less than or equal to 2.8, respectively); and, a Boolean-based approach of scores of less than or equal to 1 for a number of individual measures of disease activity.

The study  

Data from five different phase III randomized controlled trials were evaluated, representing a total of 3,306 patients with rheumatoid arthritis. The duration of these studies ranged from six to 24 months. In each study, tofacitinib was given at 5 mg twice daily or 10 mg twice daily, either as monotherapy or with background methotrexate or other conventional synthetic disease-modifying antirheumatic drugs. In one study, adalimumab was also given at 40 mg once every 2 weeks. Baseline demographics and disease characteristics were consistent across the 5 studies.  

[[{"type":"media","view_mode":"media_crop","fid":"59193","attributes":{"alt":"DAS28 (©ChaowalitSeeneha/","class":"media-image media-image-left","id":"media_crop_3418292831650","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"7493","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"font-size: 13.008px; float: left;","title":"DAS28 (©ChaowalitSeeneha/","typeof":"foaf:Image"}}]]Of the 3,306 patients included in the analysis, 1,213 patients received tofacitinib 5 mg twice daily, 1,212 patients received tofacitinib 10 mg twice daily, 679 patients received placebo, and 202 patients received adalimumab 40 mg every 2 weeks.

Across all 5 studies, the researchers found that the DAS28-4(CRP) criteria produced higher remission rates compared with the Boolean-based, the DAS28-4(ESR), SDAI, and CDAI definitions. In all cases, the DAS28-4(CRP) remission rates during active therapy were 2-fold to 5-fold higher than the DAS28-4(ESR) remission rates.

Low disease activity rates as defined by the SDAI, CDAI, and DAS28-4(CRP) were similar, and all were higher than the DAS28-4(ESR) low disease activity rates. Moreover, remission rates based on the DAS28, CDAI, and SDAI were significantly greater for both tofacitinib doses compared with placebo, and higher for tofacitinib 10 mg twice daily than for 5 mg twice daily.

“In summary, the rates of remission and low disease activity observed using SDAI and CDAI criteria were consistent across studies, while, in line with previous observations, DAS28-based criteria did not convey consistent results,” wrote Smolen and colleagues. “This was attributable to differential contributions of acute-phase reactant measures to the observed remission and low disease activity rates. These data reveal the limitations of the DAS28 as a definition of remission due to its heavy dependence on changes in acute-phase reactants. The data also show that the DAS28-4(ESR) and DAS28-4(CRP) are not interchangeable.”




This study was sponsored by Pfizer, Inc.



Smolen J., Aletaha, D., Gruben, D., et al. “Brief Report: Remission Rates With Tofacitinib Treatment in Rheumatoid Arthritis: A Comparison of Various Remission Criteria,” Arthritis and Rheumatology. Published online March 8, 2017. DOI:10.1002/art.39996

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