Revised 2-Component DAS28 Better Captures Rheumatoid Arthritis Phenotypes Associated With Treatment Outcome and Response

Compared with the 4C-DAS28, the revised 2C-DAS28 identified more subgroups of patients with rheumatoid arthritis that differ in terms treatment response, patterns of change in disease activity, and different clinical characteristics.

Compared with the 4-component (4C) disease activity score measured in 28 joints (4C-DAS28), the revised 2-component disease activity score measured in 28 joints (2C-DAS28) disease activity score identified more subgroups of patients with rheumatoid arthritis (RA) that differ in terms treatment response, patterns of change in disease activity, and different clinical characteristics, according to a study in Arthritis and Rheumatology.

Researchers from the United Kingdom and Italy included longitudinal patient data from the UK observational, multicenter Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGSS). Participants included adults who had a consultant diagnosis of RA and were about to start a biologic disease-modifying anti-rheumatic drug (DMARD). The researchers applied latent class mixed modelling (LCMM) in response to biologic treatment to 2991 patients with RA who participated in the BRAGGSS. The 4C-DAS28 and 2C-DAS28 were used as outcomes in modelling. The modified 2C-DAS28 includes only the 28-swollen joint count and C-reactive protein in its calculation.

The researchers compared patient groups with similar trajectories in regard to pre-treatment baseline characteristics (eg, disability and comorbidities) and follow-up characteristics (eg, anti-drug antibody [ADAb] events, adherence to treatments, and blood drug levels). The trajectories calculated from the 4C and 2C scores were compared to see whether characteristics were better identified by the 2C-DAS28 vs the 4C-DAS28 trajectories.

A total of 3 trajectory groups were identified with the 4C-DAS28, including a rapid group (n=2003) that improved quickly in the first observation and then either stabilized or had slight disease activity increases, a gradual group (n=919) that demonstrated slower yet consistent reductions in disease activity, and a poor responder group (n=68). The 4C-DAS28 identified information related to depression rates, with statistically higher rates found for gradual responders vs rapid responders (24.2% vs 20.4%, respectively; odds ratio [OR], 1.24; P =.08).

In contrast, the 2C-DAS28 identified 7 trajectory groups, including 2 groups of good responders, 2 groups of gradual responders, 2 groups of secondary non-responders, and 1 group of low disease activity patients. A higher prevalence of chronic bronchitis and emphysema was observed in early secondary non-responders compared with good responders (Good 1: OR, 5.38, P =.005; Good 2: OR, 5.85, P =.0005) and gradual responders (Gradual 2: OR, 5.54, P =.003).

The 2C-DAS28 slopes significantly differed (P =.002) and decreased more rapidly in participants who were adherent (mean, -0.00128; SD=0.0581) vs not adherent (mean, -.0120; SD=0.103) to treatment. The low disease activity group, identified only by the 2C-DAS28, was the least adherent group. According to the 2C-DAS28, the investigators observed more ADAb positivity in the early secondary non-responders.

Limitations of the analysis included the availability of drugs levels and ADAb measures for only a subset of patients as well as the self-reported nature of treatment adherence data.

The researchers concluded that the 2C-DAS28 trajectories captured more RA phenotypes of treatment response “and suggest that a more holistic view of patient care, considering all factors likely to influence response, should be applied to move towards precision medicine approaches.”


Dagliati A, Plant D, Nair N, et al. Latent class trajectory modelling of 2-components-DAS28 identifies multiple rheumatoid arthritis phenotypes of response to biologic disease modifying anti-rheumatic drugs [published online May 31, 2020]. Arthritis Rheumatol. doi: 10.1002/art.41379