Background/Purpose:

Assessment of
clinical markers of disease activity is routine in monitoring patients with
rheumatoid arthritis (RA) in daily practice. Changes in clinical measures may
reflect natural variation (measurement error) or “real change”.  Natural variation
is assessed in individuals who are considered to be in “steady state”. We examined natural variation of traditional clinical
disease markers in biologically treated patients with stable RA according to
EULAR response criteria.

Methods:

233 RA patients
treated with a biological agent and with stable disease were identified in the
Danish rheumatology registry (DANBIO). According to EULAR response criteria,
stable disease was defined as a change in DAS28-CRP ≤ 0.6 between two
consecutive visits. Paired data from a single set of such two consecutive
visits were extracted for each patient. Data comprised DAS28-CRP and its
components, patient global assessment (PaGl), pain, HAQ-DI and physician global
assessment (PhGl). Variation of the disease markers on the individual level was
expressed as lower and upper 95% limits of agreement (LLoA;ULoA) between two
consecutive assessments and changes on the group level as the bias (mean of
individual differences) according to the Bland-Altman method. Associations were
assessed by Pearson’s correlation analyses.

Results:

Male/female
ratio was 56/177, mean age 60±15 years, mean inter-visit time duration
22±21weeks, mean DAS28-CRP 3.1±1.2, and mean change in DAS28-CRP 0.0±0.3 (range
-0.6 to 0.6) (NS). Results of the variation analyses are shown in the Table. No
changes between the repeated tests were found on the group level but limits of
agreement in individual patients were wide for all measures. Intra-individual changes
was not explained by inter-visit time duration (r = 0.0 to -0.1, NS). Moreover,
intra-individual changes of the different measures were not or only weakly inter-correlated
(r = -0.3 to 0.1, NS or p < 0.05). Changes between the repeated tests were similar
for males and females (NS).

Conclusion:

Traditional
markers of disease activity varied substantially and irregularly over time in individual
RA patients considered to be in steady state. These variations reflect, by
definition, measurement errors, and should be taken into consideration when
monitoring patients in the daily clinic. 

Table. Agreement between two
consecutive assessments of clinical measures in RA patients with stable disease
activity (change in DAS28-CRP ≤ 0.6).

LLoA: Lower
limit of agreement; ULoA: Upper limit of agreement.