Exploring the disparity between inflammation and disability in the 10-year outcomes of people with rheumatoid arthritis

Abstract

Objectives To identify groups of people with rheumatoid arthritis (RA) with different disability trajectories over ten years, despite comparable levels of inflammation. Methods Data for this analysis came from three European prospective cohort studies of people with RA (Norfolk Arthritis Register [NOAR], Early Rheumatoid Arthritis Network [ERAN], Étude et Suivi des Polyarthrites Indifférenciées Récentes [ESPOIR]). Participants were assessed regularly over 8 (ERAN) to 10 (NOAR/ESPOIR) years. Inclusion criteria were: recruited after 1/1/2000, <24 months baseline symptom duration, and disability (Health Assessment Questionnaire [HAQ]) and inflammation (two-component disease activity score [DAS28-2C]) recorded at baseline and one other follow-up. People in each cohort also completed patient reported outcome measures at each assessment (pain, fatigue, depressive symptoms). Group-based trajectory models (GBTM) were used to identify distinct groups of people with similar HAQ and DAS28-2C trajectories over follow-up. Results This analysis included 2500 people with RA (NOAR: 1000, ESPOIR: 766, ERAN: 734). ESPOIR included more women and participants were younger (mean [standard deviation] age: NOAR: 57.1 [14.6], ESPOIR: 47.6 [12.5], ERAN: 56.8 [13.8]; women: NOAR: 63.9%, ESPOIR: 76.9%, ERAN: 69.1%). Within each cohort, two pairs of trajectories following the hypothesised pattern (comparable DAS28-2C but different HAQ) were identified. Higher pain, fatigue and depressive symptoms were associated with increased odds of being in the high HAQ trajectories. Conclusion Excess disability is persistent in RA. Controlling inflammation may not be sufficient to alleviate disability in all people with RA, and effective pain, fatigue and mood management may be needed in some groups to improve long-term function.

Influence of Social Support, Financial Status, and Lifestyle on the Disparity Between Inflammation and Disability in Rheumatoid Arthritis

“…There was a higher proportion of missing data in the validation data sets compared with ESPOIR. While a sensitivity analysis from a previous analysis showed minimal bias from these missing data (8), the validation analyses of the current paper may be susceptible to some missing data bias.…”

“…wiley.com/doi/10.1002/acr.24996]). The people in these high HAQ groups (i.e., the low inflammation-high HAQ group and the high inflammation-high HAQ group) were described as having "excess disability" in relation to their inflammation level (8). For the current analysis, the 2 subgroups characterized by excess disability were combined and compared with the groups of individuals who had similar inflammation over follow-up, but lower disability (i.e., the outcome for this analysis is excess disability compared with other individuals with RA with similar inflammation levels but lower disability).…”

“…Our previous analysis of 3 European cohort studies (including ESPOIR) analyzing the trajectories of inflammation (measured using the DAS28‐2C [ 25 ], chosen to isolate the influence of inflammation specifically [the target of pharmacologic treatment in RA], as opposed to disease activity [which is likely influenced by inflammation level plus multiple other factors]) and disability (measured using the HAQ [ 22 , 26 ]) over 10 years identified 5 subgroups (i.e., 1 trajectory with very low inflammation and disability, 2 trajectories with similar low levels of inflammation but one with higher disability than the other, and 2 trajectories with similar high levels of inflammation, again with one group having higher disability than the other [Supplementary Figure 1 , available on the Arthritis Care & Research website at http://onlinelibrary.wiley.com/doi/10.1002/acr.24996 ]). The people in these high HAQ groups (i.e., the low inflammation–high HAQ group and the high inflammation–high HAQ group) were described as having “excess disability” in relation to their inflammation level ( 8 ). For the current analysis, the 2 subgroups characterized by excess disability were combined and compared with the groups of individuals who had similar inflammation over follow‐up, but lower disability (i.e., the outcome for this analysis is excess disability compared with other individuals with RA with similar inflammation levels but lower disability).…”

“…Improvements in available treatments for RA mean that inflammation can be controlled at low levels into the long‐term for the majority of people, but for many individuals this does not correlate with improvements in disability (the so‐called “inflammation–disability gap” in RA) ( 6 , 7 ). Our previous analysis of 3 large‐scale European cohorts of individuals with early RA demonstrated that there are trajectory groups that share similar inflammation trajectories over 10 years of follow‐up but have markedly different disability trajectories ( 8 ). The level of disability in these trajectory groups was relatively fixed from baseline, indicating that factors prior to the onset of RA may influence baseline disability and thus subsequent disability.…”

“…Therefore, the aim of this study was to determine the association between specific social determinants of health (rather than deprivation indices) and antecedent events prior to the onset of RA and inflammation–disability trajectory group membership ( 8 ). Furthermore, previous research has shown that pain, fatigue, and depression are strongly associated with excess disability group membership ( 8 ). Therefore, a second objective was to explore the mediating effect of patient‐reported outcome measures on the relationship between these antecedent factors and excess disability in RA.…”