Patterns of comorbidities differentially affect long-term functional evolution and disease activity in patients with 'difficult to treat' rheumatoid arthritis

Abstract

Background: Characterisation of the long-term outcome of patients with 'difficult to treat' (D2T) rheumatoid arthritis and factors contributing to its evolution are unknown. Herein, we explored the heterogeneity and contributing factors of D2T long-term outcome.

Methods: Patients included from a prospective single centre cohort study. The EULAR definition of D2T was applied. Longitudinal clustering of functional status (modified Health Assessment Questionnaire (mHAQ)) and disease activity (Disease Activity Score-28 (DAS28)) were assessed using latent-class trajectory analysis. Multiple linear mixed models were used to examine the impact of comorbidities and their clusters on the long-term outcome.

Results: 251 out of 1264 patients (19.9%) were identified as D2T. Younger age, fibromyalgia, osteoarthritis, DAS28-erythrocyte sedimentation rate (ESR) at first biological or targeted synthetic disease-modifying antirheumatic drug (b/ts-DMARD) initiation and failure to reduce DAS28-ESR scores within the first 6 months of b/ts-DMARD therapy were significant predictors of patients becoming D2T. Long-term follow-up (total of 5872 person-years) revealed four groups of functional status evolution: 18.2% had stable, mildly compromised mHAQ (mean 0.41), 39.9% had gradual improvement (1.21-0.87) and two groups had either slow deterioration or stable significant functional impairment (HAQ>1). Similarly, four distinct groups of disease activity evolution were identified. Among the different clusters of comorbidities assessed, presence of 'mental-health and pain-related illnesses' or 'metabolic diseases' had significant contribution to mHAQ worsening (p<0.0001 for both) and DAS28 evolution (p<0.0001 and p=0.018, respectively).

Conclusion: D2T patients represent a heterogeneous group in terms of long-term disease course. Mental-health/pain-related illnesses as well as metabolic diseases contribute to long-term adverse outcomes and should be targeted in order to optimise the prognosis of this subset of rheumatoid arthritis.

Keywords: Outcome Assessment, Health Care; Patient Reported Outcome Measures; Rheumatoid Arthritis.

Figure 1

mHAQ latent-class trajectory analysis plots. Median time-to-characterisation as difficult to treat rheumatoid arthritis of each trajectory is given on the plots. mHAQ, modified Health Assessment Questionnaire.

Figure 2

DAS28-ESR latent class trajectory analysis plot. DAS28-ESR, Disease Activity Index 28-erythrocyte sedimentation rate.

Figure 3

Linear mixed models plots of predicted mHAQ values over time using time and disease clusters membership as predictors. (A) Mental health and pain related (B) cardiopulmonary (C) vascular (D) metabolic. mHAQ, modified Health Assessment Questionnaire.

Figure 4

Linear mixed models plots of predicted DAS28-ESR values over time using time and disease clusters membership as predictors. (A) Mental health and pain related (B) cardiopulmonary (C) vascular (D) metabolic. DAS28-ESR, Disease Activity Index 28-erythrocyte sedimentation rate.