Fatigue in patients with early rheumatoid arthritis undergoing treat-to-target therapy: predictors and response to treatment.

OBJECTIVES: Fatigue is a frequent symptom in rheumatoid arthritis (RA) and has high impact on quality of life. We explored associations between disease activity and fatigue in patients with early RA during the initial 24 months of modern treat-to-target therapy and predictors of fatigue after 24 months of follow-up. METHODS: Data were obtained from the treat-to-target, tight control Aiming for Remission in Rheumatoid Arthritis: a Randomised Trial Examining the Benefit of Ultrasound in a Clinical Tight Control Regime (ARCTIC) trial. Fatigue was measured on a visual analogue scale (VAS) from 0 to 100 mm and defined as clinically relevant if VAS was ≥20 mm. Baseline predictors of fatigue at 24 months were analysed by multivariable logistic regression. RESULTS: 205 patients with fatigue data at baseline and 24 months were included. Median (25th, 75th percentiles) symptom duration was 5.4 months (2.8, 10.4), fatigue VAS 37.0 mm (13.0, 62.0) and mean Disease Activity Score (DAS) 3.4 (SD 1.1) at baseline. Prevalence of fatigue declined from 69% at baseline to 38% at 24 months. Fewer swollen joints (OR 0.92, 95% CI 0.87 to 0.98, p=0.006), lower power Doppler ultrasound score (OR 0.95, 95% CI 0.90 to 0.99, p=0.027) and higher patient global assessment (PGA) (OR 1.03, 95% CI 1.01 to 1.04, p<0.001) increased the risk of clinically relevant fatigue at 24 months. Not achieving remission at 6 months was associated with a higher risk of reporting fatigue at 24 months. CONCLUSIONS: Fatigue in patients with early RA was prevalent at disease onset, with a rapid and sustained reduction during treatment. Low objective disease activity and high PGA at baseline were predictors of clinically relevant fatigue at 24 months.

Performance of the Rheumatoid Arthritis Impact of Disease (RAID) score in relation to flares in disease activity.

OBJECTIVES: To explore the performance of the EULAR-initiated patient-reported Rheumatoid Arthritis Impact of Disease (RAID) questionnaire in relation to flares in disease activity, including comparison with other disease activity outcomes. METHODS: Patients with rheumatoid arthritis in sustained remission were randomised to continued stable treatment or tapering in the ARCTIC REWIND project. In patients with flares within 12 months, we compared RAID (total score and components) at the flare visit with the visit prior to and the visit following flare, using Wilcoxon signed-rank test. Similar analyses were performed for patient global assessment, Disease Activity Score (DAS) and C reactive protein (CRP). The discriminative accuracies of RAID, patient global assessment, DAS and CRP with respect to disease activity flares were assessed by receiver operating characteristic (ROC) analyses based on logistic regression models. Flare was defined as a combination of DAS >1.6, a DAS increase ≥0.6 and ≥two swollen joints (of 44 examined) or could be recorded if patient and rheumatologist agreed that a clinically significant flare had occurred. RESULTS: In total, 248 patients were included in the analyses, with 56 flares. RAID, patient global assessment, DAS and CRP all changed significantly at the visits related to flare (p<0.001). Area under the curve (95% CI) values indicated that RAID (0.88 (0.83 to 0.93)) was significantly more accurate than CRP (0.76 (0.69 to 0.84)) in discriminating flare, and less accurate than patient global assessment (0.92 (0.87 to 0.97)) and DAS (0.94 (0.90 to 0.98)). The RAID components with highest and lowest discriminative accuracies were pain (0.91 (0.86 to 0.95)) and sleep (0.69 (0.59 to 0.79)). CONCLUSION: Disease activity flares were associated with a significant increase in median RAID, supporting its ability to respond to flare. TRIAL REGISTRATION NUMBER: NCT01881308.

Agreement between patient-reported flares and clinically significant flare status in patients with rheumatoid arthritis in sustained remission: data from the ARCTIC REWIND trials.

OBJECTIVES: To explore the agreement between patient-reported flare status and clinically significant flare status in patients with rheumatoid arthritis (RA) in sustained remission. METHOD: Patients with RA in remission for ≥12 months on stable treatment were included in the ARCTIC REWIND tapering trials and pooled 12-month data used in current analyses. Patient-reported flare status was assessed according to the Outcome Measures in Rheumatology flare questionnaire; 'Are you having a flare of your RA at this time?' (yes/no). A clinically significant flare was defined as a combination of Disease Activity Score (DAS) >1.6, increase in DAS of ≥0.6 and 2 swollen joints, or the rheumatologist and patient agreed that a clinically significant flare had occurred. Agreement coefficient, sensitivity, specificity and predictive values of patient-reported flare status with regard to clinically significant flare status were determined. RESULTS: Of 248 patients, 64% were women, age 56.1 (11.8) years, disease duration 4.1 (2.8-7.4) years, DAS 0.8 (0.3). 35% of patients reported a flare at least once, clinically significant flares were recorded in 21%. 48/53 clinically significant flares (91%) led to an intensification of disease-modifying antirheumatic drugss. In 621/682 (91%) visits, patient-reported and clinically significant flare status were in agreement, agreement coefficient 0.89. Sensitivity and specificity were both 91%, positive predictive value of patient-reported flare status 46% and negative predictive value 99%. CONCLUSION: Among patients in sustained remission, patient-reported flare status was accurate in ruling out a clinically significant flare. About half of the patient-reported flares were assessed to be clinically significant. These findings support a potential for using patient-reported flare status in remote monitoring of patients with RA in sustained remission.

Comparative analyses of responsiveness between the Rheumatoid Arthritis Impact of Disease score, other patient-reported outcomes and disease activity measures: secondary analyses from the ARCTIC study.

OBJECTIVE: To evaluate the responsiveness of the Rheumatoid Arthritis Impact of Disease (RAID) score compared with other patient-reported outcome measures (PROMs), inflammatory markers and clinical disease activity measures in patients with early rheumatoid arthritis (RA). METHODS: Disease-modifying antirheumatic drug-naïve patients with RA with short disease duration were included in the treat-to-target ARCTIC trial and followed for 24 months. The responsiveness of the RAID score was evaluated using standardised response mean (SRM) and relative efficiency (RE) with respect to tender joints by Ritchie Articular Index (RAI). SRMs and REs were also calculated for other PROMs, inflammatory markers and clinical outcome measures. An SRM with value above 0.80 was considered high. RESULTS: 230 patients with RA were included. The mean±SD symptom duration was 7.1±5.4 months and the baseline mean±SD RAID score was 4.49±2.14. At 3 months of follow-up, the mean±SD change score for RAID was -2.25±1.98 and the SRM (95% CI) -1.13 (-1.33 to -0.96). The RAID score showed high responsiveness both at 3 and 6 months (SRM≥0.80) and was more sensitive in detecting change than the reference, tender joints assessed by RAI. CONCLUSIONS: The RAID score proved to be highly responsive to change in patients with RA with short disease duration who followed a treat-to-target strategy. The RAID score was more efficient in detecting change than the reference (RAI) as well as most other PROMs.