Remission in early rheumatoid arthritis: Predictors, definitions and treatment

In this thesis Nina Paulshus Sundlisæter assessed achievement and prediction of different remission definitions in rheumatoid arthritis (RA). She also studied the association between definitions of remission and long-term outcomes, and how to treat RA patients in sustained remission. The thesis is based on data from two randomized controlled trials, ARCTIC and ARCTIC REWIND. Paulshus Sundlisæter showed that sustained remission was achievable in RA patients treated according to current recommendations, even if negative prognostic factors were present. Less joint tenderness and short symptom duration at time of disease-modifying antirheumatic drug (DMARD) initiation predicted remission. Attainment of ACR/EULAR Boolean remission had the strongest association with both a good radiographic and functional outcome. Patients in sustained remission on conventional synthetic DMARDs were randomized to either continued stable therapy or half-dose. Patients in the stable group experienced less flares and less frequent radiographic joint damage progression the next year. Thus, continued stable therapy should be the preferred choice for RA patients in sustained remission

Clinical and ultrasound remission after 6 months of treat-to-target therapy in early rheumatoid arthritis: Associations to future good radiographic and physical outcomes

Objective: To explore associations between remission, based on clinical and ultrasound definitions, and future good radiographic and physical outcome in early rheumatoid arthritis (RA). Methods: Newly diagnosed patients with RA followed a treat-to-target strategy incorporating ultrasound information in the Aiming for Remission in rheumatoid arthritis: a randomised trial examining the benefit of ultrasound in a Clinical TIght Control regimen (ARCTIC) trial. We defined 6-month remission according to Disease Activity Score, Disease Activity Score in 28 joints-erythrocyte sedimentation rate, American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean criteria, Simplified Disease Activity Index, Clinical Disease Activity Index and two ultrasound definitions (no power Doppler signal, grey scale score ≤2). Two outcomes were defined: no radiographic progression and good outcome (no radiographic progression+physical function≥general population median), both sustained 12–24 months. We calculated the ORs of these outcomes for the remission definitions. Results: Of 103 patients, 42%–82% reached remission at 6 months, dependent on definition. Seventy-one per cent of patients had no radiographic progression and 37% had good outcome. An association between 6-month remission and no radiographic progression was observed for ACR/EULAR Boolean remission (44 joints, OR 3.2, 95% CI 1.2 to 8.4), ultrasound power Doppler (OR 3.6, 95% CI 1.3 to 10.0) and grey scale remission (OR 3.2, 95% CI 1.2 to 8.0). All clinical, but not ultrasound remission criteria were associated with achievement of a good outcome. Conclusions: Our data support ACR/EULAR Boolean remission based on 44 joints as the preferred treatment target in early RA. Absence of ultrasound inflammation was associated with no radiographic progression

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 &gt;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&lt;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