Predicting responses in patients with rheumatoid arthritis to disease-modifying agents using baseline clinical data.

OBJECTIVES: The optimal treatment for active rheumatoid arthritis (RA) is unresolved, particularly in early RA. We used data from an observational cohort to develop the simple predictor algorithm and evaluated its application in two completed clinical trials in early and established RA. We assessed whether using a simple algorithm can identify patients who have persisting active disease despite treatment with disease-modifying drugs (DMARDs). We also examined if patients who have lower likelihoods of persisting active RA are likely to benefit from intensive treatment. METHODS: We developed a simple predictive score for persisting disease activity using conventional clinical assessments in an observational cohort of patients with early RA (ERAN). It was tested in two trials in early (CARDERA) and established (TACIT) RA. Persistent disease activity was defined as disease activity score for 28 joints (DAS28) >3.2 at both 6 and 12 months. RESULTS: Regression modelling identified three main predictors of persisting active disease in ERAN; tender joint counts, health assessment questionnaire (HAQ) scores and ESR. We dichotomised these predictors (≥6 tender joint counts, ≥1.0 HAQ ≥20 mm/h ESR) in a four-point prediction score. This simple prediction score predicted persisting active disease in the ERAN cohort and both CARDERA and TACIT trials. Patients with high scores were more likely to have persistently active disease at 6 and 12 months. The relationship was weaker in TACIT because no patients were without any predictive factors. CONCLUSIONS: Combining tender joint counts, ESR and HAQ in a simple predictive score prospectively identifies patients with higher risks of persistent disease activity over the next 12 months. More patients with all three risk factors had persistent active disease than those with none or one risk factor.

Rheumatoid arthritis patients with fibromyalgic clinical features have significantly less synovitis as defined by power Doppler ultrasound.

BACKGROUND: In patients with rheumatoid arthritis (RA) clinical measures of disease activity may not reliably discriminate between patients with active inflammatory disease and those with concomitant fibromyalgia (FM). Recent work has shown RA patients with a 28 tender joint count (TJC) minus swollen joint count (SJC) of 7 or more (joint count criteria) are more likely to meet classification criteria for FM. This study aimed to determine whether RA patients meeting clinical criteria for FM had lower levels of joint inflammation as determined by ultrasound (US). METHODS: RA patients with DAS28 > 2.6 were recruited. Patients underwent clinical assessment including ultrasound examination of the hands and wrists with quantification of grey scale (GS) and power Doppler (PD) synovitis. Patients completed questionnaires to assess pain, fatigue, disability and psychological comorbidity. RESULTS: Patients meeting either of the FM criteria had higher scores for disease activity, depression, disability and fatigue. Those meeting both the joint count and classification FM criteria had significantly lower levels of GS and PD inflammation on US. CONCLUSIONS: RA patients with concomitant FM, as determined by widespread soft tissue tenderness but fewer clinically inflamed joints, have higher disease activity scores but may have lower levels of synovial inflammation on US. This has implications for the identification and management of these patients who may not respond to conventional therapy and hence be more suitable for alternative approaches to treatment.

Optimal responses in disease activity scores to treatment in rheumatoid arthritis: Is a DAS28 reduction of >1.2 sufficient?

BACKGROUND: The overall benefit of intensive treatment strategies in rheumatoid arthritis (RA) remains uncertain. We explored how reductions in disability and improvements in quality of life scores are affected by alternative assessments of reductions in disease activity scores for 28 joints (DAS28) in two trials of intensive treatment strategies in active RA. METHODS: One trial (CARDERA) studied 467 patients with early active RA receiving 24 months of methotrexate monotherapy or steroid and disease-modifying anti-rheumatic drug (DMARD) combinations. The other trial (TACIT) studied 205 patients with established active RA; they received 12 months of treatment with DMARD combinations or biologic agents. We compared changes in the health assessment questionnaire (HAQ) and Euroqol-5D (EQ5D) at trial endpoints in European League Against Rheumatism (EULAR) good and moderate EULAR responders in patients in whom complete endpoint data were available. RESULTS: In the CARDERA trial 98 patients (26 %) were good EULAR responders and 160 (32 %) were EULAR moderate responders; comparable data in TACIT were 66 (35 %) and 86 (46 %) patients. The magnitude of change in the HAQ and EQ5D was greater in both trials in EULAR good responders than in EULAR moderate responders. HAQ scores had a difference in of -0.49 (95 % CI -0.66, -0.32) in the CARDERA and -0.31 (95 % CI -0.47, -0.13) in the TACIT trial. With the EQ5D comparable differences were 0.12 (95 % CI 0.04, 0.19) and 0.15 (95 % CI 0.05, 0.25). Both exceeded minimum clinically important differences in HAQ and EQ5D scores. CONCLUSIONS: We conclude that achieving a good EULAR response with DMARDs and biologic agents in active RA results in substantially improved mean HAQ and EQ5D scores. Patients who achieve such responses should continue on treatment. However, continuing such treatment strategies is more challenging when only a moderate EULAR response is achieved. In these patients evidence of additional clinically important benefits in measures such as the HAQ should also be sought.

Changing clinical patterns in rheumatoid arthritis management over two decades: sequential observational studies.

BACKGROUND: Rheumatoid arthritis (RA) treatment paradigms have shifted over the last two decades. There has been increasing emphasis on combination disease modifying anti-rheumatic drug (DMARD) therapy, newer biologic therapies have become available and there is a greater focus on achieving remission. We have evaluated the impact of treatment changes on disease activity scores for 28 joints (DAS28) and disability measured by the health assessment questionnaire scores (HAQ). METHODS: Four cross-sectional surveys between 1996 and 2014 in two adjacent secondary care rheumatology departments in London evaluated changes in drug therapy, DAS28 and its component parts and HAQ scores (in three surveys). Descriptive statistics used means and standard deviations (SD) or medians and interquartile ranges (IQR) to summarise changes. Spearman's correlations assessed relationships between assessments. RESULTS: 1324 patients were studied. Gender ratios, age and mean disease duration were similar across all cohorts. There were temporal increases in the use of any DMARDs (rising from 61% to 87% of patients from 1996-2014), combination DMARDs (1% to 41%) and biologic (0 to 32%). Mean DAS28 fell (5.2 to 3.7), active disease (DAS28 > 5.1) declined (50% to 18%) and DAS28 remission (DAS28 < 2.6) increased (8% to 28%). In contrast HAQ scores were unchanged (1.30 to 1.32) and correlations between DAS28 and HAQ weakened (Spearman's rho fell from 0.56 to 0.44). CONCLUSIONS: Treatment intensity has increased over time, disease activity has fallen and there are more remissions. However, these improvements in controlling synovitis have not resulted in comparable reductions in disability measured by HAQ. As a consequence the relationship between DAS28 and HAQ has become weaker over time. Although the reasons for this divergence between disease activity and disability are uncertain, focussing treatment entirely in suppressing synovitis may be insufficient.