• Baseline factors predicting change from the initial DMARD treatment during the first 2 years of rheumatoid arthritis: experience in the ERAN inception cohort

      Walsh, David A (2013-05)
      BACKGROUND: Outcomes in early Rheumatoid Arthritis (RA) may be improved by rapidly establishing a stable and effective disease modifying anti-rheumatic drug (DMARD) treatment regimen. We aimed to investigate whether baseline factors and initial treatment strategies are associated with changes to the first DMARD treatment, due to either Lack of Efficacy (LoE) or Adverse Drug Reaction (ADR) within 2 years of presentation. METHODS: Reasons for changes from initial DMARD therapy within 2 years of baseline, and associated factors, were examined using logistic regression in data from the Early RA Network (ERAN) inception cohort. RESULTS: Data were available for 766 participants. 410 (54%) changed their initial DMARD regime within 2 years, including 230 (56%) due to Lack of Efficacy (LoE) and 139 (34%) due to Adverse Drug Reaction (ADR). The first DMARD was recorded as methotrexate monotherapy in 336 (44%), sulphasalazine monotherapy in 273 (36%), or combined methotrexate/sulphasalazine/hydroxychlorquine in 52 (7%).Baseline predictors of changing DMARD (for all reasons) were HAQ-disability (aOR 1.44, 95% CI 1.12 - 1.86), poor mental health (aOR 1.44, 95% CI 1.16 - 1.78) and extra-articular disease (aOR 1.78, 95% CI 1.00 - 3.16). In this model, the triple combination therapy also predicted lower likelihood of DMARD change (aOR 0.30, 95% CI 0.12 - 0.79).Subgroup analyses showed that MTX monotherapy was associated with lower risk of change due to ADR. Combination therapy conferred lower risk of change due to LoE. Poor mental health was associated with change due to ADR, and extra-articular disease, HAQ-disability at baseline, and younger age predicted LoE. CONCLUSIONS: Our findings suggest that non-pharmacological interventions to improve disability and mental health, may reduce initial DMARD treatment failure.
    • Discordant inflammation and pain in early and established rheumatoid arthritis: Latent Class Analysis of Early Rheumatoid Arthritis Network and British Society for Rheumatology Biologics Register data.

      Walsh, David A (McWilliams, D. F. et al. (2016) ‘Discordant inflammation and pain in early and established rheumatoid arthritis: Latent Class Analysis of Early Rheumatoid Arthritis Network and British Society for Rheumatology Biologics Register data’, Arthritis Research & Therapy, 18, p. 295., 2016-12-13)
      ACKGROUND: Rheumatoid arthritis (RA) disease activity is often measured using the 28-joint Disease Activity Score (DAS28). We aimed to identify and independently verify subgroups of people with RA that may be discordant with respect to self-reported and objective disease state, with potentially different clinical needs. METHODS: Data were derived from three cohorts: (1) the Early Rheumatoid Arthritis Network (ERAN) and the British Society for Rheumatology Biologics Register (BSRBR), (2) those commencing tumour necrosis factor (TNF)-alpha inhibitors and (3) those using non-biologic drugs. In latent class analysis, we used variables related to pain, central pain mechanisms or inflammation (pain, vitality, mental health, erythrocyte sedimentation rate, swollen joint count, tender joint count, visual analogue scale of general health). Clinically relevant outcomes were examined. RESULTS: Five, four and four latent classes were found in the ERAN, BSRBR TNF inhibitor and non-biologic cohorts, respectively. The proportions of people assigned with >80% probability into latent classes were 76%, 58% and 72% in the ERAN, TNF inhibitor and non-biologic cohorts, respectively. The latent classes displayed either concordance between measures indicative of mild, moderate or severe disease activity; discordantly worse patient-reported measures despite less markedly elevated inflammation; or discordantly less severe patient-reported measures despite elevated inflammation. Latent classes with discordantly worse patient-reported measures represented 12%, 40% and 21% of the ERAN, TNF inhibitor and non-biologic cohorts, respectively; contained more females; and showed worse function. In those latent classes with worse scores at baseline, DAS28 and function improved over 1 year (p < 0.001 for all comparisons), and scores differed less at follow-up than at baseline. CONCLUSIONS: Discordant latent classes can be identified in people with RA, and these findings are robust across three cohorts with varying disease duration and activity. These findings could be used to identify a sizeable subgroup of people with RA who might gain added benefit from pain management strategies.
    • Predicting responses in patients with rheumatoid arthritis to disease-modifying agents using baseline clinical data

      Walsh, David A (2017-09)
      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.