UNCOVER: Understanding Near-term Care Of Very Early Rheumatoid arthritis in a national, multi-centre, randomly selected, historical inception cohort of newly diagnosed disease

Rationale. Clinical guidelines for rheumatoid arthritis (RA) pharmacotherapy recommend initiating disease modifying anti-rheumatic drugs (DMARDs) within three months of established disease and three months of symptoms are required to establish a diagnosis with certainty. Unfortunately, data on delays to accessing DMARD therapy for early RA is lacking from Canada. These patients may not be receiving optimal treatment in a timely manner. Purpose. To determine the proportion of Canadian RA patients treated with DMARDs within six months of symptom onset; to determine the predictors and components of time to treatment; and, to characterize early pharmacotherapy and clinical management in usual care. Methods. A retrospective chart audit of 339 randomly selected adult patients, clinically diagnosed with RA between June 2001 and May 2003 from the practices of 18 rheumatology specialists. Time to DMARD treatment was determined using Kaplan-Meier analysis. Multivariable logistic regression (LR) and Cox modeling using Markov Chain Monte Carlo multiple imputed data was conducted to determine predictors of delay. Bootstrapping was used to validate LR models. Median component delays and frequency estimates of pharmacotherapies and clinical assessments utilized were determined. Results. Subjects were 50 +/- 14 years at symptom onset and 75.5% were female. At baseline, subjects had a median (interquartile range) of 10 (6,14) swollen and 13 (8,19) tender joints, an erythrocyte sedimentation rate (ESR) of 32 (20,46) mm/h, and C-reactive protein (CRP) of 29 (14,37) mg/L, 69.9% of subjects were rheumatoid factor positive (RF+), 40.4% had an arthritic comorbidity, 41.9% previously consulted another rheumatologist, and the majority (85.0%) were previously treated with non-steroidal anti-inflammatory drugs (NSAIDs). Within six months of symptom onset, 39.1% were treated with DMARDs. Multivariable predictors of increased time from symptom onset to treatment included the existence of an arthritic comorbidity, female gender, and younger age at symptom onset. Previously consulting another rheumatologist and seeing an academic investigator were associated with decreased time to treatment. The major delays occurred prior to rheumatology referral (78%), of which, 27% occurred prior to NSAID therapy. Therapy with DMARDs was initiated a median of 70 days prior diagnosis confirmation. The most common first DMARDs were hydroxychloroquine (HCQ, 55.5%) and methotrexate (MTX, 40.1%). At DMARD initiation, 47.2% were prescribed a combination therapy, including multiple DMARDs for 16.5% and DMARD-corticosteroid combinations for 30.7%. Laboratory assessments frequently accompanied referral letters (81.0%). Joint examination (40.7%), pain (50.2%), function (28.9%), and radiographs (49.7%) were infrequently included in referral letters. Except for radiography (55.5%), all other assessments noted above were conducted at a frequency of greater than 80% at baseline and follow-up by the investigator. Formal assessments of disease activity (DAS, 0.3%; DAS28, 8.6%), functional (HAQ, 34.6%; MHAQ, 16.0%), and pain (VAS, 43.6%) were infrequently collected over follow-up. Conclusions. Almost 40% of RA patients are treated with DMARDs within six months of symptom onset. The largest components of delays to treatment precede referral to rheumatologic care. On average, patients are treated with DMARDs prior to the confirmation of a diagnosis. Attention should be given to the development of RA symptoms in patients with arthritic comorbidities, lesser age, and females, as these variables predict increased time to treatment. Underlying characteristics of subjects who consult a single rheumatologist leading up to diagnosis and those referred to nonacademic specialists need to be explored as they also predict increased time to treatment. In light of patients being started on DMARDs in advance of a confirmed diagnosis, as well as the low proportion of patients with high disease activity early in the disease course, the initial DMARD care provided may be considered aggressive with nearly 50% receiving either multiple DMARDs or single-DMARD-corticosteroid combinations at this time point. The potential improvement in rheumatologic care achievable with tight monitoring of patients should be met with increased frequency of formal disease activity, function, pain and radiography assessments over the course of care.