Early undifferentiated connective tissue disease. IV. Musculoskeletal manifestations in a large cohort of patients with undifferentiated connective tissue diseases compared with cohorts of patients with well‐established connective tissue diseases: Followup analyses in patients with unexplained polyarthritis and patients with rheumatoid arthritis at baseline
Authors: Alarcón Garciela S. , Willkens Robert F. , Ward John R. , Clegg Daniel O. , Morgan John G. , Ma Khe‐Ni , Williams H. James , Singer Joyce Z. , Steen Virginia D. , Paulus Harold E. , Luggen Michael E. , Polisson Richard P. , Ziminski Carol M. , Yarboro Cheryl 
Published: February 2007

Objective. To examine the musculoskeletal manifestations in a large cohort of patients (n = 410) diagnosed with either a well‐established connective tissue disease (CTD) (n = 197) or an early undifferentiated CTD (n = 213) with a symptom duration of < 1 year. This study was aimed at determining the predictive value of demographic, clinical, and laboratory features on outcome in patients with unexplained polyarthritis (UPA) (from the early undifferentiated CTD cohort; n = 67) or rheumatoid arthritis (RA) (from the well‐established CTD cohort; n = 57), over a 5‐year followup period.

Methods. Patients from both cohorts were assessed at years 1, 3, and 5. At the study visits, clinical data were collected in a standardized manner, and sera were obtained and stored. A priori criteria were established for patient ascertainment and diagnosis over the duration of the study. Standard statistics were used for comparisons of baseline characteristics in patients diagnosed as having systemic lupus erythematosus, RA, undifferentiated CTD, and UPA at entry into the cohorts. Baseline features in patients with UPA were examined according to the different subsequent outcomes (RA, CTD, or undifferentiated CTD, remission [nonpersistent], or persistent or active UPA). Baseline features in patients with RA whose disease remained active versus those in whom remission was attained were also examined. Two multivariable analyses, classification trees and polychotomous logistic regression, were performed to predict disease outcomes over time.

Results. The overall rate of ascertainment for the 410 patients ranged from 90% at year 1 to 71% at year 5. Patients with established CTDs showed a tendency for more stable diagnoses than those with early undifferentiated CTDs (90–100% versus 45–70%). Consistent baseline predictors of persistent active disease among patients with RA, in both univariate and multivariable analyses, were higher joint counts for pain and tenderness and higher erythrocyte sedimentation rate (ESR). In ∼20% of patients who were classified as having RA when they originally entered the cohort, the disease was in remission at 5 years. Twenty percent of the patients originally classified as having UPA developed RA over the duration of the study. These patients tended to be older and to have swelling of small joints at baseline. However, a consistent pattern of predictive variables could not be identified in the multivariable analyses, other than at year 1 (higher small joint counts for swelling and higher ESR).

Conclusion. Baseline features (joint counts and ESR) among RA patients were variously predictive of persistently active disease at years 1–5. Consistent baseline predictors of outcome among the patients with UPA only emerged at year 1. Remission occurred in ∼20% of RA patients, whereas a similar percentage of patients with UPA developed RA. These findings have implications with regard to treatment decisions in patients with early RA and/or UPA.