Background Early, intensive disease-modifying anti-rheumatic drug (DMARD) therapy is an effective strategy to limit disease progression in rheumatoid arthritis (RA). It was recently reported that DMARD therapy is initiated in advance of an established RA diagnosis and is questionably intensive.1,2
Objectives The objective of this study was to determine the predictors of intensive DMARD therapy in early care for RA.
Methods A retrospective cohort of newly diagnosed 339 RA patients randomly selected from 18 regional rheumatology practices was studied. Longitudinal data on DMARD intervention and baseline demographic and prognostic variables were collected. Variables specifically considered for the model included age, sex, disease activity (DAS28-3, including 28-point tender, TJC, and swollen joint counts, SJC, and erythrocyte sedimentation rate, ESR), rheumatoid factor (RF), baseline evidence of erosions, and symptom duration. The scaling of treatment intensiveness and a threshold for the outcome was determined from a literature search. Multivariable logistic regression modeling was conducted to determine the predictors of intensive therapy. A sensitivity analysis was conducted that included methotrexate (MTX) monotherapy with steroids, and hydroxychloroquine (HCQ)-sulfasalazine combination therapy as intensive therapy. Bootstrapping was used to internally validate the model.
Results The literature search revealed that combination-DMARD therapy including MTX or at least 3 DMARD, or biologic therapy was considered intensive. Three quarters of the cohort was female (75.5%), 70.5% was RF positive, and 16.2% had evidence of erosions at diagnosis. Patients were a median (interquartile range, IQR) 52 (42-63) years of age, had 14 (8-20) tender and 10 (6-14) swollen joints, an ESR of 32 (20-47) mm/h, and had a symptom duration of 9 (4-25) months. Intensive therapy was given to 18.9% of patients at diagnosis compared to 14.5% at DMARD initiation (p=0.122). The majority of patients were treated with DMARD monotherapy initially (71.1%) and at RA diagnosis (57.8%). HCQ monotherapy was used more frequently at DMARD initiation (42.2% vs 32.4 %, p=0.009). The percentage of patients not receiving DMARD therapy was greater at diagnosis (11.2 vs 2.1, p<0.0001). Higher DAS28-3 score (odds ratio (OR)=1.54, p=0.002) was predictive of intensive treatment at diagnosis and the association between decreasing age and receiving this treatment approached significance (OR=0.98, p=0.053). The c-index (standard error) for bootstrap validation was 0.688 (0.003). DAS28-3 (OR=1.50, p=0.001) and male gender (OR=2.19, p=0.006) were significant predictors of intensive intervention in the sensitivity analysis.
Conclusions Disease activity informs treatment intensiveness. In this sample, a minority of patients were treated with an intensive DMARD regimen in early RA. There were insufficient data to conclude a difference in the intensiveness of therapy between DMARD initiation and later diagnostic confirmation. Further research is required to better understand treatment decision-making and adherence at DMARD initiation and over the course of care.
Tavares R, et al. J Rheumatol 2012;39(11):2088-97.
Tavares R, et al. J Rheumatol 2011;38(11)2342-5.
Acknowledgements The authors acknowledge the UNCOVER study committee and investigators (committee: Boire G, Bombardier C, Laupacis A, Tomlinson G; investigators: Bell MJ, Boire G, Bookman AA, Blocka KL, Bykerk VP, Haraoui B, Henderson JM, Hitchon CA, Fidler WK, Fitzgerald AA, Khraishi M, Lacaille D, Lazovskis J, Mosher DP, Pope JE, Sholter DE, Thorne JC, Tremblay JL).
Disclosure of Interest None Declared