The validity of a rheumatoid arthritis medical records-based index of severity compared with the DAS28

Rheumatoid arthritis (RA) is a chronic inflammatory disease that can lead to long-term joint damage resulting in chronic pain, loss of function, and disability [1]. It causes substantial morbidity in most patients and premature mortality in many [2-5]. Some patients with severe RA may be at higher risk for complications such as infection, gastrointestinal problems, heart disease, and cancer [6,7]. However, those complications may be related to adverse effects of drug therapies rather than to the effect of RA.Several studies have reported serious but rare adverse effects of RA medications. For example, biologic agents that block the action of tumor necrosis factor-α have been investigated as the cause of serious infections, hematological cancers, and demyelinating disease [8-11]. Lymphoproliferative malignancies among users of disease modifying anti-rheumatic drugs have also been reported [12,13].Data on adverse drug events come predominantly from clinical trials, case reports, case series, and epidemiologic studies. Randomized clinical trials are limited in their ability to detect rare adverse effects because of small sample size, selection of patients least likely to experience toxicity, and short duration of follow-up. It is difficult to base causality assessment on case reports/series. Therefore, pharmacoepidemiologic studies can play a pivotal role in evaluating safety of medications used in RA. However, the severity of RA may affect the choice of medication and RA outcomes. Failing to control for RA severity in epidemiologic studies may lead to biased estimates of the association between RA drug treatment and RA outcomes. This type of bias, confounding by indication, is an important potential bias in many pharmacoepidemiologic studies [14,15].To measure RA disease severity in medical records, we defined a set of indicators of severe RA through an expert Delphi panel of rheumatologists [16]. On the basis of their findings, we developed an RA medical records-base