Introduction

Rheumatoid arthritis (RA), a chronic inflammatory disease, primarily attacks various synovial joints and certain extra-articular organs, such as pulmonary nodules [1], eyes [2], nervous system [2], kidneys [3], and so on. The occurrence of RA, which ranges from 0.5% to 2% among the general population, generally affects women in their forties and fifties, and is twice as likely to occur in women than in men [2].
RA patients are commonly treated according to the severity of the disease by using one or more of the following treatments at each visit. Escalation of therapy may proceed in a high disease activity state, and the most common treatments include methotrexate (MTX) with or without other conventional synthetic disease-modifying antirheumatic drugs (DMARDs) in further combination with biological agents. Sometimes, glucocorticoids [4, 5] may be used in severe uncontrolled cases. According to a study by Katerina C [6], the addition of glucocorticoids to MTX is usually more helpful than MTX monotherapy in early RA, and intramuscular and oral glucocorticoids were similarly effective as modes of bridging therapy. Furthermore, a combination of DMARDs is sometimes as effective as monotherapy with MTX while functional ability and radiographic progression are also taken into consideration [6].
A nonsteroidal anti-inflammatory drug (NSAID) relieves pain and stiffness but not the underlying causes of RA, while glucocorticoids blunt the immune response but cannot slow down the progression. The use of MTX and other DMARDs to slow disease progression is apparently beneficial [6], and since RA is a long-term autoimmune disease and occurs secondary to a loss of self-antigen tolerance, the advent of biologics therapies has demonstrated better outcomes [7, 8]. The addition of biologics to MTX therapy is usually favorable as well [6].
The use of biological agents has been associated with significantly increased rates of serious infections, including opportunistic infections and bacterial infections, in most studies [9], and the outcomes of adverse drug effects has resulted in most guidelines recommending biological agents to be used in patients who had responded poorly to or who were intolerant of one or more DMARDs [10]. According to one recent study [11], autoantibodies and markers of systemic or local inflammation can be present long before clinical arthritis, and the disease process evolves long before the disease is clinically detectable, i.e., early treatment in RA patients should be associated with improved outcomes [11]. Furthermore, the use of NSAIDs and steroids are associated with increased cardiovascular events and infections, respectively [12, 13], and the use of methotrexate and other DMARDs may be associated with liver toxicity and gastrointestinal side effects, making early use of a biological agent a viable option. Currently, no published large-scale study has clarified whether early treatment of RA with a biological agent, based on the aforementioned reasons, leads to a better outcome. Therefore, the aim of this study was to evaluate the daily usage of glucocorticoids and painkillers, i.e. NSAIDs, in early treatment results of biologics compared to late biologics treatment of RA patients by using a population-based claims database in Taiwan.