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.