Limitations
The study is a retrospective research, and it has all the limitation
that this kind of research should have. For example, missing data,
coding bias, loss follow up patients, different inclusion status of
patients and different treatment result in the end are all inevitable
limitations. On the other hand, it is based on a Taiwan National Health
Insurance Research database, which is reflecting only current medical
and economic situation under particular situation and in particular time
interval. This is a small piece of real-world evidence demonstrated to
the world that the early treatment with biologics could cut oral
medication in half in just two years. Nevertheless, no other objective
evidence could be provided to demonstrate the efficacy of the biologics
which is also another limitation in this study. This also affects the
statistical analyses of the results. Furthermore, the reimbursement of
biologics other than the Etanercept and the Adalimumab as first-line
treatment of RA was not available in Rituximab and Tocilizumab, and the
Golimumab was not available in Taiwan until the end of 2012. All of
which could limit the case numbers treated by the biologics other than
the Etanercept and the Adalimumab.
Besides, disease activity, genes and smoking may be involved in RA long
term treatment efficacy, which all these three factors cannot be direct
evaluated in this study. For example, we only calculated the decrease in
treatment in 50% of the days, but there are no cumulative doses in each
category of medication. The situation is similar between two groups,
which we consider these issues contribute equally to each subgroup and
may not affect the final comparison result. Also, by decreasing the use
of oral treatment (NSAIDs and glucocorticoid), it could only mean a
symptomatic effect and not necessarily have an effect on the activity or
accumulated damage of the disease (it is a bias not to have activity
measures such as DAS28 or radiographic damage on this national database
analysis). Not having measurements of poor prognosis factors such as
serology, persistent activity, smoking, extra-articular manifestations
and adherence to treatment limit the results in this large nation-wide
study.
It is therefore possible that a minor portion of the included patients
with RA were misdiagnosed from other types of arthritis, such as
seronegative arthritis. However, we have done all the effort to minimize
this entire situation by confirm the diagnosis with treatment
medication. Unfortunately, the data in the medical records did not
include enough information to assess the RA patient functional class and
is why we omitted this parameter in the statistical analyses.