Key points
- This article is the first study
that evaluate the situation of
Tocilizumab off-label use in a
Chinese tertiary hospital. There is no similar or related study
currently.
- This article evaluate the
rationality of all the involved Tocilizumab off-label use by using
real-word retrospective data and combined with evidence based medical
classification.
- After systemic literature reviewing, all of the literature source
acquired from Up-To-Date, Micromedex database, PubMed, Embase, and
clinical guidelines. The types of involved literature include RCT,
systemic review, cohort study, case report and case series. High
quality literature is selected which aiming for ensuring the study’s
reliability.
- Oxford Centre for Evidence-Based Medicine scheme and A Measurement
Tool to Assess Systematic Reviews (AMSTAR) are used to evaluate the
quality of involved literature.
- All the Tocilizumab off-label uses
are classified as five categories based on different medical evidence
supporting. For category I-III, these uses are considered as
relatively rational due to high-level evidences supporting. For
category IV, these uses have no sufficient evidences supporting which
means these uses need carefully consideration before applying. For
category V, these uses have no any evidence supporting. According to
this classification standard, the study analyzed the rationality of
off-label use of Tocilizumab in the Chinese tertiary hospital and
provide the referential value for standardized management of medicine
off-label use in hospital.Abstract
Background Tocilizumab is an recombinant humanized anti-IL-6
receptor monoclonal antibody that approved for treating rheumatoid
arthritis (RA) and systemic juvenile idiopathic arthritis (sJIA) in
China. However, tocilizumab used for some off-label indications have
been confirmed effectiveness and safety. Objective To
investigate the prevalence of tocilizumab off-label prescribing in
outpatient department of a tertiary hospital and evaluate the
rationality of these off-label prescriptions by looking through
scientific evidences. Setting Peking Union Medical College
Hospital in Beijing in China. Method Retrieving one year
tocilizumab related prescriptions from hospital electronic information
system. The standard of evaluating the on-label or off-label
prescription according to whether the indication approved by China.
Logistic regression was applied to explore predictive variables. All of
the literature source acquired from Up-To-Date, Micromedex database,
PubMed, Embase, and clinical guidelines. Main outcome measureThe percentage of off-label use, influence factors identified by
logistic regression, the rationality of off-label use. Resultsthe total prescriptions of tocilizumab was 362, which included 167
patients. 45.5% patients received tocilizumab off-label prescription.
Takayasu Arteritis was the most frequently prescribed off-label
indication. Other off-label indications were Adult-onset Still’s
disease, Systemic Lupus Erythematosus, Systemic Vasculitis, Giant Cell
Arteritis, Relapsing Polychondritis, Behcet’s Disease, Sjogren’s
Syndrome, Dermatomyositis, Systemic Scleroderma, Neuromyelitis Optic
Spectrum Disease, Castleman Disease, Polymyalgia Rheumatica,
Immune-mediated necrotizing myopathy, Ankylosing Spondylitis and
Psoriatic Arthritis. Among these off-label indications, tocilizumab was
approved for Castleman’s Diease and Giant Cell Arteritis by other
countries or regions. After searching related evidences, Takayasu
Arteritis, Adult-onset Still’s Disease, Behcet’s disease, Relapsing
Polychondritis, Neuromyelitis optic spectrum disease, systemic
scleroderma, polymyalgia rheumatica, Ankylosing Spondylitis, Sjögren’s
Syndrome, Systemic Lupus Erythematosus were recommended by up to date or
authoritative guidelines, or supported by systematic review or
meta-analysis, RCT trials, cohort study or Non-randomized controlled
trial. Dermatomyositis, Psoriatic Arthritis and Systemic Vasculitis were
supported by case report or case series. Wheras for immune-mediated
necrotizing myopathy, we found no evidence to support. The off-label use
of tocilizumab was similar among physicians with different professional
titles(R=0.039, P=0.755) based on the analysis of logistic regression.Conclusion according to our analysis, the majority of off-label
indications of tocilizumab in our hospital have evidence support. But
some indications were supported by low grade scientific evidence, more
studies are required to confirm the clinical values. For the indication
that has no evidence support, we suggest the administration should
strength supervision.
Keywords: Tocilizumab, off label use, retrospective study