Key points
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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