Results
During the study period, the total prescriptions of tocilizumab was 362, which included 170 (46.96%) on-label prescriptions and 192 (53.04%) off-label prescriptions. The prescriptions were mainly from rheumatology and immunology department, which occupied 98.9% of total prescriptions. The median patients age is 36, ranging from 14 to 87. The number of prescription physicians were 31 (chief physician 13; vice chief physician 9; attending physician 9. vice chief physician was the majority of the health care group whose ratio of prescribing off-label use prescription is 56.52% and followed by attending physician (52.97%) and chief physician (50.55%) . According to the analysis of logistic regression, the off-label use of tocilizumab was similar among physicians with different professional title(R=0.039, P=0.755).
The patient number of each off label indication was also analyzed. The total patient number is 167. According to our standard, 16 out of 18 kinds of indications were judged as off-label indications. Takayasu Arteritis(27, 16.2%) was the most frequently prescribed off-label indication. Other off-label indications were Adult-onset Still’s disease(13, 7.8%), Systemic Lupus Erythematosus(2, 1.2%), Systemic Vasculitis(13, 7.8%), Giant Cell Arteritis(5, 3.0%), Relapsing Polychondritis(4, 2.4%), Behcet’s Disease(8, 4.8%), Sjogren’s Syndrome(4, 2.4%), Dermatomyositis(5, 3.0%), Systemic Scleroderma,(4, 2.4%) Neuromyelitis Optic Spectrum Disease(1, 0.6%), Castleman Disease(1, 0.6%), Polymyalgia Rheumatica(1, 0.6%), Immune-mediated necrotizing myopathy(1, 0.6%), Ankylosing Spondylitis(1, 0.6%) and Psoriatic Arthritis(1, 0.6%). The on-label indication is Rheumatoid arthritis (74, 44.3%) and systemic juvenile idiopathic arthritis (2, 1.2%). Additionally, most of the patients(163, 97.6%) prescribed tocilizumab from the rheumatology and immunology department. Other patients were from Pneumology Department (2, 1.2%), Department of Cardiology (1, 0.6%) and Vascular Surgery Department (1,0.6%). The details are available at table 1.
According to our criterion of judging the evidence categories supporting these off label indications. Castleman’s disease and giant cell arteritis has been approved by other countries like the US, the European regulatory authorities and Japan so these two indications are classified as category I. Takayasu Arteritis, adult-onset Still’s disease, relapsing polychondritis, Behcet’s disease, systemic scleroderma, neuromyelitis optic spectrum disease and polymyalgia rheumatica are classified as category II. Besides all the category II indications have systematic review, RCT or cohort study support. Ankylosing Spondylitis, Sjögren’s Syndrome, Systemic Lupus Erythematosus are supported by systemic review, RCT, cohort study, non-randomized controlled study, so these indications are classified as category III. Dermatomyositis, Psoriatic Arthritis, Systemic Vasculitis are supported by case series report or case report, so these indications are classified as category IV. Finally, immune-mediated necrotizing myopathy have no medical evidences support so this indication is classified as category V. The details are available at table 2 and table 3.