334. Biologics in Refractory Vasculitis (BIOVAS)-overview of the clinical trial protocol
Creators: name: Maria King1, 2
Publisher: name: Zenodo
Year: 2022
Subjects: Vasculitis
ANCA
Abstracts
Giant Cell Arthritis
MPA
GPA
EGPA
Takayasu
IgA vasculitis

description: <strong>Background/ Objectives:</strong> Non-ANCA-associated vasculitides (NAAV) have a combined incidence of ~20/million/year. Currently, treatment strategies in NAAV mirror AAV treatments due to similarities in disease pathogenesis and manifestations (Mukhtyar et al. 2009; Mukhtyar et al. 2009a). One third of NAAV patients have refractory disease, and this subgroup experiences the poorest outcomes, the highest ug related toxicity and is most demanding on health resources (Trieste et al. 2012). The BIOVAS trial will investigate efficacy, safety and cost-effectiveness of 3 biologic treatments in refractory NAAV. The trial design concords with the current treatment pathway based on European League Against Rheumatism (EULAR) consensus statements (Mukhtyar 2009) <strong>Methods</strong>: The BIOVAS trial is a pragmatic, randomised, double-blind, modified-crossover trial in refractory NAAV in adults and chilen. The biologics being studied are: an anti-IL-6 receptor biologic (Tociluzumab), an anti-TNF biologic (Infliximab) and a B-cell depleting biologic (Rituximab). Patients with refractory NAAV aged 5 years or older will be randomised to a randomly generated sequence of 4 blinded interventions: the 3 biologics all administered intravenously as hospital-supplied stock and a placebo administered at the same dosing schedule as one of the three active biologics. Patients initiate first intervention at baseline, and are assessed every 120 days for disease activity and response to treatment. Those who respond continue on the first intervention until failure, severe relapse, or the end of the trial at 2 years. Patients failing to respond to an intervention or experiencing a relapse will be switched to the next intervention in their randomised sequence and continue on the second intervention until relapse, failure to respond or end of trial (figure 1: trial flow diagram). Disease activity assessment is via a modified BVAS-V3, or PVAS for participants under 16 years of age. Treatment efficacy, and safety outcomes (Serious adverse events and infections) will be analysed. Patient reported outcomes and health resource utility will be recorded, for subsequent health economics analysis. The trial ai to run at multiple centres across the UK and to recruit 140 participants with the following NAAV diseases: GCA, Takayasu’s arteritis, Polyarteritis Nodosa (PAN), cutaneous PAN, IgA vasculitis, Cogan’s synome, non-infective cryoglobulinaemia, Relapsing polychonitis, and primary angiitis of the central nervous system. The primary end-point is the number of months of response to a specific intervention and each patient will generate 1-4 end-points. A frequentist analysis will compare efficacy of biologics to placebo while Bayesian analyses will explore treatment effects for specific biologics in different vasculitic subgroups. Current status: The trial was activated in June 2021, and to date 1 site is active, with 3 patients randomised. The trial ai to run at multiple centres across the UK and to recruit 140 participants with refractory NAAV. <strong>Conclusions</strong>: The BIOVAS trial ai to provide greater evidence for the effectiveness (clinical and cost-effectiveness) of biologic treatments in refractory paediatric and adult patients with NAAV, thereby providing evidence for alternative treatment options to high-dose glucocorticoids. <strong>Disclosures: </strong>Maria King (none). David Jayne’s disclosures of commercial conflicts for companies with marketed products for 2021 are: Astra-Zeneca, Aurinia, B, Boehringer-Ingelheim, GSK, Janssen, Novartis, Roche/Genentech, Takeda &amp; Vifor. Seerapani Gopaluni-none FUNDING: This study is funded by the National Institute for Health Research (NIHR) HTA programme (project reference 17/83/01). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care