The Meteoritics Trial: Efficacy of Methotrexate after Remission-Induction with Tocilizumab and Glucocorticoids in Giant Cell Arteritis: Study Protocol for a Randomized, Double-Blind, Placebo-Controlled, Parallel Group Phase II Study

Abstract

• Background: Glucocorticoids (GC) are the standard treatment for giant cell arteritis (GCA), even though they are associated with adverse side effects and high relapse rates. Tocilizumab (TCZ), an interleukin-6 receptor antagonist, has shown promise in sustaining remission and reducing the cumulative GC dosage, but it increases the risk of infections and is expensive. After discontinuation of TCZ, only about half of patients remain in remission. Additionally, only few studies have been conducted looking at remission maintenance, highlighting the need for alternative strategies to maintain remission in GCA. Methotrexate (MTX) has been shown to significantly decrease the risk of relapse in new-onset GCA and is already a proven safe drug in many rheumatologic diseases. • Methods: This study aims to evaluate the efficacy and safety of MTX in maintaining remission in patients with GCA who have previously been treated with GC and at least six months with TCZ. We hypothesise that MTX can maintain remission in GCA patients, who have achieved stable remission after treatment with GC and TCZ, and prevent the occurrence of relapses. The study design is a monocentric, randomised, double-blind, placebo-controlled, parallel group phase II trial randomising 40 GCA patients 1:1 into a MTX or placebo arm. Patients will receive 17.5 mg MTX / matching placebo weekly by subcutaneous injection for 12 months, with the possibility of dose reduction if clinically needed. A six-month follow up takes place. The primary endpoint is the time to first relapse in the MTX group versus placebo during the 12-month treatment period. Secondary outcomes include patient- and investigator-reported outcomes and laboratory findings, as well as the prevalence of aortitis, number of vasculitic vessels, and change in intima-media thickness during the study. • Discussion: This is the first clinical trial evaluating remission maintenance of GCA with MTX after a previous treatment cycle with TCZ. Following the discontinuation of TCZ in GCA, MTX could be a safe and inexpensive drug. • Trial registration: ClinicalTrials.gov, NCT05623592. Registered 21.11.2022, https://classic.clinicaltrials.gov/ct2/show/NCT05623592?term=giant+cell+arteriitis&cond=methotrexate&draw=2&rank=1 EU Clinical Trials Register, 2022-501058-12-00 German Clinical Trials Register DRKS00030571