Efficacy and safety of mavrilimumab in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial

Abstract

Objectives: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is implicated in pathogenesis of giant cell arteritis. We evaluated the efficacy of the GM-CSF receptor antagonist mavrilimumab in maintaining disease remission.

Methods: This phase 2, double-blind, placebo-controlled trial enrolled patients with biopsy-confirmed or imaging-confirmed giant cell arteritis in 50 centres (North America, Europe, Australia). Active disease within 6 weeks of baseline was required for inclusion. Patients in glucocorticoid-induced remission were randomly assigned (3:2 ratio) to mavrilimumab 150 mg or placebo injected subcutaneously every 2 weeks. Both groups received a 26-week prednisone taper. The primary outcome was time to adjudicated flare by week 26. A prespecified secondary efficacy outcome was sustained remission at week 26 by Kaplan-Meier estimation. Safety was also assessed.

Results: Of 42 mavrilimumab recipients, flare occurred in 19% (n=8). Of 28 placebo recipients, flare occurred in 46% (n=13). Median time to flare (primary outcome) was 25.1 weeks in the placebo group, but the median was not reached in the mavrilimumab group (HR 0.38; 95% CI 0.15 to 0.92; p=0.026). Sustained remission at week 26 was 83% for mavrilimumab and 50% for placebo recipients (p=0.0038). Adverse events occurred in 78.6% (n=33) of mavrilimumab and 89.3% (n=25) of placebo recipients. No deaths or vision loss occurred in either group.

Conclusions: Mavrilimumab plus 26 weeks of prednisone was superior to placebo plus 26 weeks of prednisone for time to flare by week 26 and sustained remission in patients with giant cell arteritis. Longer treatment is needed to determine response durability and quantify the glucocorticoid-sparing potential of mavrilimumab.

Trial registration number: ClinicalTrials.gov number: NCT03827018, Europe (EUdraCT number: 2018-001003-36), and Australia (CT-2018-CTN-01 865-1).

Keywords: giant cell arteritis; glucocorticoids; inflammation; systemic vasculitis.

Conflict of interest statement

Competing interests: MCC reports a research grant from Kiniksa; consulting for Janssen, GlaxoSmithKline, and AbbVie; educational support from GlaxoSmithKline, Roche, and Vifor; and meeting attendance support from Roche and Kiniksa. SHU reports research support from Genentech and consulting for Janssen and Kiniksa. DB has nothing to disclose. EB reports receiving, as an employee of the University of Groningen Medical Center, speaker and consulting fees from Roche in 2017 and 2018, paid to the University of Groningen Medical Center. LD reports grants, personal fees, and nonfinancial support from AbbVie, Amgen, Bristol-Myers Squibb, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI; grants and personal fees from Celltrion and Galapagos; grants from Janssen, Kiniksa, and Merck Sharp & Dohme; and personal fees from Biogen and GlaxoSmithKline, outside the submitted work.Bhaskar Dasgupta, M.B.B.S., M.D., FRCP reports receiving grants and personal fees from Roche-Chugai and Sanofi and grants from AbbVie during the conduct of the study. BH has nothing to disclose. EM reports receiving clinical trial expenses from Kiniksa Pharmaceuticals during the conduct of the study; grants and personal fees from AbbVie; and personal fees from Janssen, Gilead, Novartis, Merck, and UCB, outside the submitted work. ES has nothing to disclose. BCT reports receiving personal fees from Kiniksa as a consultant member of DSMB. KJW reports grants from Kiniksa during the conduct of the study; grants from Eli Lilly, Roche/Genentech, and GlaxoSmithKline; and personal fees from Sanofi and Roche/Genentech, outside the submitted work. IW reports receiving scientific consulting fees from CSL and may receive a distribution of royalty income from the Walter & Eliza Hall Institute, which licensed intellectual property related to the alpha chain of the GM-CSF receptor. MS, TZ and LP are employees and stockholders of Kiniksa Pharmaceuticals. JFP is an employee and stockholder of Kiniksa Pharmaceuticals, and is an inventor on patent applications related to mavrilimumab. This study was funded in full by Kiniksa Pharmaceuticals.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.

Figures

Figure 1

Trial design. Patients were randomised in a 3:2 ratio to mavrilimumab or placebo using disease type (new onset or relapsing/refractory) as a stratification factor. Prednisone was tapered over the 26-week study as specified in the protocol.

Figure 2

Trial profile. Not all patients who discontinued treatment withdrew from the trial; two patients receiving mavrilimumab and two patients receiving placebo withdrew before week 26, and one patient receiving mavrilimumab withdrew between week 26 and week 38.

Figure 3

Time to first flare of giant-cell arteritis in all patients. At baseline, patients had to be in remission (defined as the absence of giant-cell arteritis signs and symptoms and erythrocyte sedimentation rate

Figure 4

Sustained remission rate of giant-cell arteritis in all patients at week 26. The difference in sustained remission at week 26 (key secondary endpoint) was statistically significant (33.3 percentage points; p=0.0038). Sustained remission was defined as the absence of flare from randomisation through week 26. Sustained remission rate was derived by Kaplan-Meier curve analysis.