The anti-GM-CSF receptor alpha monoclonal antibody mavrilimumab entailed a lower risk of flare and greater sustained remission compared with placebo in patients with giant cell arteritis.
A phase 2, randomised, placebo-controlled study investigated mavrilimumab in patients with new-onset (N/O) or relapsing refractory (R/R) giant cell arteritis (GCA) [1]. All patients had to be in corticosteroid-induced remission when starting the trial, meaning: no clinical symptoms, C-reactive protein (CRP) <1 mg/dL and erythrocyte sedimentation rate (ESR) <20 mm/h. Prednisone was tapered according to a pre-determined protocol over the 26-week study duration. In the double-blind treatment period, patients were either treated with mavrilimumab 150 mg (n=42) or placebo (n=28) subcutaneously every 2 weeks. The time to the incidence of the first GCA flare by week 26 was defined as the primary endpoint. A flare was characterised as having ESR ≥30 mm/h and/or CRP ≥1 mg/dL elevation plus 1 or more new cranial or extracranial GCA manifestations, or new/worsening vasculitis detected by imaging. The key secondary endpoint was defined as the percentage of sustained remission at week 26.
Baseline patient features included a mean age of 69.7 and 71% of patients were female. The study population consisted of 35 N/O patients and 35 R/R patients. “Clinical manifestations were predominantly cranial,” said Dr Maria Cinta Cid (Hospital Clínic of Barcelona, Spain). She further indicated that nearly 3 quarters of diagnosis confirmation by ultrasound in the study population could reflect a shift in standard-of-care.
At week 26, GCA flares were noted in 19% of the mavrilimumab patients as opposed to 46.4% of the placebo group. The median time to flare by week 26 was 25.1 weeks in the placebo group. Time to flare in the mavrilimumab group was not estimable as the events were too scarce, but when comparing mavrilimumab with placebo, there was a significantly lower hazard with mavrilimumab treatment (HR 0.38). This corresponds to a 62% reduction in risk of flare for mavrilimumab recipients (P=0.0263). Also, significantly higher rates of sustained remission were observed for mavrilimumab recipients (83.2%) compared with those receiving placebo (49.9%; P=0.0038).
Mavrilimumab was overall well tolerated and adverse events were mostly mild to moderate with a comparable distribution among the groups. Importantly, no cases of death or loss of vision happened. Out of 5 serious adverse events, 2 were in the mavrilimumab group and 3 in the placebo group, none were deemed to be drug-related. “These results are encouraging for the potential further development of mavrilimumab in GCA,” Dr Cid concluded.
- Cid MC, et al. Mavrilimumab (anti GM-CSF Receptor α Monoclonal Antibody) reduces time to flare and increases sustained remission in a phase 2 trial of patients with giant cell arteritis. L06, ACR Convergence 2020 Virtual Annual Meeting, 5-9 November 2020.
