New agent with great potential for the treatment of giant cell arteritis in the pipeline

Lower risk of flare and increased sustained remission with mavrilimumab compared with placebo were the main results of a trial for giant cell arteritis with the novel anti-GM-CSF receptor alpha monoclonal antibody.

“A substantial proportion of patients treated with tocilizumab fail treatment due to relapse or tocilizumab-related side effects. IL-6 blockade may primarily target the Th17 axis, possibly leaving significant residual Th1 activity,“ Dr Maria Cinta Cid (Hospital Clínic of Barcelona, Spain) described the current situation in the treatment of giant cell arteritis (GCA). She observed a great unmet need for new treatments in GCA [1].

Dr Cid presented a phase 2, randomised, placebo-controlled study investigating mavrilimumab in patients with new-onset (N/O) or relapsing refractory (R/R) GCA. 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 defined as having ESR ≥30 mm/h and/or CRP ≥1 mg/dL elevation plus ≥1 new cranial or extracranial GCA manifestations, or new/worsening vasculitis detected by imaging. The key secondary endpoint was defined as the percentage of patients with 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 Cid. 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 corresponded to a 62% reduction in risk of flare for mavrilimumab recipients (P=0.026). 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. Thus far, GM-CSF antagonism has been used in trials in RA and is being evaluated in other rheumatology settings and in severe COVID-19 pneumonia. We await to see where targeting of this pathway may enter the clinic.

1. Cid MC, et al. Mavrilimumab reduces time to flare and increases sustained remission in a phase 2 trial of patients with giant cell arteritis. L06, ACR Convergence 2020, 5-9 Nov.

Posted on 18 January 2021