MAVRILIMUMAB (ANTI GM-CSF RECEPTOR A MONOCLONAL ANTIBODY) REDUCES RISK OF FLARE AND INCREASES SUSTAINED REMISSION IN A PHASE 2 TRIAL OF PATIENTS WITH GIANT CELL ARTERITIS
Authors: M. C. Cid et al.
T helper (Th)1 and Th17 lymphocytes play a role in the pathogenesis of giant cell arteritis (GCA). The anti-IL-6 strategy targets the Th17 axis, its effect on Th1 is debated. Granulocyte macrophage colony stimulating factor (GM-CSF) is a mediator of Th1 and Th17 cells, thus might play an important pathogenic role in GCA.
This phase 2 RCT enrolled patients with active, biopsy- or imaging-proven new onset (N/O) or relapsing refractory (R/R) GCA. Corticosteroid-induced remission (resolution of GCA symptoms and CRP <1 mg/dL or ESR <20 mm/hr) was required by baseline. 3:2 randomization to mavrilimumab 150 mg or placebo subcutaneously every 2 weeks and protocol-defined 26-week prednisone taper starting at 20-60 mg/day. Primary efficacy endpoint: time to first adjudicated flare (ESR ≥30 mm/hr and/or CRP ≥1 mg/dL and GCA symptoms or new/worsening vasculitis on imaging) by Week 26 in all treated patients. Key secondary endpoint: sustained remission through Week 26. 70 patients (35 N/O, 35 R/R) were enrolled (mavrilimumab [N=42] or placebo [N=28]). Mean (SD) age was 69.7 (7.48) years and 71.4% were female. Flare by Week 26 occurred in 8 (19%) and 13 (46.4%) patients receiving mavrilimumab and placebo. Sustained remission at Week 26 occurred in 83.2% of patients receiving mavrilimumab and 49.9% of those receiving placebo (33.4 percentage points increase; p=0.0038). Adverse events (AEs), mostly mild to moderate, were comparable between groups. There were 5 serious AEs (mavrilimumab 2 [4.8%], placebo 3 [10.7%]), none drug-related. No deaths or vision loss occurred. No adjudicated cases of pulmonary alveolar proteinosis were observed.
The data are very promising, showing an impressive effect of neutralization of GM-CSF in preventing relapse after GC-induced remission. Whether this biologic agent targets a population of GCA which is non-responsive to IL-6 neutralizing strategies is unknown but may be speculated.