Meta-Analysis of Safety of Granulocyte-Macrophage Colony- Stimulating Factor in the Treatment of Rheumatoid Arthritis Rami Diab MD, Mohinder Vindhyal MD

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Meta-analysis of Safety of Granulocyte-Macrophage Colony- Stimulating Factor in the Treatment of Rheumatoid Arthritis Rami Diab MD, Mohinder Vindhyal MD Introduction and Background Results (continued) • Rheumatoid arthritis (RA) is characterized by chronic joint and systemic GM-CSF Placebo inflammation with potential for irreversible joint damage. AAE Total AAE Total • Not uncommonly, resistance to treatment and treatment failures limit adequate disease control. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoeitic growth factor and pro-inflammatory cytokine stimulating proliferation of mature myeloid cells secondarily endorsing inflammatory mediators with the potential to exacerbate RA. • GM-CSF monoclonal antibodies therefore represent an innovative treatment option in refractory RA. The purpose of this meta-analysis was to evaluate the Favors GM-CSF Favors Placebo safety profile of mavrilimumab (Mv) and namilumab (Nm), two novel GM-CSF Fig 1: Forest plot demonstrating statistically significant overall greater likelihood of Any Adverse Event (AAE) in monoclonal antibodies. Mavrilimumab (Mv) and Namilumab (Nm) treated patients combined vs. placebo Methods • PubMed through Oct 2019: Various iterations of keyword and MeSH term searches including GM-CSF Placebo “GM-CSF”, “monoclonal antibodies”, and “rheumatoid arthritis” were performed. AAE Total AAE Total • Selected studies investigated specific GM-CSF monoclonal antibodies in RA patients receiving at least two doses of the study drug and reported on any adverse events (AAEs) in at least one patient over at least six weeks as a primary endpoint. • Secondary endpoints included individual adverse events (IAEs) for each agent. Results Favors GM-CSF Favors Placebo • Eight randomized clinical trials evaluating Mv and Nm GM-CSF monoclonal Fig 2: Forest plot demonstrating statistically significant overall greater likelihood of Any Adverse Event (AAE) in antibodies in 908 subjects were included. Mavrilimumab (Mv) treated patients vs. placebo • Treatment group: 649 subjects • Control group: 259 subjects Conclusions GM-CSF Placebo • Taken together, treatment of RA with GM-CSF monoclonal antibodies Mv and Nm AAE Total AAE Total showed higher risk for AAE without increased risk for serious IAEs. • Excluding an increased association with hypertension seen in Mv treated patients (moderate heterogeneity), IAEs were comparable across Mv or Nm treatment and placebo groups. • Mv and Nm GM-CSF monoclonal antibodies appear to be a safe emerging Favors GM-CSF Favors Placebo treatment option for RA patients not achieving remission or low disease activity Fig 3: Forest plot demonstrating statistically significant greater association with hypertension in Mavrilimumab (Mv) with alternate agents. treated patients vs. placebo.

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