Discussion
’ disease, neutropenia, retinal artery occlusion, PD, RA
NEUTROPENIA, UNILATERAL BLINDNESS, DISEASE, RECRUITMENT, RETINAL ARTERY OCCLUSION, REMISSION, GCA, INFLAMMATORY RESPONSE
This study was designed to evaluate the efficacy and safety of sarilumab in patients with GCA; however, it was prematurely terminated, resulting in low enrollment and a limited dataset for statistical analyses. Due to the decision to discontinue all patients from the study, the interpretation of the study results was severely impeded. The decision to prematurely terminate the study was not driven by any safety issues with the administration of sarilumab.In this study, both CRP and ESR were used as a part of inclusion criteria as these are the usual inflammatory markers that correlate with disease activity and are used in general clinical practice for the monitoring of patients’ disease activity. Further, higher historical cutoff values were used for these inflammatory markers (CRP > 25 mg/L or ESR ≥ 50 mm/h) as per the study protocol eligibility criteria, to ensure a greater likelihood that the patients enrolled in the study truly had active GCA. Similar CRP and ESR levels have been required in previous trials investigating other IL-6R inhibitors for including patients [In this study, almost half of the patients in the SAR200 + 26W and SAR150 + 26W taper groups achieved SR at week 52 and week 24, which was numerically higher than that observed in the placebo groups; CRP was included as a part of the definition for disease remission, along with its normalization value of < 10 mg/L, consistent with the GiACTA trial [Unlike the GiACTA study of TCZ [In this study, there was some suggestion of a GC-sparing effect of 200 mg sarilumab, as shown by the reduced cumulative GC dose in the SAR200 + 26W taper group, but this result was not consistently observed for the lower sarilumab dose (150 mg).A majority of patients in all treatment groups experienced TEAEs, with neutropenia more frequently reported in patients who received sarilumab, as expected due to the known PD effect of IL-6R inhibition on neutrophil counts. One patient had SAEs of retinal artery occlusion and unilateral blindness, which were deemed by the investigator to be unrelated to the study drug. Overall, sarilumab was tolerable with a safety profile consistent with the previous studies in RA [Although the CRP levels varied among the study groups, they were maintained at < 10 mg/L in the sarilumab groups and were lower than those observed in the placebo groups. This aligns with the previously published data of sarilumab in patients with RA, and attributes to the blockade of IL-6 signaling pathway and subsequent inhibition of the inflammatory response by sarilumab [The main limitation of the study was its small sample size due to the early termination of the study with protracted recruitment timelines, exacerbated by the COVID-19 pandemic.