First Author: M.Stahel SWITZERLAND
Co Author(s): P.P. Ciechanowski M. Becker S. Michels 0 0 0 0 0 0 0 0 0
Back to previous
Interleukin-1β (IL-1β) is a proinflammatory cytokine involved in the pathogenesis of diabetes. Clinical studies using IL-1 β inhibitors have shown improvement in glycemic control in subjects with type 2 diabetes and a reduction of humoral inflammatory parameters. Furthermore IL-1β was detected in the vitreous of PDR, while IL-1 receptor antagonists were lowered. This study assesses the influence of a systemic IL 1-β inhibition with Canakinumab, a monoclonal antibody selectively inhibiting IL-1β, on the course of PDR, diabetic macula edema (DME), as well as systemic parameters.
Prospective, open label single centre pilot study of 24 weeks duration
Systemic therapy with 150mg Canakinumab (Ilaris®) subcutaneous is administered every 8 weeks in 10 patients with non-high risk PDR. An interim analysis was planned after 5 patients. Primary endpoint is the change in retinal neovascularisation size (NVE or NVD) in fluorescein angiography (FA). The influence on DME, best corrected visual acuity (BCVA), HbA1c and systemic inflammatory parameters were assessed as secondary endpoints. If applicable both eyes were included.
The interim analysis of the first five patients showed a reduction of mean retinal neovascularisation size from 0.69mm2 at baseline to 0.53mm2 after 24 weeks. In eyes, which demonstrated DME involving the central foveal subfield at study entry, central foveal thickness (CFT) was reduced from 314µm at baseline to 260 µm at 24 weeks and central subfield foveal thickness (CSFT) from 331µm to 292µm, respectively. For all eyes mean BCVA remained stable with 79 ETDRS letters at baseline and 80 ETDRS letters at 24 weeks. Systemic inflammatory parameters changed during study follow-up as follows: HbA1c 8.12% to 7.56%, hsCRP 1.20mg/L to 1.18mg/L, leukocyte count 7.02 x 109/L to 7.15 x 109/L and TNFα 2.83pg/ml to 2.38pg/ml. Canakinumab was well tolerated with no related serious adverse event.
The first preliminary experience with Canakinumab showed stabilization or a tendency towards regression of retinal neovascularisations within 24 weeks. Most interestingly DME involving the fovea was reduced as shown by OCT and FA. These findings may provide some evidence for beneficial ocular and systemic effects. This could indicate a potential role of IL-1β inhibition as a long-term add-on or preventive treatment in PDR and DME. Further and larger randomized studies are necessary to prove this hypothesis.