Golimumab in refractory uveitis related to spondyloarthritis. Multicenter study of 15 patients

Objective: To assess the efficacy of golimumab (GLM) in refractory uveitis associated to spondyloarthritis (SpA). Methods: Multicenter study of SpA-related uveitis refractory to at least one immunosuppressive drug. The main outcome variables were degree of anterior and posterior chamber inflammation, visual acuity, and macular thickness. Results: Fifteen patients (13 men/2 women; 18 affected eyes; mean age 39±6 years) were evaluated. The underlying SpA subtypes were ankylosing spondylitis (n=8), psoriatic arthritis (n=6) and non-radiographic axial SpA (n=1). The ocular involvement patterns were recurrent anterior uveitis in 8 patients and chronic anterior uveitis in 7. Before GLM they have received methotrexate (n=13), sulfasalazine (n=6), pulses of methylprednisolone (n=4), azathioprine (n=3), leflunomide (n=2) and cyclosporine (n=1). Ten of them had also been treated with TNF-? blockers; etanercept (n=7), adalimumab (n=7), infliximab (n=6), and certolizumab (n=1). GLM was given at the standard dose (50 mg/sc/monthly) as monotherapy (n=7) or in combination with conventional immunosuppressive drugs (n=8), mainly methotrexate. Most patients had rapid and progressive improvement of intraocular inflammation parameters. The median number of cells in the anterior chamber at 2 years (0 [0-0]) was significantly reduced compared to baseline findings (1 [0-3]); p=0.04). The mean best corrected visual acuity value also improved (0.84±0.3 at 2 years versus 0.62±0.3 at baseline; p=0.03). Only minor side effects were observed after a mean follow-up of 23±7 months. Conclusions: Our results indicate that GLM may be a useful therapeutic option in refractory SpA-related uveitis

Biocatalyzed vinyl laurate transesterification in natural deep eutectic solvents

Abstract: Purpose Natural deep eutectic solvents (NADES) represent a green alternative to conventional organic solvents as reaction medium, offering more benign properties. To efficiently design NADES for biocatalysis, a better understanding of their effect on these reactions is needed. We hypothesize that this effect can be described by separately considering (1) the solvent interactions with the substrates, (2) the solvent viscosities and (3) the enzyme stability in NADES. Methods We investigated the effect of substrate solvation and viscosity on the reaction rate; and the stability of the enzyme in NADES. To this end, we monitored the conversion over time of the transesterification of vinyl laurate with 1- butanol by the lipase enzyme Candida antarctica B in NADES of different compounds and molar ratios. Results The initial reaction rate is higher in most NADES ( varying between 1.14 and 15.07 mu mol min(-1) mg(-1)) than in the reference n-hexane (4.0 mu mol min(-1) mg(-1))), but no clear relationship between viscosity and initial reaction rate was found. The increased reaction rate is most likely related to the solvation of the substrate due to a change in the activation energy of the reaction or a change in the conformation of the substrate. The enzyme retained part of its activity after the first 2 h of reaction (on average 20 % of the substrate reacted in the 2-24 h period). Enzyme incubation in ethylene glycol-based NADES resulted in a reduced reaction rate ( 15.07 vs. 3.34 mu mol min(-1) mg(-1)), but this may also be due to slow dissolution of the substrate. Conclusions The effect of viscosity seems to be marginal next to the effect of solvation and possible enzyme-NADES interaction. The enzyme retains some of its activity during the 24-hour measurements, but the enzyme incubation experiments did not yield accurate, comparable values. [GRAPHICS]