Adalimumab specifically induces CD3+ CD4+ CD25high Foxp3+ CD127− T-regulatory cells and decreases vascular endothelial growth factor plasma levels in refractory immuno-mediated uveitis: a non-randomized pilot intervention study

Anti–tumor necrosis factor-α therapy in uveitis

“…19,76 In general, significant improvement in ocular inflammation is observed within 1 or 2 infusions of infliximab 99,132 and 2 injections of adalimumab. 18 In our experience, 2-3 months of anti-TNF-α therapy are usually sufficient to M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT assess the response to treatment. In patients who do not respond to maximal doses of anti-TNF-α therapy (e.g.…”

“…37 Interestingly, one prospective study found that adalimumab induces a reduction in plasma VEGF levels that correlates with clinical improvement. 18 Since VEGF plays a role in the pathogenesis of CME, 144 this inhibitory effect could explain the successful outcomes of adalimumab for uveitic macular edema in the largest prospective study evaluating this therapy in uveitis to date. 37 …”

“…16 In addition, treatment with TNF-α inhibitors has been associated with elevation of T-regulatory lymphocytes levels. 18,128 Diminished numbers and impaired function of T-regulatory cells are found in non-infectious uveitis, 151 active Behçet disease, 63 and Vogt-Koyanagi-Harada uveitis. 24 Indeed T-regulatory cells are considered an important part of the regulatory mechanisms that limit uveitis.…”

“…57,64 TNF-α blockade in uveitis patients leads to a reduction in serum VEGF levels. 18 This effect on VEGF levels by TNF-α blockers may explain successful outcomes when anti-TNF-α agents are used specifically to treat CME. 86 …”

“…For example, low M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT levels of T-regulatory lymphocytes have been associated with uveitis relapses, 24 whereas high levels of these cells are associated with the regression phase of uveitis. 18,128,134 The local (intraocular) use of these agents is not well studied. Whether this route of administration may be comparable or even co-adjuvant to systemic use of TNF-α inhibitors remains unclear.…”