Consider Intraocular Infliximab in Behçet's Disease Uveitis

BERLIN – A single intravitreal injection of infliximab is an effective treatment option in patients with Behçet’s disease who experience a sight-threatening acute uveitis attack but aren’t candidates for intravenous infliximab, Dr. Petros P. Sfikakis said at the annual European Congress of Rheumatology.

He presented the results of an uncontrolled pilot study involving 15 patients with Behçet’s disease who received a single intravitreal injection of infliximab (Remicade) at a dose of 1 mg in 0.05 mL on the day they experienced the onset of acute unilateral posterior uveitis.

In an earlier study, Dr. Sfikakis and his coworkers demonstrated that a single intravenous infusion of infliximab at a dose of 5 mg/kg was significantly more effective for rapid suppression of inflammation in the posterior eye segment than either high-dose intravenous methylprednisolone or intravitreal triamcinolone acetonide in Behçet’s disease patients experiencing sight-threatening attacks of acute uveitis (Rheumatology 2011;50:593-7). However, none of the participants in the new pilot study was eligible for systemic infliximab because of a history of cancer, heart failure, or latent tuberculosis.

In preclinical studies in rabbits, the investigators determined that a single intravitreal injection of 1 mg of infliximab resulted in therapeutic intraocular concentrations with essentially no systemic absorption, and that a 2-mg injection resulted in unacceptable complications.

Eleven of the 15 patients who received intravitreal infliximab were on systemic immunosuppressive therapy with various combinations of azathioprine, cyclosporine, and/or corticosteroids at the time. These background medications remained unchanged during 30 days of follow-up after intravitreal infliximab, noted Dr. Sfikakis, professor of internal medicine at Athens University and head of the rheumatology unit at the First Department of Propedeutic and Internal Medicine, Laikon University Hospital, also in Athens.

Best corrected visual acuity showed significant improvement by posttreatment day 7, and it continued to improve through day 30. Total ocular inflammation scores decreased from a baseline mean of 6.27 to 4.13 on day 7, 2.87 on day 14, and 1.13 on day 30. Indeed, by day 30 total inflammation scores of 0 had been achieved in 6 of 15 treated eyes.

In addition, profound reductions in anterior chamber cells and vitreous cells were documented. Central macular thickness decreased significantly by day 7 and continued to decrease through day 30. However, cystoid macular edema persisted through day 30 in 9 of 11 affected eyes. Retinal vasculitis was present at baseline in 10 of 15 eyes, but between days 14 and 30 it resolved in 9 of 10 cases.

Intravitreal infliximab was well tolerated by all patients, with no clinical ocular or extraocular side effects noted.

The intravitreal injection is a straightforward matter for ophthalmologists. However, Dr. Sfikakis stressed that in patients without a contraindication to systemic infliximab, the single 5-mg/kg intravenous infusion appears to be advantageous. It yielded significantly faster effects in the earlier published study than seen with intravitreal injection – and the more quickly suppression of inflammation in the posterior eye segment is achieved, the less likely are retinal scarring and damage to the optic disc.

For example, significant improvement in best corrected visual acuity was noted with intravenous infliximab on day 1 in 79% of eyes, compared with 20% with intravitreal injection. By day 7, 93% of patients treated with intravenous infliximab had achieved significant gains in best corrected visual acuity, compared with just one-third of participants in the intravitreal infliximab study. More importantly, cystoid macular edema had resolved by day 30 in all recipients of intravenous infliximab, but in only 2 of 11 affected patients who got an intravitreal injection.

Dr. Sfikakis reported having no relevant financial disclosures.

BERLIN – A single intravitreal injection of infliximab is an effective treatment option in patients with Behçet’s disease who experience a sight-threatening acute uveitis attack but aren’t candidates for intravenous infliximab, Dr. Petros P. Sfikakis said at the annual European Congress of Rheumatology.

He presented the results of an uncontrolled pilot study involving 15 patients with Behçet’s disease who received a single intravitreal injection of infliximab (Remicade) at a dose of 1 mg in 0.05 mL on the day they experienced the onset of acute unilateral posterior uveitis.

In an earlier study, Dr. Sfikakis and his coworkers demonstrated that a single intravenous infusion of infliximab at a dose of 5 mg/kg was significantly more effective for rapid suppression of inflammation in the posterior eye segment than either high-dose intravenous methylprednisolone or intravitreal triamcinolone acetonide in Behçet’s disease patients experiencing sight-threatening attacks of acute uveitis (Rheumatology 2011;50:593-7). However, none of the participants in the new pilot study was eligible for systemic infliximab because of a history of cancer, heart failure, or latent tuberculosis.

In preclinical studies in rabbits, the investigators determined that a single intravitreal injection of 1 mg of infliximab resulted in therapeutic intraocular concentrations with essentially no systemic absorption, and that a 2-mg injection resulted in unacceptable complications.

Eleven of the 15 patients who received intravitreal infliximab were on systemic immunosuppressive therapy with various combinations of azathioprine, cyclosporine, and/or corticosteroids at the time. These background medications remained unchanged during 30 days of follow-up after intravitreal infliximab, noted Dr. Sfikakis, professor of internal medicine at Athens University and head of the rheumatology unit at the First Department of Propedeutic and Internal Medicine, Laikon University Hospital, also in Athens.

Best corrected visual acuity showed significant improvement by posttreatment day 7, and it continued to improve through day 30. Total ocular inflammation scores decreased from a baseline mean of 6.27 to 4.13 on day 7, 2.87 on day 14, and 1.13 on day 30. Indeed, by day 30 total inflammation scores of 0 had been achieved in 6 of 15 treated eyes.

In addition, profound reductions in anterior chamber cells and vitreous cells were documented. Central macular thickness decreased significantly by day 7 and continued to decrease through day 30. However, cystoid macular edema persisted through day 30 in 9 of 11 affected eyes. Retinal vasculitis was present at baseline in 10 of 15 eyes, but between days 14 and 30 it resolved in 9 of 10 cases.

Intravitreal infliximab was well tolerated by all patients, with no clinical ocular or extraocular side effects noted.

The intravitreal injection is a straightforward matter for ophthalmologists. However, Dr. Sfikakis stressed that in patients without a contraindication to systemic infliximab, the single 5-mg/kg intravenous infusion appears to be advantageous. It yielded significantly faster effects in the earlier published study than seen with intravitreal injection – and the more quickly suppression of inflammation in the posterior eye segment is achieved, the less likely are retinal scarring and damage to the optic disc.

For example, significant improvement in best corrected visual acuity was noted with intravenous infliximab on day 1 in 79% of eyes, compared with 20% with intravitreal injection. By day 7, 93% of patients treated with intravenous infliximab had achieved significant gains in best corrected visual acuity, compared with just one-third of participants in the intravitreal infliximab study. More importantly, cystoid macular edema had resolved by day 30 in all recipients of intravenous infliximab, but in only 2 of 11 affected patients who got an intravitreal injection.

Dr. Sfikakis reported having no relevant financial disclosures.

BERLIN – A single intravitreal injection of infliximab is an effective treatment option in patients with Behçet’s disease who experience a sight-threatening acute uveitis attack but aren’t candidates for intravenous infliximab, Dr. Petros P. Sfikakis said at the annual European Congress of Rheumatology.

He presented the results of an uncontrolled pilot study involving 15 patients with Behçet’s disease who received a single intravitreal injection of infliximab (Remicade) at a dose of 1 mg in 0.05 mL on the day they experienced the onset of acute unilateral posterior uveitis.

In an earlier study, Dr. Sfikakis and his coworkers demonstrated that a single intravenous infusion of infliximab at a dose of 5 mg/kg was significantly more effective for rapid suppression of inflammation in the posterior eye segment than either high-dose intravenous methylprednisolone or intravitreal triamcinolone acetonide in Behçet’s disease patients experiencing sight-threatening attacks of acute uveitis (Rheumatology 2011;50:593-7). However, none of the participants in the new pilot study was eligible for systemic infliximab because of a history of cancer, heart failure, or latent tuberculosis.

In preclinical studies in rabbits, the investigators determined that a single intravitreal injection of 1 mg of infliximab resulted in therapeutic intraocular concentrations with essentially no systemic absorption, and that a 2-mg injection resulted in unacceptable complications.

Eleven of the 15 patients who received intravitreal infliximab were on systemic immunosuppressive therapy with various combinations of azathioprine, cyclosporine, and/or corticosteroids at the time. These background medications remained unchanged during 30 days of follow-up after intravitreal infliximab, noted Dr. Sfikakis, professor of internal medicine at Athens University and head of the rheumatology unit at the First Department of Propedeutic and Internal Medicine, Laikon University Hospital, also in Athens.

Best corrected visual acuity showed significant improvement by posttreatment day 7, and it continued to improve through day 30. Total ocular inflammation scores decreased from a baseline mean of 6.27 to 4.13 on day 7, 2.87 on day 14, and 1.13 on day 30. Indeed, by day 30 total inflammation scores of 0 had been achieved in 6 of 15 treated eyes.

In addition, profound reductions in anterior chamber cells and vitreous cells were documented. Central macular thickness decreased significantly by day 7 and continued to decrease through day 30. However, cystoid macular edema persisted through day 30 in 9 of 11 affected eyes. Retinal vasculitis was present at baseline in 10 of 15 eyes, but between days 14 and 30 it resolved in 9 of 10 cases.

Intravitreal infliximab was well tolerated by all patients, with no clinical ocular or extraocular side effects noted.

The intravitreal injection is a straightforward matter for ophthalmologists. However, Dr. Sfikakis stressed that in patients without a contraindication to systemic infliximab, the single 5-mg/kg intravenous infusion appears to be advantageous. It yielded significantly faster effects in the earlier published study than seen with intravitreal injection – and the more quickly suppression of inflammation in the posterior eye segment is achieved, the less likely are retinal scarring and damage to the optic disc.

For example, significant improvement in best corrected visual acuity was noted with intravenous infliximab on day 1 in 79% of eyes, compared with 20% with intravitreal injection. By day 7, 93% of patients treated with intravenous infliximab had achieved significant gains in best corrected visual acuity, compared with just one-third of participants in the intravitreal infliximab study. More importantly, cystoid macular edema had resolved by day 30 in all recipients of intravenous infliximab, but in only 2 of 11 affected patients who got an intravitreal injection.

Dr. Sfikakis reported having no relevant financial disclosures.