Adverse events after intravitreal infliximab (Remicade).

PURPOSE: To determine the tolerability of intravitreal infliximab (Remicade) in patients with refractory diabetic macular edema or choroidal neovascularization secondary to age-related macular degeneration. METHODS: This is a prospective, interventional, noncomparative, open-label, 12-week pilot study of intravitreal infliximab in four patients who failed conventional therapies. Two had diabetic macular edema and two had choroidal neovascularization secondary to age-related macular degeneration. All patients received 0.5 mg/0.05 mL intravitreal infliximab and were eligible for a second injection at 6 weeks if reinjection criteria were met. Outcome measures were best-corrected visual acuity using standard Early Treatment Diabetic Retinopathy Study refraction, central retinal thickness on optical coherence tomography, fluorescein angiography, standard electroretinography, and microperimetry. Patients were evaluated at Days 0 and 1 and Weeks 2, 6, and 12. Six months after study completion, all patients were tested for human antimouse and human antichimeric antibodies. RESULTS: At Week 12, visual acuity scores had declined in three patients. All patients had persistence of cystoid macular edema on optical coherence tomography, although two had a decrease in central retinal thickness. Three patients had an overall worsened appearance on angiography. On the final electroretinography, all patients had a decrease in maximal combined responses, from 7% to 24% from baseline, which may have been within expected variability of electroretinography data. To photopic flicker stimulus, three patients had slower latency of response, and all had decreased amplitudes. All patients declined on microperimetry. The first patient entered in the study met the criteria for a second injection because of improved standard electroretinography and microperimetry at Week 6. However, 2 weeks after the second injection, he developed panuveitis. Two other patients, after one injection only, had evidence of inflammation (vitritis or panuveitis) on examination at Week 6. Three patients developed systemic antibodies against infliximab (human antichimeric antibodies). CONCLUSION: Low-dose intravitreal infliximab was not well tolerated in this small group of patients and was both immunogenic and probably retinotoxic.

Infliximab stability after reconstitution, dilution, and storage under refrigeration.

PURPOSE: The purpose of this study was to investigate the stability of reconstituted infliximab solutions and determine whether infliximab is suitable for compounding for potential intravitreal use. METHODS: Infliximab was reconstituted, and the solution was aliquoted and stored refrigerated. On each day of testing, an aliquot was serially diluted to concentrations ranging from 50,000 pg/mL to 69 pg/mL. Each dilution was assayed by microsphere immunoassay daily for 5 days and weekly for a total of 6 weeks. The outcome measure was median fluorescence intensity measured by dual laser flow analysis of fluorochrome-labeled secondary antibodies to infliximab bound to tumor necrosis factor-alpha-coated microspheres. RESULTS: There was an increasing median fluorescence intensity for increasing infliximab concentration in a sigmoidal dose-response curve with a variable slope that was equivalent for each time point. Each respective concentration of infliximab showed nearly equivalent median fluorescence intensity for every time point over the 6-week period. CONCLUSION: The authors found that the immunoreactivity of 2 different concentrations of infliximab stored at 4 degrees C over a 6-week period remained stable. Infliximab is suitable for compounding and could be a cost-effective intravitreal medication for use in clinical practice if further study supports its safety and efficacy.