Pegaptanib

Observational studies

Adverse reactions to intravitreal injection of pegaptanib (0.3, 1, or 3 mg every 6 weeks) over 2 years have been reported in 1190 patients who took part in two concurrent, prospective, randomized, multicenter, double-masked, sham-controlled studies [ ]. The major adverse events in year 1 were: endophthalmitis (0.16% per injection), traumatic cataracts (0.07%), and retinal detachment (0.08%). In year 1 there was no difference in serious thromboembolic adverse events, vascular hypertensive disorders, or serious hemorrhagic adverse events between 892 patients who received pegaptanib and 298 who received sham treatment. There was no increase in the numbers of deaths.

Pegaptanib has been investigated in a combined study, including open administration in 37 patients, who were given 3 mg in 0.09 ml, and a randomized, double-masked, uncontrolled, multicenter study in 110 patients, who were given 1 or 3 mg in 0.09 ml [ ]. The dose of pegaptanib was three or ten times higher than the normal dose and was given every 6 weeks for 54 weeks. The mean number of injections was 9.6. No patients were lost to follow-up. Although there were urine abnormalities (proteinuria, hematuria, or altered albumin-to-creatinine ratio), these normalized after 60 weeks, or had not changed after 60 weeks, or were attributed to a disease. There were no important changes in hematological parameters, liver function, renal function, or electrolytes. There were no important changes from mean or median baseline measurements in vital signs, including BP, and no changes in electrocardiography. All but two patients had at least one adverse event and 28 of 147 (19%) had serious adverse events, most often cardiac disorders. No patient withdrew because of adverse events, and there were no differences between the groups in overall adverse event rates. Non-ocular adverse events were uncommon and there was no evidence of systemic toxicity. Five patients died before week 60 and within 60 days of the previous dose, but no deaths were considered to be related to the study treatment. There were ocular adverse events in the study eye in 138 of 147 patients (94%); most were mild to moderate in intensity. Only one ocular adverse event was reported as serious (moderate retinal hemorrhage); it was reported on day 245 and was considered to be unrelated to the treatment. There were no cases of endophthalmitis, retinal detachment, or traumatic cataract. The most common ocular adverse events were eye pain (69/147; 47%), vitreous floaters (63/147; 43%), punctate keratitis (60/147; 41%), visual disturbances (37/147; 25%), eye irritation (33/147; 22%), and increased intraocular pressure (31/147; 21%); 11 patients (7%) had mild anterior chamber inflammation. Most events occurred with similar frequencies across the treatment groups, but the incidence of increased intraocular pressure was greater with pegaptanib 3 mg. Most of the ocular adverse events were attributed by the investigators to the injection procedure, and few were attributed to the study drug. As expected, the incidence of ocular adverse events in the fellow eye was much lower than that in the study eye (35% versus 94%). Fluorescein angiography showed no retinal vascular or choroidal abnormalities in the study eye that were not expected during the natural progression of neovascular age-related macular degeneration. There were no notable delays in arteriovenous transit time, abnormalities in choroidal perfusion, or arteriolar occlusions.