Eltrombopag is an oral thrombopoietin–receptor agonist that is approved for the treatment of patients with chronic immune thrombocytopenia (ITP) and an insufficient response to prior therapy. Based on previous reports of cataract development/worsening in both eltrombopag-treated and placebo patients, the current analysis examined the occurrence and management of cataracts in eltrombopag-treated patients in the global, phase 3, open-label, long-term extension EXTEND study.

In the EXTEND study, adult patients with chronic ITP initiated eltrombopag at 50 mg/day, titrating to 25 to 75 mg/day or less often as required, based on a platelet count target range 50 to 200 × 109/L. The optimized eltrombopag dose may be maintained for >2 years after minimization of concomitant ITP medications, if any. Ocular exams in the study were performed by ophthalmologists/optometrists at enrollment and every 12 months during EXTEND.

The study population included 302 patients who received ≥1 eltrombopag doses; the median age was 50 years. The majority of patients were white (79%), female (67%), had platelet counts <30 × 109/L, and were not splenectomized. A total of 101 (33%) patients received concomitant ITP medications. The median duration of exposure to eltrombopag on the study was 2.4 years (range, 2 days-8.8 years); the mean daily dose was 50.2 mg.

At study enrollment, 192 of the 291 (66%) evaluable patients had ≥1 cataract risk factors, of which long-term corticosteroid use (142/291; 49%) was the most common risk factor recorded, followed by cigarette use, and/or diabetes mellitus. Prior to receiving eltrombopag, the presence of cataracts was recorded in 33 (11%) patients.

During EXTEND, 32 adverse events of cataracts were reported in 28 (9%) patients; of these, 12 had documented cataracts at enrollment. Per protocol, 16 of the 32 cataract events were considered serious adverse events. The majority of cataracts were of mild-to-moderate severity (grade 1, 16; grade 2, 9; grade 3, 5). The median time to cataract onset from first dose in EXTEND was 316 days (range, 43 days-5.6 years), occurring at a median age of 63 years (range, 25-79 years). Moreover, 22/28 (79%) patients with cataracts had ≥1 risk factors for cataracts, such as chronic steroid use (n = 17; 61%), diabetes mellitus (n = 6; 21%), history of intraocular surgery (n = 4; 14%), and cigarette use (n = 4; 14%).

Overall, 50% (16/32) of cataracts recorded during EXTEND were resolved; 9 were treated with surgery, and explanations were not listed for 7 others. In terms of eltrombopag treatment, 78% (25/32) of cataract incidences required no change in eltrombopag dose; 1 (3%) required dose interruption, and 4 patients withdrew from the study. A total of 15 cataracts were reported as related to incidence of cataract, 9 of which were resolved—5 with surgery, and 7 without a dose adjustment. Kaplan-Meier analysis showed that the probability of developing a cataract adverse event was <20% for the duration of the EXTEND study, with the likelihood of developing cataracts increasing with time.

Based on these study results, the authors concluded that the rate of cataract development during eltrombopag treatment was low and that there was no clear link between eltrombopag treatment and increased risk for cataract development/progression in patients with chronic ITP. However, screening and monitoring of patients for cataracts is advised prior to initiating and during eltrombopag treatment, particularly for patients with ≥1 risk factors.

Wong R, et al. ASH 2017. Abstract 1053.

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Last modified: December 28, 2017