Low-dose Ranibizumab Effective for Retinopathy of Prematurity

Low-dose Ranibizumab Effective for Retinopathy of Prematurity

NEW YORK (Reuters Health) – Low doses of anti-VEGF therapy with ranibizumab are effective in infants with retinopathy of prematurity (ROP), according to results from the CARE-ROP study.

“The CARE-ROP results show that both ranibizumab doses (24% vs. 40% of the adult dose) were equally effective in treating ROP (94% vs. 93% success in per-protocol treated eyes),” Dr. Andreas Stahl from University of Freiburg, in Germany, told Reuters Health by email. “Systemic VEGF levels were not suppressed following ranibizumab treatment.”

Vascular endothelial growth factor (VEGF) is a main driver of ROP pathophysiology. The anti-VEGF bevacizumab halts progression of severe ROP but suppresses VEGF plasma levels for weeks, raising questions about potential adverse effects on organ development in infants.

Dr. Stahl and colleagues evaluated the efficacy and safety of two doses of intravitreal ranibizumab (0.12 mg and 0.20 mg) in a randomized, double-blind trial of 19 infants (38 eyes) with ROP. Sixteen infants completed the trial (three died of causes unrelated to treatment).

The proportion of infants without the need for rescue therapy through 24 weeks, the primary endpoint, was 88.9% (8/9) in the 0.12-mg group and 85.7% (6/7) in the 0.20-mg group, according to the January 8 JAMA Pediatrics online report.

No infant with gestational age greater than 25 weeks required rescue therapy.

At the final visit, 12 of 20 eyes (60.0%) in the 0.12-mg group and 10 of 18 eyes (55.6%) in the 0.20-mg group had no ROP, and all remaining eyes had ROP stage 1 in the anterior zone II or III.

Two eyes that required rescue therapy responded well and had fully resolved ROP at the final visit.

Two infants in each group (8 eyes total) had recurrences severe enough to warrant retreatment, and their outcomes at the end of the study were either no ROP or stage 1 ROP in anterior zone II or III.

Physiologic vascularization appeared to proceed faster and to reach complete vascularization more frequently in eyes receiving lower doses of ranibizumab.

Ranibizumab treatment did not reduce mean VEGF levels in either group.

“The CARE-ROP study identified ranibizumab as an effective anti-VEGF alternative to bevacizumab, the current standard anti-VEGF agent in ROP,” Dr. Stahl said. “While both anti-VEGF agents successfully suppress pathologic vascular growth in ROP eyes, ranibizumab does not suppress systemic VEGF levels, thus limiting unwanted effects on organs, like brain and lung, that are still undergoing development at the time of ROP treatment.”

“The follow-up study period of CARE-ROP is ongoing and comprises 1-, 2- and 5-year follow-up visits with standardized pediatric and ophthalmologic examinations,” he added.

Dr. Janice C. Law from Vanderbilt University Medical Center, Nashville, Tennessee, who recently reviewed the cases of seven infants with ROP treated with bevacizumab, told Reuters Health by email that it was “great to see that the lower dose was able to regress plus disease and retinopathy immediately. (This) shows us that our current level of dosing (1/2 the concentration of adult wet, age-related macular degeneration dose) is still more than the premature infants needs to regress plus disease.”

“It is definitely a wonderful adjunct for severe cases of posterior disease or in patients who do not dilate well for laser due to increased vascular activity,” she said. “Standard of care is still laser ablation. In posterior disease, I recommend continued use of anti-VEGF, but not as monotherapy. Laser should always follow anti-VEGF treatment due to the high reactivation and recurrence rate.”

Dr. Law added, “Systemic safety will always be a concern regardless of which anti-VEGF you use (bevacizumab or ranibizumab).”

SOURCE: http://bit.ly/2qBEHeG

JAMA Pediatr 2018.

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