Is treatment with Pavblu (aflibercept) 2mg intravitreally every 4 weeks for 3 visits medically necessary for a patient with Type 2 Diabetes and Bilateral Proliferative Diabetic Retinopathy without Macular Edema?

Medical Necessity Assessment: Pavblu for Proliferative Diabetic Retinopathy Without Macular Edema

The proposed treatment plan of Pavblu 2mg every 4 weeks for only 3 visits is NOT medically necessary or appropriate for this patient, as it deviates from the FDA-approved and evidence-based dosing regimen for diabetic retinopathy without macular edema, which requires 5 initial monthly injections followed by maintenance dosing every 8 weeks.

Critical Dosing Discrepancy

The treatment plan proposes only 3 injections, but the FDA-approved dosing for Pavblu (aflibercept-ayyh) in diabetic retinopathy specifically requires:

• Initial phase: 2mg every 4 weeks for 5 injections (not 3)
• Maintenance phase: 2mg every 8 weeks thereafter 1

This patient meets CPB criteria for the indication (proliferative diabetic retinopathy), but the proposed dosing of only 3 injections represents premature discontinuation before completing the evidence-based loading phase.

Why 5 Loading Doses Are Required

The standard protocol mandates 4-6 initial injections at 4-week intervals before considering any treatment modification. 1

• Clinical evidence demonstrates that 17% of patients who do not achieve success after 4 injections will achieve success after a 5th injection, and 15% of those not responding after 5 injections will respond after a 6th injection 1
• Pharmacokinetic data shows anti-VEGF agents are unlikely to maintain therapeutic concentration beyond 28 days, necessitating monthly dosing during the initial treatment phase 1
• Stopping at 3 injections risks inadequate disease control and potential progression to vision-threatening complications 1

Clinical Context Supporting Treatment Need

This patient has regressing but still active proliferative diabetic retinopathy with:

• Bilateral panretinal photocoagulation scarring (indicating prior advanced disease) [@clinical documentation@]
• Regressed neovascularization elsewhere in the left eye [@clinical documentation@]
• Vitreomacular adhesion with traction in the right eye [@clinical documentation@]
• No macular edema present bilaterally [@clinical documentation@]

Anti-VEGF therapy is appropriate for proliferative diabetic retinopathy even without macular edema, as it causes regression of intraocular neovascularization and reduces the risk of vision-threatening complications 2, 3.

Evidence for Anti-VEGF in PDR Without DME

• Randomized trials comparing aflibercept to panretinal photocoagulation have demonstrated that VEGF inhibitors effectively cause regression of intraocular neovascularization in proliferative diabetic retinopathy 2
• The Protocol W trial showed that aflibercept reduces development of vision-threatening complications from diabetic retinopathy, with a 4-year cumulative probability of developing PDR or CI-DME with vision loss of 33.9% with aflibercept versus 56.9% with sham (P < .001) 3
• However, these benefits require consistent, protocol-adherent dosing 2

Critical Safety Concern: Treatment Adherence

A major concern with anti-VEGF monotherapy for PDR is treatment adherence. 2

• Patients with proliferative diabetic retinopathy treated solely with anti-VEGF drugs who interrupt treatment are at high risk of developing irreversible blindness 2
• This patient already has panretinal photocoagulation in place, which provides a safety net if anti-VEGF therapy is interrupted 2
• The combination of prior PRP plus anti-VEGF may be the optimal treatment approach for PDR 2

What Should Be Approved Instead

The medically necessary and appropriate treatment plan should be:

1. Pavblu 2mg intravitreally every 4 weeks for 5 injections (months 0,1,2,3,4) 1
2. Followed by maintenance dosing of 2mg every 8 weeks 1
3. With ongoing monitoring via OCT and fundus photography to assess disease activity 4

After completing the initial 5 loading doses, treatment intervals can be adjusted based on disease stability, but stopping at 3 injections represents inadequate initial therapy.

Common Pitfalls to Avoid

• Do not approve abbreviated loading regimens (fewer than 5 injections) for diabetic retinopathy, as this increases risk of treatment failure 1
• Do not confuse dosing protocols between different indications (DME vs. DR vs. AMD) - each has specific evidence-based regimens 1, 5
• Do not assume that "regressing" disease means treatment can be abbreviated - the regression may be due to prior PRP, and anti-VEGF is being added to further stabilize disease 2

Medical Necessity Determination

Question 1: Is the treatment plan medically necessary?

Yes, anti-VEGF treatment is medically necessary for this patient with active proliferative diabetic retinopathy, but NOT in the proposed dosing of only 3 injections. The medically necessary plan requires 5 initial monthly injections followed by every-8-week maintenance dosing 1.

Question 2: Is the treatment plan standard of care?

No, the proposed 3-injection regimen is NOT standard of care. The standard of care for diabetic retinopathy treatment with aflibercept requires 5 initial monthly doses followed by every-8-week maintenance 1, 5. Stopping at 3 injections represents a deviation from FDA-approved dosing and evidence-based protocols that could compromise patient outcomes.