Is medical necessity met for Ocrevus (ocrelizumab) 600 milligrams every 6 months for Relapsing-remitting multiple sclerosis?

Medical Necessity Determination for Ocrevus (Ocrelizumab) IV 600mg Every 6 Months

Medical necessity is NOT currently met for the requested Ocrevus IV 600mg every 6 months due to missing critical safety documentation required by FDA labeling and clinical policy, specifically: absence of documented hepatitis B screening, quantitative immunoglobulin levels, and unclear dosing protocol for the transition from subcutaneous to intravenous formulation. 1

Critical Missing Documentation

The FDA label for ocrelizumab explicitly requires the following before the first dose, which are not documented in the submitted records 1:

• Hepatitis B virus screening (both surface antigen and core antibody testing) - NOT DOCUMENTED
• Quantitative serum immunoglobulin screening - NOT DOCUMENTED
• Pre-medication protocol verification (methylprednisolone or equivalent corticosteroid plus antihistamine) - NOT DOCUMENTED

Dosing Protocol Concern

The most significant clinical question is whether this patient requires induction dosing (300mg + 300mg two weeks apart) or can proceed directly to maintenance dosing (600mg every 6 months). 1 The patient has been receiving Ocrevus Zunovo (subcutaneous ocrelizumab with hyaluronidase), which delivers 920mg subcutaneously every 6 months. 1 The clinical records indicate this appears to be "the first dose of Ocrevus" IV formulation, suggesting induction dosing may be appropriate, but this is not definitively clarified. 1

The FDA-approved intravenous ocrelizumab dosing for treatment-naive or switching patients is 1:

• Initial course: 300mg IV infusion, followed 2 weeks later by second 300mg IV infusion
• Subsequent doses: 600mg IV infusion every 6 months

Clinical Appropriateness of Formulation Switch

The switch from Ocrevus Zunovo (subcutaneous) to Ocrevus (intravenous) is clinically justified based on documented intolerance. 1 The medical records clearly state "Plan to switch to Ocrevus Infusions - patient did not handle Zunovo" and document worsening symptoms (headaches, fatigue, hand cramping) that began around the time of the subcutaneous Ocrevus infusion. 1

The subcutaneous formulation (Ocrevus Zunovo) has a 49% incidence of injection reactions, which can include systemic symptoms. 1 Switching to the intravenous formulation is a reasonable clinical response to formulation-specific adverse effects. 1

Underlying Disease Appropriateness

The diagnosis of relapsing-remitting multiple sclerosis (G35.A) is well-established and ocrelizumab is FDA-approved for this indication. 1 The patient's clinical history demonstrates 2:

• Diagnosis established in 2016 with demyelinating lesions on brain and spine MRI
• History of disease activity with gait instability and right foot drop
• Multifocal lesions in brain, cervical, and upper thoracic cord
• Worsening symptoms after discontinuing Tysabri and starting Ocrevus Zunovo

Ocrelizumab demonstrates significant efficacy in RRMS with 61% reduction in relapse rate and 40% reduction in disability progression compared to interferon beta-1a. 2, 3

Prior Authorization Criteria Analysis

MCG Criteria A-0977 requirements [@case summary@]:

• ✓ Age 18 years or older - MET (patient is adult)
• ✓ Relapsing-remitting multiple sclerosis - MET (diagnosis G35.A confirmed)
• ✗ No active hepatitis B infection - NOT DOCUMENTED
• ✗ No concurrent use of live vaccine - NOT DOCUMENTED
• ✗ No severe or active infection - NOT DOCUMENTED

Clinical Policy Bulletin 0264 requirements [@case summary@]:

• ✗ Hepatitis B screening before first dose - NOT DOCUMENTED
• ✗ Quantitative serum immunoglobulin screening - NOT DOCUMENTED
• ✗ Pre-medication protocol - NOT DOCUMENTED
• ? Appropriate dosing (induction vs maintenance) - UNCLEAR

Safety Monitoring Requirements

If approved, the following monitoring is mandatory per FDA labeling 1:

Before treatment initiation:

• Hepatitis B surface antigen and core antibody testing (active HBV is absolute contraindication)
• Quantitative IgG, IgA, and IgM levels (baseline for monitoring hypogammaglobulinemia)

Before each infusion:

• Pre-medication with corticosteroid and antihistamine at least 30 minutes prior
• Assessment for active infections (delay treatment if present)

During and after infusion:

• Monitor closely during all infusions
• At least 1 hour observation after initial infusion
• At least 15 minutes observation after subsequent infusions

Ongoing monitoring:

• Serial immunoglobulin levels (decreased IgG associated with increased serious infections) 1
• Clinical assessment for infections, particularly upper respiratory tract infections (40% incidence), lower respiratory tract infections (8% incidence), and herpes virus infections (6% incidence) 1
• MRI surveillance for disease activity monitoring 4, 5

Recommendation for Approval Pathway

To achieve medical necessity approval, the following must be documented:

1. Hepatitis B screening results (surface antigen and core antibody) showing no active infection 1
2. Baseline quantitative immunoglobulin levels (IgG, IgA, IgM) 1
3. Clarification of dosing protocol: Confirm whether patient requires induction dosing (300mg + 300mg) or can proceed to maintenance dosing (600mg), based on whether prior subcutaneous ocrelizumab provides adequate B-cell depletion equivalence 1
4. Pre-medication protocol confirmation for each infusion 1
5. Documentation of no active infections at time of planned infusion 1
6. Confirmation of no concurrent live vaccines 1

Once these requirements are documented, medical necessity would be met for a 3-month certification period (allowing for initial dose adjustment and safety monitoring), with subsequent 6-month certifications contingent on demonstrated tolerability and absence of serious infections or other contraindications. [@case summary@]