Is the treatment plan of continuing Vyvgart (Efgartigimod Alfa-fcab) injections weekly and decreasing Azathioprine dosage medically necessary and considered standard of care for a patient with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)?

Medical Necessity and Standard of Care Assessment for Vyvgart in CIDP

Direct Recommendation

Vyvgart (efgartigimod alfa-fcab) is FDA-approved and represents standard of care for CIDP, making this treatment plan medically necessary for a patient who has failed steroids and IVIG. 1 The continuation of weekly Vyvgart injections with gradual azathioprine reduction is appropriate given the documented clinical improvement.

FDA Approval Status and Standard of Care

Vyvgart is FDA-approved specifically for CIDP treatment, not experimental or investigational. 1

• The FDA approved efgartigimod (Vyvgart-Hytrulo) in 2024 for treatment of adult patients with CIDP based on the phase II ADHERE study. 1, 2
• For CIDP, the FDA-approved dosing is weekly subcutaneous injections (1,000 mg efgartigimod alfa with 10,000 units hyaluronidase) administered continuously, not in cycles like myasthenia gravis. 1
• This differs from the cyclic dosing used in myasthenia gravis (4-week cycles with breaks between), making continuous weekly administration the standard approach for CIDP. 1

Medical Necessity Justification

The treatment plan meets medical necessity criteria based on documented treatment failure with first-line therapies and subsequent clinical response to Vyvgart. 3

• CIDP patients who fail to respond to corticosteroids and IVIG represent approximately one-third of patients and require alternative immunotherapy. 3
• The patient's documented improvements (better balance, ability to perform daily activities, reduced paresthesias) demonstrate objective clinical benefit, which is the primary criterion for continuing therapy. 2
• In the pivotal ADHERE trial, 66% of CIDP patients achieved confirmed evidence of clinical improvement with efgartigimod, and continuing treatment reduced relapse risk by 61% compared to placebo (hazard ratio 0.39,95% CI 0.25-0.61, p<0.0001). 2

Azathioprine Tapering Strategy

Gradual reduction of azathioprine while maintaining Vyvgart is clinically appropriate, though complete withdrawal should be approached cautiously. 4, 5

• Azathioprine dosing guidelines recommend 1-3 mg/kg daily for inflammatory conditions, with dose adjustments based on clinical response. 4
• When tapering immunosuppressants in inflammatory diseases, monitoring should occur weekly during dose changes, then reduce to minimum once every 3 months at stable doses. 4, 5
• Laboratory monitoring must include complete blood count and liver function tests to detect azathioprine-related toxicity (myelosuppression, hepatotoxicity). 4, 5
• Evidence from inflammatory bowel disease suggests that complete withdrawal of azathioprine monotherapy increases relapse risk (32% relapse with withdrawal vs 14% with continuation), though this may not directly translate to CIDP patients on combination therapy. 6

Critical Safety Considerations for This Treatment Plan

Real-world transition from IVIG to efgartigimod requires careful monitoring, as severe relapses have been reported during this transition period. 7

• A 2025 case series reported that 4 of 9 patients experienced severe CIDP relapse after transitioning from IVIG to efgartigimod, with 5 others showing no improvement. 7
• The pivotal ADHERE trial did not study direct transition from IVIG to efgartigimod; instead, patients were withdrawn from IVIG to confirm active disease before starting efgartigimod. 7, 2
• Monitor closely for clinical deterioration during the first 12 weeks, using validated scales: INCAT disability scale, grip strength measurements, and MRC sum scores. 2, 8
• If deterioration occurs, consider reintroducing IVIG or increasing azathioprine dose rather than immediately discontinuing Vyvgart. 7

Monitoring Requirements for Continued Treatment

Comprehensive monitoring is essential to justify ongoing medical necessity and detect complications early. 4, 1

• Assess for infections before each Vyvgart administration, as the drug causes transient IgG reduction and delays treatment if active infection present. 1
• Monitor for hypersensitivity reactions (anaphylaxis, angioedema, dyspnea, rash, urticaria) for at least 30 minutes after each injection. 1
• Track serum IgG levels periodically, as efgartigimod reduces total IgG by approximately 43% on average. 8
• Continue azathioprine monitoring with CBC and LFTs at minimum every 3 months once stable dose achieved. 4, 5
• Evaluate vaccination status before each new treatment period, as live vaccines are contraindicated during Vyvgart therapy due to IgG reduction. 1

Treatment Duration and Reassessment

Unlike myasthenia gravis where efgartigimod is given in cycles, CIDP requires continuous weekly administration without planned breaks. 1

• The FDA label specifies continuous weekly injections for CIDP, not the 4-week cycles used in myasthenia gravis. 1
• Clinical effectiveness should be reassessed every 8-12 weeks using objective measures (INCAT scores, grip strength, functional assessments). 2, 8
• If clinical benefit plateaus or deterioration occurs despite treatment, consider alternative immunotherapies or reintroduction of IVIG. 7, 3

Common Pitfalls to Avoid

Several critical errors can compromise treatment success or patient safety:

• Do not abruptly discontinue azathioprine without close monitoring, as rebound inflammation may occur even with Vyvgart coverage. 6
• Do not assume Vyvgart will work for all CIDP patients; real-world data shows variable response rates, with some patients experiencing severe relapse. 7
• Do not administer live vaccines during Vyvgart therapy due to transient immunoglobulin reduction. 1
• Do not ignore injection site reactions (occurring in ≥15% of patients), as severe reactions may require treatment modification. 1
• Do not delay treatment for active infections; Vyvgart should be withheld until infection resolves. 1