Is the current treatment plan of Renflexis (Infliximab-abda) 5 mg/kg IV every 7 weeks medically necessary and considered standard of care for a patient with a history of Crohn's disease of the small intestine, weighing 78.5 kg?

Is Renflexis 5 mg/kg IV Every 7 Weeks Medically Necessary and Standard of Care for Crohn's Disease?

The proposed dosing regimen of Renflexis 5 mg/kg IV every 7 weeks does not align with FDA-approved labeling or current evidence-based guidelines and should not be approved as written; the standard maintenance dosing is 5 mg/kg every 8 weeks. 1

FDA-Approved Dosing and Standard of Care

The FDA-approved maintenance regimen for Renflexis (infliximab-abda) in Crohn's disease is explicitly 5 mg/kg every 8 weeks, not every 7 weeks. 1

• The FDA label for Renflexis states: "The recommended dose of RENFLEXIS is 5 mg/kg given as an intravenous induction regimen at 0,2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks thereafter for the treatment of adults with moderately to severely active Crohn's disease." 1

• For patients who lose response, the FDA label allows consideration of dose escalation to 10 mg/kg (not shortening the interval to every 7 weeks). 1

Guideline-Based Recommendations

The most recent 2024 ECCO guidelines strongly recommend infliximab at 5 mg/kg every 8 weeks as maintenance therapy for moderate-to-severe Crohn's disease, with no support for every 7-week dosing. 2

• The 2024 ECCO guidelines provide a strong recommendation (100% consensus) for infliximab maintenance therapy in moderate-to-severe Crohn's disease at the standard every 8-week interval. 2

• The 2019 British Society of Gastroenterology guidelines similarly recommend the standard every 8-week maintenance dosing. 2

• When patients experience suboptimal response, guidelines recommend dose escalation (increasing from 5 mg/kg to 10 mg/kg) rather than interval shortening. 2

Therapeutic Drug Monitoring as the Appropriate Alternative

If the patient is experiencing inadequate disease control on standard dosing, therapeutic drug monitoring should guide optimization rather than arbitrary interval shortening. 2, 3

• The British Society of Gastroenterology recommends targeting trough infliximab levels of 3-7 μg/mL, with dose optimization based on measured drug levels and antibody status. 2

• The 2020 ECCO guidelines note that the TAXIT trial demonstrated that proactive therapeutic drug monitoring with dose optimization to achieve target trough levels (3-7 μg/mL) resulted in fewer relapses compared to clinically-based dosing alone. 2

• If drug levels are suboptimal (<3 μg/mL), the appropriate response is dose intensification to 10 mg/kg every 8 weeks, not shortening the interval to every 7 weeks. 2, 3

Medical Necessity of Continued Infliximab Therapy

Infliximab therapy itself is medically necessary and standard of care for this patient with Crohn's disease of the small intestine, but the dosing frequency must align with evidence-based recommendations. 2

• The 2024 ECCO guidelines provide strong recommendations (moderate-quality evidence, 100% consensus) for infliximab as both induction and maintenance therapy in moderate-to-severe Crohn's disease. 2

• Continuation of effective anti-TNF therapy is essential to prevent disease relapse, antibody formation, and potential loss of response. 3

Common Pitfalls and How to Avoid Them

The key pitfall here is confusing dose optimization strategies: shortening intervals below the evidence-based standard is not supported and may increase immunogenicity risk. 4

• Non-standard dosing intervals that deviate from FDA labeling and guideline recommendations may increase the risk of immunogenicity and loss of response. 4, 5

• The correct approach for inadequate response is: (1) measure trough drug levels and antibodies, (2) if levels are low without antibodies, increase dose to 10 mg/kg every 8 weeks, (3) if antibodies are present, consider switching to a different anti-TNF or different class. 2, 3

Recommendation for This Case

The treatment plan should be modified to either:

1. Continue 5 mg/kg every 8 weeks if the patient is in remission (at 78.5 kg, this equals approximately 392.5 mg per dose). 1

2. Escalate to 10 mg/kg every 8 weeks if there is documented suboptimal response or inadequate drug levels (at 78.5 kg, this equals approximately 785 mg per dose). 1

3. Obtain therapeutic drug monitoring (trough infliximab level and antibodies) to guide the decision if clinical response is uncertain. 2, 3

The every 7-week interval is not supported by FDA labeling, current guidelines, or clinical trial evidence and represents a deviation from standard of care that should not be approved without compelling documentation of therapeutic drug monitoring demonstrating rapid drug clearance necessitating this specific interval. 1, 2