What are the dosing, contraindications, monitoring requirements, and alternative therapies for Renflexis (infliximab biosimilar)?

Renflexis (Infliximab-abda Biosimilar)

Renflexis is a biosimilar to infliximab (Remicade) that can be used interchangeably with the originator product for all approved indications, with standard dosing of 5 mg/kg IV at weeks 0,2, and 6 for induction, followed by maintenance every 8 weeks.

Dosing

Standard Induction and Maintenance:

• Induction: 5 mg/kg IV at weeks 0,2, and 6 1
• Maintenance: 5 mg/kg IV every 8 weeks 1
• Dose escalation: Up to 10 mg/kg and/or intervals shortened to every 4 weeks may be required for loss of response or low drug levels 1
• Dose reduction: Consider reducing when trough levels exceed 8-10 μg/mL and remission is achieved 1

The infusion should be administered over 2-3 hours 2. Biosimilar infliximab products like Renflexis demonstrate equivalent efficacy to the originator across all approved indications 3, 4.

Approved Indications

Renflexis is approved for the same indications as originator infliximab, including:

• Crohn's disease (adult and pediatric)
• Ulcerative colitis
• Rheumatoid arthritis (in combination with methotrexate)
• Ankylosing spondylitis
• Psoriatic arthritis
• Plaque psoriasis 2

Contraindications

Absolute contraindications:

• Sepsis or active serious infections 2
• Doses >5 mg/kg in patients with New York Heart Association functional class III or IV congestive heart failure 2
• Hypersensitivity to infliximab or murine proteins 5

Relative contraindications/precautions:

• History of tuberculosis or positive TB screening
• Demyelinating disease or multiple sclerosis
• History of malignancy (particularly lymphoma)
• Hepatitis B infection 2, 5

Monitoring Requirements

Pre-treatment (mandatory):

• Tuberculosis screening: PPD skin test and/or interferon-gamma release assay, plus chest radiograph 1, 2
• Hepatitis B and C screening 3
• Complete blood count (CBC)
• Liver function tests (LFTs)
• Consider hepatitis profile 2

Ongoing monitoring:

• Periodic history and physical examination
• Consider annual PPD testing 2
• Periodic CBC and LFTs 2
• Therapeutic drug monitoring: Measure serum trough levels and anti-drug antibodies in cases of partial response or loss of response to guide optimization decisions 1
• Target trough levels: >1 μg/mL for therapeutic effect 6

During infusion:

• Monitor for infusion reactions (occur in up to 20% of patients) 5
• Routine vital sign monitoring is not valuable for predicting acute infusion reactions and should only be performed if a reaction occurs 7

Combination Therapy Considerations

With immunomodulators:

• Combination therapy with azathioprine or methotrexate reduces antibody formation and improves efficacy compared to monotherapy 1, 8
• For TNF antagonists in ulcerative colitis, combination with immunomodulators is suggested over monotherapy 3
• The benefit of combination therapy must be weighed against increased lymphoma risk with thiopurines on an individual basis 1
• Pre-medication with acetaminophen, corticosteroids, or antihistamines is not routinely indicated 1

Management of Infusion Reactions

Mild to moderate reactions:

• Slow or temporarily interrupt infusion until symptoms resolve
• Administer symptomatic treatment: antihistamines, hydrocortisone, acetaminophen 5

Severe reactions:

• Discontinue infliximab permanently
• Does not necessarily preclude treatment with other anti-TNF agents 5

Alternative Therapies

For inflammatory bowel disease (moderate-to-severe UC/CD):

Higher efficacy options:

• Vedolizumab
• Upadacitinib
• Ozanimod
• Etrasimod
• Risankizumab
• Guselkumab 3

Intermediate efficacy options:

• Adalimumab
• Golimumab
• Ustekinumab
• Tofacitinib
• Filgotinib
• Mirikizumab 3

For rheumatoid arthritis:

• Etanercept (38-54% clear/nearly clear at 12 weeks with 25-50 mg twice weekly) 5
• Other TNF antagonists
• JAK inhibitors
• IL-6 inhibitors

For psoriasis:

• Etanercept (38-54% clear/nearly clear at 12 weeks) 5
• Other biologics targeting IL-17, IL-23
• JAK inhibitors

Important Safety Considerations

Serious infections:

• Tuberculosis risk is approximately 6 times higher than untreated patients with infliximab 5
• Opportunistic infections can occur
• Active disease control with effective therapy reduces overall infection risk 3

Malignancy:

• Rare cases of lymphoma, including hepatosplenic T-cell lymphoma (particularly in pediatric patients on combination therapy) 2
• Consider individual cancer risk when selecting therapy 3

Other rare adverse effects:

• Drug-induced lupus (without renal or CNS involvement)
• Cytopenia
• Demyelinating disease/MS exacerbation
• New onset or exacerbation of congestive heart failure 2

Switching and Interchangeability

Biosimilar switching:

• Single switch (originator to Renflexis) and multiple switches (originator to another biosimilar to Renflexis) show equivalent efficacy and safety 4, 9, 10
• No increased risk of loss of response or immunogenicity with switching 4, 9
• Switching between biosimilars results in significant cost savings (40% relative cost reduction for inpatient care, 53-62% price reduction per infusion) 11, 12, 13

Switching between anti-TNF agents:

• May be considered in patients intolerant or who lost response to one agent
• Response rates are lower than in anti-TNF naïve patients 1

Pregnancy Category

Pregnancy Category B 2

Common Pitfalls to Avoid

1. Do not delay TB screening - this is mandatory before initiating therapy 1
2. Do not use intermittent "as-needed" dosing - scheduled maintenance therapy reduces antibody formation and maintains efficacy better than episodic treatment 5
3. Do not continue therapy without response - evaluate efficacy after the second or third dose and discontinue if no significant response (primary treatment failure) 1
4. Do not ignore low drug levels - measure trough levels and anti-drug antibodies when response is inadequate to guide optimization 1
5. Do not assume biosimilars are inferior - Renflexis demonstrates equivalent efficacy and safety to originator infliximab across all indications 3, 4, 9