Infusion Reaction

Suggested Algorithm:

Mild Infusion Reaction	Moderate Infusion Reaction	Severe Infusion Reaction
Mild Transient Event Pruritis Flushing Myalgia Fever <38º C	Chest Tightness Urticaria Hypertension Fever <38º C	Bronchospasm Angioedema Hypotension
Slow Infusion Rate	Interrupt Infusion Urticaria --> PO 2nd Gen Antihistamine Fever --> PO Acetaminophen 500mg-1g	Immediately Stop Infusion Call for Help IM Epi 0.5mg (1:1000) Record Time: Repeat epi in 5min x 3 Supine position/ elevate legs
Resume Infusion Rate	Resume Infusion Graded Dose Challenge Starting at 10mL/h Increase to Max tolerated	O2, Face Mask IV Access 1L NS CPR prn

Secondary Prevention Protocol

Previous Mild Infusion Reaction	Previous Moderate Infusion Reaction	Previous Severe Infusion Reaction
	PO Prednisone 20mg TID 24hrs prior to the infusion Prior Urticaria? - PO 2nd Gen Antihistamine Prior Fever? PO acetaminophen 0.5-1g	Consider d/c Infliximab If no alternative: PO prednisone 50mg TID for 24hrs prior Experimental desensitization protocol (Allergy Consult)
Graded Dose challenge* Start at 10mL/h Increase to Max tolerated	Graded Dose challenge* Start at 10mL/h Increase to Max tolerated	Graded Dose challenge* Start at 10mL/h Increase to Max tolerated

Initial (*graded dose challenge) rate schedule^
Initial 15min "test dose"	10mL/h
Next 15min	20mL/h
Next 15min	40mL/h
Next 15min	80mL/h
Then, until infusion complete	150mL/h
Standard 2hr rate protocol
Initial 15min	40mL/h
Then, until infusion complete	150mL/h
Accelerated 1-h rate protocol
Initial 15min	100mL/h
Then, until infusion complete	300mL/h

^5mg/kg dose diluted in 250mL of NaCl 0.9%

Two classifications:

Immediate Infusion reactions

Reactions that develop during the course of the reaction or within 1-2hrs of the completion of the reaction
5-23% of IBD patients receiving Infliximab report immediate-type reactions
Most Common Sx:

Patients with Ab to infliximab have 2-fold increase risk of infusion reaction, 6-fold increase of serious reaction
Etiologies (proposed)

Cytokine -release syndrome
Anaphylaxis
IgG anaphylaxis (massive activation of neutrophils by monomeric or aggregated IgG and circulating immune complexes)
Complement activation
Degranulation

Severity scales have been proposed by NIH - borrowed from cancer therapy terminology

Late Infusion reactions

Reactions manifest >24hrs post infusion
1-3% of patients receiving infusion
Serum Sickness type reactions (Coombs-Gell type III reaction) - local and systemic inflammatory response caused by fixation and activation of coplement by antigen (IFX) antibody (ATI) immune complexes. Ag-Ab complex deposits in blood vessels, skin, and joint tissue
Increased risk:

Self -limited, Sx typically subside within days-wks (one single case of evolution to critical ARDS)

Biosimilars

Initial evidence (limited) suggests similar infusion reaction rates between Infliximaband Biosimilars

Primary Prevention Measures

"They make possible the administration of life-saving therapies to patients with a history of severe immediate infusion reactions. Experience with desensitisation to IFX is limited to case reports and small series studies. The reported rate of breakthrough reactions in these series reached 29%, remarkably similar to the reaction recrudescence rate observed without desensitisation. However, these reactions tended to be significantly milder and, in most cases, allowed for successful continuation of the infusion."
It involves graded administration of the offending drug, starting with extremely low doses [1:1000 and 1:100 dilutions], followed by slow, stepwise dose escalations, until the target dose is clinically tolerated.

References:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4558633/