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Antibody testing, checking for isotypes IgG and IgE, is another way to risk-
stratify patients after an episode of infusion or injection site reaction. The presence
of IgG is associated with an increased risk of hypersensitivity reactions and
decreased effectiveness of the biologic agent [ 19 ]. Concomitant use of an immuno-
modulator such as methotrexate or thiopurine can decrease risk of antibody forma-
tion, decrease or eliminate preformed antibodies, decrease risk of infusion reactions,
and improve efficacy of the biologic agent [ 8 , 12 , 18 , 21 ].
Acute infusion reactions can recur in up to one third of subsequent infusions, so
secondary prophylaxis should be considered [ 18 ]. To minimize the risk of recur-
rence of hypersensitivity reactions during subsequent infusions, patients are
generally premedicated with a corticosteroid, antihistamine, and antipyretic (see
Table 14.1) [ 19 ]. Graded dose rechallenge with the drug is thought to be effective,
since a smaller test dose theoretically induces smaller quantity of cytokine release
correlating to milder reactions [ 18 ].

Table 14.1 Clinical presentation and management of infusion and injection reaction

Acute infusion/injection reactions Delayed infusion/injection reactions

Timing of onset Within first hours of dose 3–14 days

Clinical

presentation

Mild:

Fever, nausea, vomiting, wheal

formation, pruritus, erythema

Serum sickness-like syndrome:

fever, malaise, arthralgia, myalgia,

urticaria

Severe:

Fever, hypotension, bronchospasm,

dyspnea, urticaria, angioedema,

anaphylaxis

Management Mild:

For infusion reactions: temporary

interruption of the infusion or

decreasing infusion rate, acetaminophen

650 mg po, diphenhydramine 12.5–

25 mg po/IV, and/or

methylprednisolone 20–40 mg IV

Antihistamine and acetaminophen

For injection site reactions: cooling,

topical corticosteroid, rotation of

injection sites, analgesics

Severe:

Immediate discontinuation of the drug;

management of anaphylaxis with

maintenance of airway and

hemodynamics

Medrol Dosepak or short tapering

course of prednisone

Secondary

prophylaxis

Mild:

Acetaminophen 650 mg po,

diphenhydramine 25 mg po, and

methylprednisolone 40 mg IV or

prednisone 40 mg po the day prior and

day of infusion

Methylprednisolone 40 mg IV

before infusion or prednisone 40 mg

po the day prior and day of infusion

followed by a Medrol Dosepak after

infusion

Severe:

Change of therapy is recommended. If

no alternative, desensitization

14 Noninfectious and Nonmalignant Complications of Anti-TNF Therapy