Management of reactions
A patient with a grade 3 reaction who needs to continue using the culprit monoclonal antibody should be referred to an allergist for skin testing in an effort to identify an IgE-mediated reaction.
The timing of the referral for skin testing is important: The allergist wants to test roughly 4-6 weeks after the hypersensitivity reaction. Test too early and the results will be uninformative because the patient will still be anergic. On the other hand, after 7-8 weeks the patient will have lost the allergy. So there is a sweet spot.
If the patient is skin test positive – with the caveat that skin testing in this setting is not well validated – then the allergist will suggest desensitization, usually as an inpatient.
In contrast, infusion reactions can be handled in the rheumatologist’s infusion center. They are self-limited upon repeat exposure with premedication using antihistamines, NSAIDs, oral or injectable steroids, and perhaps montelukast (Singulair).
If a patient initially thought to have an infusion reaction continues to experience reactions even after the biologic is being delivered more slowly and under the protection of premedication, it’s time to consider the possibility that what’s really going on is a cytokine-release reaction or an IgE-mediated reaction. Diagnostic skin testing is in order.
For a skin test–negative patient with a suspected cytokine-release reaction, the allergist may propose a therapeutic challenge. This is reserved for patients who the allergist believe will not experience an immediate reaction, and unlike desensitization it’s not an intervention intended to induce drug tolerance. The challenge involves giving 10% of a full dose of the biologic, waiting in the allergist’s office for 30-60 minutes, then giving the other 90% of the medication, followed by an hour of in-office observation.
The solution to severe type IV delayed hypersensitivity reactions is strict medication avoidance, not desensitization, according to Dr. Postolova.
Top offending monoclonal antibodies
Infliximab and rituximab (Rituxan) are the most common culprits when it comes to immediate hypersensitivity reactions. About 10% of infliximab-treated patients develop these reactions. Although the reaction can occur with the first dose, the peak incidence is with the seventh infusion. Patients with anti-infliximab IgG antibodies are at 140%-300% increased risk; however, concomitant disease-modifying antirheumatic drug therapy lessens that risk.
Infusion reactions or cytokine-release reactions occur upon the first infusion of rituximab in about 25% of treated rheumatology patients and in a higher proportion of cancer patients. Most of these reactions are mild and don’t recur when the biologic is administered more slowly and with premedication. Severe recurrent reactions upon subsequent exposure are much more likely to be an IgE-mediated hypersensitivity reaction.
“Stop the medication, send the patient to your local allergist for skin testing, and they’ll use a desensitization protocol if rituximab is the best drug for your patient,” Dr. Postolova advised.
She reported having no financial conflicts regarding her presentation.