Christina Ha, MD, on Immune-Mediated Events Related to Medications

“Let’s first talk about dermatological paradoxical reactions to anti-TNFs,” Dr Christina Ha said as she opened her presentation on “Immune-Mediated Events Related to Medications” during the AIBD regional meeting on September 11.

Dr Ha is a gastroenterologist with the IBD Center at Cedars-Sinai in Los Angeles, California.

“For this, we are really talking about paradoxical psoriasis. The prevalence reported across all indications for anti-TNF is report up to 29%, but for patients living with Crohn’s disease or ulcerative colitis, it’s about 2-10 % prevalence, depending on which studies you look at. And that translates to an incidence of about 5 per 100 patient-years,” Dr Ha explained.

She went on to explain how this incidence typically occurs within the first year of exposure (70% of cases), or second year (30% of cases). “There is no association with IBD location, activity, or behavior, and it typically presents as pustular, plaque, or eczema,” Dr Ha continued.

The physical exam sites of interest when examining paradoxical psoriasis associated with anti-TNFs are the scalp (looking for signs of alopecia), neck, behind the ears, palms and soles, nails, and trunk, she said.

“The key take-home points to remember about anti-TNF associated psoriasis, is that it is a class effect. And while some people may try to switch to a different anti-TNF, and that may be reasonable, it tends to reoccur with the second or third anti-TNF. It may develop days to years after anti-TNF initiation, and it does not parallel IBD activity,” Dr Ha explained.

“All phenotypes of psoriasis are possible, but palmar plantar is the most common. And even though it’s TNF-associated and a class effect, the majority of patients (60%) can continue anti-TNF with the addiction of adjuvant psoriasis therapy.”

Dr Ha presented a treatment algorithm for management, which calls for confirming the diagnosis; communicating with a dermatologist; smoking cessation by the patient; and the use of conventional treatments such as topical steroid, emollients, keratolytic therapy, vitamin D analogs, and phototherapy.

“Now let’s talk about anti-TNF associated lupus, and how it’s actually quite different from SLE,” Dr Ha continued. “The men-to-women-ratio in drug-induced lupus, or anti-TNF associated lupus, is more balanced, whereas in idiopathic SLE, it’s definitely female dominant,” she explained. Idiopathic SLE also presents a gradual symptom onset, while drug-induced lupus presents an abrupt symptom onset, and tends to have an older age of onset.

After discussing lupus-related events, Dr Ha moved onto infusion reactions associated with immunogenicity, and cited the PANTS Study, which was a prospective uncontrolled cohort study of 1610 patients focusing on infusion reaction to infliximab and adalimumab.

“So what are the different types of infusion reactions we need to aware of for our patients receiving infliximab? The first are the immediate infusion reactions —5%-23% of the time—1which can occur during the infusion, or 1 to 2 hours after” Dr Ha explained. “They tend to present with pruritus, flushing, dyspnea, and chest discomfort.” Late infusion reactions occur 1% to 3% of the time and can begin within 24 hours after the infusion, presenting with pruritic skin rashes, fever, malaise, arthralgias, and jaw pain.

To prevent  infusion reactions, Dr Ha referenced the gradual dose challenge protocol, showing a table of infliximab infusion protocols, followed by the consistent dosing: no “episodic dosing” strategies. “We know from the important SONIC study that adding a thiopurine to the infliximab not only decreases the number of infusion reactions per patient, from 17% down to 5% compared to monotherapy, but it also decreases the incidence per fusion from 4% down to 1%. What’s more controversial is the role of premedication to reduce the risk of reaction,” Dr Ha explained. She discussed how clinicians often give IV steroids to decrease immunogenicity, and antipyretics, and antihistamines, but they have no impact on infusion reaction prevention.

Managing immediate infusion reactions (IR) can be divided up into three sections, according to Dr Ha: mild IR, moderate IR, and severe IR.  Mild IR includes mild transient events, pruritus, flushing, myalgia, and a low fever. This leads to an attenuated infusion rate, antihistamines, and resumption of the infusion at an even slower rate. Moderate IR includes chest tightness, urticaria, hypertension and a low fever. This may lead to infusion interruption, managing symptoms, and resuming infusion with graded dose challenge.

“If there is a severe infusion reaction, such as bronchospasm, angioedema, and hypotension, you need to stop the infusion immediately, call for help, have your anaphylaxis kit available and inject the epinephrine, if needed, and continue protocols—check oxygen and be ready to administer CRP,” Dr Ha explained.

Dr Ha went on to discuss immunogenicity and combination therapies, patients at risk for antidrug antibodies, impact of dose escalation, impact of switching to a second anti-TNF, and the impact of switching out of class before wrapping up with an algorithm of managing anti-TNF treatment failure.

“So, let’s put this all together. What is our algorithm for managing anti-TNF? After you confirm active disease, you want to see, are their trough levels undetectable, or are their trough levels therapeutic? If their trough levels are therapeutic, you’re going to switch out of class. If their trough levels are undetectable, and they have high-titer antibodies, you’re going to want to switch to an alternative anti-TNF, but add an immunomodulator. It their antibodies are negative, you’re going to check adherence, optimize existing anti-TNF and increase dose vs shorten interval,” Dr Ha concluded.

—Angelique Platas

Reference

Ha, C. Immune-mediated events related to medications. Presented at: Advances in Inflammatory Bowel Diseases regional meeting. September 11, 2021. Virtual.