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Patients with allergies to nonsteroidal anti-inflammatory drugs (NSAIDs) could be at an increased risk for opioid use disorder, a researcher reported.

In a cohort of patients with osteoarthritis in a large hospital system in Massachusetts, those with NSAID allergies had a significantly higher risk of receiving a future diagnosis of opioid use disorder compared with patients without allergies after adjusting for demographic characteristics, insurance, and comorbidities (adjusted odds ratio 1.53, 95% CI 1.03-2.25, P=0.03), reported Lily Li, MD, of Brigham and Women's Hospital in Boston.

Between 2013-2018, patients with allergies were also significantly more likely to be prescribed opioids (OR 1.23, 95% CI 1.05-1.46, P=0.01), but less likely to be prescribed celecoxib (Celebrex, OR 0.77, 95% CI 0.6-0.9), she said at American College of Allergy, Asthma & Immunology virtual meeting.

Overall, the most common NSAIDs implicated in reactions were aspirin (25.6%), ibuprofen (12.6%), and naproxen (11.5%), whereas celecoxib accounted for just 5.7% of reactions, she noted.

"While celecoxib is considered an NSAID, due to its selectivity as a COX-2 inhibitor there is little cross-reactivity with other nonselective NSAIDs," Li said during her presentation. "It can almost always be used safely, even for patients with confirmed allergic hypersensitivity to nonselective NSAIDs."

Adverse drug reactions induced by NSAIDs -- such as gastrointestinal upset, bleeding, or headaches -- are often mistaken as a drug allergy. However, only about 20% of these reports are estimated to be true allergic hypersensitivity reactions, like cutaneous or respiratory reactions, urticaria, or anaphylaxis, Li said.

"While these types of reactions are sometimes classified as allergies by patients, they don't necessarily warrant absolute NSAID avoidance such that if a patient had a specific need for an NSAID, they may still use these medications with appropriate monitoring," Li said.

In the study, only 35% of drug interactions represented true allergic hypersensitivity reactions, most commonly rash (10.8%), angioedema (8%), and hives (9.4%), Li reported. Drug side effects made up 40.4% of adverse reactions, most commonly gastrointestinal upset (27.2%).

About a quarter of reactions were unknown, and "The high percentage of unknown or other reactions also highlights the challenges of evaluating and caring for patients with unclear reaction histories," Li said.

Overall, the proportion of patients with osteoarthritis who reported NSAID allergies was high at 9.2%, Li said. There were more women, fewer white patients, and more Black and Hispanic patients in the group of patients with allergies than the control group without allergies, Li noted.

The allergic group also had more atopic and non-atopic comorbidities versus the control group, including depression, asthma, and cardiovascular disease.

Using the same dataset, Li and colleagues have also found were at an increased risk of opioid use disorder, an increased risk of being prescribed opioids, and a lower risk of being prescribed celecoxib.

Together, the findings suggest allergists can play a key role in reducing opioid prescribing for patients with chronic pain and NSAID allergies. Providers can tease out which drug reactions are actually allergies, offer drug challenges to confirm allergen suspicions, and steer patients towards celecoxib or other alternatives to reduce prescribing, Li said.

"These patients may represent a high-risk population ideal for targeted allergy evaluation," Li said.

Study limitations included its observational nature and unmeasured confounding.

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