The opioid epidemic continues to be a serious public health problem in the United States, with opioid-related overdoses claiming the lives of more than 47,000 Americans annually. Higher opioid dosages and prescription lengths have been linked to long-term opioid use, incident opioid use disorder (OUD), and a higher risk of overdose. “It’s critical to identify patients at highest risk for OUD and to address challenges in reducing opioid use,” says Lily Li, MD.

NSAIDs are commonly prescribed for acute and chronic pain, but their use has been limited by reported NSAID-induced adverse drug reactions (ADRs). These reactions are often considered “allergies” by patients but may not necessarily warrant absolute NSAID avoidance. “NSAIDs are indicated as first-line therapy for treating musculoskeletal pain, but a reported history of NSAID allergy can preclude use of this entire medication class,” says Dr. Li. “However, more than 80% of reported NSAID ADRs represent side effects, and only a minority are consistent with true allergic hypersensitivity reactions. Allergy over-reporting can lead to avoidance of NSAIDs and may predispose some patients to use of other, potentially addictive pain medications. This can lead to negative downstream effects on patient outcomes.”

New Research Findings

For a study published in the Journal of Allergy & Clinical Immunology, Dr. Li and colleagues investigated the relationships between reported NSAID allergies, opioid prescribing, and OUD in a population of patients with chronic back pain. They collected data from electronic health records (EHRs) in more than 47,000 adult patients with at least two diagnoses for back pain and at least one outpatient visit every 2 years between 2013 and 2018. Patients reporting an NSAID ADR were defined as having an NSAID allergy. Those with two or more codes in their EHRs for opioid abuse or dependence were defined as having OUD.

“Strikingly, our study found that reported NSAID allergies were common in patients with chronic back pain, with a prevalence of 7.7%,” Dr. Li says. “This was more than twice as common as what is seen in the general population.” The association between the presence of a reported NSAID allergy and OUD was slightly higher in the entire cohort than in the propensity score matched sample (Figure). “Reported NSAID allergy was associated with increased odds for receiving opioid prescriptions and for developing OUD, even after adjusting for baseline patient characteristics, insurance status, and prior healthcare utilization,” adds Dr. Li.

Additionally, the study showed that patients with reported NSAID ADRs were more likely to receive several other alternative analgesics—including opioids—but only a minority of patients had reactions consistent with true NSAID allergic hypersensitivity by history. Several risk factors for OUD were identified by the study authors, including younger age, male sex, and Medicaid or Medicare insurance. Furthermore, those with more inpatient and outpatient visits in the prior year and patients with comorbid anxiety and depression were at greater risk for OUD.

Important Implications

The study group noted the results suggest there is a need for carefully directed evaluations and clarification of reported NSAID allergies. “Our findings indicate that the label ‘NSAID-allergic’ has important consequences on medication prescribing patterns and the development of OUD in adults with chronic back pain,” Dr. Li says. “These findings highlight the importance of involving allergists in the multidisciplinary care of patients with painful conditions and reported NSAID allergies.”

According to the researchers, it will be important to establish and adopt evidence-based algorithms for managing patients with reported NSAID-induced reactions and referring them to allergists when appropriate in the future. “Research is needed to develop risk stratification tools that target the highest-risk populations for allergy intervention with potential de-labeling and to investigate the impact of reported NSAID allergies on patient safety and clinical outcomes across different patient populations,” Dr. Li says. “These efforts are critical to reduce unnecessary opioid prescribing and to improve the overall quality and safety of care of patients with NSAID allergies.”

References

Li L, Chang Y, Song S, Losina E, Costenbader KH, Laidlaw TM. Impact of reported NSAID “allergies” on opioid use disorder in back pain. J Allergy Clin Immunol. 2020 Sep 8 [Epub ahead of print].  Available at: https://www.jacionline.org/article/S0091-6749(20)31236-7/abstract?rss=yes#%20.

Li L, Laidlaw T. Cross-reactivity and tolerability of celecoxib in adult patients with NSAID hypersensitivity. J Allergy Clin Immunol Pract. 2019;7(8):2891-2893.e4.

Blumenthal KG, Lai KH, Huang M, Wallace ZS, Wickner PG, Zhou 502 L. Adverse and hypersensitivity reactions to prescription nonsteroidal anti-inflammatory agents in a large health care system. J Allergy Clin Immunol Pract. 2017;5(3):737-743.e3.

Naik R, Goodrich G, Al-Shaikhly T, Joks R. Prevalence of long-term opioid use in patients with asthma and allergic rhinitis. J Allergy Clin Immunol Pract. 2018;141(2):AB218.

Zhou L, Dhopeshwarkar N, Blumenthal KG, Goss F, Topaz M, Slight SP, et al. Drug allergies documented in electronic health records of a large healthcare system. Allergy. 2016;71(9):1305-1313.