Trends in Pharmacologic Treatment of Chronic Idiopathic Urticaria from 2016 to 2020

Chronic idiopathic urticaria (CIU; also called chronic spontaneous urticaria) is characterized by urticaria lasting for at least 6 weeks, with or without angioedema, and with no identifiable trigger.¹ This condition affects patients of all ages, and is common with an estimated global point prevalence of 1.4%.² The average duration of CIU ranges between 1-5 years and symptoms can significantly impact patient physical and mental well-being and quality of life.³ The majority of patients remain symptomatic despite first-line therapy with high doses of daily nonsedating H1-antihistamines.^1,4 Omalizumab, an anti-immunoglobulin E monoclonal antibody, has been shown to be effective for management of moderate-severe CIU refractory to standard antihistamine therapy.⁴ Shortly after FDA approval for this indication in March 2014, omalizumab was incorporated into national practice parameter guidelines for the management of CIU.⁵ While others have examined the early adoption of omalizumab in the first year following FDA approval,^6,7 recent trends in omalizumab utilization and real-world prescribing patterns for pharmacologic treatment of CIU in the United States are unknown.

We examined utilization patterns for omalizumab and other CIU-directed therapies in patients with CIU between 7/1/2016-12/31/2020. Using deidentified claims data from a large US commercial health plan (Optum Clinformatics), we selected individuals aged ≥12 years old with a diagnosis of CIU as defined by two or more claims with an outpatient International Classification of Diseases (ICD)-9 or ICD-10 diagnosis code for urticaria (708.1, 708.8, 708.9, L50.1, L50.8, L50.9) at least 6 weeks apart, or 1 or more outpatient diagnosis codes for urticaria and 1 or more ICD-9 or ICD-10 diagnosis codes for angioedema (995.1, T78.3) at least 6 weeks apart.^6,7 Demographic characteristics, comorbid asthma, and medication dispensing information were obtained. Medications of interest included omalizumab, prescription H1 antihistamines (cetirizine, levocetirizine, fexofenadine, loratadine, desloratadine, diphenhydramine, chlorpheniramine, hydroxyzine) and H2 antihistamines (famotidine, ranitidine, cimetidine), doxepin, montelukast, oral corticosteroids, and immunosuppressant or anti-inflammatory agents (cyclosporine, dapsone, hydroxychloroquine). Descriptive statistics including means with standard deviations (SD) and counts with percentages were reported for continuous variables and categorical variables, respectively. Variables with standardized differences of <0.1 between groups were considered well-balanced.⁸ Linear regression was used to assess the relationship between rates of medication use and time. All analyses were performed using SAS Version 9.4 (SAS Institute, Cary, NC).

We identified 63,146 individuals with a diagnosis of CIU during the study period, including 35,060 patients who received prescription CIU-directed therapies (73.1% women, 64.0% white, mean age 51.0 [SD 18.9] years, 15,820 [25.1%] with co-morbid asthma). The percent of individuals receiving omalizumab steadily increased from 25% to 44.3% of all treated CIU patients between 2016 and 2020 (P<0.001) (Figure 1). Use of omalizumab was higher at all time points (increase from 32.7% to 48.1% over the study period) in the subgroup of patients receiving CIU-directed therapies who also had comorbid asthma.

Figure 1.

Utilization trends of chronic idiopathic urticaria-directed therapies in treated patients with chronic idiopathic urticaria (7/1/2016-12/31/2020)

Treatment with montelukast remained stable (range during the study period: 31.5%-34.5% of treated patients, P=0.11) while oral corticosteroid use decreased over time (39.7% to 31.1%, P<0.001). These trends persisted in subgroup analyses of patients with and without comorbid asthma. Use of hydroxyzine and doxepin decreased (23.3% to 19.5%, P<0.001 and 7.1% to 4.6%, P<0.001, respectively), while use of alternative agents including hydroxychloroquine and cyclosporine was uncommon but remained stable (range during the study period: 3.5-4.4% and 2.0%-2.9% of treated patients, respectively). Overall use of dapsone was also low, but decreased over time (1.27% to 0.95%, P=0.009).

Individuals ever prescribed omalizumab during the study period were younger (age 47.4 [SD 17.0] vs 52.0 [19.3] years, standardized difference −0.25) compared to those never prescribed omalizumab. Omalizumab-treated patients also more frequently self-identified as White (69.3% vs 62.6%, standardized difference 0.14) and less frequently identified as Hispanic (9.5% vs 13.1%, standardized difference −0.11). Sex and geographic distribution of patients did not differ between those who were and were not treated with omalizumab.

These results indicate that omalizumab use for CIU has been gradually increasing following market availability for this indication. In contrast, incident omalizumab use for asthma peaked in 2004 and has gradually decreased thereafter,⁹ which may reflect the existence of multiple asthma phenotypes and heterogeneity of response to biologics in asthmatics.¹⁰ There is evidence for decreased utilization of CIU-directed therapies following omalizumab initiation,⁶ and we also observed an overall decrease in sedating H1 receptor antagonists (hydroxyzine, doxepin) and oral corticosteroid use in patients receiving CIU-directed therapies over time. These trends persisted even in the subgroup of individuals with CIU but without comorbid asthma.

Interestingly, we noted demographic differences in age and race between individuals ever treated with omalizumab, compared to those who never received omalizumab. The reasons for these differences are unclear, and further research to address potential disparities in care is warranted.

Strengths of this study include the large cohort size, availability of dispensing and administration claims data, and generalizability of these findings to commercially insured individuals in the US. Additionally, this work reflects real-world longitudinal trends over multiple years, as compared to prior work which examined omalizumab prescribing trends between only 2014-2015.^6,7 Limitations include the under capture of over-the-counter H1 and H2 antihistamines use, as only prescription data are available in pharmacy claims. Our study design allowed for assessment of overall medication utilization trends over time, but we were unable to assess the temporal relationships between use of omalizumab and other CIU-directed therapies in individual patients. In patients with concomitant asthma and CIU, we were unable to determine the specific indication for omalizumab administration; however, the overall trends for omalizumab use over time were similar in the subgroup analyses of individuals with and without comorbid asthma. Other limitations inherent to use of administrative claims data includes missing or inaccurate data for diagnoses and prescriptions.

In conclusion, in this large cohort of privately insured patients receiving CIU-targeted therapies, use of omalizumab has steadily increased while prescriptions for sedating H1 receptor antagonists and oral corticosteroids have decreased. Treatment with montelukast is common with rates of use remaining stable over time. Potential demographic differences in the care and pharmacologic management of patients with CIU may also exist and warrant future investigation.

Abbreviations:

CIU

chronic idiopathic urticaria

ICD

International Classification of Diseases

SD

standard deviation