Real-world evidence costs of allergic rhinitis and allergy immunotherapy in the commercially insured United States population

Abstract

Objective

To assess total and allergic rhinitis (AR)-related healthcare costs among AR patients residing in the United States with a focus on patients persisting with AIT.

Methods

AR patients were identified in the IBM MarketScan database between 1 January 2014 to 31 March 2017. Patients receiving allergy immunotherapy (AIT) were identified with relevant billing codes (earliest AIT claim = index date); non-AIT patients were identified with claims containing a diagnosis code for AR (earliest AR claim = index date). AIT patients reaching 25+ injection claims were analyzed as a separate maintenance cohort. All patients were required to have continuous enrollment for 12 months preceding and following index.

Results

A total of 2,334,530 AR patients were included; 103,207 had at least 1 AIT claim, with 45,279 (43.9%) of these patients reaching maintenance, and 24,640 AIT patients (23.9%) never presenting a single injection claim. Compared to non-AIT patients, patients initiating AIT presented higher rates of baseline comorbidities, including asthma (30.1% vs. 7.5%) and conjunctivitis (21.7% vs. 4.4%). During the follow-up period, patients reaching the maintenance phase of AIT incurred lower total costs than the overall AIT cohort ($10,431±$16,606 vs. $11,612±$24,797), and also presented lower follow-up hospitalization costs ($698±$7,248 vs. $1,281±$12,991) and total medical costs ($7950±$13,844 vs. $8989±$22,019).

Conclusions

Continued efforts are needed to increase patient awareness of available options and adherence to AIT, along with reducing wastage. Despite AIT patients presenting fairly progressed disease at the time of treatment initiation, this therapy remains an economical treatment option, as it was not accompanied by substantial increases in overall healthcare expenditure, and may promote positive societal impacts beyond the direct medical costs.

What is known on this topic

• The prevalence of allergic diseases has increased over the past 50 years and affects between 10–30% of the world population.

• Allergic rhinitis (AR) poses a significant economic burden in the form of both direct and indirect costs

• Allergy immunotherapy (AIT) is the only treatment option able to modify the underlying course of the disease.

What this study adds

• Specific all-cause and AR-related healthcare costs decreased following the initiation of AIT among patients diagnosed with AR, with the largest decreases observed among AIT patients reaching the maintenance phase of treatment, while non-AIT patients showed increases in all categories assessed over a similar follow-up period.

• Cost decreases among AIT patients were observed despite increased levels of comorbidities compared to non-AIT patients, as the AIT cohort presented elevated rates of atopic dermatitis (7.1% vs. 2.7%), conjunctivitis (21.7% vs. 4.4%), asthma (30.1% vs. 7.5%), and chronic sinusitis (22.6% vs. 4.9%).

• An analysis of patients’ index subcutaneous AIT consultation revealed substantial variability in the initial treatment costs, with nearly 20% of paid amounts exceeding $1,000; given nearly 1 in 4 AIT patients who get AIT mixed never came back for their first injection, this highlights an opportunity to target frontloaded billing practices and the timing of mixing/injection as an area to minimize healthcare waste.

Keywords:

• Allergy immunotherapy
• allergic rhinitis
• healthcare costs
• wastage

Introduction

Allergic rhinitis (AR), also known as hay fever, is a condition in which inflammatory processes stimulated by environmental allergens result in sneezing, airflow obstruction, nasal pruritus, and clear nasal discharge¹. Allergic diseases have increased in prevalence across the globe over the past half century, affecting between 10–30% of the world population², with sensitization rates to common allergens in school-aged children approaching 50%³, As a chronic disease, AR is associated with significant direct costs in the form of disease management, indirect costs in the form of decreases in work productivity, and “hidden” costs associated with the management of comorbidities common to patients with AR⁴. As such, AR poses a significant economic burden to society, particularly if treatment protocols are not followed⁵.

Societal estimates of the medical costs attributed to AR in the United States (U.S.) have consistently returned values between approximately $3 and $4 billion dollars annually^6–9. A previous analysis of medical and pharmacy claims from a U.S. managed care plan demonstrated that AR patients incurred over $650 annually in direct AR-related costs, which were evenly dispersed between medical and pharmacy services, and which were elevated among patients with specific AR-related comorbidities¹⁰. Asthma, atopic dermatitis (eczema), allergic conjunctivitis, and various sleep disorders are just a few of the comorbidities commonly associated with an AR diagnosis^11–17, and recent evidence has highlighted the substantial economic burden of both asthma, particularly among those with severe disease¹⁸, and atopic dermatitis¹⁹. As such, AR is seldom an isolated disorder, and the associated sequela contributing to these “hidden” costs should be taken into consideration when assessing the true burden of this disease.

Allergen avoidance, pharmacotherapy, and immunotherapy are the primary options when considering a disease management approach²⁰. Though pharmacotherapy can suppress symptoms of AR, allergy immunotherapy (AIT) is the only therapy that can modify the underlying course of disease²¹. AIT is typically prescribed for the most severe AR, and persistence with treatment has been associated with reduced high-cost venue service use and AR-related expenditure⁵. Additionally, a recent review has demonstrated that AIT is a cost-effective option in the management of AR compared with standard drug treatment²².

However, there remains a dearth of up to date, real-world evidence studies focused on the costs of AR, particularly among the subset of patients prescribed AIT. Further, as adherence and persistence rates to AIT remain less than optimal^23–26, it will be critical to evaluate the relationship between treatment compliance/non-compliance, outcomes, and potentially healthcare wastage. Therefore, the purpose of this exploratory study was to better understand the total and AR-related healthcare costs among a large, nationally representative sample of AR patients residing in the United States, with a focus on patients prescribed AIT.

Methods

Study design and data source

This observational, retrospective study used de-identified healthcare claims from the IBM MarketScan Commercial Database spanning the period of 1 January 2014, through 31 March 2017 (study period) to evaluate the healthcare cost profiles of patient diagnosed with AR in the United States. The database comprises enrollment and demographic information, as well as inpatient medical, outpatient medical, and outpatient pharmacy claims data collected from employees, dependents, retirees, and members of >300 large self-insured U.S. employers and >25 U.S. health plans. The database includes employer and health plan sourced data from approximately 140 million individuals from 1995 to 2017.

All database records were de-identified and fully compliant with the US Health Insurance Portability and Accountability Act (HIPAA); this compliance with HIPAA regulation meant that patient consent and Institutional Review Board approval to conduct this study were unnecessary.

Patient selection and cohort assignment

To be eligible for study inclusion, patients were required to meet the following criteria:

• The presence of ≥ 1 medical or pharmacy claim for AIT, and if an absence of AIT claims, ≥ 1 claim with a diagnosis of AR (ICD-9-CM 477.x or ICD-10-CM J30.x) between 1 January 2014, and 31 March 2017

  • Current Procedural Terminology (CPT) codes for subcutaneous AIT (SCIT) included 95115; 95117; 95120; 95125; 95144; 95165; 95180; and 95199²⁷

  • The earliest service date for either an AIT or AR claim served as the index date

• At least 12 months of continuous enrollment with medical and pharmacy benefits for 12 months preceding the index date

• At least 12 months of continuous enrollment with medical and pharmacy benefits for 12 months following the index date

Additionally, for patients in the AIT cohort, the 12-month pre-index period was required to be absent of any AIT treatment, and patients were excluded if they presented any claims for venom allergies at any time during the measurement window. As the build-up phase of SCIT may entail 1–2 shots per week for 3–6 months, based on clinician recommendation, AIT patients reaching the maintenance phase of treatment were operationally defined in the current study as those presenting 25+ AIT injection claims (CPT codes 95115 and 95117) and were analyzed as a stand-alone cohort. Review of the frequency distribution of patients meeting this conservative definition corresponding to a once-weekly shot regimen for 6 months confirmed this threshold. As such, three main cohorts comprised the primary study comparisons, and included all AIT patients, AIT patients reaching the maintenance phase of treatment (25+ injection claims), and non-AIT patients. Additionally, for the analysis of healthcare wastage, the proportion of patients who discontinued AIT after a single visit was also presented.

Measures

Sample characteristics

Patient demographic characteristics were assessed on the index date and included age, sex, geographic region of residence (Northeast, North-Central, South, West, and unknown), urban or rural residency, and index year. Patient clinical characteristics were assessed during the 12-month baseline, and included the Deyo-Charlson comorbidity index (a claims-based overall measure of health)²⁸, the presence of comorbid conditions of interest (asthma, atopic dermatitis, conjunctivitis, depression, eustachian tube disorder, food allergy, headache, heartburn/reflux/GERD, migraine, otitis media, pneumonia, skin rash [including pruritus], eczema, sleep apnea, sleep disturbance, nasal polyps, chronic sinusitis, bronchitis, and any upper respiratory tract infection), the use of specific prescription medication classes (antihistamines, decongestants, intranasal corticosteroids, and nasal sprays), and the frequency of specific surgeries (polypectomy, septoplasty, sinus surgey, turbinectomy, and tympanostomy).

Outcomes

All-cause and AR/AR comorbidity-specific healthcare costs were assessed during each the 12-month baseline and 12-month follow-up period, and were reported by the following service categories: inpatient, emergency room (ER), physician office, laboratory, other outpatient services, outpatient prescriptions, and surgical procedures. AR/AR comorbidity-related healthcare costs included all inpatient medical claims with any of the following diagnosis codes in the primary position or any position on outpatient claims: AR, asthma, atopic dermatitis, conjunctivitis, eosinophilic esophagitis, eustachian tube disorder, food allergy, headache, migraine, otitis media, skin rash (including pruritus), eczema, sleep apnea, sleep disturbance, bronchitis, any upper respiratory tract infection, nasal polyps, or chronic sinusitis. Additionally, all pharmacy claims indicated for AR or AR-related treatment, and any of the five surgeries listed above (polypectomy, septoplasty, sinus surgey, turbinectomy, and tympanostomy) also contributed to disease-related costs.

As medical coding practices for the reimbursement of AIT, in particular SCIT, are known to vary, the distribution of paid amounts appearing on the initial, index SCIT claim were also examined as a separate outcome given the known issues with AIT adherence^23–26. Costs were presented for the eight distinct non-venom AIT procedure codes in use at the time of the analyses, and these visit costs were segmented into categories of the total amount claimed ($0–$99, $100–$299, $300–$499, $500–$999, $1000+). For all analyses of cost metrics, dollar amounts were inflated to 2018 USD (the final year of study data) using the medical component of the Consumer Price Index²⁹.

Statistical analysis

As this was an exploratory study, only descriptive statistics were reported for demographics, clinical characteristics, and healthcare cost measures for three cohorts: all AIT patients, AIT patients reaching the maintenance phase of treatment, and non-AIT patients. Continuous variables were summarized using means and standard deviations (SD). Categorical variables were reported using counts and percentages.

Results

A total of 2,334,530 AR patients qualified for the current study; 103,207 patients presented ≥1 AIT claim (either for preparation or administration), with 45,279 (43.9%) of these AIT patients presenting 25+ AIT injection claims (maintenance). A total of 17,757 AIT patients (17.2%) only presented a single AIT claim of any type, while 24,640 AIT patients (23.9%) only presented without any injection claims (i.e. had AIT mixed but did not receive it). The remaining 2,231,323 AR patients did not receive AIT treatment.

Groups were similar demographically, with mean patient ages in the early 30 s, and a relatively uniform dispersion between early and middle adulthood (Table 1). A greater proportion of patients receiving AIT were female compared to non-AIT patients (58.2% vs. 56.4%), and patients primarily resided in urban areas of the southern United States. During the baseline year, discordant rates of a number of comorbid conditions were observed between AIT and non-AIT cohorts, with a higher proportion of AIT patients presenting claims for atopic dermatitis (7.1% vs. 2.7%), conjunctivitis (21.7% vs. 4.4%), asthma (30.1% vs. 7.5%), chronic sinusitis (22.6% vs. 4.9%), and upper respiratory tract infections (60.3% vs. 34.2%; Table 2). Additionally, a higher proportion of AIT patients filled baseline prescriptions for decongestants (28.9% vs. 6.2%), nasal sprays (44.3% vs. 11.1%), antihistamines (16.8% vs. 4.7%), and intranasal corticosteroids (36.9% vs. 11.3%), with a higher proportion also presenting a baseline AR-related surgical procedure (4.1% vs. 0.9%) compared to non-AIT patients.

Table 1. Demographic characteristics by AIT cohorts.

	25+ AIT FILLS		ANY AIT FILLS		NO AIT FILLS
	N = 45,279		N = 103,207		N = 2,231,323
	N/Mean	%/SD	N/Mean	%/SD	N/Mean	%/SD
Age (Mean, SD)	33.2	18.0	34.2	17.3	32.0	19.2
Age categories (N, %)
18–27	4,269	9.4%	12,357	12.0%	263,302	11.8%
28–37	6,848	15.1%	16,885	16.4%	308,516	13.8%
38–47	8,574	18.9%	20,925	20.3%	361,546	16.2%
48–57	8,001	17.7%	18,564	18.0%	394,717	17.7%
58–65	4,306	9.5%	9,396	9.1%	226,072	10.1%
Sex (N, %)
Male	20,004	44.2%	43,162	41.8%	973,797	43.6%
Female	25,275	55.8%	60,045	58.2%	1,257,526	56.4%
Geographic region (N, %)
Northeast	6,751	14.9%	14,107	13.7%	330,536	14.8%
North Central	8,198	18.1%	15,357	14.9%	384,770	17.2%
South	23,725	52.4%	58,137	56.3%	1,186,081	53.2%
West	6,431	14.2%	15,088	14.6%	319,442	14.3%
Unknown	174	0.4%	518	0.5%	10,494	0.5%
Population density (N, %)
Urban	40,055	88.5%	90,275	87.5%	1,948,820	87.3%
Rural	5,051	11.2%	12,440	12.1%	272,742	12.2%
Unknown	173	0.4%	492	0.5%	9,761	0.4%
Index year (N, %)
2014	14,009	30.9%	33,157	32.1%	727,487	32.6%
2015	14,366	31.7%	33,317	32.3%	736,087	33.0%
2016	13,657	30.2%	29,777	28.9%	602,157	27.0%
2017	3,247	7.2%	6,956	6.7%	165,592	7.4%

Abbreviation. AIT, allergy immunotherapy.

Table 2. Baseline clinical characteristics by AIT cohorts.

	25+ AIT FILLS		ANY AIT FILLS		NO AIT FILLS
	N = 45,279		N = 103,207		N = 2,231,323
	N/Mean	%/SD	N/Mean	%/SD	N/Mean	%/SD
Deyo-Charlson Comorbidity Index (Mean, SD)	0.46	0.72	0.45	0.76	0.22	0.66
Comorbid conditions of interest (N, %)
Any upper respiratory tract infection	28,568	63.1%	62,229	60.3%	762,433	34.2%
Sinusitis	19,291	42.6%	41,897	40.6%	385,113	17.3%
Asthma	15,689	34.6%	31,031	30.1%	166,674	7.5%
Conjunctivitis	12,277	27.1%	22,372	21.7%	98,447	4.4%
Chronic cough	12,074	26.7%	25,033	24.3%	230,975	10.4%
Upper respiratory tract infection	11,631	25.7%	25,969	25.2%	405,578	18.2%
Chronic sinusitis	11,087	24.5%	23,365	22.6%	108,380	4.9%
Heartburn, reflux, GERD	5,748	12.7%	13,346	12.9%	143,469	6.4%
Headache	5,119	11.3%	12,928	12.5%	117,204	5.3%
Otitis media	4,980	11.0%	10,287	10.0%	196,258	8.8%
Food allergy^a	4,503	9.9%	9,181	8.9%	20,955	0.9%
Bronchitis	4,347	9.6%	9,851	9.5%	116,626	5.2%
Atopic dermatitis	3,715	8.2%	7,324	7.1%	59,502	2.7%
Depression	3,628	8.0%	9,473	9.2%	126,999	5.7%
Eczema	3,469	7.7%	7,517	7.3%	83,330	3.7%
Sleep apnea	3,365	7.4%	7,662	7.4%	82,031	3.7%
Eustachian tube disorder	3,162	7.0%	6,660	6.5%	49,032	2.2%
Skin rash (including pruritus)	2,634	5.8%	6,488	6.3%	72,505	3.2%
Sleep disturbance^b	2,594	5.7%	6,682	6.5%	79,540	3.6%
Migraine	2,428	5.4%	6,243	6.0%	61,997	2.8%
Pneumonia	1,313	2.9%	2,754	2.7%	39,751	1.8%
Nasal polyps	1,295	2.9%	2,685	2.6%	4,970	0.2%
Chronic tonsillitis	414	0.9%	985	1.0%	7,387	0.3%
Concomitant Therapy (N, %)
Nasal spray	23,653	52.2%	45,766	44.3%	246,566	11.1%
Intranasal corticosteroid	19,435	42.9%	38,058	36.9%	251,121	11.3%
Decongestant	13,626	30.1%	29,796	28.9%	139,088	6.2%
Antihistamine	8,155	18.0%	17,371	16.8%	105,286	4.7%
Surgical Procedures^c (N, %)	2,030	4.5%	4,239	4.1%	20,195	0.9%

^a Food allergy includes peanuts, milk and milk produces, eggs, seafoods, and adverse symptoms related to food contact.

^b Sleep disturbance includes insomnia, hypersomnia, circadian rhythm sleep disorders, and narcolepsy.

^c Surgical procedures include turbinectomy, endoscopic sinus surgery, septoplasty, tympanostomy, and nasal polypectomy.

Abbreviations. AIT, allergy immunotherapy; GERD, gastroesophageal reflux disease; SD, standard deviation.

Table 3 presents all-cause and AR/AR comorbidity-related healthcare cost metrics during each of the baseline and follow-up periods. In the year leading up to treatment initiation, the AIT cohort presented greater baseline all-cause total healthcare costs compared to non-AIT patients ($9,418±$20,566 vs. $5,213±$19,503), along with greater total AR-related costs ($2,482±$5,118 vs. $518±$2,252). The majority of costs were derived from medical expenditure as opposed to pharmacy expenditure, which was consistent for both all-cause and AR-related cost metrics. Across all service categories, AIT patients presented greater mean baseline costs compared to non-AIT patients, with the subset of patients who eventually reached the maintenance phase of treatment (25+ injections) presenting a slightly lower mean baseline cost compared to the overall AIT cohort ($8,447±$15,467 vs. $9,418±$20,566).

Table 3. All-cause and AR-related healthcare costs by AIT cohorts in the baseline and follow-up periods.

	25+ AIT FILLS		ANY AIT FILLS		NO AIT FILLS
	N = 45,279		N = 103,207		N =2,231,323
	N/Mean	%/SD	N/Mean	%/SD	N/Mean	%/SD
All-Cause Costs^a
Pre-Index Period
Inpatient costs	$799	$6,815	$1,091	$9,926	$981	$11,811
ER costs	$324	$1,095	$432	$1,517	$275	$1,244
Physician office visit costs	$1,004	$780	$981	$993	$480	$616
Specialist office visit costs	$260	$237	$212	$237	$20	$86
Laboratory costs	$399	$1,459	$520	$2,397	$257	$1,292
Other outpatient costs	$3,823	$9,410	$4,170	$11,955	$2,075	$10,150
Outpatient prescription costs	$2,098	$5,727	$2,222	$6,873	$1,145	$6,123
Total Medical Costs (Mean, SD)	$6,349	$13,551	$7,195	$18,270	$4,069	$17,780
Total Healthcare Costs (Mean, SD)	$8,447	$15,467	$9,418	$20,566	$5,213	$19,503
Follow-Up Period
Inpatient costs	$698	$7,248	$1,281	$12,991	$1,426	$16,790
ER costs	$288	$1,079	$416	$1,573	$370	$1,615
Physician office visit costs	$903	$802	$898	$1,140	$760	$731
Specialist office visit costs	$202	$259	$156	$258	$71	$166
Laboratory costs	$355	$1,047	$490	$2,433	$380	$1,606
Other outpatient costs	$5,706	$9,478	$5,905	$13,539	$3,180	$13,769
Outpatient prescription costs	$2,480	$7,198	$2,622	$8,674	$1,699	$8,529
Total Medical Costs (Mean, SD)	$7,950	$13,844	$8,989	$22,019	$6,116	$24,692
Total Healthcare Costs (Mean, SD)	$10,431	$16,606	$11,612	$24,797	$7,815	$27,041
AR-Related
Pre-Index Period
Inpatient costs	$66	$1,286	$76	$1,577	$29	$1,115
ER costs	$96	$513	$125	$687	$61	$434
Physician office visit costs	$515	$405	$455	$423	$126	$223
Specialist office visit costs^b	$240	$217	$192	$216	$12	$63
Laboratory costs	$10	$189	$9	$166	$3	$85
Other outpatient costs	$1,312	$3,748	$1,254	$3,875	$200	$1,579
Outpatient prescription costs	$617	$1,377	$563	$1,807	$101	$535
Surgical procedure costs^c	$295	$2,339	$271	$2,168	$32	$603
Anaphylaxis costs	$0	$0	$0	$0	$0	$0
Total Medical Costs (Mean, SD)	$1,998	$4,283	$1,919	$4,568	$417	$2,132
Total Healthcare Costs (Mean, SD)	$2,615	$4,668	$2,482	$5,118	$518	$2,252
Follow-Up Period
Inpatient costs	$22	$763	$43	$1,043	$35	$1,405
ER costs	$74	$458	$107	$671	$88	$561
Physician office visit costs	$410	$431	$363	$429	$322	$317
Specialist office visit costs	$188	$244	$141	$237	$60	$146
Laboratory costs	$4	$81	$6	$136	$5	$145
Other outpatient costs	$3,054	$3,855	$2,747	$4,663	$528	$2,749
Outpatient prescription costs	$816	$2,119	$749	$2,544	$218	$992
Surgical procedure costs	$280	$2,136	$271	$2,145	$104	$1,233
Anaphylaxis costs	$6	$90	$5	$99	$0	$0
AIT costs	$2,150	$1,205	$1,798	$1,805	$0	$0
Total Medical Costs (Mean, SD)	$3,564	$4,163	$3,266	$5,091	$978	$3,352
Total Healthcare Costs (Mean, SD)	$4,380	$4,909	$4,015	$5,950	$1,195	$3,597

^a Costs were calculated based on paid amounts of adjudicated claims, including insurer and health plan payments, and patient cost-sharing in the form of copayment, deductible, and coinsurance. All costs were adjusted for inflation using the medical care component of the Consumer Price Index (CPI) and standardized to 2018 U.S. dollars.

^b Specialist office visits include allergy, immunology, otolaryngology, or pulmonary disease providers.

^c Surgical procedures include turbinectomy, endoscopic sinus surgery, septoplasty, tympanostomy, and nasal polypectomy.

Abbreviations. AIT, allergy immunotherapy; ER, emergency room; SD, standard deviation.

Similar cost patterns emerged during the follow-up period, with the AIT cohort presenting greater mean all-cause total healthcare costs compared to non-AIT patients ($11,612±$24,797 vs. $7815±$27,041), and with patients reaching the maintenance phase of AIT presenting total mean costs values lower than the overall AIT cohort ($10,431±$16,606). Compared to the full AIT cohort, AIT maintenance patients presented lower mean follow-up hospitalization costs ($698±$7248 vs. $1281±$12,991), emergency room costs ($96±$513 vs. $125±$687), pharmacy costs ($2480±$7198 vs. $2622±$8674), and total medical costs ($7950±$13,844 vs. $8989±$22,019). Follow-up AR/AR comorbidity-related costs were naturally highest among AIT patients reaching the maintenance phase of treatment ($4380±$4909), as these patients incurred greater costs for their extended period of AIT treatment. In assessing the change in costs from baseline to follow-up, AIT patients presented reductions in nearly all service categories assessed with the exception of “other” outpatient services, where AIT treatment costs are captured. These results were largely driven by the subset of patients reaching the maintenance phase of treatment (Figure 1). The non-AIT group showed increases in all categories assessed.

Figure 1. All-cause and AR-related cost differences baseline to follow-up by AIT cohorts.

As less than half of AIT patients reached the maintenance phase of treatment, with 17% only presenting a single AIT claim of any type, and 23.9% never presenting a single AIT injection claim, analyses of the initial SCIT claim were undertaken to quantify potential AIT-related healthcare wastage. The cost associated with the index claim for SCIT varied greatly, with a mean value of $674±$832. Fifty-five percent of index SCIT claims carried a paid amount of less than $500, though 20% of these claims were observed with cost values in excess of $1000. Figure 2 presents the procedure codes with the largest variance in costs for the index SCIT claim. Procedure code 95165 (preparation and provision of antigens for allergen immunotherapy)²⁷ was used in 78% of the first claims, and carried an average cost of $748±$849 per claim, with 21% of the paid amounts on these claims exceeding $1000. Among patients presenting a single AIT claim, 30.4% of these sole visits were associated with costs in excess of $1000, with 12.8% in excess of $2000 As such, patients presenting with a single AIT claim managed to incur nearly half the costs associated with AIT compared to patients presenting at least 25 injections ($976±$1367 vs. $2150±$1205).

Figure 2. Cost distribution of index SCIT claims by select Current Procedural Terminology codes.

Discussion

This study presents a real-world examination of the cost profiles of patients diagnosed with AR in the United States, with a focus on those patients prescribed AIT. The AIT cohort presented higher rates of numerous baseline allergy-related comorbidities compared to non-AIT patients, including asthma (30.1% vs. 7.5%), chronic sinusitis (22.6% vs. 4.9%), and upper respiratory tract infections (60.3% vs. 34.2%), suggesting those patients most severely impacted by the disease were most likely to initiate AIT. These translated into higher baseline and all-cause costs for the AIT cohort compared to non-AIT. However, from the year prior to AIT initiation to the year following, patients in the AIT cohort presented cost decreases in the majority of service categories assessed, including inpatient hospital and ER costs, while the non-AIT group showed increases in all categories assessed. AIT patients reaching the maintenance phase of treatment were observed to present the largest reductions in expenditure from baseline to follow-up

Total annual healthcare costs were relatively low for the full AIT and non-AIT cohorts ($11,612±$24,797 vs. $7815±$27,04) compared to other chronic diseases in which long-term maintenance treatment may be indicated^30,31. The lack of additional healthcare costs associated with prolonged use of AIT is noteworthy, as the maintenance group actually incurred lower annual healthcare costs than the AIT group as a whole ($10,431±$16,606 vs. $11,612±$24,797). For most therapeutic classes, adherence and persistence is often associated with significantly increased medical and/or pharmacy costs in the short term, which are not consistently offset by reductions in other healthcare spend³², and has long been cited by patients as one of the reasons for medication non-adherence³³. As such, results demonstrate that despite AIT patients presenting fairly progressed disease at the time of AIT initiation based on their increased levels of allergy-related comorbidities compared to non-AIT patients, AIT remains an economical treatment option and is not expected to be accompanied by notable increases in overall healthcare expenditure.

In the current study, less than half of AIT patients reached the maintenance phase of treatment, which may be partially explained by the fact that nearly a quarter of patients never presented a single injection claim. The sub-analysis of the initial, index SCIT claims revealed a curious pattern of variables costs, particularly when juxtaposed against this observed low rate of AIT persistence. Medical procedure coding practices for the reimbursement of AIT may vary, partly driven by the discrepancies in accepted code usage across health insurance plans. Present results demonstrated substantial variability in the initial treatment costs for SCIT, along with a high mean cost, and with nearly 20% of paid amounts exceeding $1000. The observed spread in claimed amounts may be reflective of certain physicians’ willingness and ability to bill for allergen extracts, which would be administered over multiple successive office visits. This up front-billing may contribute to healthcare waste, particularly as almost 1 in 4 patients never actually received a single AIT injection. Sublingual AIT (SLIT) tablets, which have been FDA approved since 2014³⁴, may present a better option to promote persistence and adherence for some proportion of the AR population and comes with less up front billing. A number of therapy-related factors have been shown to correlate negatively with treatment adherence, including the route of administration and complexity of the regimen³⁵. As SLIT is taken at home orally once a day, this may present a more convenient option for select patients. Though the direct comparison of adherence rates between SLIT and SCIT have been variable^36,37, these can often be traced to the inherent difficulties comparing two routes of administration, often leading to bias grounded in differences in how adherence is defined and thresholds for compliance are set. Regardless, improved patient treatment matching efforts and patient education on AIT maintenance treatment in general may be warranted, in which the timing and proportion of AR patients identified for candidates for SCIT or SLIT is maximized.

As AR has also been shown to have significant impacts on quality of life and work productivity, there is more than a direct economic benefit to be realized when the disease is treated timely and appropriately. Studies have reported the direct impact of AR on mood, anxiety, depression, social life, sleeping, cognitive function, school performance, and overall quality of life^38,39, with specific clinical, immunological, and functional parameters of the disease directly tied to quality of life indices⁴⁰. Further, results of a systematic review demonstrate that 35% of patients with AR report impairment on the job, also with a direct relationship to symptom severity^41,42. The total indirect cost estimates of AR vary considerably from 0.1 billion to 9.7 billion USD annually, with per-person costs of $593^9,43. Improving the overall quality of life for these patients, along with the promotion of increased productivity, will result in significant societal cost savings beyond direct medical expenditure, which will be critical as the increasing trend in the prevalence of AR is likely to continue due to a variety of environmental and lifestyle-based causes^44,45]. Thus, it may be advantageous for patients to initiate AIT earlier in the course of their disease, which could hinder the development of a more severe disease and minimize the onset of allergy-related comorbidities.

Limitations

Studying AR in administrative claims data does come with some limitations. First, AR can often be managed without intervention of a physician (e.g. over the counter medications), meaning there will be a period of time where AR patients do not generate any claims with an AR diagnosis until the disease reached more severe levels. As such, the true length of disease for patients in the current sample is unknown. Additionally, the current study required a minimum of 2 years of continuous commercial health coverage. Therefore, results of this analysis may not be generalizable to AR patients who change or lose insurance, to those with Medicare/Medicaid insurance, and to the uninsured. Also, though patients were followed for two years, the long-term clinical outcomes of AR will likely require an extended follow-up window, as AIT will require multiple years before its full therapeutic benefit is realized. Additionally, administrative claims data are subject to data coding limitations and data entry error, which may result in missing or erroneous data. Finally, patient receiving SLIT tablet prescriptions were also included in the analyses, and may differ in some ways from those receiving SCIT. Analyses focused solely on SLIT tablet patients may be warranted as a follow-up to the current investigation.

Conclusion

In summary, this study presents the results of a real-world examination of the direct costs associated with AR in the United States, particularly among those treated with AIT, which remains the only available treatment option which can induce allergen-specific immune tolerance. Results demonstrate that despite AIT patients presenting fairly progressed disease at the time of treatment initiation, this therapy remains an economical treatment option, as it was not accompanied by increases in overall healthcare expenditure. In fact, from baseline to follow-up, patients receiving AIT presented cost decreases in the majority of service categories assessed, including inpatient hospital and ER costs, while the non-AIT group showed increases in all categories assessed. The observed increase in the allergy-related comorbidity load at the onset of AIT suggest these patients are delaying this therapy until their disease is severe, while analyses focused on patients’ initial AIT claim revealed substantial variability in costs for these visits, highlighting an area of healthcare wastage for patients who do not persist with therapy. Taken together, continued efforts are needed to increase patient awareness of available options and adherence to AIT to improve patient treatment matching efforts, including use of SLIT tablets. Given the known indirect costs of AR and the toll this disease can take on general quality of life, the full societal impact of optimal disease management approaches will extend beyond the direct medical costs.

Transparency

Declaration of funding

This work was supported by ALK-Abelló.

Declaration of financial/other relationships

KR, DW, MA and EH were employed by ALK-Abelló during the execution of this study. JT is employed by IBM Watson Health as a consultant and received funding from ALK-Abelló to conduct this study. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Previous presentation

A preliminary analysis of select data appearing in the current manuscript was presented at the AMCP 2020 annual meeting, April 21-24.

Acknowledgements

Lisa Elliott is greatly acknowledged for her assistance with the development of various elements of the initial study design.