Abstract
Objective
To investigate the impact of steroid-eluting implants after endoscopic sinus surgery (ESS) on health care resource use (HCRU) in chronic rhinosinusitis patients with (CRSwNP) and without (CRSsNP) nasal polyps.
Methods
This retrospective, observational cohort study using real-world evidence data included adult patients with CRS who underwent ESS in 2015–2019 with at least 24 months of data before and after ESS. Patients who received implants were matched to patients who did not based on a propensity score developed using baseline characteristics and NP status. HCRU was compared between cohorts within each CRSwNP and CRSsNP subgroup using chi-square tests (binary variables).
Results
The implant cohort in the CRSwNP subgroup had fewer all-cause outpatient (90.0% vs. 93.9%, p < .001) and all-cause otolaryngology (64.3% vs. 76.4%, p < .001) visits as well as fewer endoscopy (40.5% vs. 47.4%, p = .005) and debridement (48.8% vs. 55.6%, p = .007) procedures than the non-implant cohort. The implant cohort in the CRSsNP subgroup had fewer all-cause outpatient (88.9% vs. 94.2%, p < .001) and all-cause otolaryngology (53.5% vs. 74.4%, p < .001) visits as well as fewer endoscopy (31.8% vs. 41.7%, p < .001) and debridement (36.7% vs. 53.4%, p <.001) procedures than the non-implant cohort. Revision sinus surgery was reduced in the implant cohort in both subgroups, and reached statistical significance in the CRSwNP subgroup (3.8% vs. 6.0%, p = .039) but not in the CRSsNP subgroup (3.6% vs. 4.2%, p = .539).
Conclusions
Overall, patients receiving implants had lower HCRU for 24 months after sinus surgery independent of nasal polyp status, and revision surgery was reduced in CRSwNP patients. These findings provide additional evidence that long-term reductions in HCRU may be achieved with steroid-eluting implant use during sinus surgery.
Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have a disproportionately higher burden of disease and consume greater healthcare resources than chronic rhinosinusitis patients without nasal polyps (CRSsNP).
CRSwNP patients represent approximately 30% of CRS patients who undergo surgery, but their clinical course is disproportionally complicated by disease recurrence and revision surgery.
Steroid-eluting sinus implants have been shown in clinical trials to improve short-term postoperative outcomes after endoscopic sinus surgery (ESS) in CRS patients in general.
A recent real-world evidence study reported that steroid-eluting sinus implants following ESS were associated with a reduction in HCRU in CRS patients followed for 18 months, but the impact of implants on HCRU in CRSwNP and CRSsNP patients separately remains unknown.
What is known on this topic
In this observational study, reduced HCRU was observed in CRSwNP and CRSsNP patients who receive steroid-eluting sinus implants.
Use of implants in CRSwNP and CRSsNP patients was associated with a significant reduction in healthcare visits (all-cause outpatient, all-cause otolaryngology), and sinus procedures (endoscopy, debridement).
Revision surgery was significantly reduced in the implant cohort of CRSwNP patients and trended lower in the implant cohort of CRSsNP patients.
Use of implants had no significant impact on all-cause ER/urgent care visits or sinus-related imaging.
What this study adds
Introduction
The overall prevalence of CRS in the United States is approximately 3–6%, while the direct costs to the US healthcare system are estimated to fall between $7 and $13 billion per yearCitation1–3. CRS presents in two broadly defined clinical phenotypes depending on the presence (CRSwNP) or absence (CRSsNP) of nasal polyps.
CRS patients who fail to respond to conservative medical therapy may be offered endoscopic sinus surgery (ESS)Citation4. While estimates vary, CRSwNP patients represent nearly one-third of CRS patients who undergo ESSCitation5. Patients with CRSwNP are widely recognized to have a greater burden of disease, to be more prone to disease recurrence, and to more frequently require revision surgery, resulting in greater overall healthcare resource utilization than CRS patients without nasal polypsCitation6. While overall ESS success rates in CRS approach 76–98%Citation7, surgical success in CRSwNP patients is considerably lower and CRSwNP patients can expect to require more frequent revision surgeriesCitation8.
Oral steroids remain integral to the management of nasal polyp recurrence in CRSwNP patients, but their use may be complicated by harmful systemic side effectsCitation9. The search for alternative, better-tolerated therapies has yielded the development of new treatments such as monoclonal antibody therapy, but these therapies are expensive and their cost-effectiveness has been called into questionCitation10. Conversely, economic analyses of steroid-eluting sinus implants have demonstrated that the upfront costs of implants are offset by ultimate downstream savingsCitation2,Citation11,Citation12.
Placed at the completion of ESS, corticosteroid-eluting sinus implants (implants) each deliver localized, sustained release of 370 micrograms of mometasone furoate directly onto healing sinus tissue for up to 30 days after surgery. Implants have been shown in clinical trials to improve short-term surgical outcomes, reducing the need for post-operative interventions, oral steroid use, and rates of occlusion or restenosis through post-operative day 30Citation13. Corticosteroid-eluting sinus implantsFootnotei have been approved by the US Food and Drug Administration (FDA) for use in patients 18 years of age and older following ethmoid, frontal, or maxillary sinus surgery. Currently, none of the implants is approved for use in the sphenoid sinus.
A recent real-world evidence data study of CRS patients who received steroid-eluting sinus implants after ESS documented reductions in healthcare resource use for up to 18 months after surgeryCitation14. While the study included both CRSwNP and CRSsNP patients, separate data for each clinical phenotypes were not provided.
This study seeks to examine whether ESS performed withsinus implants is associated with reductions in HCRU in CRSwNP patients, despite their greater disease severity, and in CRSsNP patients separately. The analysis incorporates data from the Reg-ENTSM registry (an otolaryngology-based specialty-specific data source), refinements to inclusion and exclusion criteria used previouslyCitation14, and a 24-month post-operative study period.
Methods
Study design
This retrospective observational cohort study included adult patients with CRS who underwent ESS between 1 January 2015 and 31 December 2019. The study population was derived from multisource databases containing healthcare claims and electronic medical record (EMR) data in the US. The datasets are de-identified and compliant with the Health Insurance Portability and Accountability Act. Descriptions of the datasets were submitted to an Institutional Review Board for approval, and the datasets were determined to be exempt.
This study included comparisons between patients who received a corticosteroid-eluting sinus implant (“implant cohort”) and those who did not (“non-implant cohort”), and between the implant and non-implant cohorts within subgroups based on the presence (CRSwNP) or absence (CRSsNP) of nasal polyps. The frequency of select HCRU measures was summarized and compared between cohorts and within subgroups.
Data sources
This study was conducted using data from the OM1 Real-World Data Cloud (OM1, Inc, Boston, MA) and the Reg-ENTSM registry (American Academy of Otolaryngology-Head and Neck Surgery/Foundation [AAO-HNS/F], Alexandria, VA). The Reg-ENT registry is connected to OM1’s real-world data and evidence platforms through a data partnership between OM1, Inc and AAO-HNS/FCitation15,Citation16. This data linkage enables a more rapid and complete assessment of otolaryngology-specific data for real-world evidence research.
The OM1 dataset is derived from deterministically linked, de-identified, individual-level healthcare claims, EMR records, and other data sources covering over 300 million patients in the US since 2013. The EMR data are from sources geographically representative of the US population and include medication history, prescription information, laboratory results, and diagnoses documented by a health care provider. Medical and pharmacy claims data are linked to the clinical data to fill gaps in patients’ clinical care. The medical and pharmacy claims contain billing and coding history on inpatient and outpatient encounters from acute care facilities, ambulatory surgery centers, and clinics.
AAO-HNS/F’s Reg-ENT registry is the first and largest national-level repository of otolaryngology-specific data. The registry collects complete EMR and billing data from a large, representative network of clinical otolaryngology practices in the US, as well as from ancillary services such as audiometry. The data are derived directly from EMRs on a regular basis and stored in a central repository covering the full range of ear, nose, and throat (ENT) conditions seen in clinical practice, their treatments, and outcomes. All data are de-identified. The registry includes data from approximately 3000 clinicians, 500 practices, and 25 million ENT patient visits since 2015.
Patient selection and cohort assignment
Patients were required to have a diagnosis of CRS on the date of their ESS or within 24 months prior. All patients were required to have at least 24 months of claims data before and after their ESS. Patients with a prior history of ESS and patients who underwent balloon sinus dilation only were excluded. Use of sinus implants was identified on the day of the surgery. For subgroup analyses, patients were further classified as CRSwNP or CRSsNP. CRS and NP were identified based on relevant International Classification of Diseases (ICD-9th or 10th Revision) diagnosis codes, and ESS and sinus implants were identified based on the presence of relevant procedure codes ().
Table 1. Diagnosis and procedure codes for identification of CRS, NP, Sinus Implants, ESS, and Sinus-related Procedures.
Healthcare resource use
The following HCRU measures were ascertained over a 24-month period after the index surgery: revision sinus surgery (excluding balloon sinus dilation), all-cause outpatient visits, all-cause otolaryngology visits, all-cause emergency room (ER)/urgent care visits, sinus-related procedures (endoscopy, debridement, polypectomy), and sinus-related imaging (CT, MRI). Revision sinus surgery, endoscopy, debridement, and polypectomy were identified based on relevant procedure codes listed in .
Statistical methods
To account for differences in CRS severity and other pre-surgery characteristics, patients in the non-implant cohort were matched to patients in the implant cohort based on a propensity score (PS) that predicted implant use versus no implant use. The PS was calculated using logistic regression modeling for the probability of receiving an implant. The logistic regression model included the following baseline variables: demographics (age, sex, race), presence of allergic rhinitis and/or asthma, the overall comorbidity burden as measured by the Deyo-Charlson comorbidity index (an overall measure of health based on ICD 9th and 10th Revision diagnosis codes for a range of comorbidities), sinus type treated at index surgery, year of surgery, and duration of the baseline period. Baseline variables were assessed during the 24 months prior to and including the index surgery. To reduce the potential for residual confounding in subgroup analyses, re-matching was performed within each subgroup (i.e., CRSwNP, with and without implants; CRSsNP, with and without implants) using PS generated for the overall cohortCitation17,Citation18.
Descriptive statistics were used to summarize baseline demographics, surgery history and clinical characteristics, and HCRU during follow-up. Chi-square tests were used to compare outcomes between patients who received implants and those who did not, in the overall cohort and within subgroups stratified by the absence or presence of nasal polyps. All tests were two-sided with alpha = 0.05. Statistical analyses were performed using SAS 9.4 (SAS Institute, Cary, NC).
Results
The overall study population comprised 3418 patients (1709 in the implant and non-implant cohort, respectively). There were 1638 patients with CRSwNP (819 in each cohort) and 1780 patients with CRSsNP (890 in each cohort).
The matched cohorts in the subgroups and in the overall population were similar with respect to age, sex, and race. Within the subgroups, a male predominance was observed for CRSwNP (54.3% vs. 45.7%), while a female predominance was observed for CRSsNP (57.5% vs. 42.3%). A higher proportion of the implant cohort than non-implant cohort had commercial insurance (87.2% vs. 81.8%), while a lower proportion had Medicaid or Medicare insurance (3.1% vs. 8.3%) (). Comorbid conditions in the CRSwNP and CRSsNP subgroups were well-balanced, with prevalence differences of ≤5% between the implant and non-implant cohorts ().
Table 2. Demographic characteristics by subgroup and cohort.
Table 3. Baseline characteristics by subgroup and cohort.
Independent of implant status, CRSwNP patients underwent more extensive index sinus surgery than CRSsNP patients for all sinus types. All surgeries were primary per study design and nearly all index surgeries were performed in outpatient facilities ().
Table 4. Characterization of index sinus surgery by subgroup and cohort.
During 24 months after the index surgery, revision surgery was significantly lower in the implant cohort than in the non-implant cohort within the CRSwNP subgroup (3.8% vs. 6.0%, p = .039) and trended in the same direction within the CRSsNP subgroup but did not reach statistical significance (3.6 vs. 4.2%, p = .539) ().
Table 5. Repeat sinus surgery during the 24 months following index sinus surgery by subgroup and cohort.
For the CRSwNP subgroup, all-cause outpatient visits (90.0% vs. 93.9%, p = .004) and all-cause ENT visits (64.3% vs. 76.4%, p < .001) were significantly lower in the implant cohort. In the CRSsNP subgroup, all-cause outpatient visits (88.9% vs. 94.2%, p < .001) and all-cause ENT visits (53.5% vs. 74.4%, p < .001) were likewise significantly reduced in the implant cohort. The percentage of patients with all-cause ER/urgent care visits was similar within the CRSwNP and CRSsNP subgroups, as well as within the overall study population ().
Table 6. Healthcare resource utilization during 24 months following index sinus surgery by subgroup and cohort.
Patients in the implant cohort were significantly less likely to undergo endoscopy (36.0% vs. 44.6%, p < .001) and debridement (42.5% vs. 54.5%, p < .001) compared to those in the non-implant cohort. Subgroup analyses showed similar reductions in sinus procedures in both CRSwNP patients (endoscopy 40.5% vs. 47.4%, p = .005; debridement 48.8% vs. 55.6%, p = .007) and CRSsNP patients (endoscopy 31.8% vs. 41.7%, p < .001; debridement 36.7% vs. 53.4%, p < .001) ().
Sinus-related imagings were broadly similar in CRSwNP and CRSsNP subgroups regardless of whether patients received implants (). A significantly higher percentage of CRSsNP patients who received implants underwent a sinus-related MRI than patients who did not receive an implant. (2.0% vs. 0.8%, p = .027). The proportion of patients in the overall study population who underwent sinus-related imaging during the 24 months following surgery was nearly identical between the implant and non-implant cohorts (CT: 9.2% vs. 9.1%, p = .906; MRI: 1.8% vs. 1.4%; p = .410).
Discussion
This observational RWE study found reductions in HCRU for 24 months postoperatively in both CRSwNP and CRSsNP patients who underwent endoscopic sinus surgery with steroid-eluting implants compared to a matched cohort that underwent sinus surgery alone. A lower percentage of the patients who received implants required all-cause outpatient and all-cause otolaryngologist visits. Patients who received implants were also observed to experience fewer sinus-related endoscopy and fewer sinus-related debridement procedures. Despite a greater burden of disease and more extensive surgery in nasal polyp patientsCitation1, the reductions in HCRU outcomes observed in the CRSsNP patients and the overall study population were also seen in the CRSwNP subgroup.
Patients in the CRSwNP subgroup who received implants had the greatest reduction in revision surgery during the 24-month study period. While not statistically significant, patients in the CRSsNP subgroup showed a consistent trend toward reduced revision surgery after implant placement. Although the study followed patients for 24 months postoperatively, the study period may nevertheless be insufficient to capture a statistically significant difference in revision surgery in CRSsNP patients between implant and non-implant cohorts.
These observations of reduced revision surgery in CRSwNP patients after implant use are particularly compelling given that such patients are known to be more prone to disease recurrence and revision surgeryCitation6. Further investigation may be warranted to confirm these findings.
Within the CRSwNP subgroup, revision surgery was less common in the implant cohort than in the non-implant cohort for all sinus types. In CRSsNP patients, maxillary revision surgery was less common in the implant cohort, while ethmoid, frontal, and sphenoid revision surgery was less common in the non-implant cohort. The overall revision surgery percentages of 3.6–6.0% noted in this study are consistent with the revision sinus surgery rates seen at 2 years in other studiesCitation19, but well below the long term estimated revision sinus surgery rate of 15% over 10 yearsCitation20.
The findings of this study reinforce the results of clinical trials that demonstrated the efficacy of steroid-eluting implants in improving sinus surgery postoperative outcomes through postoperative day 30 and they extend the observations of previous RWE studies to 24 months postoperatively. The reduction in HCRU seen in this study further corroborates the cost-effectiveness of steroid-eluting implants observed by othersCitation2,Citation11,Citation12,Citation14.
Strengths of this study include the addition of data from the Reg-ENT registry, previously unavailable, which yielded greater availability of all-cause ENT and urgent care visits, as well as postoperative sinus debridement. The study period was a full 24 months postoperatively. Inclusion criteria were refined to restrict the clinical diagnosis of CRS to ICD codes only and ESS to CPT codes only, consistent with contemporary research in the fieldCitation20. To establish a more uniform set of CRS patients, patients who underwent an index surgery consisting of balloon sinus dilation only as well as those with a prior history of ESS were excluded from the dataset. The study design provided for a direct comparison of HCRU outcomes in CRSwNP and CRSsNP subgroups. Confounding by baseline characteristics was controlled through PS-matching at the cohort level and matching on the PS was repeated for the CRSwNP and CRSsNP subgroups.
Caution is always warranted when interpreting results of studies of this nature. Although the matched implant and non-implant cohorts were well-balanced on measured baseline characteristics, residual confounding by unmeasured characteristics remains possible. The PS matching relied on data available in EMR and claims records, and may not remove all confounding, particularly for unmeasured variables, such as disease and/or nasal polyp severity. There remains an implicit assumption that clinical practices between the cohorts differ only in the use of steroid-eluting sinus implants, yet patients receiving implants may also receive more thorough surgery and more meticulous postoperative care. These considerations may affect HCRU and warrant further investigation.
Limitations
There are limitations inherent in retrospective study designs and the secondary use of data. While the sinus types operated on during the index surgery and revision surgeries are reported, the dataset did not allow for determination of the specific sinuses where implants were placed, nor of the number of implants placed. Since the non-implant cohort was matched to the patients in the implant cohort, the revision surgery rates and HCRU observed in the non-implant cohort may not be generalizable to a larger population of less severely diseased CRS patients who do not receive implants during sinus surgery. Despite the multi-source nature of the dataset, incomplete data capture may have occurred: only 53.5–76.4% of patients had an otolaryngology visit during the 24-month study period. The COVID-19 pandemic may have restricted access to both office visits and elective procedures in 2020 and 2021, yet the percentage of patients with these encounters would be expected to be higher in most clinical practices, suggesting incomplete data capture. The HCRU observed in the dataset may underestimate total HCRU as services paid for out-of-pocket or otherwise are not captured in the claims or EMR data; however, this would not be expected to bias the findings as it should apply to both groups of patients. The study did not assess differences in postoperative medication use such as inhaled nasal corticosteroids, saline rinses, antibiotics or oral steroids as these therapies are low cost, frequent components of the postoperative standard of careCitation9 and would be expected to be similar regardless of implant status. Chances of statistically significant findings due to multiple comparisons also cannot be ruled out.
Conclusions
In this retrospective, observational RWE study, CRSwNP and CRSsNP patients who received steroid-eluting sinus implants after ESS had significantly lower HCRU over 24 months compared to patients who underwent ESS alone. Revision surgery over 24 months was significantly reduced in implant patients in the CRSwNP subgroup. These findings provide additional evidence that long-term reductions in HCRU may be achieved with steroid-eluting sinus implant use during sinus surgery in the challenging CRSwNP population as well as in CRSsNP patients.
Transparency
Declaration of funding
Intersect ENT, Inc. (now Medtronic) engaged and provided funding to OM1, Inc. to conduct this study.
Declaration of financial/other relationships
VH, KM, and IT are employees of OM1, Inc. AKG is a former employee of Intersect ENT, Inc. JEK was a paid consultant to Intersect ENT, Inc. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Author contributions
Conception/design of the study: VH, IT, AG, JEK; Acquisition/analysis of the data: VH, KM, IT; Interpretation of the data: All authors; Drafting of the paper or revising it critically for intellectual content: All authors; Final approval of the version to be published: All authors. All authors agree to be accountable for all aspects of the work.
Acknowledgements
The authors would like to thank Gwendolyn Moser (OM1) for assistance with project management, Harry Cheng and Zhaohui Su (OM1) for assistance with the study analysis, and Xiaomin Deng and Declan Tuffy (Medtronic) for their contributions to the interpretation of results.
Notes
i PROPEL family of sinus implants (PROPEL, PROPEL Mini and PROPEL Contour), Intersect ENT, Inc., Menlo Park, CA, USA. PROPEL is indicated following ethmoid sinus surgery, PROPEL Contour is indicated following frontal and maxillary sinus surgery, and PROPEL Mini is indicated following ethmoid and frontal sinus surgery.
References
- Banerji A, Piccirillo JF, Thawley SE, et al. Chronic rhinosinusitis patients with polyps or polypoid mucosa have a greater burden of illness. Am J Rhinol. 2007;21(1):19–26.
- Rudmik L. Economics of chronic rhinosinusitis. Curr Allergy Asthma Rep. 2017;17(4):20.
- Smith KA, Orlandi RR, Rudmik L. Cost of adult chronic rhinosinusitis: a systematic review. Laryngoscope. 2015;125(7):1547–1556.
- Rosenfeld RM, Piccirillo JF, Chandrasekhar SS, et al. Clinical practice guideline (update): adult sinusitis. Otolaryngol Head Neck Surg. 2015;152(2 Suppl):S1–S39.
- Sedaghat AR, Kuan EC, Scadding GK. Epidemiology of chronic rhinosinusitis: prevalence and risk factors. J Allergy Clin Immunol Pract. 2022;10(6):1395–1403.
- Ference EH, Suh JD, Tan BK, et al. How often is sinus surgery performed for chronic rhinosinusitis with versus without nasal polyps? Am J Rhinol Allergy. 2018;32(1):34–39.
- Musy PY, Kountakis SE. Anatomic findings in patients undergoing revision endoscopic sinus surgery. Am J Otolaryngol. 2004;25(6):418–422.
- DeConde AS, Mace JC, Levy JM, et al. Prevalence of polyp recurrence after endoscopic sinus surgery for chronic rhinosinusitis with nasal polyposis. Laryngoscope. 2017;127(3):550–555.
- Orlandi RR, Kingdom TT, Smith TL, et al. International consensus statement on allergy and rhinology: rhinosinusitis 2021. Int Forum Allergy Rhinol. 2021;11(3):213–739.
- Scangas GA, Wu AW, Ting JY, et al. Cost utility analysis of dupilumab versus endoscopic sinus surgery for chronic rhinosinusitis with nasal polyps. Laryngoscope. 2021;131(1):E26–e33.
- Rizzo JA, Rudmik L, Mallow PJ, et al. Budget impact analysis of bioabsorbable drug-eluting sinus implants following endoscopic sinus surgery. J Med Econ. 2016;19(9):829–835.
- Javanbakht M, Saleh H, Hemami MR, et al. A corticosteroid-eluting sinus implant following endoscopic sinus surgery for chronic rhinosinusitis: a UK-based cost-effectiveness analysis. Pharmacoecon Open. 2020;4(4):679–686.
- Santarelli GD, Han JK. Evaluation of the PROPEL® mini sinus implant for the treatment of frontal sinus disease. Expert Opin Drug Deliv. 2016;13(12):1789–1793.
- Hoffman V, Mortimer KM, Mulder K, et al. Real-world evidence analysis of the impact of steroid-eluting implants on healthcare resource use among chronic rhinosinusitis patients undergoing sinus surgery. Curr Med Res Opin. 2022;38(3):375–381.
- Schmalbach CE, Brereton J, Bowman C, et al. American academy of Otolaryngology-Head and neck surgery/foundation reg-ent registry: purpose, properties, and priorities. Otolaryngol Head Neck Surg. 2021;164(5):964–971.
- AAO-HNSF partners with OM1 to empower more measured and precise care and treatments for otolaryngology-head and Nneck surgery [Internet]. 2020; [28 May 2020, cited 30 August 2022]. Available from: https://bulletin.entnet.org/home/article/21247900/aao-hnsf-partners-with-om1-to-empower-more-measured-and-precise-care-and-treatments-for-otolaryngology-head-and-neck-surgery.
- Wang SV, He M, Jin Y, et al. A review of the performance of different methods for propensity score matched subgroup analyses and a summary of their application in peer-reviewed research studies. Pharmacoepidemiol Drug Saf. 2017;26(12):1507–1512.
- Wang SV, Jin Y, Fireman B, et al. Relative performance of propensity score matching strategies for subgroup analyses. Am J Epidemiol. 2018;187(8):1799–1807.
- Stein NR, Jafari A, DeConde AS. Revision rates and time to revision following endoscopic sinus surgery: a large database analysis. Laryngoscope. 2018;128(1):31–36.
- Smith KA, Orlandi RR, Oakley G, et al. Long-term revision rates for endoscopic sinus surgery. Int Forum Allergy Rhinol. 2019;9(4):402–408.