Cryoablation, Radiofrequency Ablation and Laser Ablation for Treatment of Chronic Rhinitis - CAM 701168

Description
Ablation therapy is proposed as an alternative to medical management for patients with chronic rhinitis symptoms. Ablation therapy includes cryoablation (also known as cryosurgical ablation, cryosurgery, or cryotherapy), radiofrequency ablation, and laser ablation. Ablation therapy is thought to correct the imbalance of autonomic input to the nasal mucosa thereby reducing nasal antigen responses and vascular hyperreactivity.

Background 
Ablation therapy is proposed as an alternative to medical management for patients with chronic rhinitis symptoms. Ablation therapy includes cryoablation (also known as cryosurgical ablation, cryosurgery, or cryotherapy), radiofrequency ablation, and laser ablation.Ablation therapy is thought to correct the imbalance of autonomic input to the nasal mucosa thereby reducing nasal antigen responses and vascular hyperreactivity.

Medical management is the standard of care for chronic rhinitis. Surgical options such as vidian nerve resection have been investigated for patients with chronic rhinitis refractory to multiple medical therapies, and cryoablation is proposed as a less invasive alternative. Vidian neurectomy has not been widely adopted however, due to the need for general anesthesia, risk of serious adverse events (e.g., dry eyes in up to 25% of patients), and uncertainty about the procedure's long-term benefits.1 

To quantify the severity of chronic rhinitis and to assess treatment response, various outcome measures can be used, including radiologic scores, endoscopic grading, and patient-reported quality of life measures. The primary outcome measures relevant for the treatment of chronic rhinitis are patient-reported symptoms and quality of life. Examiner evaluation of the nasal and sinus appearance and polyp size may provide some information about treatment outcomes, but these evaluations are limited by the lack of universally accepted standards. 

Frequently used outcome measures for treatments of chronic rhinitis in adults are shown in Table 1. A consensus on the minimally clinically important difference (MCID) for some of these outcomes has not been established. The Food and Drug Administration (FDA) guidance on drugs for rhinitis recommends patient-reported total nasal symptom scores as the primary measure of efficacy. The FDA guidance on drugs for rhinitis does not specify a MCID for patient-reported symptom measures, but notes that a MCID should be prespecified in studies and the rationale explained. 

Six months of follow-up is considered necessary to demonstrate efficacy. Adverse events can be assessed immediately (perioperative complications and postoperative pain) or over the longer term.

Table 1. Outcome Measures for Chronic Rhinitis Interventions

Outcome Measures Description Minimal Clinically Important Difference Timing
Symptoms Reflective Total Nasal Symptom Score (rTNSS) Sum of 4 individual subject-assessed symptom scores for rhinorrhea, nasal congestion, nasal itching, and sneezing, each evaluated using a scale of 0 = none, 1 = mild, 2 = moderate, or 3 = severe.
Maximum 12 points.
Not established; 30% change from baseline has been proposed At least 6 months or longer
The Chronic Sinusitis Survey (CSS) Measure of symptoms and medication usage over an 8-week recall period. Includes 3 questions regarding symptoms and 3 regarding medication usage, yielding a total score, symptom subscore, and medication subscore. Ranges from 0 to 100 in which a low CSS score represents greater symptoms and/or medication usage. Not established At least 6 months or longer
Visual Analog Scale (VAS) Patient-reported. Not established At least 6 months or longer
Disease-Specific Quality of Life Sino-Nasal Outcome Test-20 (SNOT-20)

Patients complete 20 symptom questions on a categorical scale (0 [no bother] to 5 [worst symptoms can be]).

Average rankings can be reported over all 20 symptoms, as well as by 4 subclassified symptom domains.
The possible range of SNOT-20 scores is 0 to 5, with a higher score indicating a greater rhinosinusitis-related health burden.
SNOT-22, a variation of the SNOT-20, includes 2 additional questions (on “nasal obstruction” and “loss of smell and taste”)

SNOT-20: change in score of 0.8 or greater

SNOT-22: change in score of 8.9 points

At least 6 months or longer
Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Measures the functional (physical, emotional, and social) problems associated with rhinitis. Not established At least 6 months or longer
VAS Patient-reported. Not established At least 6 months or longer
Adverse events Various; patient- and clinician reported Potential procedure- and device-related adverse events include postoperative pain, epistaxis, and dry eyes. Not applicable Immediately post procedure to 6 months or longer

Regulatory Status
In February 2019, the Clarifix™ device (Stryker) was cleared for use in adults with chronic rhinitis through the 510(k) process (K190356).2 Clearance was based on substantial equivalence to the predicate device, ClariFix (K162608). The only modification to the subject device was an update to the indications for use to include adults with chronic rhinitis.

In December 2019, the RhinAer™ stylus (Aerin Medical) was cleared by the FDA through the 510(k) process as a tool to treat chronic rhinitis (K192471).3 Clearance was based on equivalence in design and intended use of a predicate device, the InSeca ARC Stylus (K162810). The RhinAer stylus includes modification of the InSeca ARC stylus shaft components and flexibility.

There are currently no laser ablation devices with FDA clearance for treatment of chronic rhinitis.

Policy
Cryoablation for chronic rhinitis (allergic or nonallergic) is investigational/unproven therefore is considered NOT MEDICALLY NECESSARY.

Radiofrequency ablation for chronic rhinitis (allergic or nonallergic) is investigational/unproven therefore is considered NOT MEDICALLY NECESSARY.

Laser ablation for chronic rhinitis (allergic and nonallergic) is investigational/unproven therefore is considered NOT MEDICALLY NECESSARY. 

Policy Guidelines
See the Codes Table for details. 

Benefit Application
BlueCard/National Account Issues 
State or federal mandates (e.g., Federal Employee Program) may dictate that certain U.S. Food and Drug Administration‒approved devices, drugs, or biologics may not be considered investigational, and thus these devices may be assessed only by their medical necessity. 

Rationale 
Evidence reviews assess the clinical evidence to determine whether the use of a technology improves the net health outcome. Broadly defined, health outcomes are length of life, quality of life, and ability to function including benefits and harms. Every clinical condition has specific outcomes that are important to patients and to managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens; and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms.

To assess whether the evidence is sufficient to draw conclusions about the net health outcome of a technology, 2 domains are examined: the relevance and the quality and credibility. To be relevant, studies must represent one or more intended clinical use of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The randomized controlled trial (RCT) is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. Randomized controlled trials are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice.

Cryoablation for Chronic Rhinitis
Clinical Context and Therapy Purpose
Cryoablation is proposed as an alternative to medical management for patients with chronic rhinitis.

The question addressed in this evidence review is: Does the use of cryoablation improve the net health outcome in patients with chronic rhinitis?

The following PICO was used to select literature to inform this review.

Population
The relevant population of interest is adults age 18 and older with chronic allergic or nonallergic rhinitis.

Rhinitis is defined as symptomatic inflammation of the paranasal sinuses and nasal cavity. Chronic rhinitis is usually defined as rhinorrhea with or without nasal congestion symptoms despite medical therapy lasting longer than 3 months. Allergic rhinitis is defined as an immunoglobulin E (IgE)–mediated inflammatory response of the nasal mucous membranes after exposure to inhaled allergens. Symptoms include rhinorrhea (anterior or post nasal drip), nasal congestion, nasal itching, and sneezing. Allergic rhinitis can be seasonal or perennial, with symptoms being intermittent or persistent.

Interventions
Cryoablation for chronic rhinitis involves destruction of tissue in the posterior nasal nerve region. The procedure is thought to correct the imbalance of autonomic input to the nasal mucosa, reducing nasal antigen responses and vascular hyperreactivity.

The Clarifix system uses nitrous oxide to freeze nasal tissue, causing nerve damage. The procedure can be performed under local anesthesia.

Comparators
The comparator of interest is medical management.

Options for the medical management of chronic rhinitis include allergen avoidance, nasal saline irrigation, and pharmacologic therapy (e.g., intranasal glucocorticoids, topical antihistamines, oral antihistamines, ipratropium).

For allergic rhinitis, treatment options include evaluation with appropriate allergy testing and the offering of immunotherapy.

Outcomes
The general outcomes of interest are symptoms, change in disease status, quality of life, and treatment-related morbidity.

To quantify the severity of chronic rhinitis and to assess treatment response, various outcome measures can be used, including radiologic scores, endoscopic grading, and patient-reported quality of life measures. The primary outcome measures relevant for the treatment of chronic rhinitis are patient-reported symptoms and quality of life. Examiner evaluation of the nasal and sinus appearance and polyp size may provide some information about treatment outcomes, but these evaluations are limited by the lack of universally accepted standards.

Frequently-used outcome measures for treatments of chronic rhinitis in adults are shown above in Table 1 (see Background). Six months of follow-up is considered necessary to demonstrate efficacy. Adverse events can be assessed immediately (perioperative complications and postoperative pain) or over the longer term.

Study Selection Criteria
Methodologically credible studies were selected using the following principles:

  • To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;
  • In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
  • To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
  • Studies with duplicative or overlapping populations were excluded.

Review of Evidence
Systematic Reviews
Kompelli et al. (2018) conducted a systematic review of cryoablation for chronic rhinitis, identifying 15 nonrandomized studies enrolling a total of 1266 patients (Table 2).4 Across all of the studies, 63% to 95.7% of patients noted improvement in overall symptoms, and no serious adverse events were reported. The authors concluded that although the procedure appeared to be safe and efficacious, methodological weaknesses and heterogeneity limited the strength of conclusions that could be drawn from this body of evidence. In addition to their uncontrolled design, most studies were outdated, published between 1977 and 1997. Only 1 study, reported by Hwang et al. (2017) used an FDA-cleared device and a validated outcome measure.5 This study is discussed in detail, along with other recent nonrandomized studies, in the following section.

Table 2. Systematic Review of Cryoablation for Chronic Rhinitis

Study Literature Search Date Study Inclusion/Exclusion Criteria Population Inclusion Criteria Included Outcomes Risk of Bias Assessment Method Statistical Methods Studies Included Main Conclusions
Kompelli et al. (2018)4 February 2018 Inclusion: Studies with the primary
objective of assessing the efficacy of cryotherapy on chronic rhinitis.

Exclusion: Case reports, review articles, and nonhuman studies; studies describing the use of cryotherapy for medical diseases other than chronic rhinitis; studies not in English that could not be translated.
Chronic rhinitis patients were classified as allergic rhinitis, nonallergic rhinitis (vasomotor rhinitis), or mixed using the original author’s criteria Complications, treatment efficacy, and length of follow-up. Cochrane Handbook for Systematic Reviews of Interventions (version 5.1.0) No meta-analysis or statistical tests performed due to expected heterogeneity in outcome metrics

N = 15 studies (9 nonallergic rhinitis only, 1 allergic rhinitis only, 3 allergic and nonallergic rhinitis cohorts, 2 with mixed symptoms of allergic and nonallergic rhinitis).

N=1266 patients

All studies noted improvement in symptoms, with 63% to 95.7% of patients noting improvement in overall symptoms.

Among 6 studies reporting complications, 55 patients experienced complications (8.6%), none were considered serious. Most common were epistaxis, nasal obstruction, nasal crusting, and ear blockage.

Most studies were outdated, published between 1977 and 1997. Only 1 study used an FDA-cleared device and a validated outcome measure.

Randomized Controlled Trials
One RCT conducted by Del Signore et al. (2021)6 compared cryoablation using the Clarifix system with a sham procedure in 133 adults (age ≥ 21 years) with chronic rhinitis. Outcomes assessed included the reflective Total Nasal Symptom Score (rTNSS) and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score. Duration of follow-up was 3 months. Individuals randomized to active cryoablation were more likely than those in the sham group to respond to treatment (73.4% vs. 36.5%, p<.001), based on a rTNSS reduction of >30%. Active cryoablation was also associated with greater reductions in RQLQ score from baseline at 3-month follow-up (-1.5, 95% confidence interval [CI], -1.8 to -1.2) versus sham cryoablation (-0.8, 95% CI, -1.1 to -0.5; p < .001). This study is limited by the short duration of follow-up.

Nonrandomized Studies
Three recent single arm, nonrandomized studies including 149 patients, reported in 4 publications, have evaluated cryoablation for patients with chronic rhinitis. Characteristics and results of these studies are shown in Tables 3 and 4. The largest study (N = 98) was reported by Chang et al. (2020),7 with 2-year follow-up data on a subset of patients (n = 62) reported by Ow et al. (2021)8. Scores on the rTNSS improved significantly over baseline at 1 month, 3 months, 6 months, and 9 months, and improvements were sustained for up to 2 years among those patients who enrolled in the follow-up study. Smaller single-arm studies reported by Hwang et al. (2017)5 and Gerka Stuyt et al. (2021)9 also reported improvements in symptoms from baseline (Table 4). Chang et al. (2020) reported 2 serious procedure-related adverse events: severe epistaxis occurring on posttreatment day 19 due to a pledget inadvertently left in the nasal cavity from the day of treatment, and 1 case of mild epistaxis occurring on posttreatment day 36 which resolved with in-office cautery. Of 72 patients completing a telephone questionnaire about procedure-related discomfort, 56 (77.8%) experienced some degree of pain or discomfort. Seventeen patents reported severe headache, 5 reported severe nasal pain, and 2 reported severe sinus pain.7 No serious adverse events were reported in the other studies (see Table 4).

Key limitations of these studies are summarized in Tables 5 and 6. A major limitation was their uncontrolled, open-label design. Additionally, loss to follow-up was high and MCID were not pre-specified for important outcome measures. Randomized controlled trials are needed to confirm improvements in symptom scores observed in nonrandomized studies.

Table 3. Nonrandomized Studies of Cryoablation for Chronic Rhinitis- Characteristics

Study Study Design Location Dates Inclusion/Exclusion Criteria Patient Characteristics Treatment Duration of Follow-up
Hwang et al. (2017)5 Prospective, single-arm, open-label 3 sites, US Not reported Inclusion:
Adult patients with rhinorrhea with or without nasal congestion symptoms despite medical therapy longer than 3 months; minimum rhinorrhea and/or congestion subscores of 2 as part of the TNSS

Exclusion:
Patient-reported history of chronic rhinosinusitis, severe septal deviation precluding visualization of the middle meatus, endoscopic findings of polyps or purulence in the middle meatus, septal perforation, or prior sinus or nasal surgery that significantly altered the anatomy of the posterior nasal cavity.
N = 27

Mean age, 53.3 (SD 3.3) years;
63% female;
Race not reported;
48% were atopic
Cryoablation performed in an office setting under local anesthesia 1 year
Chang et al. (2020)7,Ow et al. (2021)8; NCT03181594 Prospective, single-arm, open-label 6 sites, US 2017 – 2020 Inclusion:

Age 21 years or older, with all of the following:

  • Moderate-to-severe symptoms of rhinorrhea (defined as individual symptom rating of 2 or 3 on the rTNSS)
  • Mild-to-severe symptoms of congestion (individual symptom rating of 1, 2, or 3 on the rTNSS) and Minimum total score of 4 (out of 12) on the rTNSS at the time of the treatment visit
  • Chronic symptoms for 6 months or longer
  • Inadequate symptom relief from at least 4 weeks of treatment with intranasal steroids
Exclusion:
  • Clinically significant nasal or sinus anatomy that limits the ability to visualize/access the posterior nasal cavity or to accommodate the device
  • Rhinitis medicamentosa, moderate-to-severe ocular symptoms, nasal or sinus infection, or recent history of epistaxis
  • Coagulation disorder or anti-coagulant treatment
  • Known sensitivity to the planned anesthetic agent(s)
  • Cryoglobulinemia, paroxysmal cold hemoglobinuria, cold urticaria, or Raynaud’s disease
  • Pregnancy
N = 98

Mean age, 58.6 (SD 16.2) years;
64.3% female;
91.8% identified as Caucasian;
70 (71.4%) with nonallergic rhinitis and 28 (28.6%) with allergic rhinitis
Cryoablation performed in an office setting under local anesthesia 2 years (n = 62)
Primary data collection at 9 months
Gerka Stuyt et al. 20219 Prospective, single-arm, open-label 7 sites, US Not reported Inclusion:
Age over 18 years, diagnosis of chronic rhinitis, and failure of medical therapy for a duration of at least 3 months.

Exclusion:
Active or chronic nasal/sinus infections, structural abnormalities restricting device from accessing the posterior middle meatus, cerebrospinal fluid leaks, rhinitis medicamentosa, confounding systemic conditions (i.e. granulomatosis with polyangiitis, Sjogren’s syndrome, cystic fibrosis, primary ciliary dyskinesia), active intranasal recreational drug use, recurrent history of epistaxis, coagulopathy, pregnancy, or nasopharyngeal malignancy.
N = 24

Mean age 60.04 (SD 16.7) years;
50% female;
Race not reported;
16 (67%) with nonallergic rhinitis; 3 (12.5%) with allergic; 5 (20.8%) with mixed
Cryoablation performed in an office setting under local anesthesia 1 year

rTNSS: Reflective Total nasal symptom score; SD: standard deviation; N; sample size;

Table 4. Nonrandomized Studies of Cryoablation for Chronic Rhinitis- Results

Study Symptoms Quality of Life Concomitant medication use Adverse events Periprocedural Pain
Hwang et al. (2017)5 Mean reduction from baseline in rTNSS (SD):
  • 30 days (n = 27): 2.6 (0.3); p < .001
  • 90 days (n = 27): 2.7 (0.4); p < .001
  • 180 days (n = 21): 2.3 (0.5); p < .001
  • 1 year (n = 15):1.9 (0.3); p < .001
Not assessed Not assessed Day 1 post procedure: 100% reported no or mild bleeding, 44% severe ear blockage, 4% severe nasal dryness; there was 1 moderate nosebleed 27 days post-procedure 74% reported no or mild pain/discomfort
Chang et al. (2020)7 (Outcomes through 9 months), Ow et al. (2021)8 (Outcomes from 12 through 24 months); NCT03181594 Mean change from baseline in rTNSS score (SD)
  • 30 days (n = 97): 2.9 (1.9); p < .001
  • 90 days (n = 96): 3.0 (2.3); p < .001
  • 180 days (n = 95): 3.0 (2.1); p < .001
  • 270 days (n = 92): 3.0 (2.4); p < .001
Median change from baseline in rTNSS score (IQR)
  • 12 months (n = 54): -3.0 (-4.0, -1.0); p < .001
  • 18 months (n = 54): -3.0 (-5.0, -2.0); p < .001
  • 24 months (n = 57): -4.0 (-5.0, -2.0); p < .001
Mean change from baseline in RQLQ score (SD)
  • 90 days (n = 96): 1.5 (1.2); p < .001
Median change from baseline in RQLQ score (IQR)
  • 18 months (n = 54): -2.1 (-3.1, -1.1); p < .001
  • 24 months (n = 57): -2.1 (-3.0, -0.8); p < .001
5 patients started using ipratropium bromide during the study period due to persistent rhinitis symptoms. Of 154 medications that 98 patients were using at baseline, 33 (21.4%) medications were discontinued during the study period. 31 treatment-related adverse events (2 serious: nosebleed)

16 of 72 (22.2%) patients assessed reported no pain or discomfort

17 reported severe headache, 5 severe nasal pain, 2 severe sinus pain

Gerka Stuyt et al. (2021)9 Mean 12-hour TNSS score (SD):
  • Baseline: 6.92 (2.8); p < .001
  • 30 days: 3.17 (2.4); p < .001
  • 90 days: 2.92 (1.4); p < .001
  • 1 year: 3.08 (2.6); p < .001
Mean 2-week TNSS score (SD):
  • Baseline: 7.75 (3.1); p < .001
  • 30 days: 3.79 (2.1); p < .001
  • 90 days: 3.88 (1.8); p < .001
  • 1 year: 3.76 (2.1); p < .001
Not assessed 12/18 patients assessed (66.7%) had eliminated or reduced the use of medication to manage their rhinitis when compared to their preoperative baseline. No patients developed epistaxis, palate numbness, or dry eye complications. Patients experienced only minimal discomfort during and post-procedure

IQR: interquartile range; rTNSS: Reflective Total nasal symptom score; RQLQ: Rhinoconjunctivitis Quality of Life Questionnaire; SD: standard deviation; N; sample size;

Table 5. Study Relevance Limitations

Study Populationa Interventionb Comparatorc Outcomesd Duration of Follow-upe
Hwang et al. (2017)5     No comparison group    
Chang et al. (2020)7, Ow et al. (2021)8; NCT03181594     No comparison group 5. Clinically significant difference for Total Nasal Symptom Score was not prespecified  
Gerka Stuyt et al. (2021)9     No comparison group    

The study limitations stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.
Population key: 1. Intended use population unclear; 2. Clinical context is unclear; 3. Study population is unclear; 4. Study population not representative of intended use.
Intervention key: 1. Not clearly defined; 2. Version used unclear; 3. Delivery not similar intensity as comparator; 4.Not the intervention of interest.
Comparator key: 1. Not clearly defined; 2. Not standard or optimal; 3. Delivery not similar intensity as intervention; 4. Not delivered effectively.
Outcomes key: 1. Key health outcomes not addressed; 2. Physiologic measures, not validated surrogates; 3. No CONSORT reporting of harms; 4. Not establish and validated measurements; 5. Clinical significant difference not prespecified; 6. Clinical significant difference not supported.
Follow-Up key: 1. Not sufficient duration for benefit; 2. Not sufficient duration for harms.

Table 6. Study Design and Conduct Limitations

Study

Allocationa

Blindingb

Selective Reportingc

Data Completenessd

Powere

Statisticalf

Hwang et al. (2017)5 1. Not randomized 1. Open label 1. Not registered 1. 6/27 (22%) lost to follow-up at 180 days, 12 (44%) lost to follow-up at 1 year 1. Power calculation not reported (N = 27); study authors note small sample size as a limitation  
Chang et al. (2020)7, Ow et al. (2021)8; NCT03181594 1. Not randomized 1. Open label   1. Through 9 months, 7/98 (7.1%) excluded from analysis: 4 lost to follow-up, 3 excluded due to resumption of ipratropium use during the study period

62 of 98 patients (63.2%) enrolled in the longer-term follow-up study.

72/98 (73.5%) patients completed post-procedure pain questionnaire.
   
Gerka Stuyt et al. (2021)9 1. Not randomized 1. Open label 1. Not registered 1. 6 of 24 lost to follow-up at 1 year (25%) 1. Power calculation not reported (N = 24); study authors note small sample size as a limitation  

The study limitations stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.
Allocation key: 1. Participants not randomly allocated; 2. Allocation not concealed; 3. Allocation concealment unclear; 4. Inadequate control for selection bias.
Blinding key: 1. Not blinded to treatment assignment; 2. Not blinded outcome assessment; 3. Outcome assessed by treating physician.
Selective Reporting key: 1. Not registered; 2. Evidence of selective reporting; 3. Evidence of selective publication.
Data Completeness key: 1. High loss to follow-up or missing data; 2. Inadequate handling of missing data; 3. High number of crossovers; 4. Inadequate handling of crossovers; 5. Inappropriate exclusions; 6. Not intent to treat analysis (per protocol for noninferiority trials).
Power key: 1. Power calculations not reported; 2. Power not calculated for primary outcome; 3. Power not based on clinically important difference.
Statistical key: 1. Analysis is not appropriate for outcome type: (a) continuous; (b) binary; (c) time to event; 2. Analysis is not appropriate for multiple observations per patient; 3. Confidence intervals and/or p values not reported; 4. Comparative treatment effects not calculated.

Section Summary: Cryoablation
For individuals with chronic rhinitis who receive cryoablation, the evidence includes a RCT, nonrandomized studies, and a systematic review of nonrandomized trials. Relevant outcomes are symptoms, change in disease status, quality of life, and treatment-related morbidity. Three single-arm, open-label studies enrolling a total of 149 patients reported improvements from baseline in patient-reported symptom scores up to 1 year. Sustained improvement for up to 2 years was observed in 1 study; however, only 62 of 98 patients enrolled in the longer-term follow-up phase. In the largest study, there were 2 serious procedure-related adverse events (2.0%), and 77.8% of patients who responded to a post-procedure questionnaire reported some degree of pain or discomfort. Study limitations, including lack of a control group and high loss to follow-up, preclude drawing conclusions from this body of evidence. The RCT used a sham control group, follow-up was limited to 3 months. A systematic review of 15 nonrandomized studies reported improvements with cryoablation; however, only 1 study used an approved device and validated outcome measuring.

Radiofrequency Ablation for Chronic Rhinitis
Clinical Context and Therapy Purpose
Radiofrequency ablation is proposed as an alternative to medical management for patients with chronic rhinitis.

The question addressed in this evidence review is: Does the use of radiofrequency ablation improve the net health outcome in patients with chronic rhinitis?

The following PICO was used to select literature to inform this review.

Population
The relevant population of interest is individual with chronic allergic or nonallergic rhinitis.

Rhinitis is defined as symptomatic inflammation of the paranasal sinuses and nasal cavity. Chronic rhinitis is usually defined as rhinorrhea with or without nasal congestion symptoms despite medical therapy lasting longer than 3 months. Allergic rhinitis is defined as an IgE–mediated inflammatory response of the nasal mucous membranes after exposure to inhaled allergens. Symptoms include rhinorrhea (anterior or post nasal drip), nasal congestion, nasal itching, and sneezing. Allergic rhinitis can be seasonal or perennial, with symptoms being intermittent or persistent.

Interventions
Radiofrequency ablation for chronic rhinitis involves destruction of tissue in the posterior nasal nerve region. The procedure is thought to correct the imbalance of autonomic input to the nasal mucosa, reducing nasal antigen responses and vascular hyperreactivity.

The RhinAerStylus is a handheld device designed for use under local anesthesia. The device delivers radiofrequency energy at a temperature of 60 degrees Celsius to the posterior nasal nerve region.

Comparators
The comparator of interest is medical management.

Options for the medical management of chronic rhinitis include allergen avoidance, nasal saline irrigation, and pharmacologic therapy (e.g., intranasal glucocorticoids, topical antihistamines, oral antihistamines, ipratropium).

For allergic rhinitis, treatment options include evaluation with appropriate allergy testing and the offering of immunotherapy.

Outcomes
The general outcomes of interest are symptoms, change in disease status, quality of life, and treatment-related morbidity.

To quantify the severity of chronic rhinitis and to assess treatment response, various outcome measures can be used, including radiologic scores, endoscopic grading, and patient-reported quality of life measures. The primary outcome measures relevant for the treatment of chronic rhinitis are patient-reported symptoms and quality of life. Examiner evaluation of the nasal and sinus appearance and polyp size may provide some information about treatment outcomes, but these evaluations are limited by the lack of universally accepted standards.

Frequently-used outcome measures for treatments of chronic rhinitis in adults are shown above in Table 1 (see Background). Six months of follow-up is considered necessary to demonstrate efficacy. Adverse events can be assessed immediately (perioperative complications and postoperative pain) or over the longer term.

Study Selection Criteria
Methodologically credible studies were selected using the following principles:

  • To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;
  • In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
  • To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
  • Studies with duplicative or overlapping populations were excluded.

Review of Evidence
Randomized Controlled Trials
Stolovitsky et al. (2021) conducted an RCT comparing radiofrequency ablation using the RhinAer device with sham treatment.10 The trial enrolled 117 adults (age 18 to 85 years; mean age 57 years) with chronic rhinitis. Use of medication to treat chronic rhinitis was allowed in both groups. Based on an intention to treat analysis that accounted for all randomized participants, after 3-months follow-up the proportion of participants with a ≥ 30% improvement in rTNSS score was higher in the active radiofrequency ablation group (66.7%, 95% CI 55.1% to 76.9%) than in the sham group (41.0%, 95% CI 25.6% to 57.9%; p = .01). A similar number of participants in the active (9.1% [7/77] and sham groups (12.8% [5/39] increased their medication use during the study. Limitations of the study include the short duration of follow-up. Follow-up is ongoing, and publication of longer-term results is planned.

Nonrandomized studies
Ehmer et al. (2021) reported the results of a 1-year nonrandomized study of radiofrequency ablation for treatment of chronic rhinitis.11 Study characteristics and results are summarized in Tables 7 and 8. The study found radiofrequency ablation associated with reductions from baseline (indicating improvement of symptoms) in rTNSS score at 12 and 52 weeks. The proportion of responders to treatment, based on an improvement of ≥30% in rTNSS score, was greater than 80% at all timepoints. This study is limited by the nonrandomized, open-label design and lack of control group (Tables 9 and 10).

Table 7. Nonrandomized Studies of Radifrequency Ablation for Chronic Rhinitis - Characteristics

Study Study Design Location Dates Inclusion/Exclusion Criteria Patient Characteristics Treatment Duration of Follow-up
Ehmer et al. (2021)11, Prospecitve, single-arm, open label 5 sites, U.S. 2018 – 2019
Chronic rhinitis of at least 6 months duration
Refractory to medical management (defined as an inadequate response after at least 4 weeks usage of intranasal steroids)
rTNSS score ≥ 6
N = 50

Mean age 57.9 years (SD 11.9); 42% female; 94% white, 4% Asian, 2% American Indian/Alaska Native; 42% allergic rhinitis, 34% nonallergic rhinitis, 24% unknown etiology

Radiofrequency ablation (device heated to 60° C) performed in an office setting 1 year

rTNSS: Reflective Total nasal symptom score.

Table 8. Nonrandomized Studies of Radiofrequency Ablation for Chronic Rhinitis - Results

Study Symptoms Concomitant medication use Adverse events Periprocedural Pain
Ehmer et al. (2021)11 Mean rTNSS score:
  • Baseline: 8.5 (95% CI 8.0 to 9.0)
  • 12 weeks: 3.4 (95% CI 2.8 to 4.1)
  • 52 weeks: 3.6 (95% CI 3.0 to 4.3)
Proportion of responders based on ≥ 30% improvement from baseline in rTNSS score:
  • 12 weeks: 87.8% (95% CI 75.8% to 94.3%)
  • 26 weeks: 91.7% (95% CI 80.4% to 96.7%)
  • 52 weeks: 80.9% (95% CI 67.5% to 89.6%)
Proportion with increased concomitant medication use during the study:
  • Antihistamines/ decongestants: 12.8%
  • Decongestant nasal spray: 4.3%
  • Steroid nasal spray: 6.4%
Serious adverse events: 2 (N = not reported;
any adverse event: 16 (N = 8)
Mean post-treatment pain score
(VAS 0 – 100): 18.1

CI: confidence interval; rTNSS: Reflective Total nasal symptom score; VAS: visual analog score.

Table 9. Study Relevance Limitations

Study Populationa Interventionb Comparatorc Outcomesd Duration of Follow-upe
Ehmer et al. (2021)11     No comparison group    

The study limitations stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.
a Population key: 1. Intended use population unclear; 2. Clinical context is unclear; 3. Study population is unclear; 4. Study population not representative of intended use.
b Intervention key: 1. Not clearly defined; 2. Version used unclear; 3. Delivery not similar intensity as comparator; 4.Not the intervention of interest.
c Comparator key: 1. Not clearly defined; 2. Not standard or optimal; 3. Delivery not similar intensity as intervention; 4. Not delivered effectively.
d Outcomes key: 1. Key health outcomes not addressed; 2. Physiologic measures, not validated surrogates; 3. No CONSORT reporting of harms; 4. Not establish and validated measurements; 5. Clinical significant difference not prespecified; 6. Clinical significant difference not supported.
e Follow-Up key: 1. Not sufficient duration for benefit; 2. Not sufficient duration for harms.

Table 10. Study Design and Conduct Limitations

Study

Allocationa

Blindingb

Selective Reportingc

Data Completenessd

Powere

Statisticalf

Ehmer et al. (2021)11 1. Not randomized 1. Open label        

The study limitations stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.
a
Allocation key: 1. Participants not randomly allocated; 2. Allocation not concealed; 3. Allocation concealment unclear; 4. Inadequate control for selection bias.

b Blinding key: 1. Not blinded to treatment assignment; 2. Not blinded outcome assessment; 3. Outcome assessed by treating physician.
c Selective Reporting key: 1. Not registered; 2. Evidence of selective reporting; 3. Evidence of selective publication.
d Data Completeness key: 1. High loss to follow-up or missing data; 2. Inadequate handling of missing data; 3. High number of crossovers; 4. Inadequate handling of crossovers; 5. Inappropriate exclusions; 6. Not intent to treat analysis (per protocol for noninferiority trials).
e Power key: 1. Power calculations not reported; 2. Power not calculated for primary outcome; 3. Power not based on clinically important difference.
f Statistical key: 1. Analysis is not appropriate for outcome type: (a) continuous; (b) binary; (c) time to event; 2. Analysis is not appropriate for multiple observations per patient; 3. Confidence intervals and/or p values not reported; 4. Comparative treatment effects not calculated.

Section Summary: Radiofrequency Ablation
For individuals with chronic rhinitis who receive radiofrequency ablation, the evidence includes a RCT and a nonrandomized study. Results from the RCT suggest that radiofrequency ablation is more effective than sham ablation in improving short-term rTNSS scores. Results from a 1-year, nonrandomized, uncontrolled study also found radiofrequency ablation associated with improvements in rTNSS scores at timepoints up to 1 year. Randomized controlled trials directly comparing radiofrequency ablation with medical management and with longer follow-up are needed to confirm the efficacy of radiofrequency ablation for treatment of chronic rhinitis.

Laser Ablation for Chronic Rhinitis
Clinical Context and Therapy Purpose
Laser ablation is proposed as an alternative to medical management for patients with chronic rhinitis.

The question addressed in this evidence review is: Does the use of laser ablation improve the net health outcome in patients with chronic rhinitis?

The following PICO was used to select literature to inform this review.

Population
The relevant population of interest is individual with chronic allergic or nonallergic rhinitis.

Rhinitis is defined as symptomatic inflammation of the paranasal sinuses and nasal cavity. Chronic rhinitis is usually defined as rhinorrhea with or without nasal congestion symptoms despite medical therapy lasting longer than 3 months. Allergic rhinitis is defined as an IgE–mediated inflammatory response of the nasal mucous membranes after exposure to inhaled allergens. Symptoms include rhinorrhea (anterior or post nasal drip), nasal congestion, nasal itching, and sneezing. Allergic rhinitis can be seasonal or perennial, with symptoms being interittent or persistent.

Interventions
Laser ablation for chronic rhinitis involves destruction of tissue in the posterior nasal nerve region. The procedure is thought to correct the imbalance of autonomic input to the nasal mucosa, reducing nasal antigen responses and vascular hyperreactivity.

There are currently no laser ablation devices with FDA clearance for treatment of chronic rhinitis.

Comparators
The comparator of interest is medical management.

Options for the medical management of chronic rhinitis include allergen avoidance, nasal saline irrigation, and pharmacologic therapy (e.g., intranasal glucocorticoids, topical antihistamines, oral antihistamines, ipratropium).

For allergic rhinitis, treatment options include evaluation with appropriate allergy testing and the offering of immunotherapy.

Outcomes
The general outcomes of interest are symptoms, change in disease status, quality of life, and treatment-related morbidity.

To quantify the severity of chronic rhinitis and to assess treatment response, various outcome measures can be used, including radiologic scores, endoscopic grading, and patient-reported quality of life measures. The primary outcome measures relevant for the treatment of chronic rhinitis are patient-reported symptoms and quality of life. Examiner evaluation of the nasal and sinus appearance and polyp size may provide some information about treatment outcomes, but these evaluations are limited by the lack of universally accepted standards.

Frequently-used outcome measures for treatments of chronic rhinitis in adults are shown above in Table 1 (see Background). Six months of follow-up is considered necessary to demonstrate efficacy. Adverse events can be assessed immediately (perioperative complications and postoperative pain) or over the longer term.

Study Selection Criteria
Methodologically credible studies were selected using the following principles:

  • To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;
  • In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
  • To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
  • Studies with duplicative or overlapping populations were excluded.

Review of Evidence
Nonrandomized studies
Krespi et al. (2020) conducted a nonrandomized study evaluating laser ablation for treatment of chronic rhinitis.12 The study enrolled 32 adults treated with an endoscopic diode laser in an outpatient setting. Duration of follow-up was 3 months. Mean rTNSS was reduced from 6.0 (standard deviation [SD 0.7]) at baseline to 2.3 (SD 0.4) at 3-month follow-up. Adverse events were not reported. The study had multiple limitations, including the small sample size, uncontrolled design, and duration of follow-up less than 6 months. Randomized studies comparing laser ablation with medical management and with longer follow-up are needed to determine efficacy and safety.

Section Summary: Laser Ablation
Evidence on laser ablation for chronic rhinitis is limited to a single nonrandomized study with 3 months followup. Although laser ablation reduced rTNSS scores, additional studies are needed to determine the efficacy and safety of laser ablation for treatment of chronic rhinitis. 

Summary of Evidence
For individuals with chronic rhinitis who receive cryoablation, the evidence includes a RCT, nonrandomized studies, and a systematic review of nonrandomized trials. Relevant outcomes are symptoms, change in disease status, quality of life, and treatment-related morbidity. Three single-arm, open-label studies enrolling a total of 149 patients reported improvements from baseline in patient-reported symptom scores up to 1 year. Sustained improvement for up to 2 years was observed in 1 study; however, only 62 of 98 patients enrolled in the longer-term follow-up phase. In the largest study, there were 2 serious procedure-related adverse events (2.0%), and 77.8% of patients who responded to a post-procedure questionnaire reported some degree of pain or discomfort. Study limitations, including lack of a control group and high loss to follow-up, preclude drawing conclusions from this body of evidence. The RCT used a sham control group, and follow-up was limited to 3 months. Randomized controlled trials directly comparing cryoablation with standard medical management and with longer follow-up are needed. A systematic review of 15 nonrandomized studies reported improvements with cryoablation; however, only 1 study used an approved device and validated outcome measuring, limiting conclusions from this systematic review. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals with chronic rhinitis who receive radiofrequency ablation, the evidence includes an RCT and a nonrandomized study. Results from the RCT suggest that radiofrequency ablation is more effective than sham ablation in improving short-term rTNSS scores. Results from a 1-year, nonrandomized, uncontrolled study also found radiofrequency ablation associated with improvements in rTNSS scores at timepoints up to 1 year. Randomized controlled trials directly comparing radiofrequency ablation with medical management and with longer follow-up are needed to confirm the efficacy of radiofrequency ablation for treatment of chronic rhinitis. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Evidence on laser ablation for chronic rhinitis is limited to a single small nonrandomized study with 3 months followup. Although laser ablation reduced rTNSS scores, additional studies are needed to determine the efficacy and safety of laser ablation for treatment of chronic rhinitis. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

The purpose of the following information is to provide reference material. Inclusion does not imply endorsement or alignment with the evidence review conclusions. 

Practice Guidelines and Position Statements
Guidelines or position statements will be considered for inclusion in ‘Supplemental Information' if they were issued by, or jointly by, a U.S. professional society, an international society with U.S. representation, or National Institute for Health and Care Excellence (NICE). Priority will be given to guidelines that are informed by a systematic review, include strength of evidence ratings, and include a description of management of conflict of interest.

No clinical practice guidelines on cryoablation, radiofrequency ablation, or laser ablation for chronic rhinitis were identified through clinical consultation or literature searches conducted through Jan. 5, 2022.

American Academy of Allergy, Asthma, and Immunology
A 2020 practice parameter update on rhinitis from the American Academy of Allergy, Asthma, and Immunology did not address ablation techniques, including cryoablation, radiofrequency ablation, or laser ablation.13

U.S. Preventive Services Task Force Recommendations
Not applicable 

Ongoing and Unpublished Clinical Trials
Some currently ongoing and unpublished trials that might influence this review are listed in Table 11.

Table 11. Summary of Key Trials   

NCT No. Trial Name Planned Enrollment Completion Date
Ongoing      
NCT04154605a ClariFix Rhinitis Randomized Controlled Trial 133 Jul 2022
NCT04533438a The RhinAer Procedure for Treatment of CHronic RhInitis - A Prospective, MulticeNter Randomized ConTrolled TRial Comparing RhinAer to Sham Control (RHINTRAC) 120 Apr 2023
NCT04614324a A Prospective, Open Label, Multi-Center Study Using the RhinAer Procedure for Treatment of Subjects Suffering With Chronic Rhinitis 140 Aug 2024
Unpublished
     
NCT04684875a A Prospective, Multi-center, Non-Randomized Study to Evaluate the Quality of Life Impact and Symptoms After Treatment Using Low Power Radiofrequency Energy Applied to the Posterior Nasal Nerve Area for Symptomatic Relief of Chronic Rhinitis 45 Aug 2021

NCT: national clinical trial.
a  Denotes industry-sponsored or cosponsored trial.

References 

  1. Lieberman P.L.. Chronic nonallergic rhinitis. In: UpToDate, Corren J (Ed), UpToDate, Waltham, MA. https://www.uptodate.com/contents/chronic-nonallergic-rhinitis. Accessed January 25, 2022.
  2. Food & Drug Administration. Clarifix 510(k) Premarket Notification. 2019 (K190356) https://fda.report/PMN/K190356/19/K190356.pdf. Accessed January 25, 2022.
  3. Food & Drug Administration. RhinAer (RHIN1 Stylus) 510(k) Premarket Notification. 2019 (K192471). Accessed January 3, 2022.
  4. Kompelli AR, Janz TA, Rowan NR, et al. Cryotherapy for the Treatment of Chronic Rhinitis: A Qualitative Systematic Review. Am J Rhinol Allergy. Nov 2018; 32(6): 491-501. PMID 30229670
  5. Hwang PH, Lin B, Weiss R, et al. Cryosurgical posterior nasal tissue ablation for the treatment of rhinitis. Int Forum Allergy Rhinol. Oct 2017; 7(10): 952-956. PMID 28799727
  6. Del Signore AG, Greene JB, Russell JL, et al. Cryotherapy for treatment of chronic rhinitis: 3-month outcomes of a randomized, sham-controlled trial. Int Forum Allergy Rhinol. Jan 2022; 12(1): 51-61. PMID 34355872
  7. Chang MT, Song S, Hwang PH. Cryosurgical ablation for treatment of rhinitis: A prospective multicenter study. Laryngoscope. Aug 2020; 130(8): 1877-1884. PMID 31566744
  8. Ow RA, O'Malley EM, Han JK, et al. Cryosurgical Ablation for Treatment of Rhinitis: Two-Year Results of a Prospective Multicenter Study. Laryngoscope. Sep 2021; 131(9): 1952-1957. PMID 33616224
  9. Gerka Stuyt JA, Luk L, Keschner D, et al. Evaluation of In-Office Cryoablation of Posterior Nasal Nerves for the Treatment of Rhinitis. Allergy Rhinol (Providence). Jan-Dec 2021; 12: 2152656720988565. PMID 33598336
  10. Stolovitzky JP, Ow RA, Silvers SL, et al. Effect of Radiofrequency Neurolysis on the Symptoms of Chronic Rhinitis: A Randomized Controlled Trial. OTO Open. Jul-Sep 2021; 5(3): 2473974X211041124. PMID 34527852
  11. Ehmer D, McDuffie CM, Scurry WC, et al. Temperature-Controlled Radiofrequency Neurolysis for the Treatment of Rhinitis. Am J Rhinol Allergy. Jan 2022; 36(1): 149-156. PMID 34382444
  12. Krespi YP, Wilson KA, Kizhner V. Laser ablation of posterior nasal nerves for rhinitis. Am J Otolaryngol. May 2020; 41(3): 102396. PMID 31948695
  13. Dykewicz MS, Wallace DV, Amrol DJ, et al. Rhinitis 2020: A practice parameter update. J Allergy Clin Immunol. Oct 2020; 146(4): 721-767. PMID 3270722

Coding Section 

Codes Number Description
CPT 30999 Unlisted procedure, nose
  30117 Excision or destruction (eg, laser), intranasal lesion; internal approach
  31299 Unlisted procedure, accessory sinuses
HCPCS C9771 Nasal/sinus endoscopy, cryoablation nasal tissue(s) and/or nerve(s), unilateral or bilateral
ICD10-CM J30.0-J31.0 Rhinitis code range (chronic, allergic, non-allergic, seasonal)
TOS Surgery  
POS  Outpatient   

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive. 

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross Blue Shield Association technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies and accredited national guidelines.

"Current Procedural Terminology © American Medical Association. All Rights Reserved" 

History From 2020 Forward     

03/08/2022 

Interim review updating policy to include radiofrequency ablation and laser ablation. The previous version of the policy only addressed cryoablation. Also updating title, description, background, rationale and references. 

01/06/2022

New Policy

Complementary Content
${loading}