3‐Year Outcomes of Temperature‐Controlled Radiofrequency Ablation of the Posterior Nasal Nerve in Patients With Chronic Rhinitis

ABSTRACT

Background

Temperature‐controlled radiofrequency (TCRF) ablation of the posterior nasal nerve has been shown to improve chronic rhinitis (CR) symptoms and quality of life (QoL). This study assesses the durability of TCRF's effectiveness and safety 3 years post‐procedure in patients with perennial allergic CR and nonallergic CR.

Methodology

This prospective, multicenter, single‐blinded, randomized controlled trial included a sham control arm and long‐term follow‐up. Analysis combined patients from the active treatment and control crossover arms. Outcomes include reflective total nasal symptom score (rTNSS), postnasal drip (PND), and cough scores, as well as QoL measured by the Mini Rhinoconjunctivitis Quality‐of‐Life Questionnaire (MiniRQLQ).

Results

Of 104 patients who underwent TCRF, 59 participated in the 3‐year follow‐up. The baseline mean rTNSS was 8.2 (95% confidence interval [95% CI, 7.9–8.6]), reduced to 3.5 (95% CI, 2.9–4.1) at 3 years, a 57.3% reduction and mean change of −4.7 (95% CI, −5.3 to −4.1; p < 0.0001). Most patients (79.7%) were responders. Cough scores decreased from a mean baseline of 1.5 (95% CI, 1.3–1.7) to 0.7 (95% CI, 0.5–0.9; mean change, −0.8; p < 0.0001). PND symptoms were also reduced from 2.5 (95% CI, 2.4 – 2.7) to 1.4 (95% CI, 1.2–1.7; mean change, −1.1; p < 0.0001). No severe adverse events were reported throughout the study, and no adverse events were reported between 24 months and 36 months of follow‐up.

Conclusion

TCRF ablation of the posterior nasal nerve provided sustained safety and improvement in CR symptoms, cough, postnasal drip, and patient‐reported QoL at 3 years, supporting its long‐term safety and efficacy in CR.

1. Introduction

The posterior nasal nerve (PNN) comprises both sympathetic and parasympathetic fibers that originate from postganglionic neurons. The parasympathetic fibers originate from cranial nerve VII (facial nerve), pass through the pterygopalatine ganglion, and subsequently innervate nasal tissue, mediating various autonomic functions [1]. Hyperactivity of the PNN contributes to chronic rhinitis (CR) symptoms such as rhinorrhea, sneezing, nasal congestion, and itching. Refractory CR caused by hyperactive PNNs may be treated using surgical approaches such as Vidian and endoscopic posterior nasal neurectomy procedures [2, 3]. As a less invasive option, radiofrequency ablation can be used to disrupt nerve activity, reduce CR symptoms, and reduce CR medication burden [4, 5, 6, 7, 8]. These procedures are effective approaches to permanently or semipermanently treat the parasympathetic nervous supply to the nasal mucosa [3, 9].

A previous single‐arm pivotal study demonstrated that PNN ablation using the minimally invasive temperature‐controlled radiofrequency (TCRF) device (RhinAer, Aerin Medical, Mountain View, CA) effectively and safely reduced CR symptom burden and patient‐reported quality of life (QoL) at 3 months [5, 8], with sustained benefits through 2 years post‐procedure [4, 6]. In an initial report from the RHINTRAC randomized controlled trial (RCT), we showed that TCRF ablation of the PNN using RhinAer was superior to a sham procedure in improving the symptoms of CR 3 months post‐procedure [7]. Furthermore, symptom improvement was maintained 2 years post‐procedure in both the active treatment and the sham crossover groups included in this trial [10, 11]. Extended follow‐up was conducted to confirm the long‐term efficacy and safety of TCRF neurolysis of the PNN as a treatment for CR. Here, we present the 3‐year clinical outcomes of TCRF ablation in a combined cohort of patients receiving active treatment in the RHINTRAC RCT.

2. Methods

2.1. Study Design

This study is a long‐term follow‐up of a prospective, multicenter, single‐blinded (patient) RCT with a sham procedure control arm. The primary study used a superiority design with a 2:1 center‐stratified block randomization scheme. Patients were unblinded after the primary endpoints at 3 months. Eligible patients from the sham control arm who agreed to continue participation were allowed to crossover to active treatment. Index sham control patients who were not eligible for crossover or did not wish to continue participating exited the study. Participants in this optional extended follow‐up study were invited to participate after completing the 24‐month primary study. At the end of the 24‐month follow‐up period, 79 patients remained in the study. These patients were offered the option to participate in an extended follow‐up study involving survey questionnaires via remote study visits. Of these, 59 patients opted to participate in the 36‐month follow‐up, while 17 chose not to continue, and 3 were lost to follow‐up. For this long‐term follow‐up, we evaluated all patients who underwent active treatment, including those from the original active treatment group and those who crossed over from the sham treatment group. These patients were combined into a single active treatment group for analysis, with a new baseline established, and followed for up to 36 months post‐procedure.

2.2. Study Participants

This follow‐up study included patients diagnosed with CR who were enrolled at 16 centers across the U nited States. This study was approved by the Western Institution Review Board (IRB) and center‐specific IRBs, including Rush University Medical Center IRB, Vanderbilt University IRB, and Houston Methodist IRB. It was registered at clinicaltrials.gov (NCT04533438) and conducted in accordance with the Declaration of Helsinki and Good Clinical Practice Guidelines.

A complete list of the patient inclusion and exclusion criteria is provided in Table S1. Key inclusion criteria were patients aged 18–85 years, CR symptoms (≥ 6 months), a total 24‐h reflective total nasal symptom score (rTNSS) ≥ 6, moderate to severe symptom of rhinorrhea (rTNSS rhinorrhea sub score 2–3), and mild to severe symptom of nasal congestion (rTNSS sub score 1–3). Key exclusion criteria were anatomic obstructions limiting access to the posterior nasal passage; altered anatomy of the posterior nose as a result of prior sinus or nasal surgery/injury; active nasal or sinus infection; history of significant dry eye, chronic epistaxis, nosebleeds, rhinitis medicamentosa, head/neck irradiation, seasonal allergic rhinitis, a predisposition to excessive bleeding, anticoagulation therapy that could not be discontinued before the procedure, and prior procedure or surgery for CR; and a predisposition to poor wound healing (in the opinion of the investigator) [7].

2.3. Active Treatment Procedure

Treatment was performed in an office‐based setting using the RhinAer® System, which includes the Aerin Console and a single‐use, disposable RhinAer stylus that delivers bipolar radiofrequency energy to target tissue. Patients received topical anesthesia followed by lidocaine (with or without epinephrine) administered by submucosal injection. TCRF treatment was administered at up to five nonoverlapping positions in the PNN area, targeting the areas of the posterior middle meatus and posterior portion of the inferior turbinate. Treatment settings were temperature, 60°C; power, 4 W; treatment time, 12 s; and no cooling time. No repeat (touch‐up) procedures were allowed at any time. All investigators were board‐certified otolaryngologists trained in the use of the device.

2.4. Patients’ Assessment

2.4.1. Rhinitis Symptoms (rTNSS, Cough, and Postnasal Drip)

The rTNSS is a widely adopted tool used to assess patient‐rated severity of nasal symptoms [12], covering four key symptoms: rhinorrhea, nasal congestion, nasal itching, and sneezing. The rTNSS was recorded at baseline and through the 3‐year follow‐up. The study's primary clinical endpoint was the mean change in rTNSS at each follow‐up compared to the baseline. A responder was defined as achieving a ≥ 30% improvement (decrease) in rTNSS from baseline, a threshold recognized as the minimal clinically important difference (MCID) [13]. The percentage of patients reporting each rTNSS subscore was also recorded at baseline and each follow‐up.

Self‐reported symptoms of cough and postnasal drip were assessed using a 4‐point scale: 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms, and 3 = severe symptoms. These ratings were recorded at baseline and each follow‐up visit.

2.4.2. Quality of Life

QoL was assessed at baseline and each follow‐up using the validated Mini Rhinoconjunctivitis Quality‐of‐Life Questionnaire (MiniRQLQ) based on a 1‐week recall [14]. The MiniRQLQ consists of 14 questions across 5 domains: activity limitations (n = 3), practical problems (n = 2), nose symptoms (n = 3), eye symptoms (n = 3), and other symptoms (n = 3). Responses to the MiniRQLQ were recorded on a 7‐point scale: 0 = not troubled, 1 = hardly troubled at all, 2 = somewhat troubled, 3 = moderately troubled, 4 = quite a bit troubled, 5 = very troubled, and 6 = extremely troubled. A responder was defined as achieving ≥ 0.4 points improvement from the baseline; this is the MCID for MiniRQLQ [14].

2.4.3. Medication

This study is pragmatic, so the protocol did not dictate medication use. Medications for CR symptoms were recorded at baseline and through the 3‐year follow‐up. The names, frequency, and doses of medications were documented and classified as antihistamines, decongestants, oral leukotriene inhibitors, intranasal corticosteroid sprays, intranasal anticholinergic sprays, allergy immunotherapy, and others (combination medication and expectorant). Medication use was assessed at baseline (yes/no) and relative to baseline at each follow‐up. At each follow‐up, patients were asked if they had started new medications, increased doses, maintained the same dosage, decreased doses, or discontinued any medications. The overall medication burden for a patient was determined by evaluating all medication classes taken by the patient at the 3‐year follow‐up and comparing them to baseline.

2.4.4. Safety

Device‐ and procedure‐related adverse events (AEs) were recorded throughout the 3‐year follow‐up. The frequency and severity of reported device‐related, procedure‐related, and serious AEs (SAEs) were documented.

2.5. Statistical Analysis

Statistical analysis was performed using SAS/STAT version 9.4 (SAS Institute, Cary, NC). The justification for this study's sample size has been previously reported [7]. Patient demographics and other baseline characteristics were summarized using frequencies and percentages for categorical variables and descriptive analysis of means, medians, and standard deviations (SDs) for continuous variables. Demographic characteristics, responder rate, and change in rTNSS and MiniRQLQ were compared between patients included in the 3‐year analysis (3‐year) and those not included in the 3‐year analysis (no 3‐year) using t‐tests for continuous variables and Fisher's exact tests for categorical variables.

A negative change indicates a decrease (improvement) in the rTNSS total score, rTNSS subscore, postnasal drip score, and cough score. Generalized estimating equation models with multiple time point comparisons were used to evaluate the repeated measures of continuous data (rTNSS, MiniRQLQ) over time; statistical significance was set at an alpha level of 0.05. Adjusted (least squares) mean, mean change, % change, and 95% CI, are presented along with p values for the changes between baseline and follow‐up visits. The proportion (%) of responders and the 95% CI, were also calculated. A sensitivity analysis comparing the rTNSS responder rates of patients not participating in the 36‐month follow‐up to those who did participate was conducted using a Fisher's Exact test.

A mixed model with repeated measures (MMRM) was used to account for the multiple assessments per patient in this longitudinal analysis to evaluate significant differences in the rTNSS and miniRQLQ scores between timepoints. Within‐group p values were assessed for significance, with an alpha level of 0.05.

3. Results

3.1. Demographics and Baseline Characteristics

At baseline, 104 eligible patients underwent the RhinAer treatment procedure: 77 patients from the active treatment group and 27 patients from the sham treatment crossover. Of the 104 patients who underwent active treatment, 101, 97, 88, 79, and 59 were evaluated at 3 months, 6 months, 1 year, 2 years, and 3 years post‐procedure, respectively. Over the 3 years of the study, a total of 45 patients exited the study. Of those, 16 patients were lost to follow‐up, 1 crossover patient had treatment aborted, 1 patient withdrew, 1 patient died (reasons unrelated to the study), 17 patients did not agree to participate in the extended follow‐up study, and 9 patients underwent additional nasal procedures (vidian neurectomy, septoplasty/turbinate reduction, cryotherapy, turbinate reduction). Figure 1 shows the patient disposition for each analysis group over time. Patients’ mean age at baseline was 57.3 (SD 14.7), and the mean body mass index (BMI) was 28.0 (SD 5.9). Most (62.5%) of the participants were female. The study population included both allergic and nonallergic patients, with nearly all (98%) patients having rhinitis for > 1 year. At the 3‐year follow‐up, patients’ mean age was 56.5 (SD 13.2), BMI was 28.1 (SD 6.2), and 36 (61.0%) were female. Demographic characteristics, nasal exam findings, prior nasal surgery, and % of patients with rhinitis > 1 year did not differ between patients included in the 36‐month analysis and those who were not (p > 0.05). However, the distribution of rhinitis types differed between these groups (p = 0.001). A summary of the patient's demographics, nasal exam findings, and prior nasal surgery is presented in Table 1.

FIGURE 1.

Flowchart illustrating patient enrollment, allocation, follow‐up, and analysis across the study period.

TABLE 1.

Patient demographics ^a .

	All Patients (N = 104) b	Patients with 36‐month (N = 59) c	Patients with no 36‐month (N = 45) d	p Value (36‐month vs. no 36‐month) e
Age, years, mean, (SD)	57.3 (14.7)	56.5 (13.2)	58.4 (16.6)	0.5273
BMI, kg/m2 mean (SD)	28.0 (5.9)	28.1 (6.2)	27.8 (5.6)	0.8299
Sex, n (%)
Female	65 (62.5%)	36 (61.0%)	29 (64.4%)	0.7206
Race, n (%)				0.4892
Asian	1 (1%)	1 (2%)	0 (0%)
Asian, White	1 (1%)	1 (2%)	0 (0%)
Black or African American	5 (5%)	3 (5%)	2 (4%)
Other	0 (0%)	0 (0%)	0 (0%)
White	95 (91%)	54 (92%)	41 (91%)
Declined to answer	2 (2%)	0 (0%)	2 (4%)
Nasal exam findings
Turbinate enlargement	3 (3%)	3 (5%)	0 (0%)	0.2564
Nasal polyps	20 (19%)	13 (22%)	7 (16%)	0.4062
Prior nasal surgery f	38 (37%)	21 (36%)	17 (38%)	0.8187
Rhinitis type, n (%)				0.0010
Allergic	15 (14%)	3 (5%)	12 (27%)
Nonallergic	46 (44%)	25 (42%)	21 (47%)
Mixed allergic and nonallergic	1 (1%)	0 (0%)	1 (2%)
Unknown	42 (40%)	31 (53%)	11 (24%)
Rhinitis > 1‐year n (%) g	102 (98%)	58 (98%)	44 (98%)	1.000
Baseline rTNSS	8.2 (1.9)	8.2 (2.0)	8.3 (1.9)	0.6779

Abbreviations: BMI, body mass index; rTNSS, 24‐h reflective total nasal symptom score; SD, standard deviation.

^a Continuous variables are presented as mean (M) and standard deviation (SD). Categorical measures are presented as numbers (% of total).

^b Number of patients who underwent the RhinAer treatment procedure: this includes 77 patients from the active treatment group and 27 patients from the sham group who crossed over.

^c Number of patients who reached the 3‐year follow‐up.

^d Number of patients who were not included in the 3‐year follow‐up analysis.

^e Statistical analysis between patients who reached 3‐year analysis and those who did not.

^f Includes inferior and/or middle turbinate reduction/excision, polyp removal, septoplasty, rhinoplasty, sinuplasty, functional endoscopic sinus surgery, chemical cauterization, epistaxis control with grafting, and uvuloplasty. Some patients may have undergone multiple procedures. Include combination medication and expectorant.

^g Numbers and percentages represent those endorsing a “yes” response.

3.2. Patient‐Reported Outcome Measures

There was a significant reduction in the rTNSS from a baseline mean score of 8.2 (95% CI, 7.9–8.6) to an adjusted mean score of 3.5 (95% CI, 2.9–4.1) at the 3‐year follow‐up. This represents a mean change of −4.7 (95% CI, −5.3 to −4.1; p < 0.0001), a 57.1% improvement from baseline. This improvement in rTNSS was consistent with those observed at 3 months (mean change −3.6 [95% CI, −4.1 to −3.1]; p < 0.0001, 43.3% improvement), 6 months (mean change −4.2 [95% CI, −4.7 to −3.7]; p < 0.0001, 50.9% improvement), 1 year (mean change −4.8 [95% CI, −5.3 to −4.3]; p < 0.0001, 57.7% improvement), and 2 years (mean change −5.3 [95% CI, −5.8 to −4.7]; p < 0.0001, 63.9% improvement). Figure 2 shows the mean rTNSS and 95% CI, at baseline and each follow‐up. Table S2 provides the responder rate, rTNSS scores, mean changes from baseline, 95% CI, and p values for all follow‐ups. Although numeric differences were observed in the distributions of the rTNSS total score between the 2‐ and 3‐year follow‐up visits, a post hoc exploratory analysis comparing pairwise successive study visits (3 vs. 6 months, 6 vs. 12 months, 12 vs. 24 months, and 24 vs. 36 months) confirmed that most improvements occurred within the first 12 months, with no significant changes thereafter, p = 0.09 (Table S3).

FIGURE 2.

Reflective total nasal symptom score (rTNSS) over time. Adjusted mean rTNSS and 95% confidence intervals at baseline and follow‐up. Significant reduction in rTNSS at each timepoint compared to baseline (p < 0.0001).

A total of 79.7% (95% CI, 67.2%–89.0%) of patients responded to the treatment at the 3‐year follow‐up. This is consistent with the percentage of responders at 3 months (69.3% [95% CI, 59.3%–78.1%]), 6 months (72.2% [95% CI, 62.1%–80.8%]), 1 year (79.5% [95% CI, 69.6%–87.4%]), and 2 years (87.3% [95% CI, 78.0%–93.8%]). Figure 3 depicts the responder rate at each follow‐up interval. For comparison, 76.7% (95% CI, 61.4%–88.2%) of the patients with no 36‐month analysis (n = 45) were responders to treatment at their last follow‐up, and the responder rate was not significantly different between patients included in the 36‐month analysis and those not included (p = 0.72). There was a significant reduction in the rTNSS individual symptom score (rhinorrhea, congestion, nasal itching, and sneezing) at the 3‐years follow‐up compared to the baseline, p < 0.0001. Figure S1 shows the adjusted mean and 95% CI, of each rTNSS individual symptom score at baseline and each follow‐up. Table S4 presents the distribution of symptom severities, showing a shift from moderate/severe symptoms at baseline to mild/none at follow‐ups (p < 0.001). Table S5 further confirms significant reductions in individual symptom scores, which stabilized after the first 12 months (p < 0.001).

FIGURE 3.

Responder rate over time. Percentage of patients achieving ≥ 30% improvement in rTNSS from baseline at each follow‐up. Bars indicate 95% confidence interval.

Cough and postnasal drip symptoms also declined significantly. Cough decreased from a mean score of 1.5 (95% CI, 1.3–1.7) at baseline to an adjusted mean score of 0.7 (95% CI, 0.5–0.9) at 3‐year follow‐up with a mean change of −0.8 [95% CI, −1.1 to −0.6]; p < 0.0001). Postnasal drip symptoms decreased from 2.5 (95% CI, 2.4–2.7) at baseline to an adjusted mean score of 1.4 (95% CI, 1.2–1.7) at 3‐year follow‐up with a mean change of −1.1 [95% CI, −1.4 to −0.9], p < 0.0001). Figure 4 illustrates the mean score of cough and postnasal drip symptoms over time. There was a notable shift in the severity of each rTNSS subscore, as well as cough and postnasal drip, from severe/moderate at baseline to mild/none at the 3‐year follow‐up. Figure 5 shows the distribution of rhinitis symptom severity (rTNSS, cough, and postnasal drip) at baseline and each follow‐up time point.

FIGURE 4.

Postnasal drip and cough symptoms over time. Adjusted mean and 95% confidence intervals of postnasal drip and cough scores at baseline and follow‐up. Significant reduction compared to baseline (p < 0.0001).

FIGURE 5.

Distribution of symptom severity over time. Percentage of patients reporting severity of each rTNSS subscore (rhinorrhea, nasal congestion, nasal itching, sneezing), cough, and postnasal drip at baseline and each follow‐up.

No significant difference in response rates was found at any time point between those not participating in the study between 24 and 36 months (n = 20) and those completing the study through 36 months (n = 59) (e.g., 3 months: 75.0% vs. 69.0%, p = 0.7781; 12 months: 85.0% vs. 79.7%, p = 0.7485; 24 months: 95.0% vs. 84.7%, p = 0.4376; Table S6), demonstrating that those who exited the study did not introduce bias and impact the overall results. Similarly, change from baseline rTNSS scores did not significantly differ between the two groups at any timepoint, and the degree of symptom reduction between the two groups was comparable through 24 months (Table S7).

The MiniRQLQ score significantly decreased from a mean score of 3.3 (95% CI, 3.0–3.5) at baseline to an adjusted mean score of 1.5 (95% CI, 1.2–1.8) at 3 years follow‐up. This represents a mean change of −1.8 (95% CI, −2.0 to −1.5; p < 0.0001), a 53.6% improvement. This reduction in MiniRQLQ score aligns with those observed at 3 months (mean change −1.5 [95% CI, −1.8 to −1.3]; p < 0.0001, 46.6% improvement), 6 months (mean change −1.7 [95% CI, −1.9 to −1.5]; p < 0.0001, 50.6% improvement), 1 year (mean change −1.8 [95% CI, −2.0 to −1.6]; p < 0.0001, 54.6% improvement), and 2 years (mean change −1.9 [95% CI, −2.1 to −1.7]; p < 0.0001, 57.6% improvement). Figure 6 shows the MiniRQLQ adjusted mean and 95% CI, at baseline and each follow‐up.

FIGURE 6.

Mini rhinoconjunctivitis quality of life questionnaire (MiniRQLQ) scores over time. Adjusted mean MiniRQLQ scores and 95% confidence intervals at baseline and follow‐up. Significant improvement in quality of life compared to baseline (P<.0001).

Furthermore, 76.3% [95% CI, 63.4%–86.4%] of patients were MiniRQLQ responders  at the 3‐year follow‐up. This is consistent with the percentage of responders at 3 months (79.2% [95% CI, 70.0%–86.6%]), 6 months (87.6% [95% CI, 79.4%–93.4%]), 1 year (81.8% [95% CI, 72.2%–89.2%]), and 2 years (81.0% [95% CI, 70.6%–89.0%]). Figure 7 shows the MiniRQLQ responder rate at each follow‐up. For comparison, 86.1% (95% CI, 63.4%–86.4%) of patients with no 36‐month analysis were responders to treatment at their last follow‐up, and the responder rate was not significantly different between patients included in the 36‐month analysis and those not included (p = 0.22).

FIGURE 7.

MiniRQLQ responder rate over time. Percentage of patients achieving an MCID of ≥ 0.4‐point improvement in MiniRQLQ from baseline at each follow‐up. Bars indicate 95% confidence intervals.

The percentage of patients achieving MiniRQLQ MCID, MiniRQLQ scores, and mean change from baseline over time is shown in Table S8, with the proportion of patients achieving the MCID remaining high across all follow‐ups, with 76.3% still meeting this threshold at 3 years. These findings indicate that not only did patients experience sustained reductions in symptom burden, but the majority also maintained clinically meaningful improvements in QoL over time. Table S8 also confirms that MiniRQLQ scores improved significantly from baseline and remained stable across all time points. All MiniRQLQ domain scores (activity limitations, practical problems, nose symptoms, eye symptoms, and other symptoms) significantly decreased at each follow‐up compared to baseline, p < 0.0001 (Table S9), indicating long‐term enhancement of participants’ QoL.

Exploratory pairwise comparisons of MiniRQLQ scores at successive study visits (3 vs. 6 months, 6 vs. 12 months, 12 vs. 24 months, and 24 vs. 36 months) did not demonstrate any significant differences between successive follow‐up visits (Table S10), demonstrating the long‐term stability of these QoL improvements.

3.3. Medications

At baseline, 43 out of 59 (72.9%) patients were taking one or more medication classes. At 3 years, 4/43 (9.3%) had stopped taking all medications, and 8/43 (18.6%) had stopped or decreased use in one or more medication classes without starting or increasing another medication. Specifically, compared to baseline medication use, 8 out of 30 (26.7%) patients use antihistamines, 3 out of 5 (60.0%) patients use decongestants, 7 out of 20 (35.0%) patients use corticosteroid sprays, and 6 out of 7 (85.7%) patients using anticholinergics either stopped or reduced use at the 3‐year follow‐up. Table 2 provides details on the change in usage for each medication class.

TABLE 2.

Change in medication use.

Medication class	Patients using at baseline N (%) (N = 59)	Medication change category	No of patients N (%) a	Patients starting medication after baseline N (%) b
Antihistamines	30 (50.8)			6 (10.2)
		No change	20 (66.7)
		Increased dose	2 (6.7)
		Decreased dose	3 (10.0)
		Stopped	5 (16.7)
Decongestants	5 (8.5)			1 (1.7)
		No change	2 (40.0)
		Increased dose	0 (0.0)
		Decreased dose	0 (0.0)
		Stopped	3 (60.0)
Leukotriene inhibitors	2 (3.4)			1 (1.7)
		No change	2 (100)
		Increased dose	0 (0.0)
		Decreased dose	0 (0.0)
		Stopped	0 (0.0)
Nasal steroid sprays c	20 (33.9)			4 (6.8)
		No change	11 (55.0)
		Increased dose	2 (10.0)
		Decreased dose	2 (10.0)
		Stopped medication	5 (25.0)
Nasal anticholinergic Sprays	7 (11.9)			4 (6.8)
		No change	1 (14.3)
		Increased dose	0 (0.0)
		Decreased dose	1 (14.3)
		Stopped medication	5 (71.4)
Immunotherapy	0 (0.0)			1 (1.7)
		No change	0 (0.0)
		Increased dose	0 (0.0)
		Decreased dose	0 (0.0)
		Stopped medication	0 (0.0)
Other d	2 (3.4)			0 (0.0)
		No change	2 (100.0)
		Increased dose	0 (0.0)
		Decreased dose	0 (0.0)
		Stopped	0 (0.0)

^a Percentage of the patients who used the medication class at baseline.

^b Percentage of the total patients.

^c Nasal steroid spray includes intranasal compound spray.

^d Other is the sum of ‘combination’ and expectorant.

3.4. Safety

AEs up to 6 months and 1 year have been previously reported for the crossover and index active treatment groups, respectively. No new device‐ or procedure‐related AEs were reported between 1 and 3 years of follow‐up. No SAEs were reported throughout the study.

4. Discussion

CR is characterized by the inflammation of the nasal mucosa, which results in symptoms such as rhinorrhea, sneezing, nasal congestion, and itching. Furthermore, cough and postnasal drip are intractable symptoms of CR, often inadequately managed [15]. Ablation of the PNN has recently been established as a safe and effective alternative to surgical procedures when managing CR symptoms that are refractory to medical management [4, 5, 6, 7]. This long‐term follow‐up study shows that following a single TCRF ablation of the PNN, the significant decrease (improvement) in CR symptoms burden (rhinorrhea, nasal congestion, nasal itching, sneezing) previously reported at 3‐month through 2‐year follow‐up was sustained through 3‐year follow‐up.

This study demonstrates that TCRF ablation of the PNN ablation provides durable symptom management for rhinitis, with sustained efficacy observed at 3 years post‐procedure. The responder rate, defined as >≥ 30% improvement in rTNSS from baseline, exceeded the MCID established for PNN cryosurgical ablation [16]. Notably, 80% of patients met this response criteria at 3 years. Beyond the sustained improvement in rhinitis symptoms (rhinorrhea, nasal congestion, nasal itching, sneezing), patients also reported long‐term relief in cough and postnasal drip, symptoms often overlooked in rhinitis research. TCRF ablation effectively reduces postnasal drip and cough symptoms and has been shown to contribute to the symptomatology of CR [15] despite the weak to moderate Spearman's correlation coefficient demonstrated by Gorelik et al. Given the association between CR and impaired health‐related QoL, the sustained QoL improvements reported after a single TCRF ablation underscore the procedure's lasting benefits.

The PNN is a peripheral branch of the sphenopalatine ganglion that supplies sensory, parasympathetic, and sympathetic innervation to the nasal mucosa [9, 17]. Hyperactivity within the PNN leads to an excessive release of neuropeptides, triggering neurogenic inflammation and exacerbating refractory vasomotor and allergic CR symptoms [18]. By denervating the nasal mucosa through PNN ablation, parasympathetic stimulation and blood flow to the nasal mucosa are reduced, providing lasting relief of CR symptoms [19]. The TCRF procedure specifically targets the posterior middle meatus and the posterior portion of the inferior turbinate in the region of the PNN, located distal to the pterygopalatine ganglion. This approach minimizes side effects, such as dry eye, associated with nasal nerve neurectomy.

Despite the potential for nerve regeneration at a rate of 1–5 mm/day [20, 21], participants in this long‐term follow‐up study reported sustained symptom relief and QoL improvements 3 years post‐procedure. While the rTNSS total score and miniRQLQ declined numerically between the 2‐ and 3‐year timepoints, post hoc analyses found no significant changes between the study visits through 3 years, demonstrating the durability of results (Tables S3 and S10).

Similarly, responder rates remained stable, suggesting lasting clinical benefit despite potential nerve regeneration (Table S3). Importantly, no significant differences when comparing response rates over time were observed between patients who completed the 36‐month follow‐up and those who exited the study using data until their last known study visit, indicating that symptom recurrence was unlikely to be a major factor in attrition (Table S4). Additionally, QoL improvements were sustained, with no significant decline between 24‐ and 36‐month assessments (Table S8). These findings reinforce the long‐term durability of TCRF ablation, demonstrating that symptom relief and QoL improvements persist well beyond the initial treatment period.

These findings add to the body of knowledge on the safety and efficacy of PNN ablation for reducing rhinitis symptoms. More invasive procedures like vidian neurectomy can effectively treat CR; however, significant complications, including dry eye, cheek and dental numbness, disturbance of eye movements, and blindness, are possible [3, 22]. Notably, these complications have not been observed following TCRF PNN ablation [2, 23]. In addition, unlike other minimally invasive PNN ablation procedures such as cryotherapy, there have been no reports of severe, persistent post‐procedural cold stimulus headaches. The most common complications possible with TCRF ablation of the PNN include nasal dryness, transient pain or discomfort, crusting, and minor epistaxis (nosebleeds), which are typically mild and self‐limiting. In the current study, all device‐ and procedure‐related AEs were reported within the first 6 months, underscoring the long‐term safety of the TCRF ablation of the PNN.

Another advantage of the TCRF procedure compared to more invasive surgical options is that it is a minimally invasive procedure that can be performed in‐office with local anesthesia, resulting in fewer procedure‐related AEs and no reported SAEs. Additional long‐term studies are required to evaluate the cost‐effectiveness of the TCRF procedure compared to vidian neurectomy and PNN neurectomy for managing chronic refractory rhinitis.

The challenges associated with long‐term follow‐up studies include patient attrition due to loss to follow‐up, participation in additional or alternative treatments, and patient mortality. The major limitation of this study is the rate of participant attrition at the 3‐year follow‐up. Of the patients who did not participate in the 36‐month follow‐up, 38% exited the study after completing the 24‐month primary study. However, 77% of the patients who did not participate in the 3‐year follow‐up were responders to treatment, and 86% had an MCID of ≥ 0.4 in MiniRQLQ at their last follow‐up. Although recurrence of rhinitis symptoms or rhinitis‐related QoL may not have influenced nonparticipation in the 3‐year follow‐up, it remains possible that those who did not enroll experienced a recurrence of rhinorrhea symptoms, and whether they required further treatment is unknown.

One limitation of this study is the lack of confirmatory allergy testing, which would have allowed for a more precise classification of allergic versus nonallergic rhinitis. Instead, patient classification was based on self‐reported history and prior physician diagnoses. Despite this limitation, our findings suggest that TCRF provides sustained symptom improvement regardless of rhinitis subtype, which has been similarly described by Ehmer et al. [6], indicating its potential efficacy across different patient populations.

Another challenge of this study is the lack of control over medication use due to the pragmatic design. Nevertheless, our findings indicate that 35% of patients taking corticosteroid sprays and 85.7% of patients taking anticholinergics at baseline had either stopped or decreased use at 3 years, suggesting that TCRF PNN ablation provides a lasting benefit by reducing patient medication burden. While a greater proportion of patients continued or initiated antihistamine use compared to anticholinergics, it may suggest that these patients are more prone to being sensitive to their symptoms posttreatment, and antihistamines allow them to maintain better control of their rhinitis with minimal additional intervention.

5. Conclusion

In conclusion, the results of this 3‐year long‐term follow‐up study show that TCRF ablation of the PNN is a durable, safe, and effective minimally invasive procedure for reducing CR symptoms and medication use burden and improving the patient's QoL.

Conflicts of Interest

J. Pablo Stolovitzky: Consultant for Aerin Medical, Medtronic, Cryosa, and Dyanosic. Randall A. Ow: Advisor/consultant for Aerin Medical, speaker for Sanofi/Regeneron, GSK, and Optinose, advisor to Medtronic. Stacey L. Silvers: Consultant for Aerin Medical, 3D Matrix, and Lyra Therapeutics Medical Advisory Board for STStent. Marc Dean: Consultant for Aerin Medical, 3D Matrix, STStent, Immertec, and VSEEHealth. Ahmad R. Sedaghat: Research funding from Aerin Medical. Katie Phillips: Medical advisory board with Sanofi/Regeneron. Equity in Sound Health. Masayoshi Takashima: Consultant for Aerin Medical, Medtronic, Acclarent, and LivaNova. The other authors declare no conflicts of interest.

Supporting information

Supporting Information

Stolovitzky J. P., Ow R. A., Silvers S. L., et al. “3‐Year Outcomes of Temperature‐Controlled Radiofrequency Ablation of the Posterior Nasal Nerve in Patients With Chronic Rhinitis.” International Forum of Allergy & Rhinology 15, no. 9 (2025): 15, 915–925. 10.1002/alr.23577