Durability Of Treatment Effects Research Articles

Sustained increase of pinch strength after traction treatment for symptomatic distal interphalangeal joint osteoarthritis

BackgroundSymptomatic distal interphalangeal joint osteoarthritis is a common joint disease that causes hand disability and reduces quality of life. There are few conservative treatment options for this condition. The purpose of this study was to investigate the effect of traction treatment on symptomatic distal interphalangeal joint osteoarthritis. MethodsThis prospective, longitudinal study involved multiple time-series observations and within-subject controls. The most painful distal interphalangeal joints in patients with hand osteoarthritis were treated by daily, 15-min joint traction at home using a finger trap orthosis. The corresponding contralateral digits were used as within-subject controls. The primary outcome measure was two-point pinch strength, and the secondary outcome measures were radiographic findings and treatment adherence. Longitudinal and pairwise comparison analyses of the treated and control digits examined improvements in two-point pinch strength at months 1, 3, and 6 from baseline. The durability of treatment effects after treatment discontinuation was investigated at month 12. ResultsEighteen treated digits and 18 corresponding control digits were eligible for analysis. There was a significant increase in two-point pinch strength after 1-month traction, and this increase was maintained until month 6 despite the absence of radiographic changes. Compared to controls, significant improvement in two-point pinch strength relative to baseline was seen at every observation time point, with a moderate to large effect size. There was no time–treatment interaction. Treatment adherence was high. At months 3 and 6, around 60–80 % of digits were voluntarily treated. Pinch strength was comparable between months 6 and 12, with greater improvement than in the control group. ConclusionJoint traction treatment can improve pinch strength in symptomatic distal interphalangeal joint osteoarthritis. Larger, randomized studies on traction treatment and the effect on hand function are warranted.

Two-year outcomes of radiofrequency device treatment of the nasal valve for nasal airway obstruction.

Temperature-controlled radiofrequency (TCRF) device treatment of nasal valve dysfunction (NVD) was superior to a sham procedure control in reducing the symptoms of nasal airway obstruction (NAO) in this randomised controlled trial (RCT). Two-year outcomes for 108 patients actively treated in a prospective, multicenter, patient-blinded RCT were used to determine treatment effect durability and changes in medication/nasal dilator usage. A responder was defined as ≥ 20 reduction in NOSE score or 1 reduction in severity class. The mean (SD) age of patients was 48.5 (12.3) years; 66 (61.1%) women. Baseline NOSE score was 76.3. The 2-year responder rate was 90.4% and NOSE score treatment effect was -41.7; 54.7% improvement. Of 57 patients using medications/nasal dilators at baseline, 45 (78.9%) either stopped all use (33.3%) or stopped/decreased (45.6%) use in >=1 class at 2 years. Concurrent septal deviation, septal swell body, or turbinate enlargement did not significantly affect the odds of exhibiting a NOSE score of ≤ 25 at 2 years. TCRF device treatment of NVD resulted in significant and sustained improvements in the symptoms of NAO at 2 years, accompanied by a substantial reduction in medication/nasal dilator use.

A Digital Cognitive-Physical Intervention for Attention-Deficit/Hyperactivity Disorder: Randomized Controlled Trial.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders among children. Pharmacotherapy has been the primary treatment for ADHD, supplemented by behavioral interventions. Digital and exercise interventions are promising nonpharmacologic approaches for enhancing the physical and psychological health of children with ADHD. However, the combined impact of digital and exercise therapies remains unclear. The aim of this study was to determine whether BrainFit, a novel digital intervention combining gamified cognitive and exercise training, is efficacious in reducing ADHD symptoms and executive function (EF) among school-aged children with ADHD. This 4-week prospective randomized controlled trial included 90 children (6-12 years old) who visited the ADHD outpatient clinic and met the diagnostic criteria for ADHD. The participants were randomized (1:1) to the BrainFit intervention (n=44) or a waitlist control (n=46) between March and August 2022. The intervention consisted of 12 30-minute sessions delivered on an iPad over 4 weeks with 3 sessions per week (Monday, Wednesday, and Friday after school) under the supervision of trained staff. The primary outcomes were parent-rated symptoms of attention and hyperactivity assessed according to the Swanson, Nolan, and Pelham questionnaire (SNAP-IV) rating scale and EF skills assessed by the Behavior Rating Inventory of Executive Function (BRIEF) scale, evaluated pre and post intervention. Intention-to-treat analysis was performed on 80 children after attrition. A nonparametric resampling-based permutation test was used for hypothesis testing of intervention effects. Among the 145 children who met the inclusion criteria, 90 consented and were randomized; ultimately, 80 (88.9%) children completed the study and were included in the analysis. The participants' average age was 8.4 (SD 1.3) years, including 63 (78.8%) male participants. The most common ADHD subtype was hyperactive/impulsive (54/80, 68%) and 23 (29%) children had severe symptoms. At the endpoint of the study, the BrainFit intervention group had a significantly larger improvement in total ADHD symptoms (SNAP-IV total score) as compared to those in the control group (β=-12.203, 95% CI -17.882 to -6.523; P<.001), owing to lower scores on the subscales Inattention (β=-3.966, 95% CI -6.285 to -1.647; P<.001), Hyperactivity/Impulsivity (β=-5.735, 95% CI -8.334 to -3.137; P<.001), and Oppositional Defiant Disorder (β=-2.995, 95% CI -4.857 to -1.132; P=.002). The intervention was associated with significant reduction in the Metacognition Index (β=-6.312, 95% CI -10.973 to -1.650; P=.006) and Global Executive Composite (β=-5.952, 95% CI -10.214 to -1.690; P=.003) on the BRIEF. No severe intervention-related adverse events were reported. This novel digital cognitive-physical intervention was efficacious in school-age children with ADHD. A larger multicenter effectiveness trial with longer follow-up is warranted to confirm these findings and to assess the durability of treatment effects. Chinese Clinical Trial Register ChiCTR2300070521; https://www.chictr.org.cn/showproj.html?proj=177806.

Is repeated mistake-making an effective treatment strategy for perfectionism? Findings from a randomized controlled trial

Background and objectivesPerfectionism has been linked to self-criticism, procrastination, and psychological disorders. In a previous study, an exposure-based treatment for perfectionism (ETP), which included exposures targeted at concern over mistakes, showed positive outcomes when compared to waitlist. The aim of this study was to further investigate ETP by comparing it to a stress-management condition and assessing durability of treatment effects by conducting a one-month follow-up assessment. MethodsEighty-five individuals with elevated perfectionism were randomly assigned to receive ETP (n = 43) or a stress management treatment (n = 42). ETP involved repeatedly practicing mistake-making by completing computerized tasks engineered to cause individuals to make mistakes. The stress management condition included listening to videos and answering questions about healthy habits, such as diet, exercise, and sleep, as well as viewing calming videos. Participants completed eight treatment sessions as well as baseline, post-test, and one month follow-up self-report questionnaires. ResultsContrary to predictions, compared to ETP, stress management led to significantly lower overall perfectionism, depression, generalized anxiety, and social anxiety at post and significantly lower depression, generalized anxiety, and social anxiety at follow-up. Further, individuals who completed ETP did not habituate to the exposure tasks, but distress increased from the first to the last treatment session. LimitationsThe duration of treatment was relatively brief. ConclusionsThis study highlights the importance of using active psychological control conditions in treatment outcome studies and the need to test various components of treatments for perfectionism to observe what may be effective or even potentially iatrogenic.

Empowered Relief, cognitive behavioral therapy, and health education for people with chronic pain: a comparison of outcomes at 6-month Follow-up for a randomized controlled trial.

We previously conducted a 3-arm randomized trial (263 adults with chronic low back pain) which compared group-based (1) single-session pain relief skills intervention (Empowered Relief; ER); (2) 8-session cognitive behavioral therapy (CBT) for chronic back pain; and (3) single-session health and back pain education class (HE). Results suggested non-inferiority of ER vs. CBT at 3 months post-treatment on an array of outcomes. Here, we tested the durability of treatment effects at 6 months post-treatment. We examined group differences in primary and secondary outcomes at 6 months and the degree to which outcomes eroded or improved from 3-month to 6-month within each treatment group. Empowered Relief remained non-inferior to CBT on most outcomes, whereas both ER and CBT remained superior to HE on most outcomes. Outcome improvements within ER did not decrease significantly from 3-month to 6-month, and indeed ER showed additional 3- to 6-month improvements on pain catastrophizing, pain bothersomeness, and anxiety. Effects of ER at 6 months post-treatment (moderate term outcomes) kept pace with effects reported by participants who underwent 8-session CBT. The maintenance of these absolute levels implies strong stability of ER effects. Results extend to 6 months post-treatment previous findings documenting that ER and CBT exhibit similarly potent effects on outcomes.

Long-term follow-up of acceptance-enhanced behavior therapy for trichotillomania

Acceptance-enhanced behavior therapy for trichotillomania (AEBT-TTM) is effective in reducing trichotillomania (TTM) symptoms, but the durability of treatment effects remains in question. This study analyzed 6-month follow-up data from a large randomized clinical trial comparing AEBT-TTM to an active psychoeducation and supportive therapy control (PST). Adults with TTM (N=85; 92% women) received 10 sessions of AEBT-TTM or PST across 12 weeks. Independent evaluators assessed participants at baseline, post-treatment, and 6 months follow-up. For both AEBT-TTM and PST, self-reported and evaluator-rated TTM symptom severity decreased from baseline to follow-up. TTM symptoms did not worsen from post-treatment to follow-up. At follow-up, AEBT-TTM and PST did not differ in rates of treatment response, TTM diagnosis, or symptom severity. High baseline TTM symptom severity was a stronger predictor of high follow-up severity for PST than for AEBT-TTM, suggesting AEBT-TTM may be a better option for more severe TTM. Results support the efficacy of AEBT-TTM and show that treatment gains were maintained over time. Although AEBT-TTM yielded lower symptoms at post-treatment, 6-month follow-up outcomes suggest AEBT-TTM and PST may lead to similar symptom levels in the longer term. Future research should examine mechanisms that contribute to long-term gain maintenance.

Two-year outcomes of radiofrequency device treatment of the nasal valve for nasal airway obstruction

BACKGROUND: Temperature-controlled radiofrequency (TCRF) device treatment of nasal valve dysfunction (NVD) was superior to a sham procedure control in reducing the symptoms of nasal airway obstruction (NAO) in this randomised controlled trial (RCT). METHODOLOGY: Two-year outcomes for 108 patients actively treated in a prospective, multicenter, patient-blinded RCT were used to determine treatment effect durability and changes in medication/nasal dilator usage. A responder was defined as ≥20% reduction in NOSE score or ≥1 reduction in severity class. RESULTS: The mean (SD) age of patients was 48.5 (12.3) years; 66 (61.1%) women. Baseline NOSE score was 76.3. The 2-year responder rate was 90.4% and NOSE score treatment effect was −41.7; 54.7% improvement. Of 57 patients using medications/nasal dilators at baseline, 45 (78.9%) either stopped all use (33.3%) or stopped/decreased (45.6%) use in ≥1 class at 2 years. Concurrent septal deviation, septal swell body, or turbinate enlargement did not significantly affect the odds of exhibiting a NOSE score of ≤25 at 2 years. CONCLUSIONS: TCRF device treatment of NVD resulted in significant and sustained improvements in the symptoms of NAO at 2 years, accompanied by a substantial reduction in medication/nasal dilator use.

Abstract 14132: Thirty-Six Month Results in Patients With Resistant Hypertension After Endovascular Ultrasound Renal Denervation in the RADIANCE-HTN TRIO Trial

Background: Endovascular ultrasound renal denervation (uRDN) has been shown to reduce blood pressure (BP) and medication burden in patients with resistant hypertension in the multicenter, blinded, randomized, sham-controlled RADIANCE-HTN TRIO trial through 6 months. We report the 36-month safety and durability of treatment effect on office BP (OBP) in the patients treated with uRDN. Methods: Patients with hypertension resistant to a 3-drug single-pill confirmed by daytime ambulatory BP ≥135/85 mmHg were randomized to uRDN (n=69) or sham procedure (n=67). From 2-5 months, if monthly home BP was ≥135/85 mmHg, prespecified standardized stepped-care antihypertensive treatment including an aldosterone antagonist (AA) was started under blinding to treatment assignment. After 6 months, patients were unblinded and received antihypertensive medications (AHM) at treating physicians’ discretion. We assessed changes in OBP of the uRDN group at 36 months vs. baseline and screening. Results: Forty-nine of 69 (71%) patients (age: 53.0 ± 7.4 years; 18% female) originally randomized to uRDN completed their 36-month follow-up. OBP at screening in those patients was 159/103 ± 15/10 mmHg on a mean of 3.9 AHM with 33% of patients on AA. Baseline OBP after starting the single-pill combination was 153/99 mmHg. At 36 months OBP changed by -14.5/-9.0 mmHg from screening (p&lt;0.001 for both) and -8.0/-5.0 mmHg from baseline (p=0.007; p=0.02) on a mean of 3.7 AHM with 41% of patients on AA. At 36 months, OBP change from baseline was irrespective of whether or not patients were taking AA. Given ambulatory BP was used to qualify patients at baseline, some patients had OBP &lt;140/90 mmHg. For those with baseline OBP ≥140/90 (n=39), change in OBP at 36 months from baseline was -12.9/-7.4 mmHg (p&lt;0.001 for both) on mean 3.6 AHM. No new uRDN-related long-term safety concerns were identified. Conclusion: In patients with resistant hypertension, the effectiveness and safety of uRDN were durable to 36 months.

Long-term Follow-up After Aneurysm Treatment with the Flow Redirection Endoluminal Device (FRED) Flow Diverter

IntroductionThis study focuses on long-term outcomes after aneurysm treatment with either the Flow Re-Direction Endoluminal Device (FRED) or the FRED Jr. to investigate the durability of treatment effect and long-term complications.MethodsThis study is based on a retrospective analysis of a prospectively maintained patient data base. Patients treated with either FRED or FRED Jr. between 2013 and 2017 at our institution, and thus a possibility for ≥ 5 years of follow-up, were included. Aneurysm occlusion rates, recurrence rates, modified Rankin scale score shifts to baseline, and delayed complications were assessed.ResultsIn this study 68 patients with 84 aneurysms had long-term follow-up with a mean duration of 57.3 months and 44 patients harboring 52 aneurysms had a follow-up ≥ 5 years with a mean follow-up period of 69.2 months. Complete occlusion was reached in 77.4% at 2 years and increased to 84.9% when the latest available imaging result was considered. Younger age and the absence of branch involvement were predictors for aneurysm occlusion in linear regression analysis. After the 2‑year threshold, there were 3 reported symptomatic non-serious adverse events. Of these, one patient had a minor stroke, one a transitory ischemic attack and one had persistent mass effect symptoms due to a giant aneurysm, none of these resulted in subsequent neurological disability.ConclusionThis long-term follow-up study demonstrates that the FRED and FRED Jr. are safe and effective for the treatment of cerebral aneurysms in the long term, with high rates of complete occlusion and low rates of delayed adverse events.

779-P: Intensification of Glucagon-Like Peptide-1 Receptor Agonists Therapy with First and Second Generation Basal Insulins—The RESTORE-G Real-World Study

ADA guidelines suggest that in patients needing insulin treatment, combination therapy with a glucagon-like peptide 1 receptor agonist (GLP1-RA) is recommended for greater efficacy, durability of treatment effect, and weight and hypoglycemia benefit. However, when treatment with GLP1-RA needs to be intensified, switch to insulin approach is still very common. It is also known that second generation basal insulins (2BI) provide similar or improved efficacy with a better safety profile compared to first generation basal insulins (1BI). Aim of this RESTORE-G sub-study was to perform a propensity-score adjusted comparative effectiveness analysis of adding-on/switching to 2BI vs. 1BI in patients on GLP1-RA therapy (±oral hypoglycemic agents) needing intensification. Table shows sample sizes, patients characteristics and effectiveness results. Data shows that 2BI vs. 1BI was associated with significantly larger improvements in HbA1c and FBG both in add-on and switch approaches. In the switch approach, 2BI produced lower weight gain versus 1BI. Switching vs. adding on was associated with a more frequent use of short acting insulin. Both 1BI and 2BI were poorly titrated. Disclosure R.Napoli: Advisory Panel; Sanofi, Eli Lilly and Company, Novo Nordisk, Research Support; Novo Nordisk, AstraZeneca, Speaker's Bureau; Sanofi, Eli Lilly and Company, Novo Nordisk, AstraZeneca, MSD Life Science Foundation. M.Larosa: None. A.Nicolucci: Board Member; AstraZeneca, Research Support; Novo Nordisk, Sanofi, Sobi, Shionogi &amp; Co., Ltd., AlfaSigma, Speaker's Bureau; Boehringer Ingelheim and Eli Lilly Alliance. M.Rossi: Research Support; Sanofi, Novo Nordisk, Shionogi &amp; Co., Ltd., AlfaSigma. R.Candido: None. Restore-g study group: n/a. Funding Sanofi

0393 Durability of treatment effects for a stepped-care model integrating digital therapy for insomnia

Abstract Introduction A stepped-care model going from digital cognitive behavioral therapy for insomnia (dCBT-I) to clinician-led CBT-I (fCBT-I) has been shown to be acutely effective. However, the sustainability of the effects over longer periods of time has not yet been examined. This study tested the durability of treatment effects of this stepped-care approach two years following the end of treatment. Methods 1018 individuals with insomnia (DSM-5 diagnostic criteria) were randomized into two conditions at step 1: dCBT-I (N=613), or an online sleep education control (N=624). Participants in the dCBT-I condition who did not remit (ISI&amp;gt;9) were further randomized to either face-to-face CBT-I (N=103) or sleep education (N=104). Insomnia remission and treatment gains at 2-year follow-up were compared across treatment conditions. Results Among step-1 non-remitters, odds of insomnia remission for those who stepped-up to fCBT-I was almost three times higher (60% in remission) than those who received the step-2 control (33% in remission), OR = 2.95, 95% CI [1.3, 6.7]. Odds of remission was not significantly different between those who remitted at step-1 (64% in remission at year 2) and those who received fCBT-I, OR = 3.53, 95% CI [1.7, 7.5]. The treatment gains were higher in the fCBT-I group (9.6 point improvement from baseline) compared to those who remitted at step-1 (7.7 point improvement from baseline) (Cohen’s d = 0.44). Conclusion Preliminary evidence indicate that the treatment effects of this stepped-care model are durable two years after treatment. Support (if any) Support for this study was provided from the National Institute of Mental Health R56MH115150 and R01MH122636 awarded to Dr. Christopher Drake.

Safety and effectiveness of the sodium-glucose cotransporter inhibitor bexagliflozin in cats newly diagnosed with diabetes mellitus.

Bexagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor. A pilot study has shown that bexagliflozin can decrease dependence on exogenous insulin in cats with diabetes mellitus (DM). To evaluate the safety and effectiveness of bexagliflozin as a monotherapy for DM in previously untreated cats. Eighty-four client-owned cats. Historically controlled prospective open-label clinical trial. Cats were dosed PO with 15 mg bexagliflozin once daily for 56 days, with a 124-day extension to evaluate safety and treatment effect durability. The primary endpoint was the proportion of cats experiencing a decrease in hyperglycemia and improvement in clinical signs of hyperglycemia from baseline on day 56. Of 84 enrolled cats, 81 were evaluable on day 56, and 68 (84.0%) were treatment successes. Decreases in mean serum glucose, fructosamine, and β-hydroxybutyrate (β-OHB) concentrations were observed, and investigator assessments of cat neurological status, musculature, and hair coat quality improved. Owner evaluations of both cat and owner quality of life were favorable. The fructosamine half-life in diabetic cats was found to be 6.8 days. Commonly observed adverse events included emesis, diarrhea, anorexia, lethargy, and dehydration. Eight cats experienced serious adverse events, 3 of which led to death or euthanasia. The most important adverse event was euglycemic diabetic ketoacidosis, diagnosed in 3 cats and presumed present in a fourth. Bexagliflozin decreased hyperglycemia and observed clinical signs in cats newly diagnosed with DM. As a once-daily PO medication, bexagliflozin may simplify management of DM in cats.

Long-Term PAE Results: What Do We Know.

Prostatic artery embolization (PAE) is a minimally invasive technique with proven safety and efficacy to treat lower urinary tract symptoms (LUTS) due to benign prostatic obstruction (BPO) or benign prostatic hyperplasia (BPH). In this review, we discuss the required level of evidence to implement and adopt treatment options for patients with LUTS due to BPO/BPH. Focus is given on the long-term (>3 years) data after PAE with reported outcomes including cohort sizes, follow-up times, reintervention rates (repeat PAE and prostatectomy), need for LUTS/BPO medical therapy, and improvements in International Prostate Symptom Score/quality of life score, peak flow rate (Qmax), postvoid residual, prostate volume, and prostate-specific antigen. The durability of treatment effects after PAE and need for prostatic reinterventions need to be taken into consideration when discussing treatment options with patients and referring colleagues from other medical specialties. Developments in medical devices used for PAE have allowed for a continuous drop in unilateral PAE rates over the last 12 years and will probably play a role in optimizing technical and thus clinical outcomes for patients with LUTS due to BPH/BPO.

Parenting Acceptance and Commitment Therapy: An RCT of an online course with families of children with CP

AimTo test an online course Parenting Acceptance and Commitment Therapy (PACT) in an RCT with families of children with cerebral palsy (CP), predicting improvements in emotional availability and parent and child adjustment. Method67 families of children (2–10 years) with CP participated. Families were randomly assigned to waitlist control or PACT. Assessments at baseline, post-intervention and at six-month follow up (durability of intervention effects) focussed on emotional availability, adjustment and quality of life. Analysis consisted of repeated measure linear regression models. ResultsAt postintervention (T2), an intervention effect was demonstrated for two aspects of observed emotional availability: parental non-intrusiveness MD = 0.68 (−0.56 to 1.92), p = 0.050 and child involvement, MD = 0.91 (−0.36 to 2.18), p = 0.011. An intervention effect was also found for the parent-reported emotional availability in terms of child involvement. Further intervention effects were found in parent-report measures of child quality of life (social wellbeing and acceptance, participation and physical health), parental mindfulness, parental acceptance, support, social connection, and meaning. No effects were found on parent or child adjustment. Analyses focussed on durability of intervention effect, collapsed across groups, indicated that effects persisted at 6 month follow up (T4). InterpretationPACT demonstrated an intervention effect for two aspects of emotional availability−parental non-intrusiveness and child involvement−as well as parental mindfulness and child quality of life. Parents reported increased comfort with the CP diagnosis, higher likelihood to seek support, higher likelihood to stay connected to others and greater meaningful living. PACT is an effective online/telehealth parenting support intervention for parents of children with CP.

Durability of Treatment Effects for a Randomized Placebo-Controlled Trial of 8-Week Self-Administered At-Home Behavioral Skills-Based Virtual Reality for Chronic Low Back Pain: Six-Month Follow-Up

Durability of Treatment Effects for a Randomized Placebo-Controlled Trial of 8-Week Self-Administered At-Home Behavioral Skills-Based Virtual Reality for Chronic Low Back Pain: Six-Month Follow-Up

Thrombopoietin receptor agonists and rituximab for treatment of pediatric immune thrombocytopenia: A systematic review and meta-analysis of prospective clinical trials.

Children with immune thrombocytopenia (ITP) may require second-line ITP therapies. The high remission rate in pediatric patients, need for extended-duration use of thrombopoietin receptor agonists (TPO-RAs), drug adherence, potential side effects, monitoring, and cost effectiveness are factors that should be considered in decision-making about second-line therapies. Rituximab (RTX) has been used off-label for years to treat ITP but there are limited studies about its efficacy and safety in children. To date, no studies have directly compared TPO-RAs with RTX for the treatment of childhood ITP. This systematic review analyzed the overall platelet response, durability of treatment effect, and safety for RTX use in comparison to TPO-RAs in pediatric ITP. MEDLINE/PubMed, EMBASE, Cochrane Library, and Web of Science databases were searched through December 2020 and meta-analysis was conducted using proportions of success/failure for each intervention in the selected studies. The proportion of participants achieving the primary endpoint of a platelet response above 50,000 was similar for TPO-RAs (proportion=0.71, 95% CI: 0.63-0.78) and RTX (proportion=0.68, 95% CI: 0.53-0.82). However, considerable variation was found between the two groups with regards to the sustainability of the response and other secondary outcomes such as need for rescue and adverse events. RTX was associated with higher rates of rescue therapy. In this analysis of prospective pediatric ITP studies, RTX and TPO-RAs had similar rates of overall platelet response but differed in other important measures. Prospective comparative studies are needed to better characterize second-line treatments for pediatric ITP.

PRELIMINARY ESTIMATES OF OFF-TREATMENT DURABILITY OF GEFAPIXANT ACROSS TWO PHASE 3 STUDIES OF PARTICIPANTS WITH REFRACTORY OR UNEXPLAINED CHRONIC COUGH

TOPIC: Respiratory Care TYPE: Original Investigations PURPOSE: In two phase 3, randomized, placebo-controlled trials (COUGH-1, NCT03449134; COUGH‑2, NCT03449147), 52 weeks of twice-daily (BID) treatment with gefapixant 45 mg, a P2X3-receptor antagonist, significantly reduced patient-reported cough severity and improved cough-related quality of life in participants with refractory or unexplained chronic cough (RCC and UCC, respectively). This exploratory, observational study in a subset of participants from COUGH-1 and COUGH-2 evaluated the 3-month off-treatment durability of gefapixant in participants with a treatment response after 1 year of treatment. METHODS: Participants from a subset of study sites in select countries who completed 1 year of treatment in COUGH-1 or COUGH-2 and were ≥80% compliant with the completion of patient-reported outcome entries and ≥80% adherent to study intervention through the main and extension study periods were eligible. Responders at 52 weeks from baseline were defined as those who achieved a ≥30-mm reduction on the cough severity visual analog scale (VAS), a ≥1.3-point increase on the Leicester Cough Questionnaire (LCQ), or a ≥1.3- or ≥2.7-point reduction on the Cough Severity Diary (CSD). Treatment durability was assessed as the proportion of responders in each treatment group (ie, placebo, gefapixant 15 mg BID, or gefapixant 45 mg BID) after the 3-month off-treatment phase (Week 64). RESULTS: Of 163 participants enrolled in the off-treatment study, 58, 55, and 50 had received placebo, gefapixant 15 mg, or gefapixant 45 mg, respectively, in COUGH-1 or COUGH-2. Participant characteristics were generally comparable with the overall study population and across intervention groups. At Week 52, 52%, 43%, and 74% of participants were VAS responders in the placebo, gefapixant 15 mg, and gefapixant 45 mg groups, respectively, with 91%, 67%, and 86% of responders demonstrating a response at Week 64. At Week 52, 63%, 83%, and 81% of participants were LCQ responders, respectively, with 88%, 87%, and 80% of responders demonstrating a response at Week 64. For the CSD cutoff of ≥1.3-point reduction from baseline, 67%, 77%, and 91% of participants were responders at Week 52, respectively, with 93%, 78%, and 92% of responders demonstrating a response at Week 64. For the CSD cutoff of ≥2.7-point reduction, 44%, 43%, and 79% of participants were responders at Week 52, respectively, with 90%, 80%, and 71% of responders demonstrating a response at Week 64. CONCLUSIONS: A high proportion of participants with RCC or UCC who demonstrated a treatment response after 52 weeks of study intervention demonstrated a response after a 3-month off-treatment period, with consistent results across VAS, LCQ, and CSD outcomes. CLINICAL IMPLICATIONS: This exploratory study suggests treatment with gefapixant 45 mg for 52 weeks may result in some durability of treatment effect. Further data will help inform durability after treatment cessation. DISCLOSURES: Advisory Committee Member relationship with Merck Please note: $1001 - $5000 by Surinder Birring, source=Web Response, value=Consulting fee Consultant relationship with Merck Please note: 2017-2021 Added 04/28/2021 by Peter Dicpinigaitis, source=Web Response, value=Consulting fee Employee No relevant relationships by Lorcan McGarvey, source=Web Response Advisory Committee Member relationship with Merck Please note: $5001 - $20000 by Alyn Morice, source=Web Response, value=Consulting fee Advisory Committee Member relationship with Bellus Please note: $5001 - $20000 by Alyn Morice, source=Web Response, value=Consulting fee Advisory Committee Member relationship with Bayer Please note: $5001 - $20000 by Alyn Morice, source=Web Response, value=Consulting fee Advisory Committee Member relationship with Sanofi Please note: $5001 - $20000 by Alyn Morice, source=Web Response, value=Consulting fee Employee relationship with MSD Please note: 11/2016 to current Added 05/06/2021 by David Muccino, source=Web Response, value=Salary Employee relationship with Merck Sharp & Dohme Corp. Please note: May 1995 - present Added 04/30/2021 by Allison Nguyen, source=Web Response, value=Salary Advisory Committee Member relationship with GSK Please note: $1001 - $5000 by Ian Pavord, source=Web Response, value=Consulting fee Employee relationship with Merck & Co., Inc. Please note: 7 years Added 04/30/2021 by Jonathan Schelfhout, source=Web Response, value=Salary Scientific Medical Advisor relationship with Merck Please note: $1001 - $5000 by Jaclyn Smith, source=Web Response, value=Consulting fee Scientific Medical Advisor relationship with Vitalograph Ltd Please note: $5001 - $20000 by Jaclyn Smith, source=Web Response, value=Grant/Research Support Grant Funding relationship with Merck Please note: 2020-2022 Added 05/01/2021 by Jaclyn Smith, source=Web Response, value=Grant/Research Support Employee relationship with Merck & Co, Inc Please note: 2019 to Present Added 04/30/2021 by Ping Xu, source=Web Response, value=Salary

Efficacy of a Single-Session "Empowered Relief" Zoom-Delivered Group Intervention for Chronic Pain: Randomized Controlled Trial Conducted During the COVID-19 Pandemic.

BackgroundCognitive behavioral therapy–pain is an evidence-based treatment for chronic pain that can have significant patient burden, including health care cost, travel, multiple sessions, and lack of access in remote areas.ObjectiveThe study aims to pilot test the efficacy of a single-session videoconference-delivered empowered relief (ER) intervention compared to waitlist control (WLC) conditions among individuals with chronic pain. We hypothesized that ER would be superior to WLC in reducing pain catastrophizing, pain intensity, and other pain-related outcomes at 1-3 months posttreatment.MethodsWe conducted a randomized controlled trial involving a web-based sample of adults (N=104) aged 18-80 years with self-reported chronic pain. Participants were randomized (1:1) to 1 of 2 unblinded study groups: ER (50/104, 48.1%) and WLC (54/104, 51.9%). Participants allocated to ER completed a Zoom-delivered class, and all participants completed follow-up surveys at 2 weeks and 1, 2, and 3 months posttreatment. All the study procedures were performed remotely and electronically. The primary outcome was pain catastrophizing 1-month posttreatment, with pain intensity, pain bothersomeness, and sleep disruption as secondary outcomes. We also report a more rigorous test of the durability of treatment effects at 3 months posttreatment. Data were collected from September 2020 to February 2021 and analyzed using intention-to-treat analysis. The analytic data set included participants (18/101, 17.8% clinic patients; 83/101, 82.1% community) who completed at least one study survey: ER (50/101, 49.5%) and WLC (51/104, 49%).ResultsParticipants (N=101) were 69.3% (70/101) female, with a mean age of 49.76 years (SD 13.90; range 24-78); 32.7% (33/101) had an undergraduate degree and self-reported chronic pain for 3 months. Participants reported high engagement (47/50, 94%), high satisfaction with ER (mean 8.26, SD 1.57; range 0-10), and high satisfaction with the Zoom platform (46/50, 92%). For the between-groups factor, ER was superior to WLC for all primary and secondary outcomes at 3 months posttreatment (highest P<.001), and between-groups Cohen d effect sizes ranged from 0.45 to 0.79, indicating that the superiority was of moderate to substantial clinical importance. At 3 months, clinically meaningful pain catastrophizing scale (PCS) reductions were found for ER but not for WLC (ER: PCS −8.72, 42.25% reduction; WLC: PCS −2.25, 11.13% reduction). ER resulted in significant improvements in pain intensity, sleep disturbance, and clinical improvements in pain bothersomeness.ConclusionsZoom-delivered ER had high participant satisfaction and very high engagement. Among adults with chronic pain, this single-session, Zoom-delivered, skills-based pain class resulted in clinically significant improvement across a range of pain-related outcomes that was sustained at 3 months. Web-based delivery of ER could allow greater accessibility of home-based pain treatment and could address the inconveniences and barriers faced by patients when attempting to receive in-person care.Trial RegistrationClinicalTrials.gov NCT04546685; https://clinicaltrials.gov/ct2/show/NCT04546685

Cost Effectiveness of Cognitive Behavioral Therapy for the Treatment of Subjective Tinnitus in Australia.

The aim of this study was to conduct an economic evaluation for the treatment of subjective tinnitus using different modalities of cognitive behavioral therapy (CBT) in Australia. A decision tree model was used to conduct a cost-utility analysis for CBT to determine the cost effectiveness for tinnitus treatments, in terms of cost per responder and cost per quality-adjusted life-year (QALY), from a health system perspective using a 2-year time horizon. Meta-analysis was used to differentiate the levels of effectiveness between three delivery methods for CBT: individual face-to-face care (fCBT), group sessions (gCBT), and a supported internet program (iCBT). One-way sensitivity analysis and probabilistic sensitivity analysis (PSA) explored the uncertainty surrounding model inputs and outcomes. Results were presented as incremental cost-effectiveness ratios compared with no treatment, and as net monetary benefit at a $50,000 willingness-to-pay threshold. Compared with no treatment, the incremental cost per responder was $700 for gCBT, $871 for iCBT, and $1380 for fCBT. The base case incremental cost-effectiveness ratio was $35,363 per QALY for fCBT, $17,935 per QALY for gCBT, and $22,321 per QALY for iCBT compared with no treatment, although there was substantial uncertainty around the QALY gain for responders. Net monetary benefit was $356 (fCBT), $555 (gCBT), and $487 (iCBT), indicating the treatments were cost effective compared with no treatment. One-way sensitivity analysis revealed the results were most sensitive to the probability of a positive response to treatment and treatment length. The PSA found the probability of being cost effective compared with no treatment for gCBT was 99.8%, iCBT 98.4%, and fCBT 71.5% at a willingness-to-pay of $50,000 per QALY, although QALY gain remained at a fixed value in the PSA. CBT for tinnitus was likely to be cost effective compared with no treatment regardless of treatment modality, assuming they are not mutually exclusive. Of the interventions, gCBT was the lowest cost per responder and lowest cost per QALY. Internet CBT obtained comparable economic outcomes due to similar treatment effectiveness and cost. Group CBT and iCBT warrant greater adoption in clinical practice for the treatment of subjective tinnitus. Further research on preference-based utility measures for varying levels of tinnitus severity and the durability of treatment effect is required to enhance the quality of economic evaluation in this field.

25572 Impact of risankizumab on the duration of PASI90 achievement: A post hoc analysis of 4 phase III clinical trials

Psoriasis Area and Severity Index (PASI) 90 has increasingly been used as the treatment target in psoriasis. This study compared the durability of treatment effect for risankizumab vs other therapies. Data from 4 randomized phase 3 studies of risankizumab, UltIMMa-1, UltIMMa-2, IMMvent, and IMMhance were pooled. Patients were classified into 5 groups based on their treatment experience during the 1-year follow-up period: risankizumab (RISA) only, RISA followed by re-randomization to RISA or placebo (RISA & RISA/PBO), adalimumab (ADA) followed by re-randomization to ADA or RISA (ADA & ADA/RISA), ustekinumab (UST) only, and placebo followed by RISA. The proportion of patients achieving PASI90 was plotted at each visit to construct a PASI90 curve. The number of days and proportion of days with PASI90 over a year was estimated using an area under the curve approach. Nonresponder imputation was used for missing PASI observations. A total of 2101 patients were included in this analysis. Mean age was 47.5 years, 70% were males, and mean duration since psoriasis diagnosis was 18.6 years. Patients treated with RISA only experienced the longest PASI90 duration (245.7 days [67.3% over 1-year]), followed by patients treated with RISA & RISA/PBO (228.5 [62.6%]), and ADA & ADA/RISA (183.8 [50.4%]). Patients treated with placebo followed by RISA (156.8 [43.0%]) and UST only (154.2 [42.2%]) experienced the shortest PASI90 duration. Patients with moderate to severe psoriasis treated with risankizumab exhibited longer durations of PASI90 than patients treated with other therapies.