Relative Efficacy Research Articles

A pilot trial of a brief intervention for cannabis use supplemented with a substance-free activity session or relaxation training.

Cannabis use is increasing among college students and commonly co-occurs with anxiety symptoms in this age group. Interventions that reduce anxiety may also reduce cannabis use. Behavioral economic theory suggests that substance use reductions are most likely when there is an increase in substance-free reinforcement. This randomized pilot trial evaluated the efficacy of a brief motivational intervention (BMI) for cannabis supplemented by either a substance-free activity session (SFAS) or a relaxation training (RT) session for reducing cannabis use, problems, craving, and anxiety symptoms. One hundred thirty-two college students (Mage = 19.9; 54% female; 67% White, 31% Black) who reported five or more past-month cannabis use days were randomized to: (a) assessment-only (AO); (b) BMI plus SFAS; or (c) BMI plus RT. Participants in the BMI conditions received two individual counselor-administered sessions plus a brief phone booster session. Outcomes were evaluated 1- and 6-months postintervention. Relative to assessment, both BMI + SFAS and BMI + RT were associated with significant reductions in cannabis problems and craving at 1-month follow-up, and significant reductions in anxiety at 6-month follow-up. Relative to AO, BMI + RT was associated with significant reductions in cannabis use at 1-month follow-up. There were no differences between BMI conditions. This pilot trial was not adequately powered to conclusively evaluate relative efficacy but provides preliminary support for the short-term efficacy of both two-session interventions for reducing anxiety and cannabis-related risk among nontreatment seeking emerging adults. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Stereotactic radiosurgery with versus without embolization for intracranial dural arteriovenous fistulas: a systematic review and meta-analysis.

Stereotactic radiosurgery (SRS) has been established as a safe and alternative treatment for dural arteriovenous fistulas (dAVFs). While embolization alone is the most commonly used modality for the treatment of dAVFs, the adjunctive use of embolization with SRS, with the growing use of SRS, has gained increasing interest in the past few years. However, the relative efficacy and safety of SRS combined with embolization versus SRS alone for dAVFs remains uncertain. Hence, this systematic review aimed to evaluate the efficacy of SRS with adjunctive embolization for intracranial dAVFs. A systematic review and meta-analysis was conducted by searching electronic databases, including PubMed, Embase, and the Cochrane Library, up to August 2023. All studies evaluating the utilization of adjunctive embolization and SRS for dAVFs were included. Risk of bias was assessed using the Newcastle-Ottawa Scale. A meta-analysis was conducted on the suitable outcomes. Eighteen studies involving 715 patients were included. The mean age of the participants in the study was 64.30 years in the adjunctive embolization group and 60.51 years in the SRS-alone group. In the adjunctive embolization group 41.3% of patients were female, compared with 47.1% in the SRS-only group. The dAVF obliteration rates were 64.7% and 65.7% in the adjunctive embolization and SRS-alone groups, respectively. These obliteration rates were comparable between the two groups (p = 0.96), as were the symptom improvement rates (p = 0.35). Adverse events were rare, and were more commonly associated with the adjunctive embolization procedure, although further causal analysis was not possible. This study provides evidence that adjunctive embolization plus SRS provides similar obliteration and symptom improvement rates compared with SRS alone, with both having very limited SRS-related adverse events. Considering the added burden and adverse events of additional endovascular treatment, the authors recommend embolization be reserved for more complex dAVFs or when embolization can potentially be curative alone or provide more rapid symptomatic relief or protection during the radiosurgical latency period.

Monitoring of general anesthesia by qCON and qNOX indices versus conventional clinical parameters in urological surgery: A randomized controlled clinical trial

Background: Awareness during anesthesia is a major anesthetic concern. Depth of anesthesia is commonly assessed in clinical practice by the patient’s clinical signs and symptoms such as blood pressure, heart rate variability, and body movement. At present, many studies have focused on qCON monitoring for sedative depth, but only a few studies have focused on qNOX monitoring for analgesic depth. Aims and Objectives: The aim of the present study was to evaluate the relative efficacy of qCON and qNOX versus commonly used vital signs such as blood pressure and heart rate in monitoring the anesthetic depth and analgesia. Materials and Methods: A total of 100 patients of either sex and of ASA Physical status I & II, scheduled for urogenital surgeries, were selected and randomly placed into two groups. Group A was monitored by conventional clinical technique and Group B was monitored by qCON and qNOX indices. The primary outcome was the total dose of propofol and fentanyl required to maintain the depth of anesthesia and analgesia. The secondary outcomes were propofol and fentanyl adjustment frequency, infusion duration, and quality of recovery from anesthesia. Results: Results showed statistically significant differences between the two groups in mean dose of both propofol (P=0.000) and fentanyl (P=0.006), adjustment frequency of both propofol (P=0.000) and fentanyl (P=0.010), time required to voluntary eye-opening (P=0.000) and extubation time (P=0.000) and visual analog scale score (P=0.000). There was no statistically significant difference found in infusion duration (P=0.317) and Ramsay Sedation Score (P=0.709) between the groups. Conclusion: Using the qCON and qNOX indices, an anesthesiologist can monitor the depth of anesthesia and analgesia more effectively and can adjust the anesthetic or analgesic drug dosing in a better possible way with lesser requirement of drugs than with conventional clinical monitoring.

Comparative efficacy of non-pharmacological interventions on sleep quality in old adults: A systematic review and network meta-analysis.

To compare the effectiveness of non-pharmacological interventions in enhancing sleep quality in older people. Sleep problems in older adults have become increasingly prominent. Sleep problems not only affect the health and quality of life of older people, but also the range of chronic diseases caused by sleep problems also impose a huge burden on social services and health care. Non-pharmacological interventions are an effective alternative to pharmacological therapies, but it is unclear which non-pharmacological therapies are most effective in enhancing sleep quality in older adults. A systematic review and network meta-analysis based on PRISMA-NMA. A total of seven databases were searched from the establishment of the database to March 2023. After literature screening and data extraction, the Cochrane Bias assessment tool 2.0 version of randomised controlled trials (RCTs) was used to evaluate literature quality. A network meta-analysis was performed to evaluate the relative efficacy of the non-pharmacological interventions on sleep quality. A total of 71 RCTs involving nine non-pharmacological interventions were included. The results of the network meta-analysis showed that the joint intervention may be the most effective non-pharmacological intervention to enhance sleep quality in older adults. This study confirms that non-pharmacological interventions can improve sleep quality in older adults. The use of non-pharmacological interventions can be promoted by healthcare professionals in the future to improve the quality of sleep and thus the physical and mental health of older people. This evidence suggests that joint interventions may be most effective. Therefore, in the future, a combination of non-pharmacological interventions could be used to maximise their effectiveness in improving sleep quality in older people and promoting healthy aging. No patient or public contribution is not applicable to this study.

The safety, immunogenicity, and efficacy of heterologous boosting with a SARS-CoV-2 mRNA vaccine (SYS6006) in Chinese participants aged 18 years or more: a randomized, open-label, active-controlled phase 3 trial

ABSTRACT Continuous emergence of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), enhanced transmissibility, significant immune escape, and waning immunity call for booster vaccination. We evaluated the safety, immunogenicity, and efficacy of heterologous booster with a SARS-CoV-2 mRNA vaccine SYS6006 versus an active control vaccine in a randomized, open-label, active-controlled phase 3 trial in healthy adults aged 18 years or more who had received two or three doses of SARS-CoV-2 inactivated vaccine in China. The trial started in December 2022 and lasted for 6 months. The participants were randomized (overall ratio: 3:1) to receive one dose of SYS6006 (N = 2999) or an ancestral receptor binding region-based, alum-adjuvanted recombinant protein SARS-CoV-2 vaccine (N = 1000), including 520 participants in an immunogenicity subgroup. SYS6006 boosting showed good safety profiles with most AEs being grade 1 or 2, and induced robust wild-type and Omicron BA.5 neutralizing antibody response on Days 14 and 28, demonstrating immunogenicity superiority versus the control vaccine and meeting the primary objective. The relative vaccine efficacy against COVID-19 of any severity was 51.6% (95% CI, 35.5–63.7) for any variant, 66.8% (48.6–78.5) for BA.5, and 37.7% (2.4–60.3) for XBB, from Day 7 through Month 6. In the vaccinated and infected hybrid immune participants, the relative vaccine efficacy was 68.4% (31.1–85.5) against COVID-19 of any severity caused by a second infection. All COVID-19 cases were mild. SYS6006 heterologous boosting demonstrated good safety, superior immunogenicity and high efficacy against BA.5-associated COVID-19, and protected against XBB-associated COVID-19, particularly in the hybrid immune population. Trial registration: Chinese Clinical Trial Registry: ChiCTR2200066941

A Comparative Study of the Efficacy of Platelet-rich Plasma Therapy versus Topical Application of 0.1% Tretinoin Gel in the Management of Striae Gravidarum

Abstract Aim: To determine the relative efficacy of platelet rich plasma therapy versus topical 0.1% tretinoin gel in the management of striae gravidarum. Objectives: To determine the degree of response to platelet rich plasma therapy in comparison with topical 0.1% tretinoin gel in striae gravidarum and to determine the treatment of choice amongst platelet rich plasma and topical 0.1% tretinoin gel. Material and Methods: Study design - A randomised control cross sectional comparative study among the female patients with striae gravidarum was carried out at department of Dermatology, Venereology & Leprosy, Base Hospital, Delhi Cantt, New Delhi. Results: There was early and fast clinical improvement in PRP group with continuous clinical improvement noticed in successive sittings although degree of improvement was lower in 5th and 6th sittings. There was also an earlier plateau of response, in tretinion group after 04 sittings with mild or little improvement in the last 02 sittings in comparison to the PRP group. Conclusion: Platelet Rich Plasma therapy was effective as compared to topical 0.1% Tretinoin gel in the management of Striae gravidarum. PRP had better treatment outcome as well as patient satisfaction.

A matching-adjusted indirect comparison of results from REDUCE and RESPECT—two randomized trials on patent foramen ovale closure devices to prevent recurrent cryptogenic stroke

Aims Two randomized clinical trials, REDUCE and RESPECT, demonstrated that patent foramen ovale (PFO) closure in combination with antithrombotic therapy was more effective for the prevention of recurrent ischemic stroke compared with antithrombotic therapy alone. The aim of this study was to determine the relative efficacy and safety of the PFO closure devices used in REDUCE (HELEX and CARDIOFORM Septal Occluders) compared with the device used in RESPECT (Amplatzer PFO Occluder). Methods An unanchored matching-adjusted indirect comparison (MAIC) of the PFO closure arms of the REDUCE and RESPECT trials was performed using patient-level data from REDUCE weighted to match baseline characteristics from RESPECT. Comparisons of the following outcomes were made between the devices assessed in the trials: risk of recurrent ischemic stroke; recurrent ischemic stroke one year after randomization; any serious adverse event (SAE) related to the procedure or device; and atrial fibrillation or atrial flutter as an SAE related to the procedure or device. Results After conducting the MAIC, baseline characteristics were well-matched between the two trials. Compared to RESPECT, PFO closure using the devices from REDUCE resulted in a hazard ratio of 0.46 (95% confidence interval [CI] 0.15–1.43; p = 0.17) for the risk of recurrent stroke. For the recurrence of stroke after one year, SAE related to the procedure or device, and atrial fibrillation or atrial flutter as SAE related to the procedure or device, the MAIC resulted in a rate difference of −0.68 (95%CI −2.06 to 0.70; p = .34), −1.29 (95%CI −3.82 to 1.25; p = .32), and −0.19 (95%CI −1.16 to 0.78; p = .71), respectively. These findings were consistent across scenario analyses. Conclusions This MAIC analysis found no statistically significant differences in efficacy and safety outcomes between PFO closure with the HELEX and CARDIOFORM Septal Occluders versus the Amplatzer PFO Occluder, as used in the REDUCE and RESPECT trials.

Pro-environmental behavior regarding single-use plastics reduction in urban-rural communities of Thailand: Implication for public policy.

The study investigates residents' behavior towards reducing the use of single-use plastic (SUP), specifically in the context of food packaging. The widespread view holds that pro-environmental behavior (PB) results from a person's moral and rational deliberations. In reducing single-use plastic (SUP) consumption and waste, the relative roles of rationality and morality models in validating PB among rural and urban residents are not yet clear. In this empirical study, we compared the relative efficacy of two models for explaining people's SUP reduction behavior: the theory of planned behavior (TPB; rationality) and the value belief norm (VBN; morality). We investigated Thailand's rural (Sichang Island) and metropolitan (Nonthaburi city) areas. As a result, we surveyed people living on Sichang Island (n = 255) and in Nonthaburi city (n = 310). We employed structural equation modeling (SEM) for data analysis in this study. Findings showed that while morality better justified all the study participants' SUP reduction behavior, rationality underpinned behaviors of rural residents, while morality better explained the actions of city residents. We discussed future theoretical development and a policy roadmap based on these findings.

The dopamine D2 receptors antagonist Veralipride inhibits carbonic anhydrases: solution and crystallographic insights on human isoforms.

The inhibitory effects of veralipride, a benzamide-class antipsychotic acting as dopamine D2 receptors antagonist incorporates a primary sulfonamide moiety and was investigated for its interactions with carbonic anhydrase (CA) isoforms. In vitro profiling using the stopped-flow technique revealed that veralipride exhibited potent inhibitory activity across all tested hCA isoforms, with exception of hCA III. Comparative analysis with standard inhibitors, acetazolamide (AAZ), and sulpiride, provided insights for understanding the relative efficacy of veralipride as CA inhibitor. The study reports the X-ray crystal structure analysis of the veralipride adduct with three human (h) isoforms, hCA I, II, and CA XII mimic, allowing the understanding of the molecular interactions rationalizing its inhibitory effects against each isoform. These findings contribute to our understanding of veralipride pharmacological properties and for the design of structural analogs endowed with polypharmacological properties.

Different Chemotherapy Regimens and Pathologic Complete Response in Triple-Negative Breast Cancer: An Updated Network Meta-Analysis of Phase 3 Trials.

Background and Objectives: Currently, the standard treatment for non-metastatic triple-negative breast cancer (TNBC) consists of a systemic neoadjuvant (or perioperative) anthracycline plus taxane-based chemotherapy, delivered either sequentially or concomitantly. We performed a network meta-analysis (NMA) to compare the relative efficacy of different neoadjuvant treatments for TNBC in terms of pathologic complete response (pCR). Materials and Methods: The MEDLINE, Embase, and Cochrane databases were searched from database inception to 1 November 2023. Randomized clinical trials were used that enrolled adults with stage I-III TNBC and provided data on pCR defined as residual ypT0/TisN0M0. Between-group comparisons were estimated using risk ratios (RRs) with 95% credible intervals (95% CrIs). The primary outcome was the pCR rate. Results: 1129 citations were screened, and 12 randomized clinical trials were included. In Bayesian comparisons, all regimens, except anthracycline/taxanes plus gemcitabine or capecitabine, resulted in a higher pCR than the standard regimen in both direct and indirect comparisons. In particular, immunotherapy-based regimens resulted in more than double the pCR compared to historical regimens (RR = 2.3, 95% CI 1.9-2.9) and ranked as being the optimal regimen with a probability of 97%. Disease-free survival was better for immune checkpoint inhibitor-based chemotherapy (HR = 0.36, 95% 1.21-2.09) than for historical regimens. Conclusion: This meta-analysis confirmed that incorporating immunotherapy with neoadjuvant platinum-based chemotherapy is the best option to guarantee remarkable pathologic downstaging and improve clinical outcomes.

Applications of chemical bird repellents for crop and resource protection: a review and synthesis

Non-lethal repellents are needed to protect newly planted and ripening crops, to prevent valuable resources from being damaged by some wild birds worldwide. We systematically searched all scientific publications, patents and product registrations to develop a current review and synthesis regarding chemical bird repellents for wildlife researchers, ecologists, managers and conservationists. We then developed a database regarding the testing procedures and repellency results associated with the published and unpublished literature. For this comprehensive database, we developed an ‘index of success’, or relative efficacy level (e.g. effective in most experiments), associated with each tested bird repellent. We found 345 papers published in 1948–2022, including 2994 tests of 1478 repellent chemicals. From 224 publications regarding seed repellents, chemicals that were effective in most experiments and tested in three or more experiments include fungicides (cycloheximide, thiuram), insecticides (carbamates, imidacloprid), starlicide (3-chloro-p-toluidine hydrochloride), human pharmaceuticals (aminopyridine, quinine sulfate), petroleum distillate (paranapthalene), alkaloids (caffeine, quinine sulfate), monoterpenes (d-pulegone) and naturally occurring or synthetic polyphenolic compounds (anthraquinone). Among 114 publications regarding repellents used for foliar/fruit applications, chemicals that were effective in most experiments include activated charcoal, anthraquinone and carbamate. Among other bird repellents that were reportedly effective in most experiments, chemicals used for water applications and tested in three or more experiments include benzaldehyde, ortho-aminoacetophenone and sodium chloride; chemicals used as bait repellents include anthraquinone, methyl anthranilate and 2-carbamoyloxyethyl(trimethyl)azanium chloride; and the single chemical regarded as an area repellent was methyl anthranilate. There are currently 17 registered bird repellent products in the USA for five active ingredients, including anthraquinone, capsaicin, methiocarb, methyl anthranilate and polybutene. Future research and development of chemical bird repellents should include biopesticides (i.e. pesticides derived from natural materials) and pesticides that are already registered for human food use. The future discovery of repellent active ingredients and repellent products can be facilitated by an understanding of the scientific literature, patents and product registrations regarding bird repellent applications summarised in this review.

A matching-adjusted indirect comparison of the efficacy of elranatamab versus teclistamab in patients with triple-class exposed/refractory multiple myeloma

For patients with triple-class exposed/refractory multiple myeloma (TCE/RMM), where effective treatments options are limited, B-cell maturation antigen and CD3-directed bispecific antibodies offer a promising new approach. Teclistamab gained conditional approval in Europe and accelerated Food and Drug Administration (FDA) approval based on the MajesTEC-1 trial (NCT03145181). Elranatamab, approved by the FDA demonstrated its safety and efficacy in the MagnetisMM-3 trial (NCT04649359). Given the absence of head-to-head trials, an unanchored matching-adjusted indirect comparison (MAIC) was conducted to assess their relative efficacy. Key baseline characteristics were adjusted to be comparable between the two trials. In the MAIC, elranatamab demonstrated significantly better objective response rate and progression-free survival (PFS) than teclistamab, and numerically better complete response, duration of response, and overall survival (OS). These results suggest that elranatamab is an efficacious option for treating patients with TCE/R MM.

Pulmonary vein capture is a predictor for long-term success of stand-alone pulmonary vein isolation with cryoballoon ablation in patients with persistent atrial fibrillation.

The mechanisms of AF development and progression are still not completely understood. Despite the relative efficacy of ablation, the risk of AF recurrence is substantial, particularly in patients with persistent AF (perAF). At present we do not have any reliable intra-procedural electrophysiologic predictors of long-term success of AF ablation other than pulmonary vein isolation. We evaluated selected intraprocedural pulmonary vein characteristics that may be helpful in future guidance of persistent AF ablation. 390 consecutive procedures using cryoballoon for initial AF ablation were divided by clinical presentation (paroxysmal or persistent AF), and by pulmonary vein (PV) response to pacing after completion of ablation (discrete electrogram elicited with pacing-"PV capture" or not-"Control"). Patients were followed (median 20 months) for recurrent atrial arrhythmias as the primary end point of the study. PV capture was identified in 20.3% and 17.1% and patients with paroxysmal and persistent AF respectively (ns). In patients with persistent AF presence of PV capture was associated with significantly better outcomes compared to patients without PV capture (p < 0.001). In the group "persistent AF and PV capture", an initial strategy of PV isolation and reisolation of the PVs (without additional lesions) for patients with recurrent atrial arrhythmias resulted in 20/23 (87%) patients in sinus rhythm off antiarrhythmic medications at study completion. In patients with paroxysmal AF, PV capture was not associated with outcome benefits. Specific electrophysiologic characteristics of PV (PV capture cycle length: PVCCL) did not have an impact on AF recurrence, although 25% shortening of PVCCL was observed after 60 s periods of pacing at short cycle lengths. No background demographic patient characteristic differences were identified between patients with vs. without PV capture. The presence of PV capture was associated with better outcomes in patients with persistent AF. PV capture may identify those patients with persistent AF in whom cryoballoon PV isolation alone is sufficient as an initial ablation procedure and as the primary ablation strategy for recurrent AF.

Reversal of High Fat Diet-Induced Obesity, Systemic Inflammation, and Astrogliosis by the NLRP3 Inflammasome Inhibitors NT-0249 and NT-0796.

Systemic and cerebral inflammatory responses are implicated in the pathogenesis of obesity and associated metabolic impairment. While the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome has been linked to obesity-associated inflammation, whether it contributes to the development or maintenance of obesity is unknown. We provide support for a direct role of saturated fatty acids, such as palmitic acid, as NLRP3 activating stimuli in obese states. To investigate whether NLRP3 activation contributes to the pathogenesis of diet-induced obesity (DIO) in mice, we tested two different clinical-stage NLRP3 inflammasome inhibitors. We demonstrate a contributory role of this key inflammasome to established obesity and associated systemic and cerebral inflammation. By comparing their effects to calorie restriction, we aimed to identify specific NLRP3-sensitive mechanisms contributing to obesity-induced inflammation (as opposed to be those regulated by weight loss per se). In addition, a direct comparison of an NLRP3 inhibitor to a glucagon like peptide-1 receptor agonist, semaglutide (Wegovy), in the DIO model allowed an appreciation of the relative efficacy of these two therapeutic strategies on obesity, its associated systemic inflammatory response, and cerebral gliosis. We show that two structurally distinct, NLRP3 inhibitors, NT-0249 and NT-0796, reverse obesity in the DIO mouse model and that brain exposure appears necessary for efficacy. In support of this, we show that DIO-driven hypothalamic glial fibrillary acidic protein expression is blocked by dosing with NT-0249/NT-0796. While matching weight loss driven by semaglutide or calorie restriction, remarkably, NLRP3 inhibition provided enhanced improvements in disease-relevant biomarkers of acute phase response, cardiovascular inflammation, and lipid metabolism. SIGNIFICANCE STATEMENT: Obesity is a global health concern that predisposes individuals to chronic disease such as diabetes and cardiovascular disease at least in part by promoting systemic inflammation. We report that in mice fed a high-fat, obesogenic diet, obesity is reversed by either of two inhibitors of the intracellular inflammatory mediator NLRP3. Furthermore, NLRP3 inhibition reduces both hypothalamic gliosis and circulating biomarkers of cardiovascular disease risk beyond what can be achieved by either the glucagon like peptide-1 agonist semaglutide or calorie restriction alone.

Comparison of Three Airway Maneuvers of Jaw Thrust, Two-Handed E-C Technique With Head in Neutral Position, and Two-Handed E-C Technique With Head Fully Extended: A Prospective, Randomized, Double-Blind Crossover Study.

Background Bag-mask ventilation is an essential life-saving skill. The E-C technique of mask holding is the most popular. In patients with suspected cervical injury, the jaw thrust maneuver is recommended instead of the E-C technique with head tilt-chin lift. Should jaw thrust fail to produce adequate chest rise, the operator is advised to switch to the E-C technique with the head tilt-chin lift maneuver with head extension as it is vital to move oxygen into the lungs. We hypothesized that the E-C clamp with the head in the neutral position without head tilt might permit adequate ventilation without producing excessive movement of the cervical spine, which in turn might translate as less strain to the cervical spine. Methods In this prospective, randomized, double-blind, crossover study, we evaluated the relative efficacy of three airway maneuvers in opening the airway in anesthetized and paralyzed adults: jaw thrust, two-handed E-C technique with head in the neutral position, and two-handed E-C technique with head fully extended. The tidal volume generated during mechanical ventilation using these three techniques was considered as the primary outcome. Seventy-two subjects were recruited for this trial and all three techniques of mask holding were performed in each of these subjects in a sequence as dictated by a randomization table. Results The jaw thrust technique provided a mean tidal volume significantly higher than the two-handed E-C technique, with the head in the neutral position (p<0.001). Similarly, the two-handed E-C technique with the head fully extended provided a mean tidal volume significantly higher than the two-handed E-C technique with the head in neutral position (p<0.011). The mean tidal volume obtained with jaw thrust and two-handed E-C technique with head fully extended were comparable (p=0.78). Conclusion The two-handed E-C technique with the head fully extended, and the jaw thrust technique both produce good and comparable tidal volumes. The two-handed E-C technique with the head in a neutral position provides adequate though lower tidal volumes as compared to the other two techniques.

544 - Cost-per-responder analysis of tralokinumab versus dupilumab in patients with moderate-to-severe atopic dermatitis in the US and Canada

Abstract Introduction/Background Biologic treatments such as tralokinumab and dupilumab are therapeutic options for adult patients with moderate-to-­severe atopic dermatitis (AD) who do not achieve adequate control with topical treatments or phototherapy. To date, no trials have been conducted to directly evaluate the relative efficacy of these biologic treatments. Objectives Applying indirect comparison of efficacy, we examined the cost-per-responder of tralokinumab compared to dupilumab in combination with topical corticosteroids (TCS) for the treatment of moderate-to-serve AD in the United States (US) and Canada. Methods A cost-per-responder analysis was undertaken considering the Eczema Area and Severity Index 75 (EASI-75) and Investigator’s Global Assessment (IGA-0/1) response criteria over a 32-week period. For each treatment, the cost-per-­responder was computed by multiplying the treatment cost by the number needed to treat (NNT). Efficacy data were derived from an unanchored matching-adjusted indirect comparison (MAIC) utilizing patient-level data from ECZTRA-3 (tralokinumab) and aggregate data from LIBERTY AD CHRONOS (dupilumab). Treatment cost was defined as the drug cost of the biologic treatment with a duration corresponding to 32 weeks. TCS cost was not considered. Treatments were assumed to be administered every 2 weeks (Q2W). The costs were estimated based on Wholesale Acquisition Costs (WAC) from the US and ex-factory prices via the McKesson price list for Canada. All prices were converted to US dollars ($). Sensitivity analyses (SA) were conducted with every 4 week (Q4W) dosing beginning at week 16 for 10% and 20% of patients treated with tralokinumab. Results For the US, the average cost-per-responder was $62,714 (Q4W SA: 10%: $61,239; 20%: $59,763) for tralokinumab versus $63,993 for dupilumab considering the EASI-75 response criteria, while the average cost-per-responder was $82,419 (Q4W SA: 10%: $80,480; 20%: $78,450) for tralokinumab versus $118,835 for dupilumab considering the IGA 0/1 response criteria. For Canada, the average cost-per-responder was $22,846 (Q4W SA: 10%: $22,308; 20%: $21,771) for tralokinumab versus $26,475 for dupilumab considering the EASI-75 response criteria, while the average cost-per-responder was $30,024 (Q4W SA: 10%: $29,317; 20%: $28,611) for tralokinumab versus $49,165 for dupilumab considering the IGA 0/1 response criteria. Conclusions Assessing EASI-75 and IGA-0/1 response criteria at 32 weeks, this analysis indicates that tralokinumab in combination with TCS is associated with lower costs-per-responder compared with dupilumab in combination with TCS in the treatment of moderate-to-severe AD in the US and Canada.

The equivalence of psychodynamic therapy and cognitive behavioral therapy for depressive disorders in adults: A meta-analytic review.

Meta-analyses on the relative efficacy of psychodynamic psychotherapy (PDT) and cognitive behavioral therapy (CBT) for depressive disorders are limited by heterogeneity in diagnostic samples and comparators and a lack of equivalence testing. We addressed this through a meta-analytic test of the equivalence of manualized PDT and CBT in treating adults with depressive disorders as determined by diagnostic interviews. Sensitivity analyses evaluated the impact of pretreatment differences, mixed diagnostic samples, author allegiance, study quality, year of publication and outliers on findings. A comprehensive literature search across multiple databases using reliable screening methods identified nine randomized controlled trials directly comparing manualized PDT and CBT for diagnosed depressive disorders in adults. Following pre-registration, we employed random effect models for our meta-analyses and two one-sided test procedures for equivalence testing. Independent raters determined that all studies were of adequate quality. Immediately posttreatment, depressive symptoms were statistically equivalent across PDT and CBT (k = 9; g = -0.11, 90% confidence interval [90% CI]: -0.24 to 0.02, pequivalence = .048, pNHST = .212, I2 = 32.7). At follow-up, the longest time point within a year, depressive symptoms were neither statistically equivalent nor statistically different (k = 6; g = -0.16, 90% CI: -0.31 to -0.02, pequivalence = .184, pNHST = .126, I2 = 0.00). The efficacy of manualized PDT is equal to manualized CBT immediately at posttreatment for depressive disorders in the adult general population. Nevertheless, insufficient data exists to reach a conclusion regarding equivalence at follow-up.

Efficacy and safety of autologous haematopoietic stem cell transplantation versus alemtuzumab, ocrelizumab, ofatumumab or cladribine in relapsing remitting multiple sclerosis (StarMS): protocol for a randomised controlled trial

IntroductionAutologous haematopoietic stem cell transplantation (aHSCT) is increasingly used as treatment for patients with active multiple sclerosis (MS), typically after failure of disease-modifying therapies (DMTs). A recent phase III trial,...

Outcomes following surgical interventions for hypothalamic hamartomas: protocol for a systematic review and individual patient data meta-analysis

IntroductionHypothalamic hamartomas (HHs) are deep-seated congenital lesions that typically lead to pharmacoresistant epilepsy and a catastrophic encephalopathic syndrome characterised by severe neuropsychological impairment and decline in quality of life. A...

Comparative efficacy, quality of life, safety, and tolerability of atogepant and rimegepant in migraine prevention: A matching-adjusted indirect comparison analysis.

Comparative evaluations of preventive migraine treatments can help inform clinical decision making for managing migraine in clinical practice. An anchored matching-adjusted indirect comparison analysis was conducted using pooled participant-level data from two phase 3 atogepant trials (ADVANCE and PROGRESS) and one phase 2/3 rimegepant trial (BHV3000-305) to evaluate the relative efficacy and safety/tolerability of atogepant and rimegepant as preventive migraine treatments. Participants receiving atogepant 60 mg once daily, rimegepant orally disintegrating tablet 75 mg once every other day, and placebo were included. Only participants meeting the BHV3000-305 inclusion/exclusion criteria were analyzed: ≥6 monthly migraine days and ≤18 monthly headache days at baseline. The primary efficacy assessment of interest was change in monthly migraine days across weeks 1-12. There were 252 participants in the atogepant group and 348 in the rimegepant group. Across weeks 1-12, atogepant 60 mg demonstrated a significantly greater reduction in mean monthly migraine days compared with rimegepant 75 mg (mean difference [95% CI]: -1.65 [-2.49, -0.81]; p < 0.001). Both atogepant and rimegepant demonstrated similar safety/tolerability profiles. In this matching-adjusted indirect comparison analysis, oral atogepant 60 mg once daily demonstrated a significantly greater reduction in monthly migraine days compared with rimegepant 75 mg orally disintegrating tablet once every other day.