Rescue Medication Use Research Articles

Randomized double-blind pilot study of universal, species abundant, multiallergen subcutaneous immunotherapy for moderate-severe allergic rhinitis

BackgroundAllergic rhinitis affects approximately 10% to 20% of people living in industrialized nations leading to significant morbidity and large health care expenditures. Individualized high-dose, single-species allergen immunotherapy has been found to be effective in treating allergic rhinitis but can be associated with significant risks including anaphylaxis. Few studies have evaluated the safety and efficacy of universal low-dose multiallergen immunotherapy (MAIT). ObjectiveTo determine the efficacy and safety of a universal MAIT formula for the treatment of allergic rhinitis. MethodsPatients with moderate-severe perennial and seasonal allergic rhinitis were randomized in a double-blind, placebo-controlled fashion to receive a novel, subcutaneous MAIT regimen containing a unique mixture of more than 150 aeroallergens, including several cross-reactive species. All patients received the exact same universal immunotherapy formula regardless of which specific skin tests were positive. Primary outcome measures at 8 and 12 weeks of therapy included validated clinical assessments, total nasal sinus score and mini-rhinoconjunctivitis quality of life questionnaire, and the use of rescue medications. ResultsA total of 31 patients (n = 31) were randomized to receive MAIT vs placebo. By week 12, MAIT resulted in a −4.6 (−58%) decrease in the combined total nasal sinus score and rescue medication score (daily combined score) compared with −1.5 (−20%) for placebo (P = .04). Likewise, MAIT resulted in a decrease in the mini-rhinoconjunctivitis quality of life questionnaire score of −34.9 (−68%) compared with −17 (−42%) for the placebo (P = .04). Mild adverse events were uncommon and with similar frequency among the groups. ConclusionA novel, universal, and high-species abundant MAIT formula was well tolerated and resulted in significant improvement in symptoms of moderate-severe allergic rhinitis. The results of this pilot study should be considered preliminary, pending further randomized clinical trials.

“Extrafine single inhaler triple therapy effect on health status, lung function and adherence in COPD patients: A Panhellenic prospective non-interventional study – The TRIBUNE study”

The extrafine single inhaler triple therapy (efSITT) containing beclometasone dipropionate/formoterol fumarate/glycopyrronium 87/5/9 μg has proved to be efficacious in patients with Chronic Obstructive Pulmonary Disease (COPD) in randomized control trials. TRIBUNE study aimed to assess the efSITT effectiveness on health status, lung function, adherence and rescue medication use in COPD patients in Greece in a real-world setting.This was a 24-week prospective, multicenter, observational study in 1,195 patients with moderate/severe COPD and history of at least one exacerbation during the previous year despite dual therapy. Health status (COPD Assessment Test/CAT), lung function parameters and rescue medication use were recorded at baseline, 3 (Visit 2/V2) and 6 months (Visit 3/V3) after treatment. Adherence (Test of Adherence to Inhalers/TAI) and self-reported overall impression of health condition change (Visual Analogue Scale/VAS) were recorded at V2 and V3.Mean CAT score decreased from 20.9 points at V1, to 15.1 at V2 and 13 at V3 (p < 0.001, all pair comparisons). 85.9% of patients achieved a CAT decrease of minimal clinically important difference (MCID) or more (≥2) at V3, compared to V1. Mean FEV1 increased from 1.4 ± 0.5 L on V1, to 1.6 ± 0.5 L on V3 (p < 0.001, N = 275). The percentage of patients with “good adherence” increased from 58.4% (V2) to 64.0% (V3). Rescue medication use and VAS also significantly improved.The efSITT achieves improved outcomes on health status, lung function and rescue medication use as well as satisfactory adherence and patient-reported improvement of health condition, in moderate/severe COPD patients previously treated with a dual combination in a Greek real-world setting.

Topical Ocular TRPV1 Antagonist SAF312 (Libvatrep) for Postoperative Pain After Photorefractive Keratectomy.

Evaluation of safety and efficacy of topical ocular SAF312 (Libvatrep) in post-photorefractive keratectomy (PRK) pain. In this placebo (vehicle)-controlled, participant- and investigator-masked study, 40 participants were randomized (1:1) to two treatment sequences in a bilateral PRK crossover design (SAF312 2.5% followed by vehicle [or vice versa], one eye drop, four times daily for 72hours after PRK). Primary endpoints were visual analog scale (VAS) pain scores at 6hours after first drop of study drug and average VAS scores over 0 to 12hours postoperatively. Secondary endpoints included postoperative oral rescue medication (ORM) use and adverse events (AEs). All 40 participants completed the study. Both primary endpoints were met; mean difference in VAS pain scores between SAF312- and vehicle-treated eyes was -11.13 (P = 0.005, -25%) at 6hours postoperatively and -8.56 (P = 0.017, -22%) over 0 to 12hours. Mean VAS pain scores with SAF312 were consistently lower than with vehicle from 1hour postoperatively up to 30hours (P ≤ 0.10 observed in 8/11 time points). Less ORM was taken with SAF312 up to 0 to 72hours postoperatively, with a trend of fewer participants taking ORM at 0 to 24hours postoperatively with SAF312 versus vehicle. No serious AEs were reported. All ocular AEs were mild and transient, and none were drug related. SAF312-treated eyes showed no delay in wound healing and had a lower grade 4 conjunctival hyperemia 24hours postoperatively versus vehicle-treated eyes. SAF312 was well tolerated and effective in reducing ocular pain post-PRK. Topical SAF312 presents a new therapeutic option for patients undergoing PRK.

Post hoc analysis examining symptom severity reduction and symptom absence during food challenges in individuals who underwent oral immunotherapy for peanut allergy: results from three trials

PurposePeanut allergy and its current management, involving peanut avoidance and use of rescue medication during instances of accidental exposure, are burdensome to patients and their caregivers and can be a source of stress, uncertainty, and restriction. Physicians may also be frustrated with a lack of effective and safe treatments other than avoidance in the current management of peanut allergy. Efficacy, determined using double-blind, placebo-controlled food challenges (DBPCFCs), of oral immunotherapy with peanut (Arachis hypogaea) allergen powder-dnfp (PTAH; Palforzia®) was demonstrated versus placebo in children and adolescents aged 4 to 17 years in multiple phase 3 trials; continued benefit of PTAH was shown in a follow-on trial. The DBPCFC is a reproducible, rigorous, and clinically meaningful assessment accepted by regulatory authorities to evaluate the level of tolerance as an endpoint for accidental exposures to peanut in real life. It also provides useful clinical and patient-relevant information, including the amount of peanut protein an individual with peanut allergy can consume without experiencing dose-limiting symptoms, severity of symptoms, and organs affected upon ingestion of peanut protein. We explored symptoms of peanut exposure during DBPCFCs from phase 3 and follow-on trials of PTAH to further characterize treatment efficacy from a perspective relevant to patients, caregivers, and clinicians.MethodsSymptom data recorded during screening and/or exit DBPCFCs from participants aged 4 to 17 years receiving PTAH or placebo were examined post hoc across three PTAH trials (PALISADE [ARC003], ARC004 [PALISADE follow-on], and ARTEMIS [ARC010]). The maximum peanut protein administered as a single dose during DBPCFCs was 1000 mg (PALISADE and ARTEMIS) and 2000 mg (ARC004). Symptoms were classified by system organ class (SOC) and maximum severity. Endpoints were changes in symptom severity and freedom from symptoms (ie, asymptomatic) during DBPCFC. Relative risk (RR) was calculated for symptom severity by SOC and freedom from symptoms between groups; descriptive statistics were used to summarize all other data.ResultsThe risk of any respiratory (RR 0.42 [0.30–0.60], P < 0.0001), gastrointestinal (RR 0.34 [0.26–0.44], P < 0.0001), cardiovascular/neurological (RR 0.17 [0.08–0.39], P < 0.001), or dermatological (RR 0.33 [0.22–0.50], P < 0.0001) symptoms was significantly lower in participants treated with PTAH versus placebo upon exposure to peanut at the end of the PALISADE trial (ie, exit DBPCFC). Compared with placebo-treated participants (23.4%), the majority (76.3%) of PTAH-treated participants had no symptoms at the exit DBPCFC when tested at the peanut protein dose not tolerated (ie, reactive dose) during the screening DBPCFC. Significantly higher proportions of PTAH-treated participants were asymptomatic at doses ≤ 100 mg in the exit DBPCFC compared with placebo-treated participants (PALISADE: 69.35% vs 12.10%, RR 5.73 [95% confidence interval (CI) 3.55–9.26]; P < 0.0001; ARTEMIS: 67.42% vs 13.95%, RR 4.83 [95% CI 2.28–10.25]; P < 0.0001); findings were similar at peanut protein doses ≤ 1000 mg (PALISADE: RR 15.56 [95% CI 5.05–47.94]; P < 0.0001; ARTEMIS: RR 34.74 [95% CI 2.19–551.03]; P < 0.0001). In ARC004, as the period of PTAH maintenance became longer, greater proportions of participants were asymptomatic at doses of peanut protein ≤ 1000 mg in the exit DBPCFC (from 37.63% after ~ 6 months of maintenance treatment [exit DBPCFC of PALISADE] to 45.54% after ~ 13 months and 58.06% after ~ 20 months of overall PTAH maintenance treatment).ConclusionsPTAH significantly reduced symptom severity due to exposure to peanut, which is clinically relevant. When exposed to peanut, participants with peanut allergy treated with PTAH rarely had moderate or severe respiratory or cardiovascular/neurological symptoms. Oral immunotherapy with PTAH appears to reduce frequency and severity of allergic reactions in individuals with peanut allergy after accidental exposure to peanut and may enable them and their families to have an improved quality of life.Trial registration ClinicalTrials.gov, NCT02635776, registered 17 December 2015, https://clinicaltrials.gov/ct2/show/NCT02635776?term=AR101&draw=2&rank=7; ClinicalTrials.gov, NCT02993107, registered 08 December 2016, https://clinicaltrials.gov/ct2/show/NCT02993107?term=AR101&draw=2&rank=6; ClinicalTrials.gov, NCT03201003, registered 22 June 2017, https://clinicaltrials.gov/ct2/show/NCT03201003? term = AR101&draw = 2&rank = 9

Vitamin D and its association with severity and control of childhood bronchial asthma.

Bronchial asthma is a common disease in childhood. Vitamin D deficiency is a common unidentified nutritional deficiency. In spite of high prevalence, an association between the two has not been well understood. Our study aimed to determine serum Vitamin D levels among asthmatic children and its association with clinical severity and level of control. A hospital-based cross-sectional study was conducted from 2017 to 2019 where 64 recurrent wheezers, classified into 6-15 years and the under 5 wheezers as per Global Initiative for Asthma guidelines, were included. The group of asthmatic children was comparable with respect to their demographic profiles with good adherence and proper inhaler use. Serum Vitamin D levels were estimated using an enzyme-linked immunosorbent assay and classified using the US Endocrine Society classification. Association between Vitamin D status and outcome variables was analyzed using Chi-square test, Fisher's exact test, unpaired t-test, and ANOVA. Among the 64 wheezers, 29 (45.3%) had intermittent symptoms and 35 (54.7%) had persistent symptoms. Mean Vitamin D levels in the entire study population were in deficiency range (18.96 ng/ml ± 2.23). Persistent asthmatics had significantly lower Vitamin D levels (13.75 ng/ml) as compared to intermittent asthmatics (28.52 ng/ml). Those asthmatics who had hypovitaminosis D had higher rates of hospitalization (P = 0.048), increased use of rescue medications (P = 0.008), and poor symptom control (P = 0.001). Asthmatic children had a higher incidence of reduced Vitamin D levels showing a statistically significant association. There is also a significant association between Vitamin D level and poor symptom control, hospitalization for exacerbations, and requirement of rescue medication in asthmatic children.

Effect Of Tezepelumab On Rescue Medication Use And Night-Time Awakenings In Patients With Severe, Uncontrolled Asthma: Results From The NAVIGATOR Study

Tezepelumab, a human monoclonal antibody that blocks thymic stromal lymphopoietin (TSLP), reduced asthma exacerbations over 52 weeks in patients with severe, uncontrolled asthma in the phase 3 NAVIGATOR study (NCT03347279). In this post hoc analysis, the effect of tezepelumab on patient-reported rescue medication use and night-time awakenings was analyzed.

P526 A prediction model for successful increase of adalimumab dose intervals: analysis of the pragmatic open-label randomised controlled non-inferiority LADI trial

Abstract Background We showed in the pragmatic open-label randomised controlled non-inferiority LADI trial that increasing adalimumab (ADA) dose intervals was non-inferior to conventional dosing for persistent flares in CD patients in stable remission, while infection-related adverse events (AE) were reduced. This was counterbalanced by lower rates of clinical remission and more gastro-intestinal AEs after 48 weeks. In the current study we aimed to develop a prediction model to identify patients who could successfully increase their ADA dose interval. Methods This is a secondary analysis of the intervention group of the LADI trial. In this group, patients in steroid-free clinical remission for ≥ 9 months (Harvey-Bradshaw Index (HBI) &amp;lt; 5, CRP &amp;lt; 10 mg/L and faecal calprotectin (FCP) &amp;lt; 150 µg/g), on conventional ADA dosing increased ADA intervals to 3 and then to 4 weeks. A successful dose interval increase was defined as: no persistent flare (&amp;gt;8 weeks), no intervention-related severe AE, no rescue medication use, and an increased dose interval while in clinical and biochemical remission at week 48. Candidate baseline predictors were selected after a study group consensus meeting (Table 1). Prediction models were based on logistic regression. Four variable selection strategies were used: inclusion of all variables as a naïve reference model, stepwise backwards regression, LASSO with minimal lambda, and LASSO using the ‘one standard error’ rule. Models were evaluated on discrimination and calibration. Missing data were multiply imputed and models were internally validated using bootstrap optimism correction. Results The four models were developed on 109 patients, of which 59.1% experienced the outcome of successful dose interval increase (Table 1). Apparent performance of the models was adequate, with areas under the receiver operating characteristic curves (AUC) between 0.60 and 0.67 (Table 2 and Figure 1). Predicted probabilities from LASSO-based models were too modest (Table 2 and Figure 2). Internal validation showed optimism-corrected AUCs around 0.5 (Table 2), meaning that models could not identify patients who successfully increased their ADA dose interval. Optimism-corrected calibration estimates for the naïve model and backwards selection showed overfitting on the data. Internally validated predicted probabilities from LASSO-based models were too modest. Conclusion After 48 weeks, approximately 60% of patients could successfully increase their ADA dose interval without major negative clinical impact, but these could not be identified with a series of different prediction models. Risks and benefits of this strategy should be discussed with individual patients based on their risk perception and medication preferences.

322 Efficacy and safety of lebrikizumab in moderate-to-severe atopic dermatitis: 52-week results of two randomized, double-blinded, placebo-controlled phase 3 trials (ADvocate1 and ADvocate2)

Abstract Lebrikizumab (LEB) is a novel, high-affinity monoclonal antibody that selectively binds to interleukin (IL)-13. To evaluate the efficacy and safety of LEB monotherapy in patients with moderate-to-severe atopic dermatitis (AD) in two identical phase 3 trials ADvocate1 (ADv1) and ADvocate2 (ADv2). Patients who responded to LEB 250 mg every 2 weeks (LEB Q2W) at the end of the 16-week induction period were re-randomized in a 2 : 2 : 1 ratio to receive LEB Q2W, LEB 250 mg every 4 weeks (LEB Q4W) or placebo (LEB withdrawal) for an additional 36 weeks. Response, at week 16, was defined as achieving an IGA (0, 1) with a ≥2-point improvement or EASI75 and no use of rescue medication. Efficacy outcomes reported at week 52 included IGA (0, 1), EASI 75, ≥4-point reduction in Pruritis Numeric Rating Scale (NRS), EASI 90 and DLQI ≥4-point. Safety analysis was conducted on all patients who received ≥1 dose of LEB. Patients maintained IGA (0, 1) in LEB Q2W (ADv1, 75.8%; ADv2, 64.6%), LEB Q4W (ADv1, 74.2%; ADv2, 80.6%) and LEB withdrawal (ADv1, 46.5%; ADv2, 49.8%). Maintenance of EASI75 was, in LEB Q2W (ADv1, 79.2%; ADv2, 77.4%), LEB Q4W (ADv1, 79.2%; ADv2, 84.7%) and LEB withdrawal (ADv1, 61.3%; ADv2, 72.0%). For Pruritus NRS ≥4-point improvement from baseline, patients-maintained improvement in the LEB Q2W (ADv1, 81.2%; ADv2, 90.3%), LEB Q4W (ADv1, 80.4%; ADv2, 88.1%) and LEB withdrawal (ADv1, 65.4%; ADv2, 67.6%). Maintenance of EASI90 was, in LEB Q2W (ADv1, 66.1%; ADv2, 61.5%), LEB Q4W (ADv1, 66.6%; ADv2, 67.4%) and LEB withdrawal (ADv1, 45.5%; ADv2, 36.9%). DLQI ≥4-point improvement from baseline was LEB Q2W (ADv1, 64.0%; ADv2, 59.0%), LEB Q4W (ADv1, 62.7%; ADv2, 73.0%) and LEB withdrawal (ADv1, 57.7%; ADv2, 45.5%). TEAEs were reported by 58.1% (ADv1) and 67.8% (ADv2) LEB-treated patients at week 52. Serious adverse events were reported by 3.3% of ADv1 patients and 2.7% of ADv2 patients. In ADv1 and ADv2, 2.3% and 3.9% of patients reported an adverse event leading to treatment discontinuation, respectively. Both LEB Q2W and LEB Q4W maintained improvement in all reported outcomes for the treatment of moderate-to-severe AD through 52 weeks. The safety profile was consistent with previously published data.

Doublet or Triplet Antiemetic Prophylaxis for Nausea and Vomiting Induced by Trastuzumab Deruxtecan: an Open-Label, Randomized, and Multicenter Exploratory Phase 2 Study.

Background: Trastuzumab deruxtecan is classified as an anticancer agent that poses a moderate emetic risk in the international guidelines for antiemetic therapy. The guidelines recommend emesis prophylaxis using a two-drug combination therapy comprising a 5-hydroxytryptamine-3 receptor antagonist (5-HT3RA) and dexamethasone (DEX). However, the high incidence of nausea and vomiting associated with trastuzumab deruxtecan is problematic. The National Comprehensive Cancer Network guideline version 1.2023 classified trastuzumab deruxtecan as having a high risk of emesis and changed its recommendation to a triplet regimen including a neurokinin-1 receptor antagonist (NK1RA). However, the emetogenic potential of trastuzumab-deruxtecan and the optimal antiemetic prophylaxis are controversial. Hence, this exploratory phase 2 study aimed to assess the efficacy and safety of treatment comprising 5-HT3RA and DEX with or without a NK1RA in preventing trastuzumab deruxtecan-induced nausea and vomiting. Methods: We conducted an open-label and randomized exploratory phase 2 study at 14 centers in Japan. Patients with breast cancer who were scheduled to receive trastuzumab deruxtecan were enrolled in this study. The patients were randomly assigned to receive granisetron and DEX (arm GD) or granisetron, DEX, and aprepitant (fosaprepitant; arm GDA). The primary endpoint was complete response (CR; no emesis or no rescue therapy) during the overall phase (120 h after the start of trastuzumab deruxtecan). Results: Between September 2020 and March 2023, 40 patients were randomly assigned to the GD (n = 19) or GDA (n = 21) arm. In the GDA arm, one patient who did not complete the use of the rescue medication listed in the diary was excluded from the efficacy analysis, which included the use of rescue medication. The CR rates during the overall phase were 36.8% and 70.0% in the GD and GDA arms, respectively (odds ratio 0.1334; 95% confidence interval [CI]: 0.0232-0.7672; P = 0.0190), with a difference of 33.2%. No grade 3 or 4 toxicity related to antiemetic therapy was observed. Conclusions: Patients receiving trastuzumab deruxtecan require triple therapy, including mandatory NK1RA administration.

Symptom versus exacerbation control: an evolution in GINA guidelines?

The article traces the concept of asthma control within GINA guidelines over the past 25 years. In the first 15 years after 1995, the main objective of asthma management was to obtain the control of all clinical and functional characteristics of asthma. A landmark study (GOAL) showed for the first time that a good control of asthma is a reasonable outcome that can be achieved in a large proportion of asthmatics with a regular appropriate treatment. In the following years, more emphasis was placed on the role of exacerbations as critical manifestations of poor asthma control, whose frequency is associated with excessive FEV1 decline and increased risk of death. Accordingly, the 2014 GINA report makes a clear distinction between the control of the day-by-day symptoms and the reduction in the risk of severe exacerbations, stating that both conditions should be obtained. The 2019 update included a significant change in the management of mild asthma, prioritizing the prevention of exacerbations to that of mild symptoms. This view was repeated in the 2021 update, where the prevention of exacerbations, together with an acceptable symptom control with a minimal use of rescue medication, appeared to be the real main goal of asthma management. While a discrepancy between current symptoms and exacerbations may be present in mild asthma, a significant relationship between these two features is observed in moderate-severe asthma: a persistent poor symptom control is a major risk factor for exacerbations, whereas achieving symptom control through regular treatment is associated with a reduction in exacerbation rate. Thus, the opinion that frequent symptoms are not important in the absence of acute exacerbations should be discouraged, whereas education of patients to a good symptom perception and to improve adherence to regular treatment should be implemented. Furthermore, the persistence of risk factors, such as increased airway inflammation, even in a patient with minor daily symptoms, should be considered for optimizing treatment.

Diagnosis and treatment of Hymenoptera venom allergy: S2k Guideline of the German Society of Allergology and Clinical Immunology (DGAKI) in collaboration with the Arbeitsgemeinschaft für Berufs- und Umweltdermatologie e.V. (ABD), the Medical Association of German Allergologists (AeDA), the German Society of Dermatology (DDG), the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery (DGHNOKC), the German Society of Pediatrics and Adolescent

Diagnosis and treatment of Hymenoptera venom allergy: S2k Guideline of the German Society of Allergology and Clinical Immunology (DGAKI) in collaboration with the Arbeitsgemeinschaft für Berufs- und Umweltdermatologie e.V. (ABD), the Medical Association of German Allergologists (AeDA), the German Society of Dermatology (DDG), the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery (DGHNOKC), the German Society of Pediatrics and Adolescent

Rilzabrutinib versus placebo in adults and adolescents with persistent or chronic immune thrombocytopenia: LUNA 3 phase III study.

Immune thrombocytopenia (ITP) is characterized by primarily autoantibody-mediated platelet destruction and impaired platelet production resulting in thrombocytopenia and an increased risk of bleeding. Other manifestations include increased risk of thrombosis and diminished quality of life. Current treatment approaches are directed toward lowering the rate of platelet destruction or stimulating platelet production to prevent bleeding. Rilzabrutinib is an oral, reversible, potent Bruton tyrosine kinase inhibitor that was specifically designed to treat immune-mediated diseases and mediates its therapeutic effect through a dual mechanism of action: (1) inhibiting B-cell activation and (2) interrupting antibody-coated cell phagocytosis by Fc gamma receptor in spleen and liver. A 24-week dose-finding phase I/II study of rilzabrutinib in patients with ITP showed a 40% platelet response (⩾2 consecutive platelet counts of ⩾50 × 109/L and increase from baseline ⩾20 × 109/L without rescue medication use) and a well-tolerated safety profile with only grade 1/2 transient adverse events across dose levels. Assess the efficacy and safety of oral rilzabrutinib in adult and adolescent patients with persistent or chronic ITP. Rilzabrutinib 400 mg BID is being evaluated in the ongoing LUNA 3 multicenter, double-blind, placebo-controlled phase III study. The primary endpoint is durable platelet response, defined as achieving platelet counts of ⩾50 × 109/L for at least two-thirds of ⩾8 available weekly scheduled platelet measurements during the last 12 weeks (including ⩾2 available measurements within the last 6 weeks) of the 24-week blinded treatment period in the absence of rescue therapy. Ethical guidelines and informed consent are followed. The LUNA 3 trial will further investigate rilzabrutinib's safety and efficacy in adult and adolescent patients, with the primary goal of addressing a major objective in treating patients with ITP: durability of platelet response. ClinicalTrials.gov NCT04562766: https://clinicaltrials.gov/ct2/show/NCT04562766; EU Clinical Trials Register EudraCT 2020-002063-60: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2020-002063-60.

Avatrombopag treatment response in patients with immune thrombocytopenia: the REAL-AVA 1.0 study.

Thrombopoietin-receptor agonists (TPO-RAs) are used to treat immune thrombocytopenia (ITP), a disorder characterized by prolonged low platelet counts (PCs) that pose a risk of serious bleeding episodes. Avatrombopag (AVA) is the most recently approved TPO-RA for the treatment of chronic ITP. A high proportion of patients responded to AVA in clinical trials, and treatment was well-tolerated; however, limited real-world effectiveness data have been reported to date. To describe demographic and clinical characteristics, treatment patterns, and outcomes following the initiation of AVA in patients with ITP in the United States. This is a retrospective study using administrative claims data from the Komodo Healthcare Map (1 February 2017 to 28 February 2022) linked with PC laboratory data. Patients with ⩾1 diagnosis of ITP, ⩾1 paid prescription for AVA (index date), and ⩾1 month of pharmacy coverage after AVA initiation were selected. Baseline characteristics and follow-up steroid, immunosuppressant, and rescue medication use were described. The percentage of patients achieving clinically meaningful PC thresholds (⩾30 × 109/l) were assessed among patients with ⩾1 PC following AVA initiation and prior to AVA discontinuation/switch (effectiveness subgroup). A total of 205 patients met eligibility criteria and 49% reported TPO-RA use in the prior 6 months. Approximately 70% and 93% of patients did not require use of steroid or immunoglobulin rescue medication during follow-up, respectively. Among patients with concomitant steroid (n = 75) or immunosuppressant (n = 7) use at AVA initiation, 35% and 57% discontinued those treatments, respectively. Of the 21 patients in the effectiveness subgroup, 81% achieved clinically meaningful PC thresholds. A high proportion of evaluable patients with ITP in this real-world study achieved clinically meaningful PCs, without requiring rescue medication during AVA treatment, with many able to discontinue baseline concomitant steroid or immunosuppressant utilization. Despite limited availability of PC data, these results are consistent with results from the AVA pivotal clinical trials.

Efficacy of Second-Line Treatments in Chronic Urticaria Refractory to Standard Dose Antihistamines.

The prevalence of chronic urticaria (CU) is increasing worldwide, and it imposes a major burden on patients. Few studies have evaluated the efficacy of second-line treatments of CU, particularly for patients being considered for costly third-line treatments such as omalizumab. We compared the efficacy and safety of second-line treatments of CU refractory to standard doses of nonsedating H1-antihistamines (nsAHs). This 4-week, prospective, randomized, open-label trial divided patients into 4 treatment groups: 4-fold updosing of nsAHs, multiple combination of 4 nsAHs, switching to other nsAHs, and adjunctive H2-receptor antagonist. The clinical outcomes included urticaria control status, symptoms, and rescue medication use. This study included 109 patients. After 4 weeks of second-line treatment, urticaria was well-controlled, partly controlled, and uncontrolled in 43.1%, 36.7%, and 20.2% of patients, respectively. Complete control of CU was achieved in 20.4% of patients. Among the patients with high-dose nsAHs, the proportion with well-controlled status was higher compared to the patients who received standard doses (51.9% vs. 34.5%, P = 0.031). No significant difference was observed in the proportion of well-controlled cases between the updosing and combination treatment groups (57.7% vs. 46.4%, P = 0.616). However, increasing the dose of nsAHs 4-fold was associated with a higher rate of complete symptom control compared to multiple combination treatment with 4 nsAHs (40.0% vs. 10.7%, P = 0.030). Logistic regression analysis confirmed the higher efficacy of updosing of nsAHs for complete control of CU compared to the other treatment strategies (odds ratio, 0.180; P = 0.020). In patients with CU refractory to standard doses of nsAHs, both updosing of nsAHs 4-fold and multiple combination treatment with 4 nsAHs increased the rate of well-controlled cases without causing significant adverse effects. Updosing of nsAHs is more effective for complete CU control than combination treatment.

Homeopathy for seasonal allergic rhinitis: rationale, design and methods of the three-armed randomized controlled HOMEOSAR trial

BackgroundPatients with seasonal allergic rhinitis (SAR) frequently use homeopathic therapy. Although there is some evidence that homeopathy may be effective in treating symptoms of SAR, there is a lack of high-quality clinical trials. Therefore, the aim of the homeopathy for SAR (HOMEOSAR) trial is to determine the efficacy of individualized or standardized homeopathic drug treatment compared to placebo regarding rhinitis-related quality of life in patients with SAR.MethodsThis randomized, placebo-controlled, double-blind, three-armed intervention study will be conducted at two university hospital outpatient clinics for complementary and integrative medicine in Berlin and in 12 office-based practices specializing in homeopathic treatment in Germany. A total of 270 patients with clinical symptoms of SAR and positive allergy test to birch and grass pollen will receive homeopathic anamnesis and subsequently be randomized into (a) standardized homeopathic drug treatment with Galphimia Glauca (potency D6), (b) individualized homeopathic drug treatment (D6), or (c) placebo. All three groups can receive on-demand rescue medication as needed. Treatment will consist of two consultations and daily intake of the study medication for 4 weeks during the pollen season. The primary outcome is the mean overall score of the Rhinitis Quality of Life Questionnaire (RQLQ) in weeks 3 and 4, analyzed using analysis of covariance (adjusted for baseline RQLQ overall score and study center). A closed testing procedure will be used to control the overall type I error comparing the 3 treatment groups. Secondary outcomes include the overall RQLQ and its seven domain scores, responder status (decrease in RQLQ overall score of at least 0.5 points compared to the baseline value), use of rescue medication, intensity of total and individual SAR symptoms based on visual analog scale, generic health-related quality of life, safety, utilization of health care resources and associated costs. In addition, a qualitative data analysis is planned.ConclusionThe results of our study will contribute to clarifying the possible therapeutic effects of homeopathic drug treatment for patients with SAR.Trial registrationThis study has been registered in the German Clinical Trial Registry with trial ID DRKS00018081 on June 09, 2020.

760: KALMED: KETAMINE FOR SEVERE AGITATION MANAGEMENT IN THE EMERGENCY DEPARTMENT

Introduction: Acute agitation is a common presentation in the emergency department (ED) and is of high concern due to safety risks for patients and the healthcare team. As a result, it is crucial to efficiently relieve agitation in these patients. Numerous studies conducted in the pre-hospital setting and the ED have found ketamine to be an effective agent with quicker onset of action than benzodiazepines or antipsychotics for initial control of acute agitation. Ketamine dosing in these studies ranged from 2-5 mg/kg IM (intramuscular). To date, there is no study comparing low-dose (LD), ~2 mg/kg, versus standard dose (SD), 4-5 mg/kg, ketamine IM for acute agitation.The purpose of this study was to assess the effectiveness and safety of ketamine IM < 2.5 mg/kg versus > 2.5 mg/kg for severe agitation. Methods: This was a single-center, retrospective, two-arm cohort. Adult patients that received ketamine IM for acute agitation in the ED were included in this study. Patients were excluded if they received another sedative within 30 minutes of ketamine administration. The primary outcome was resolution of agitation at 15 minutes after ketamine administration. Resolution of agitation was defined as documentation from a healthcare provider, lack of additional sedative agent within 30 minutes from ketamine administration, or ability to complete necessary procedures. The secondary outcomes included use of agitation rescue medications within 30 minutes, adverse events, and time to medical clearance. Results: Of the 82 patients with an IM ketamine order that were evaluated, 68 met the study criteria. The LD cohort included 52 patients while 16 patients received SD ketamine. Mean age, sex, baseline psychiatric/substance abuse history were similar between groups. Successful sedation was similar between groups, LD 88.5% compared to SD 93.8%, (p=0.998). Rescue sedation was required in 16% of LD patients in the low-dose group and 6.3% of SD patients (p=0.32). Respiratory intervention was required in 13.5% in LD arm and 31.4% in SD (p=0.89). Conclusions: LD and SD IM ketamine resulted in similar rates of successful sedation in acutely agitated patients in the ED.

Comparison of two techniques of airway anaesthesia for awake fibreoptic nasotracheal intubation in patients with anticipated difficult airway

Introduction: The success of awake fibreoptic assisted intubation often depends on the adequacy of anaesthesia of the airway and patient comfort for the procedure. Aim: To compare the standard technique (nerve block) of airway anaesthesia with simple aspiration of lignocaine. Methods: Thirty patients in whom difficult airway was anticipated were randomly allocated into either Group A (Aspiration) and Group B (Nerve block). In Group A, 0.2 mL/kg of 1.5% lignocaine was trickled on to the dorsum of the tongue while the patient was encouraged to breathe through the mouth. In Group B, superior laryngeal nerve block and intratracheal injection of lignocaine was used. Fibreoptic bronchoscopy was then carried out by a consultant anaesthesiologist, who was blinded to the local anaesthetic technique used. The patient responses to instrumentation of pharynx, glottis and trachea, and tolerance of the endotracheal tube were noted. Results: Two cases were excluded from the study because of bleeding resulting in subsequent loss of visualisation of glottis through bronchoscope. There was no statistical or clinical difference in the patient responses between the two groups (P &gt; 0.05) due to fibreoptic bronchoscope in the pharynx, larynx and endotracheal tube in the trachea or with regard to the use of rescue medications. Conclusions: Aspiration of 1.5% lignocaine (0.2 mL/kg) provides clinically comparable conditions for intubation as the nerve block technique for awake fibreoptic nasotracheal intubation in patients with anticipated difficult airway.

The First Randomized, Double-Blind, Placebo-Controlled Phase 2 Study to Evaluate the Efficacy and Safety of an FcRn Inhibitor, Rozanolixizumab, in Patients With Leucine-Rich Gliomainactivated 1 Autoimmune Encephalitis

Objective To evaluate efficacy and safety of rozanolixizumab for treatment of leucine-rich glioma inactivated 1 (LGI1) autoimmune encephalitis (AIE). Background LGI1 AIE is a clinically homogeneous syndrome mediated by autoantibodies, predominantly of the IgG4 subclass, characterized by seizures, cognitive impairment and neuropsychiatric symptoms. No approved treatment options are available, and current treatment paradigms are variable. Rozanolixizumab is a fully humanized monoclonal antibody that can be delivered subcutaneously and inhibits the IgG binding region of the neonatal Fc receptor (FcRn), reducing the concentration of circulating IgG-antibodies, including pathogenic IgG-autoantibodies. Design/Methods This multicenter, randomized, double-blind, placebo-controlled LEGIONE study (NCT04875975) is the first Phase 2 study to evaluate efficacy and safety of FcRn inhibition as treatment for LGI1 AIE. The study is recruiting adults with serum LGI1-autoantibodies, considered for intravenous methylprednisolone treatment, with new-onset disease (0-12 months prior to study entry). At screening, patients with prior diagnosis of epilepsy unrelated to LGI1 AIE, IgG level =5.5 g/L, clinically relevant infection or history of neoplastic disease will be excluded. Alongside a typical steroid taper, ∼68 patients will be randomized 1:1 to subcutaneous infusion of rozanolixizumab or placebo for 24 weeks, stratified by time from disease onset and cognitive function (measured by the Repeatable Battery for the Assessment of Neuropsychological Status) at randomization. Primary endpoint is measured by seizure freedom (28 consecutive days of no seizures maintained until the end of the treatment period). Secondary endpoints are change in cognitive function, use of rescue medication, time to onset of seizure freedom and safety and tolerability of rozanolixizumab. Exploratory pharmacokinetic/pharmacodynamic and biomarker-based endpoints are anticipated. Results Study background, rationale and design will be presented. Conclusions The LEGIONE study is the first randomized, double-blind, placebo-controlled Phase 2 study to evaluate the efficacy and safety of an FcRn inhibitor, rozanolixizumab, in patients with leucine-rich glioma-inactivated 1 autoimmune encephalitis and is enrolling patients.

Adherence to inhaled corticosteroids in relation to quality of life and symptoms of anxiety and depression in asthma

ABSTRACT Background Poor asthma control, often caused by non-adherence with controller medication, is a well-known risk factor for impaired quality of life (QoL) and major mood disorders (MMD). Previous studies have shown a relationship between non-adherence, lower QoL, and MMD across chronic diseases, but the relationship remains uncertain in asthma. Methods All asthma patients followed at the respiratory outpatient clinic at Copenhagen University Hospital – Hvidovre were invited to fill-in the Hospital Anxiety and Depression Scale (HADS) and the Mini Asthma Quality of Life Questionnaire (miniAQLQ). Medication Possession Ratio (MPR) was calculated using pharmacy redemption data. Relationships between questionnaire scores, inhaled corticosteroid MPR and use of rescue medication were investigated using Pearson correlation and multivariable linear regression adjusted for age, sex, FEV1, and GINA Step. Data from scheduled visits were collected from patients’ medical records. Results A total of 308 patients (73% females, median age 51 years (interquartile range (IQR) 37, 62)) completed the questionnaires and had 1-year medication data available. Median adherence to inhaled corticosteroids (ICS) was 57% (35%, 75%) with 18% of patients having adherence above 80%. Of the participating patients, 14% and 27% reported depressive and anxiety-related symptoms, respectively, and 72% reported impaired QoL. In correlation analyses, ICS adherence was not significantly associated with either prevalence of MMD symptoms or impaired QoL in asthma patients. However, a strong correlation was found between ACQ-6 and both MMD symptoms and impaired QoL, as well as between rescue medication use and impaired QoL. In adjusted analysis, however, the latter correlation was no longer statistically significant. Conclusion Our results suggest that ICS adherence is not directly correlated with either impaired quality of life or major mood disorder symptoms in asthma patients. Self-reported asthma control, on the other hand, is strongly correlated with both QoL and MMD.

Patient experience of moderate asthma attacks: qualitative research in the USA and Germany

BackgroundThere is limited information available on the impact of moderate asthma exacerbations, often called “asthma attacks” (i.e., those not requiring hospitalisation or treatment with systemic corticosteroids) on patients’ lives. This multi-country qualitative study explored the patient experience of these events.MethodsSemi-structured concept elicitation interviews were conducted in the USA and Germany with adult patients with asthma who had experienced a moderate asthma exacerbation in the prior 30 days. Physicians with experience in managing patients with asthma were also interviewed. Interviews explored patients’ experience of symptoms and impact of moderate exacerbations and associated exacerbation triggers and treatment patterns. Physicians were also asked about their interpretation of a clinical definition and treatment of a moderate exacerbation.ResultsTwenty-eight patient (n = 20 in the USA, n = 8 in Germany) and six physician (n = 3 in the USA, n = 3 in Germany) interviews were conducted. During their moderate exacerbation, all patients reported experiencing shortness of breath, which many considered to be severe and the most bothersome symptom. Wheezing was also reported by all patients and considered severe by two thirds of patients. Most patients also reported coughing and chest tightness. All or almost all patients reported that moderate exacerbation caused fatigue/tiredness and impacted their physical functioning, emotional functioning, activities of daily living and work/school life. Most patients reported using rescue or maintenance inhalers to alleviate symptoms of the exacerbation. Conceptual saturation (i.e., the point at which no new concepts are likely to emerge with continued data collection) was achieved. Findings were used to develop a patient-focused conceptual model of the experience of moderate asthma exacerbations, outlining concepts related to triggers, symptoms, impact, and treatment from the patient perspective. Physician data was consistent with patient reports and complemented the conceptual model.ConclusionsFindings from concept elicitation interviews highlight the increased frequency, duration and severity of asthma symptoms and increased rescue medication use during moderate asthma exacerbations compared with the typical daily asthma experience, which have a substantial impact on patients’ lives.