Meaningful Clinical Improvement Research Articles

Differences in uni-dimensional breathlessness measures and thresholds for clinical response in a randomised controlled trial in people with chronic breathlessness: an exploratory study

IntroductionOptimally measuring improvements in chronic breathlessness in clinical practice and research continues to evolve. The aim of this study was to consider the performance of uni-dimensional measures in chronic breathlessness...

Three-Year Efficacy and Safety of Mirikizumab Following 152 Weeks of Continuous Treatment for Ulcerative Colitis: Results From the LUCENT-3 Open-Label Extension Study.

Mirikizumab, a p19-directed interleukin-23 monoclonal antibody, has demonstrated induction of clinical remission at week 12 with maintenance through week 104 in patients with moderately-to-severely active ulcerative colitis (UC). Results are presented from the LUCENT-3 open-label extension study through week 152. Of 868 LUCENT clinical trial program mirikizumab-treated induction patients, 544 were responders of whom 365 were rerandomized to mirikizumab maintenance. Of these, 324 completed week 52 and 316 entered extension treatment (286 week 52 responders; 179 week 52 remitters). Efficacy and safety outcomes are reported for mirikizumab-treated LUCENT-3 participants, including biologic-failed patients, with data for week 52 maintenance responders/remitters. Discontinuations or missing data were handled by nonresponder imputation, modified nonresponder imputation (mNRI), and observed cases. Using mNRI, 81.6% of week 52 responders demonstrated clinical response at week 152. Week 152 remission rates for week 52 responders included clinical (56.1%), corticosteroid-free (CSF; 54.5%), endoscopic (61.0%), histologic-endoscopic mucosal remission (HEMR; 52.6%), symptomatic (74.9%), and bowel urgency (BU; 58.6%). At week 152, 53.3% of week 52 responders achieved histologic-endoscopic mucosal improvement (HEMI) and 74.3% achieved BU clinically meaningful improvement (CMI). Among week 52 remitters, 85.4% showed a clinical response at week 152, with clinical (70.1%), CSF (68.9%), endoscopic (72.0%), HEMR (63.4%), symptomatic (81.4%), and BU (60.8%) remission. At week 152, among week 52 remitters, 64.0% of patients achieved HEMI and 75.6% achieved BU CMI. Stool frequency, rectal bleeding, BU, and abdominal pain score reductions from induction baseline to maintenance week 52 were sustained through week 152 for week 52 completers. Overall, in the safety population, 7.4% of patients reported severe adverse events (AEs); 5.3% discontinued treatment due to AEs. AEs of special interest included opportunistic infection (1.8%), hepatic disorders (3.2%), cerebrocardiovascular events (1.5%), and malignancy (0.3%). Patients with antidrug antibodies reduced over time from 23.6% in year 1 to 3.2% in year 3. Symptomatic, clinical, endoscopic, histologic, and quality-of-life outcomes support long-term sustained benefit of mirikizumab treatment up to 152 weeks in patients with UC, including biologic-failed patients, with no new safety concerns. ClinicalTrials.gov: NCT03518086; NCT03524092; NCT03519945.

An Ethics Consult Documentation Simplification Project: Summation of Participatory Processes, User Perceptions, and Subsequent Use Patterns.

Healthcare ethics consultants in the Veterans Health Administration (VHA) document consults in an enterprise-wide web-based database entitled IEWeb, serving as a system of record for healthcare ethics documentation at 1300 VA facilities. The need arose to evolve the database from an ethics process training resource into a more streamlined documentation repository that captures essential consult elements. A VHA National Center for Ethics in Health Care (NCEHC) Improvement Team convened for three tasks: (1) Specify and prioritize IEWeb changes (occurred via six focus groups composed of "new user" and "super user" cohorts with analysis of existing documentation patterns); (2) Pilot the changes regionally (via regional communication, training, and reviews of pre-post use patterns); and (3) Measure the impact of national change implementation on user perspectives (via pre-and post-change implementation polls). Focus groups identified six implementable priority areas for ethics consult documentation improvement, including the development of a usable consult summary note for ready conversion from IEWeb fields into the electronic health record. Post-IEWeb updates showed an increased number of consults documented, a reduction in "time to consult documentation closure" by a mean of 4.5days, and a clinically-meaningful improvement in the quality of documentation (78% of ethics questions scored "above-bar" on the validation tool pre- vs. 89% scored "above-bar" post-IEWeb changes, n = 140). According to national survey findings, the number of consultants documenting "all" consults in IEWeb increased, satisfaction increased, and perception of documentation difficulty decreased. IEWeb simplification enabled ethics consultants to re-focus their documentation completion efforts by decreasing perception of documentation burden while improving documentation frequency and quality in a clinically-meaningful way.

5183 Tirzepatide Improved Health-Related Quality of Life in People with Obesity or Overweight: Results from SURMOUNT-4 Phase 3 Trial

Abstract Disclosure: T.M. Gibble: Employee; Self; Employment and stockholder, Eli Lilly and Company. D. Cao: Employee; Self; Employment and stockholder, Eli Lilly and Company. M. Murphy: Employee; Self; Employment and stockholder, Eli Lilly and Company. I. Jouravskaya: Employee; Self; Employment and stockholder, Eli Lilly and Company. B. Liao: Employee; Self; Employment and stockholder, Eli Lilly and Company. Background: Tirzepatide is approved in the U.S. for treatment of type 2 diabetes (T2D) and obesity. In the phase 3 SURMOUNT-4 trial with randomized withdrawal of tirzepatide maximum tolerated dose (MTD) after the first 36 weeks, continuing tirzepatide for 88 weeks led to a mean weight reduction of 25.3% from baseline compared to 9.9% for those who switched to placebo (PBO).1 This analysis evaluated the effects of tirzepatide versus PBO on health-related quality of life (HRQoL) outcomes using the SURMOUNT-4 trial data. Methods: Adults (n=783) with body mass index ≥30 or ≥27 kg/m2 and ≥1 obesity-related complication (excluding T2D) were enrolled in an open-label lead-in period to receive tirzepatide once weekly for 36 weeks, escalated to MTD (10 mg or 15 mg). At week (W) 36, 670 participants were randomized 1:1 to continue tirzepatide MTD (n=335) or were switched to PBO (n=335) for 52 weeks. HRQoL was evaluated using Short Form-36 Version 2 Health Survey (SF-36 v2) acute form and Impact of Weight on Quality of Life-Lite-Clinical Trials Version (IWQOL-Lite-CT), where last observation before discontinuation was carried forward. Higher scores reflected better levels of functioning. Least square means (LSM) and estimated treatment differences (ETD) between tirzepatide versus PBO were calculated using an analysis of covariance model. Proportion of people achieving clinically meaningful improvement (CMI) in SF-36v2 physical functioning score (change from baseline ≥5.76) was also assessed. Results: LSM changes in SF-36 v2 and IWQOL-Lite-CT scores were comparable during lead-in (W0 to W36) between people randomized to tirzepatide and PBO. Significant improvements were observed from W36 to W88 in SF-36v2 Physical Component Score (PCS), Mental Component Score (MCS), and all domains for tirzepatide versus PBO, with LSM (ETD) as follows: PCS, 54.9, 53.1 (1.8); MCS, 54.6, 52.9 (1.7); physical functioning, 54.2, 51.6 (2.6); role-physical, 54.3, 53.3 (1.1); bodily pain, 54.7, 53.1 (1.6); general health, 56.7, 54.1 (2.6); vitality, 57.0, 55.4 (1.6); social functioning, 54.2, 52.9 (1.3); role-emotional, 53.0, 51.1 (1.9), and mental health, 55.4, 52.9 (2.4), respectively; all p<0.05. Proportion of people achieving CMI (%) in SF-36v2 physical functioning from W0 to W88 was higher for tirzepatide than those who switched to PBO (≥ 5.76, 52.0 and 36.2). Tirzepatide showed significant improvements in IWQOL-Lite-CT scores versus PBO from W36 to W88, with LSM scores (ETD) as follows: total, 86.4, 75.3 (11.1); psychosocial, 87.7, 75.6 (12.1); physical function, 85.7, 76.2 (9.4); and physical, 83.8, 74.7 (9.1), respectively; all p<0.001. Conclusion: In SURMOUNT-4 trial, adults with overweight or obesity continuing on tirzepatide showed significant and sustained improvements in HRQoL versus those switching to PBO. 1Sattar N. 59th Annual Meeting European Association for the Study of Diabetes; Oct 2023; Germany. Presentation: 6/3/2024

Connecting Practice to Data: Implementation Strategies to Increase Collection of Core Outcome Measures in an Inpatient Rehabilitation Facility.

To describe a quality improvement project aimed at increasing collection of a "Core Set" of functional outcome measures in an inpatient rehabilitation facility (IRF), characterize implementation strategies used across 4 study phases, and evaluate program adoption and maintenance. A 30-bed brain injury unit of a 132-bed IRF. Participants included physical therapists (5 full-time, 2 part-time, and 30 hourly as needed) and 764 individuals with traumatic brain injury (TBI) who received care during the project period. In this descriptive observational study, we operationalize implementation strategies selected for 4 project phases: Exploration, Preparation, Implementation, and Sustainment. We define each implementation strategy using the Expert Recommendations for Implementing Change and report on program adoption and maintenance. Adoption (proportion of TBI-related admissions with completed outcome measures) and maintenance (adoption over 4years). Preparation phase strategies focused on local adaptations, education, environmental preparation, and collaboration with informatics. Implementation phase strategies included reminders, feedback, champions, and iterative adjustments. Sustainment strategies focused on integration into standard practice. Adoption increased postinitiation for all measures except one. Despite improvements, a notable portion of measures remained incomplete. Increases in outcome measure collection were maintained for 2 to 4years, but a significant decline in paired admission and discharge scores suggests a reduced ability to monitor change over time. This study provides an example of a clinically driven quality improvement project and selected implementation strategies used to increase the collection of standard outcome measures in IRF. By leveraging the Expert Recommendations for Implementing Change framework, we aim to enhance comparability with similar efforts elsewhere. The results demonstrate the program's successes and challenges, highlighting the need for interdisciplinary clinical and research collaboration to support the translation of knowledge between research and clinical practice and inform meaningful improvements in care across TBI rehabilitation.

#1168 Responsiveness to roxadustat in chronic kidney disease associated anemia patients by baseline hemoglobin: a secondary analysis of ROXSTAR Registry

Abstract Background and Aims Anemia is a common complication of chronic kidney disease (CKD), and associated with increased morbidity and mortality, as well as a reduced quality of life (QoL). Various studies have shown anemia treatment in CKD patients improved the QoL. However, in ROXSTAR Registry (ChiCTR2100046322), although roxadustat corrected anemia and maintained hemoglobin (Hb) effectively, no improvement in QoL was observed. Hence, we conduct this secondary analysis of ROXSTAR to evaluate the Hb response to roxadustat treatment and the change of QoL in dialysis-dependent (DD) and non-dialysis-dependent (NDD) patients stratified by baseline Hb. Method This was a secondary analysis using existing data collected in the ROXSTAR Registry. DD & NDD Patients who received at least one dose of roxadustat and had at least one post baseline Hb were included. We described the Hb response to roxadustat in patients with lower baseline (Hb <80) g/L & higher baseline Hb (≥80 g/L). The changes from baseline to week 12 & week 24 in Quality of Life (QoL) assessed by SF-36 Vitality (V) & Physical Function (PF) subscales, and Rapid Assessment of Physical Activity (RAPA) Strength & Flexibility scores were also analyzed respectively. Results Overall, 1998 patients (1508 DD patients and 490 NDD patients) were included, there were 238 patients (131 male [55.0%]) with a mean (standard deviation [SD]) age of 49.1 (13.6) years in the lower baseline Hb group, and 1760 patients (947 male [53.8%]) with a mean age of 50.3 (13.5) in the higher baseline Hb group. The overall mean baseline Hb was 97.3 (13.9) g/L, with 71.4 (7.2) g/L and 100.8 (10.5) g/L in the two groups respectively. The median (min, max) ferritin and mean transferrin saturation were 149.6 (3.3, 2304.0) ng/mL & 22.8% (15.5) % in the lower baseline Hb group and 169.8 (3.8, 3966.0) ng/mL & 30.6% (15.7%) in the higher baseline Hb group. More patients with CRP above normal limit were in the lower baseline Hb group (30.7%) compared to patients in the other group (19.7%) (Table 1). Mean weekly roxadustat dose started at 320 mg and was maintained during the first 12 weeks (correction phase) then slightly decreased to 300 mg from week 12 until week 52 (maintenance phase) in patients with baseline Hb <80 g/L, while it was from 286 mg to 260 mg during the correction phase then decreased and maintained at around 230 mg from week 12 to week 52 in patients with baseline Hb ≥80 g/L. The mean Hb change from baseline averaged over weeks 24-36 and 36-52 was 31.9 [95% CI: 29.9, 33.9] g/L & 33.7 [95% CI: 31.8, 35.6] g/L in the lower baseline Hb group, and 11.3 [95% CI: 10.6, 12.0] g/L & 11.1 [95% CI: 10.5, 11.8] g/L in the higher baseline Hb group. The proportion (%) of patients with mean Hb ≥100 g/L averaged over the same period were 58.8% [95% CI: 51.8%, 65.7%] & 68.6% [95% CI: 61.8%, 75.3%] in the lower baseline Hb group, and 86.5% [95% CI: 84.7%, 88.3%] & 88.2% [95% CI: 86.5%, 90.0%] in the higher baseline Hb group. Patients with baseline Hb <80 g/L had numerically higher mean increases from baseline to week 12 and 24 in SF-36 V and PF sub-scores (Table 2), though no clinical meaningful change was observed in either group. Conclusion Roxadustat effectively corrected anemia in DD and NDD patients regardless of baseline Hb level. There was no clinical meaningful improvement in QoL for either group. The weekly dose of roxadustat to correct and maintain Hb was higher in patient with baseline Hb <80 g/L than in patients with baseline Hb ≥80 g/L.

Minimally Invasive versus Open Transforaminal Lumbar Interbody Fusion in Obese Patients: A Propensity Score-Matched Study.

Retrospective review of prospectively collected data. This study aimed to compare the clinical outcomes of obese patients undergoing minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and open TLIF. The perioperative benefits of minimally invasive surgery in obese patients have been described. However, there is limited literature on the patient-reported outcomes (PROs), satisfaction and return to work following MIS-TLIF and open TLIF in this subgroup of patients. Obese patients (BMI ≥30.0kg/m2) who underwent a primary, one- to two-level open and MIS-TLIF were stratified and matched using propensity scoring. Operative time, length of stay and perioperative outcomes were recorded. Patient-reported outcomes (PROs) including Oswestry Disability Index, Short Form-36 Physical Component Score, Mental Component Score, Visual Analogue Scale for back pain and leg pain were compared at each postoperative time point. Achievement of minimal clinically important difference (MCID), patient satisfaction and return to work were also assessed. Revision procedures were recorded at mean 10±3.3 years follow-up. In total, 236 obese patients were included: 118 open TLIF and 118 MIS-TLIF. Length of stay was longer in the Open TLIF cohort and there was a trend towards a higher complication rate. However, there was no difference in operative time, transfusions or readmissions. Patients who underwent open TLIF reported worse ODI (P=0.043) and VAS leg pain at 2 years, although the latter did not reach statistical significance (P=0.095). Achievement of MCID for each PRO, patient satisfaction and return to work were also comparable. Obese patients who underwent MIS-TLIF had a shorter length of stay and improved functional disability at 2 years compared those who underwent open TLIF. However, a similar proportion achieved a clinical meaningful improvement. Patient satisfaction and return to work were also comparable at 2 years. Level III, retrospective cohort study.

Increasing the etanercept dose in a treat-to-target approach in juvenile idiopathic arthritis: does it help to reach the target? A post-hoc analysis of the BeSt for Kids randomised clinical trial

BackgroundEtanercept has been studied in doses up to 0.8 mg/kg/week (max 50 mg/week) in juvenile idiopathic arthritis (JIA) patients. In clinical practice higher doses are used off-label, but evidence regarding the relation with outcomes is lacking. We describe the clinical course of JIA-patients receiving high-dose etanercept (1.6 mg/kg/week; max 50 mg/week) in the BeSt for Kids trial.Methods92 patients with oligoarticular JIA, RF-negative polyarticular JIA or juvenile psoriatic arthritis were randomised across three treat-to-target arms: (1) sequential DMARD-monotherapy (sulfasalazine or methotrexate (MTX)), (2) combination-therapy MTX + 6 weeks prednisolone and (3) combination therapy MTX + etanercept. In any treatment-arm, patients could eventually escalate to high-dose etanercept alongside MTX 10mg/m2/week.Results32 patients received high-dose etanercept (69% female, median age 6 years (IQR 4–10), median 10 months (7–16) from baseline). Median follow-up was 24.6 months. Most clinical parameters improved within 3 months after dose-increase: median JADAS10 from 7.2 to 2.8 (p = 0.008), VAS-physician from 12 to 4 (p = 0.022), VAS-patient/parent from 38.5 to 13 (p = 0.003), number of active joints from 2 to 0.5 (p = 0.12) and VAS-pain from 35.5 to 15 (p = 0.030). Functional impairments (CHAQ-score) improved more gradually and ESR remained stable. A comparable pattern was observed in 11 patients (73% girls, median age 8 (IQR 6–9)) who did not receive high-dose etanercept despite eligibility (comparison group). In both groups, 56% reached inactive disease at 6 months. No severe adverse events (SAEs) occurred after etanercept dose-increase. In the comparison group, 2 SAEs consisting of hospital admission occurred. Rates of non-severe AEs per subsequent patient year follow-up were 2.27 in the high-dose and 1.43 in the comparison group.ConclusionsEscalation to high-dose etanercept in JIA-patients who were treated to target was generally followed by meaningful clinical improvement. However, similar improvements were observed in a smaller comparison group who did not escalate to high-dose etanercept. No SAEs were seen after escalation to high-dose etanercept. The division into the high-dose and comparison groups was not randomised, which is a potential source of bias. We advocate larger, randomised studies of high versus regular dose etanercept to provide high level evidence on efficacy and safety.Trial registrationDutch Trial Register; NTR1574; 3 December 2008; https://onderzoekmetmensen.nl/en/trial/26585.

THE EFFECT OF OSTEOARTHRITIS GRADE ON PATIENT-REPORTED OUTCOME MEASURES AFTER TOTAL HIP ARTHROPLASTY: A SYSTEMATIC REVIEW AND META-ANALYSIS

Although total hip arthroplasty (THA) is beneficial for many patients with hip osteoarthritis (OA), a subset of patients experience minimal benefit. It is therefore pertinent to understand the predictors of poor functional outcome to facilitate shared decision making. One such predictor is preoperative radiographic OA severity. The aim of this systematic review was to determine whether preoperative radiographic OA severity could predict postoperative patient-reported outcome measures (PROMs) and satisfaction rates after THA.This systematic review was conducted according to PRISMA guidelines, and the protocol published in PROSPERO (ID:Â CRD42023445918). A literature search was performed using Embase, MEDLINE and Cochrane Library databases. Demographics, radiographic OA severity, PROMs, satisfaction, and complications after THA were collected. A meta-analysis was performed, where appropriate, using a random-effects model.Of 631 identified articles, 12 were included in the final analysis (8,034 participants; mean age 65.2, 38.1% male, mean BMI 29.1 kg/m2). There were three key findings. Firstly, those with mild OA are less likely to achieve a meaningful clinical improvement in PROMs (odds ratio (OR) 0.50, 95% confidence interval (CI) 0.38, 0.65; p < 0.00001). Secondly, two studies indicates that postoperative patient satisfaction was lower in participants with mild OA. Thirdly, participants with mild arthritis experience less improvement in SF-36 physical functioning (mean difference (MD) -8.31, 95% CI -10.97, -5.64; p < 0.00001) and role physical (MD -5.59, 95% CI -8.40, -2.77; p < 0.0001), but showed higher improvement in general health (MD 1.68, 95% CI 0.31, 3.06; p = 0.02).Patients with mild OA, as determined radiographically, are less likely to achieve meaningful clinical improvements in PROMs and have lower postoperative satisfaction after THA. This information will improve collaborative decision-making in the preoperative period.

Bicycling for Rehabilitation of Persons With Parkinson Disease: A Scoping Review.

Exercise is beneficial for persons with Parkinson disease (PwPD). The overarching purpose of this scoping review was to provide guidance to clinicians and scientists regarding current evidence for bicycling exercise for PwPD. A scoping review was conducted to examine the heterogeneous literature on stationary bicycling for PwPD to reduce motor symptoms and body function structure impairments, improve activities and motor performance, and reduce disease severity. The Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines were followed. PubMed, CINAHL, and PEDro were searched from inception to January 23, 2023. Articles reporting original data on relevant outcome measures were included. Search results were screened and articles were extracted. Data were analyzed quantitatively with percentages of significant and clinically meaningful findings and qualitatively to extract themes. Bicycling was categorized using bicycle types (assisted, nonassisted) and training modes (speed, aerobic, force). A high percentage of the 34 studies showed statistical significance for reducing motor symptoms (83%), body function structure impairments (78%), disease severity (82%), and improving activities (gait 72%, balance 60%). Clinically meaningful findings were achieved in 71% of the studies for reduction in disease severity and in 50% for improving gait. The literature on bicycling for PwPD has evolved from speed to aerobic studies. The terminology describing types of bicycling was simplified. Of all the outcomes reported, reduction of disease severity achieved the highest frequency of clinical meaningful improvements. Bicycling was comparable with other forms of aerobic training for walking speed and endurance. Opportunities for translation to practice and research are presented.

Long-term safety, tolerability, and efficacy of efgartigimod (ADAPT+): interim results from a phase 3 open-label extension study in participants with generalized myasthenia gravis.

ADAPT+ assessed the long-term safety, tolerability, and efficacy of efgartigimod in adult participants with generalized myasthenia gravis (gMG). ADAPT+ was an open-label, single-arm, multicenter, up to 3-year extension of the pivotal phase 3 ADAPT study. Efgartigimod was administered in treatment cycles of 4 intravenous infusions (one 10 mg/kg infusion per week). Initiation of subsequent treatment cycles was individualized based on clinical evaluation. Safety endpoints included incidence and severity of adverse events. Efficacy endpoints assessed disease severity using Myasthenia Gravis-Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores. As of January 2022, 151 participants had rolled over to ADAPT+ and 145 had received ≥1 dose of efgartigimod, of whom, 111 (76.6%) were AChR-Ab+ and 34 (23.4%) were AChR-Ab-. Mean study duration (treatment plus follow-up) was 548 days, and participants received up to 17 treatment cycles, corresponding to 217.6 participant-years of exposure. In the overall population, 123 (84.8%) participants reported ≥1 treatment-emergent adverse event; most frequent were headache (36 [24.8%]), COVID-19 (22 [15.2%]), and nasopharyngitis (20 [13.8%]). Clinically meaningful improvement (CMI) in mean MG-ADL and QMG scores was seen as early as 1 week following the first infusion across multiple cycles in AChR-Ab+ and AChR-Ab- participants. Maximal MG-ADL and QMG improvements aligned with onset and magnitude of total IgG and AChR-Ab reductions. For AChR-Ab+ participants at any time point in each of the first 10 treatment cycles, more than 90% had a maximum reduction of ≥2 points (CMI) in MG-ADL total score; across the 7 cycles in which QMG was measured, 69.4% to 91.3% of participants demonstrated a maximum reduction of ≥3 points (CMI) in QMG total score. Many participants demonstrated improvements well beyond CMI thresholds. In AChR-Ab+ participants with ≥1 year of combined follow-up between ADAPT and ADAPT+, mean number of annualized cycles was 4.7 per year (median [range] 5.0 [0.5-7.6]). Results of ADAPT+ corroborate the substantial clinical improvements seen with efgartigimod in ADAPT and support its long-term safety, tolerability, and efficacy, as well as an individualized dosing regimen for treatment of gMG. https://classic.clinicaltrials.gov/ct2/show/NCT03770403, NCT03770403.

Patients with longstanding psoriatic arthritis can achieve DAPSA remission or low disease activity and it correlates to better functional outcomes: results from a Latin-American real-life cohort

BackgroundPatients with psoriatic arthritis (PsA) experience reduced physical function and impaired quality of life. Better patient-reported functional outcomes are found when lower disease activity is achieved.ObjectivesTo evaluate the variation of physical function by HAQ-DI over time in PsA patients treated with standard therapy in a real-life setting: to verify predictors of achieving a minimum clinically important difference (MCID) in function by HAQ-DI (ΔHAQ-DI ≤ − 0.35) and to measure the impact of achieving REM/LDA on long-term function by HAQ-DI.MethodsThis is a longitudinal analysis of a real-life retrospective cohort. Data from PsA patients with at least 4 years of follow-up in the PsA clinic from 2011 to 2019 were extracted from electronic medical records. The variations of physical function by HAQ-DI and disease activity by DAPSA over time were calculated. A multivariate hierarchical regression model was applied to verify predictors of MCID in HAQ-DI. A comparison of HAQ-DI variation between patients with DAPSA REM, LDA, moderate and high disease activity was made using the generalized estimating equation model (GEE), adjusted by Bonferroni test. The Spearman correlation method was applied to verify the correlation of ΔDAPSA and ΔHAQ-DI over time. Statistical analysis was performed in SPSS program version 21.0.ResultsSeventy-three patients were included in the analysis. Physical function measured by HAQ-DI was determined by PsA disease activity measured by DAPSA (p < 0.000). A moderate and statistically significant correlation between ΔDAPSA and ΔHAQ-DI was observed (rs = 0.60; p < 0.001). Only patients in DAPSA REM demonstrated a constant decline in HAQ-DI scores during the follow-up. White ethnicity and older age at baseline were predictors for not achieving MCID in HAQ-DI [RR 0.33 (0.16–0.6795% CI p = 0.002) and RR 0.96 (0.93–0.9895% CI p < 0.000), respectively, while higher scores of HAQ-DI at baseline were predictors of achieving MCID [RR 1.71 (1.12–2.6095%CI p = 0.013)].ConclusionsIn PsA, patients who maintained DAPSA REM/LDA over time had better long-term functional outcomes. Higher HAQ-DI scores at baseline, non-white ethnicity and younger age were predictors for achieving a clinical meaningful improvement of HAQ-DI.

Association of achieving clinical disease control criteria and patient-reported outcomes in bimekizumab-treated patients with active psoriatic arthritis: results from two phase III studies.

Psoriatic arthritis (PsA) is a chronic inflammatory disease that causes pain and fatigue, reduces physical function, and negatively impacts health-related quality of life (HRQoL). In the phase III BE OPTIMAL and BE COMPLETE studies, bimekizumab demonstrated clinical efficacy and meaningful improvements in patient-reported outcome (PRO) measures in biologic disease-modifying antirheumatic drug (bDMARD)-naïve patients, and those who had prior inadequate response/intolerance to tumor necrosis factor inhibitors (TNFi-IR). To examine the association between achieving increasingly stringent clinical disease control criteria and improvements in PRO measures in patients with active PsA receiving bimekizumab. Post hoc analysis of two phase III studies. BE OPTIMAL and BE COMPLETE assessed subcutaneous bimekizumab 160 mg every 4 weeks in bDMARD-naïve and TNFi-IR patients with active PsA. Disease control was assessed using American College of Rheumatology (ACR) response criteria, Minimal Disease Activity, Disease Activity Index for Psoriatic Arthritis, and the composite outcome of ACR50 and 100% improvement in Psoriasis Area and Severity Index. Associations between clinical disease control criteria and PRO measures of pain, fatigue, physical function, and HRQoL were assessed at week 16 and week 52/40 (BE OPTIMAL/BE COMPLETE). Achievement of increasingly stringent clinical disease control criteria was generally associated with sequentially greater improvements in all PRO measures, including pain. At week 52/40, 94.7% of bDMARD-naïve and 97.6% of TNFi-IR patients achieving ACR70 reported ⩾50% improvements in pain from baseline, and the greatest numerical improvements (-48.5 bDMARD-naïve; -54.7 TNFi-IR). This pattern was evident as early as week 16 and sustained when assessed at week 52/40 across the majority of clinical disease control criteria and PRO measures reported. The achievement of increasingly stringent thresholds of disease control was associated with corresponding greater improvements in PROs, for patients receiving bimekizumab treatment, irrespective of prior TNFi use. NCT03895203, NCT03896581, and NCT04009499.

OP88 Translating Patient Reported Measure Score Into Specific Outcomes From The Patient Perspective–Example Using Health Assessment Questionnaire-Disability Index

IntroductionTo facilitate communication of clinical study results among patients, clinicians, and payers, this post-hoc analysis examined the association between achieving the Health Assessment Questionnaire-Disability Index (HAQ-DI) clinical meaningful improvement (CMI) and normalization of individual daily activities using pooled clinical trial data of patients with moderate-severe psoriatic arthritis (PsA).MethodsPatients with active PsA (n=1,120) who participated in two Phase III trials were administered the HAQ-DI at baseline and weeks (W) 24 and 52. The HAQ-DI is a patient-reported instrument measuring functional status that is validated for rheumatological diseases including PsA. It contains 20-items assessing activities of daily living using a 0-3 Likert scale [0=able to perform activity without difficulty (normalization) through to 3=unable to perform activity]; 0.35 or more improvement in total HAQ-DI represents the CMI in PsA patients. Study participants with baseline item-specific scores more than zero (indicating some level of impairment) who experienced both 0.35 or more improvement in total HAQ-DI and item-specific score equal to zero, were compared over time.ResultsThe proportion of patients with compromised ability to perform individual activities at baseline ranged from 42.3 percent (Difficulty Turning Faucet) to 84.1 percent (Difficulty Doing Chores). Fourteen of 20 activities with 60 percent or more of patients reporting impairment at baseline decreased to one of 20 activities in patients reaching the CMI at W24. Fourteen of 20 activities with 50 percent or more of patients reporting no impairment at W24 increased to 18 of 20 activities at W52. Notably, the proportion of patients reporting impairment for the two outlier activities at W52 (Reach-Get Down 5lb Item/Doing Chores) decreased during the follow-up period by 28 percent and 30 percent, respectively, despite presenting as very challenging at baseline.ConclusionsPsA patients achieving a clinically meaningful change in total HAQ-DI over time were more likely to achieve normalization of individual daily activities. Translating changes in patient-reported outcome scores to specific symptom or functional improvements are meaningful to help patients understand clinical trial results, as well as to communicate with payers the value of accessing treatment for specific health conditions.

Clinical Benefits of Baricitinib Therapy According to Scalp Hair Regrowth in Patients with Severe Alopecia Areata.

The present analyses report integrated results from BRAVE-AA1 (NCT03570749) and BRAVE-AA2 (NCT03899259) on the clinical benefits of baricitinib treatment on the basis of the amount of scalp hair regrowth through 52weeks of treatment. This posthoc analysis was conducted with data from patients who were treated continuously for 52weeks with baricitinib 4mg or 2mg. Clinical outcomes were assessed using the Severity of Alopecia Tool (SALT) and Clinician-Reported Outcome (ClinRO) for Eyebrow (EB) and Eyelash (EL) hair. Secondary measures included the Hospital Anxiety and Depression Scale and Skindex-16 adapted for alopecia areata. At week52, patients were classified into three subgroups: SALT ≤ 20 response, intermediate response (achieved a 30% improvement from baseline (SALT30) without a SALT score ≤ 20), or nonresponse (never achieved SALT30). The criterion of SALT30 approximates a minimal clinical meaningful response to therapy. At week52, with baricitinib 4 mg treatment, the greatest (70%) improvement in EB and EL was observed in responders, but approximately 50% of patients with intermediate response and 20% of nonresponders experienced complete/nearly complete EB and EL regrowth. Improvement in emotional distress was directionally related to improvements in scalp hair regrowth, while impact on quality of life was proportionately greater for the responder subgroup. Clinically meaningful regrowth in eyebrow and eyelash hair can occur in the absence of complete scalp hair regrowth after treatment with baricitinib. Emotional distress and quality of life improvement is most associated with obtaining a clinical meaningful improvement in scalp hair. BRAVE-AA1, ClinicalTrials.gov number, NCT03570749, start date, 24September2018; BRAVE-AA2, ClinicalTrials.gov number, NCT03899259, start date, 8July2019.

Effectiveness of rehabilitation intervention in persons with Friedreich ataxia.

The relevance of rehabilitation in progressive neurological disorders, such as Friedreich's Ataxia (FRDA), has yet to be convincingly proven. FRDA is characterized by ataxia, loss of gait, scoliosis, cardiomyopathy, dysarthria and dysphagia, with reduced life expectancy. The disease onset is usually in adolescence, leading to progressive disability. Omaveloxolone has been recently approved as the first pharmacological treatment for FRDA in adults and adolescents aged 16 years and older. Regarding non-pharmacological therapies, neurorehabilitation is a valuable aid in addressing the symptoms and in maintaining the residual functioning. We performed a prospective observational cohort study to evaluate the efficacy of inpatient rehabilitation (IR) for people with FRDA. A total of 42 individuals (29 adults and 13 children) with FRDA were recruited. There were 27 ambulant and 15 non-ambulant participants. The patients underwent IR of 3 and 4 weeks in children and adults, respectively. The IR treatment was designed to be applied within a multidisciplinary setting, so FRDA patients underwent, in addition to physiotherapy, also occupational therapy, practical manual activities and psychological support aiming to enhance transferable skills useful in the activities of daily living. The primary outcome was the Scale for the Assessment and Rating of Ataxia (SARA). Other measures were: Friedreich Ataxia Rating Scale (FARS) and Nine Hole Peg Test (NHPT). Furthermore, we used the 6 Minute Walk Test (6MWT), the Timed Up and Go (TUG) and the Berg Balance Scale (BBS) only on ambulant subjects. Outcomes were evaluated at baseline and at the end of the treatment. We report that the IR significantly improves motor performance and ataxia symptoms in patients with FRDA. Our study shows significant functional improvement in all the outcome measures used, except for NHPT bilaterally. FARS and SARA scores post-IR are significatively reduced when compared (p < 0.001). We demonstrate that IR programs in FRDA can provide a meaningful clinical improvement in terms of outcome measures. These findings could be useful when approaching progressive neurological disorders.

Tapinarof Cream 1% Once Daily for the Treatment of Plaque Psoriasis: Case Photography of Clinical Outcomes from Three Phase3 Trials.

Tapinarof cream 1% (VTAMA®; Dermavant Sciences, Inc.) is a non-steroidal, topical, aryl hydrocarbon receptor agonist approved by the US Food and Drug Administration (FDA) to treat plaque psoriasis in adults and under investigation for the treatment of psoriasis in children down to 2years of age, and for atopic dermatitis in adults and children down to 2years of age. The PSOARING phase3 clinical trial program evaluated tapinarof cream 1% once daily (QD) in adults with mild to severe plaque psoriasis for up to 52weeks (NCT03956355, NCT03983980, NCT04053387). Here we present case photography documenting outcomes in the PSOARING trials. Cases illustrate various outcomes across different body areas, including responses meeting the formal FDA-mandated regulatory endpoint of a Physician Global Assessment (PGA) score of 0 (clear) or 1 (almost clear) and a decrease of at least 2points from baseline at week12, meaningful clinical improvement not meeting this formal endpoint, patient-reported outcomes, and pre-specified adverse events of special interest (AESIs). Tapinarof cream 1% QD demonstrated rapid and highly statistically significant efficacy, with improvements in disease activity and quality of life. In addition, a high rate (40.9%; n = 312/763) of complete disease clearance (PGA = 0) was achieved, and improvements exceeding National Psoriasis Foundation treatment goals were demonstrated. After first achieving complete disease clearance (PGA = 0), patients treated with tapinarof experienced an approximately 4-month remittive effect off therapy. Incidence and severity of folliculitis and contact dermatitis AESIs were generally mild or moderate, localized to the site of application, and associated with low discontinuation rates. Medical images are of importance in trials of dermatologic therapies to inform clinical decision-making and enhance patient assessment. Tapinarof cream 1% QD is efficacious and well tolerated in patients with mild to severe plaque psoriasis, with clinically relevant improvements seen early in the course of treatment.Clinicaltrials.gov numbers: NCT03956355, NCT03983980, NCT04053387.

Immune Checkpoint Inhibitors in "Special" NSCLC Populations: A Viable Approach?

Over the last decade, the therapeutic scenario for advanced non-small-cell lung cancer (NSCLC) has undergone a major paradigm shift. Immune checkpoint inhibitors (ICIs) have shown a meaningful clinical and survival improvement in different settings of the disease. However, the real benefit of this therapeutic approach remains controversial in selected NSCLC subsets, such as those of the elderly with active brain metastases or oncogene-addicted mutations. This is mainly due to the exclusion or underrepresentation of these patient subpopulations in most pivotal phase III studies; this precludes the generalization of ICI efficacy in this context. Moreover, no predictive biomarkers of ICI response exist that can help with patient selection for this therapeutic approach. Here, we critically summarize the current state of ICI efficacy in the most common "special" NSCLC subpopulations.

Investigating the factors associated with meaningful improvement on the SF-36-PFS and exploring the appropriateness of this measure for young people with ME/CFS accessing an NHS specialist service: a prospective cohort study

ObjectivesPaediatric myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is relatively common and disabling, but little is known about the factors associated with outcome. We aimed to describe the number and characteristics of...

Effect of multimodal intervention care on cachexia in patients with advanced cancer compared to conventional management (MIRACLE): An open-label, parallel, randomized, phase 2 trial.

e24135 Background: Cancer Cachexia (CC) is a multi-factorial process characterized by progressive weight loss, muscle mass and fat tissue wasting, and adversely affecting their quality of life and survival in patients with advanced stage of cancer. We investigated the efficacy and safety of a multi-modal intervention including anti-inflammation, omega-3-fatty acids, nutritional supplement with counselling, physical exercise, psychiatric intervention as well as Bojungikki-tang which mediates immune-modulation and reverse chronic inflammation and wasting condition as a complementary and alternative medicine compared to patients receiving best supportive care. Methods: Eligible criteria included patients with advanced stage of gastrointestinal (gastric, colorectal and pancreaticobiliary) as well as lung cancer undergoing active palliative chemotherapy. Patients are randomized into experimental arm (Multi-modal intervention care: MIC) versus control arm (Conventional Palliative Care, CPC). MIC are comprised of daily oral medications; ibuprofen 400 mg three times a day, omega-3-fatty acid 1 g twice a day, Bojungikki-tang 3.75g twice a day, oral nutritional supplement (HAMONILAN SOLN) 200 ml twice a day, and weekly physical exercise (60 minutes per visit), psychiatric assessment on every other week, and nutritional counselling total four times during the study period. CPC included basic nutritional counselling for two times provided by National Health Insurance Service, and megestrol acetate as needed (ie, anorexia≥grade 2). All interventions were provided during 12 weeks per subject. Co-primary outcomes are total lean body mass changes and handgrip strength change from the baseline. Secondary outcomes included change of fat mass and total body mass, lean body mass, and quality of life assessment (KCT0004967, NCT 04907864). Results: A total of 112 patients was planned to be assigned to the two arms (56 in each group), however, the study was terminated due to low accrual rate and the expiration of the study approval period of the national research fund, after enrolling up to 56 subjects (28 in each group). Demographic findings were even distributed between arms. The difference of median changes of total lean body mass in MIC group after 12 weeks of intervention, was numerically increased without statistical significance compared to CPC group (MIC vs CPC, 91 vs. -295 g, p= 0.3863). There was no difference of median changes of handgrip strength between MIC and CPC groups (MIC vs CPC, 0.4 vs. 0.9, p= 0.2319). Other secondary outcomes showed no differences, either. Conclusions: Multimodal intervention in this study did not show clinical meaningful improvement. We have to further investigate another method to improve cachexia. Clinical trial information: NCT04907864 .