Clinically Important Change in SF-12v2 Physical (PCS) and Mental (MCS) Component Summary Scores for Patients with Cold Agglutinin Disease: An Analysis Using the Phase 3 CARDINAL and CADENZA Studies

Introduction Cold Agglutinin Disease (CAD) is an autoimmune condition resulting in hemolytic anemia; the subsequent fatigue causes a reduction in patient's physical and mental health-related quality of life (HRQoL). Sutimlimab (formerly BIVV009) is a humanized monoclonal anti-C1s antibody with a clinical trial program to support its development as a treatment for CAD. CARDINAL (NCT03347396) and CADENZA (NCT03347422) are Phase 3 clinical trials that assessed the treatment-related change in HRQoL using the 12-item Short-Form Health Survey (version 2) (SF-12v2) in patients with CAD treated with sutimlimab. This analysis aimed to estimate the clinically important change (CIC) in SF-12v2 physical (PCS) and mental (MCS) component summary scores, using pooled data from CARDINAL and CADENZA. Methods CARDINAL was an open-label, single-arm, multicenter study for patients with CAD with a recent blood transfusion. CADENZA was a randomized, double-blind, placebo-controlled, multicenter study; patients with CAD (without a recent blood transfusion) were randomized 1:1 to receive sutimlimab or placebo. In both studies, patients underwent efficacy and safety assessments for 6 months (Part A). Data from the Part A 26-week component of both studies were combined for these analyses. CIC, defined as mean score change divided by SD at baseline, gave treatment effect sizes of 0.2 (small), 0.5 (moderate) or 0.8 (large), allowing for interpretation of patient-reported outcomes by pre-determining clinically meaningful improvements in physical and mental well-being. Anchor- and distribution-based analyses were performed to estimate the CIC for the following patient-reported outcome measures: Patient Global Impression of (fatigue) Severity (PGIS) and Patient Global Impression of Change (PGIC). Anchor-based approaches (mean change and model-based) examined the relationship between change in SF-12v2 PCS and MCS scores and change in related anchor variables: change in PGIS, PGIC (from baseline to Week 26) and hemoglobin levels (g/dl) (from baseline to the mean value of Weeks 23, 25 and 26). The independent variable was change in PCS and MCS scores and dependent variables were binary (improvement vs. no improvement) in model-based analyses. Results Fifty-five patients with SF-12v2 data available were included from CARDINAL (n=17) and CADENZA (n=38). The median (range) age was 70 (46-88) years and 76% of patients were female (n=42). Mean (SD) PCS and MCS scores at baseline were 40.9 (7.8) and 47.3 (9.1), respectively. From baseline to Week 26, mean (SD) changes in PCS and MCS scores were 4.1 (7.1) and 3.1 (11.6), respectively. Correlations between changes in PCS and MCS scores and PGIS, hemoglobin, and self-report of change in PGIC at Week 26 ranged from 0.36 to 0.55, indicating moderate associations (Table 1). When using an anchor-based approach that evaluated mean change in PCS and MCS scores, CIC estimates ranged from 2.9 to 7.4 for PCS and 2.2 to 7.0 for MCS (Table 2). Results from the 2 model-based anchor approaches, which estimated CIC using receiver operating characteristic curves and an adjusted logistic regression-based approach ranged from 2.0 to 7.3 for PCS and 1.1 to 4.1 for MCS (Table 2). Distribution-based analyses determined the CIC to be 3.9 and 4.6 for PCS and MCS, respectively, when based on one-half of the standard deviation of baseline scores, and 3.5 (PCS) and 4.1 (MCS) when based on the standard error of measurement. The median estimate produced by all anchor-based methods were closely aligned with results of distribution-based analyses. Therefore, taking into consideration all approaches, the median CICs for CAD patients for PCS and MCS were 3.9 and 2.8, respectively. Conclusion In this analysis, patients with CAD had median CIC values of 3.9 and 2.8 for PCS and MCS, respectively. In a previous study, anchor-based analyses for the general population gave CIC scores of 3.0 for both PCS and MCS (Maruish ME et al. 3 rd edition; Lincoln, RI; 2012). The results of this study converge well with those estimates observed for the general population involving thousands of observations. This analysis also demonstrated that meaningful physical and mental health benefits (including a reduction in fatigue) were associated with improvements in hemoglobin levels, a main clinical outcome measure of CAD. Figure 1 Figure 1. Disclosures Joly: Sanofi: Current Employment. Kosinski: QualityMetric Incorporated, LLC: Current Employment. Shafer: Sanofi: Current Employment, Current equity holder in publicly-traded company; Pfizer: Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months, Ended employment in the past 24 months. Wardecki: Sanofi: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months, Other: May hold shares and/or stock options with Sanofi. Karaouni: BMAPS SARL(Geneva, Switzerland): Current Employment; Sanofi: Consultancy. Hill: Amgen: Honoraria; Alexion: Honoraria; ReAlta: Consultancy; Sanofi: Consultancy; Grifols: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Argenx: Consultancy; Apellis: Consultancy, Honoraria.

Minimal important change and responsiveness of the Migraine Disability Assessment Score (MIDAS) questionnaire

Background The MIDAS is the most used questionnaire to evaluate migraine-related disability, but its utility to assess treatment response remains unclear. Our aim was to estimate the MIDAS’ minimal important change (MIC) value and its responsiveness. Methods A total of 103 patients were enrolled in a non-pharmacological, preference-based clinical trial. MIDAS and global rating of self-perceived change (GRoC) scores were collected at baseline, after 5 weeks of treatment, 4-weeks and 3-months follow-up after treatment. Anchor-based approaches were used to establish MIC values and responsiveness. Findings In all 3 timepoint comparisons, MIDAS presented a MIC of 4.5 points. A moderate positive correlation was identified between the MIDAS change and GRoC scores. The area under the curve ranged from 0.63 to 0.68. Conclusions This study showed that MIDAS has a limited responsiveness to change. A change of 4.5 points or more represents a clinically important change for patients with high frequent migraine and chronic migraine receiving non-pharmacological treatment.

1013 Dupuytren’s Contracture Treatment with XIAPEX Injection: Reviewing A Single Surgeon's Experience

Aim To review a single surgeon's experience for the treatment of Dupuytren's disease with XIAPEX injection and the clinical outcomes as measured by a URAM score. Method Retrospective review of patient notes, clinical photography and URAM scores for patients who underwent the procedure between August 2013 and October 2016. Results 33 patients underwent the procedure. 25 patients completed pre and post URAM scores. Average pre procedure score was 19.4 and avergae post procedure score was 3.28 a difference of 16.12 (clinically important change for URAM score is 2.9). Average pre procedure MCPJ contracture was 46.67 degrees and average post procedure contracture was 3.3 degrees. Average pre procedure PIPJ contracture was 66.8 degrees and average post procedure contracture was 8.2 degrees. Where both MCPJ and PIPJ affected of the same digit average pre procedure MCPJ and PIPJ contracture was 60 degrees. The post procedure contracture was 0 degrees in the MCPJ and 29.7 degrees in the PIPJ. 1 patient underwent surgery for progressive disease. Conclusions XIAPEX injection has shown a clinically significant result in the treatment of Dupuytren's disease. There were minimal complications and only 1 patient needed further surgery. However, a small sample size thus conclusions have to be cautious.

“When will this end? Will it end?” The impact of the March-June 2020 UK Covid-19 lockdown response on mental health: a longitudinal survey of mothers in the Born in Bradford study

ABSTRACTObjectivesTo determine clinically important change in anxiety and depression from before to during the first UK Covid-19 lockdown and factors related to this change, including ethnic differences.DesignPre-Covid and lockdown surveys nested within two longitudinal Born in Bradford cohort studies.Participants1,860 mothers with a child aged 0-4 or 9-13, 48% Pakistani heritageMain outcome measuresOdds ratios (OR) for a clinically important increase (5 points) in depression (PHQ-8) and anxiety (GAD-7) in unadjusted regression analyses, parsimonious multivariate modelling to explore ethnicity and mental ill health and lived experience of mothers captured in open text questions.ResultsClinically important depression and anxiety increased from 11% to 19%, and 10% to 16% respectively from before to during the first Covid-19 lockdown. Loneliness during lockdown was most strongly associated with increases in depression (OR: 8.37, 95% CIs: 5.70-12.27) and anxiety (8.50, 5.71-12.65), followed by financial insecurity (6.23, 3.96-9.80; 6.03, 3.82-9.51). Other strongly associated variables included food and housing insecurity, a lack of physical activity and a poor partner relationship.When level of financial insecurity was taken into account, Pakistani heritage mothers were less likely than White British mothers to experience an increase in depression (0.67, 0.51-0.89) and anxiety (0.73, 0.55-0.97).Responses to open text highlighted a complex inter-play of health anxieties, mental load, loss of social support and coping strategies, and financial insecurity contributing to mental ill health. Positive aspects of lockdown were also reported, including a more relaxed pace of life.ConclusionsMental ill health has worsened with the Covid-19 lockdown, particularly in those who are lonely, economically insecure and/or of White British ethnicity. Mental health problems may have longer term consequences for public health. Strategies to mitigate adverse impacts of future lockdowns on mental health should focus on those factors we highlight as associated with worsening mental health.

Changes in quality of life and dyspnoea after hospitalization in COVID-19 patients discharged at home

Background: To date, the effects of COVID-19 pneumonia on health-related quality of life (HRQoL) and dyspnea are unknown.Methods: In a real-life observational study, 20 patients with COVID-19-related pneumonia received usual care plus erdosteine (300 mg twice daily) for 15 days after hospital discharge following local standard operating procedures. At discharge (T0) and on Day 15 (T1), participants completed the St George’s Respiratory Questionnaire (SGRQ), the modified Medical Research Council (mMRC) scale of dyspnoea during daily activity, the BORG scale for dyspnoea during exertion, and Visual Analogue Scale (VAS) for dyspnoea at rest. Paired t-tests compared scores at T0 and T1.Results: The mean (SD) SGRQ total score decreased from 25.5 (15.5) at T0 to 16.9 (13.2) at T1 (p<0.01); 65% of patients achieved a clinically important change of ≥4 points. SGRQ domain scores (symptoms, activity, and impact) were also significantly reduced (all p<0.01). The mean (SD) VAS score decreased from 1.6 (1.7) to 1.4 (2.5); p<0.01. The mean mMRC score decreased significantly (p=0.031) and 30% of patients achieved a clinically important change of ≥1 point. The mean (SD) Borg score increased from 12.8 (4.2) to 14.3 (2.4); p<0.01.Conclusion: The present proof of concept study is the first to report HRQoL in patients with COVID-19. During 15 days after hospital discharge, patients reported significant improvements in HRQoL and dyspnoea at rest and during daily activities.

Responsiveness and longitudinal validity of the Persian version of COMI to physiotherapy in patients with non-specific chronic low back pain

Background and aimsThe Core Outcome Measures Index (COMI) is a short, self-reported questionnaire for assessing important outcomes in patients with low back pain (LBP). The present study was conducted to explore the responsiveness and longitudinal validity of the Persian COMI (COMI-P) in patients with non-specific chronic LBP.MethodsIn this prospective cohort study of patients with non-specific chronic LBP receiving physiotherapy, patients completed a booklet containing the COMI-P, Persian Functional Rating Index (FRI-P), and a visual analogue scale (VAS) for pain before and after the end of ten-sessions of physiotherapy. Patients also completed a global rating of change scale (GRCS) at the end of the physiotherapy. Responsiveness was examined by means of internal responsiveness methods [t-test, standard effect size (SES); standardized response mean (SRM), and Guyatt responsiveness index (GRI)] and external responsiveness methods [correlation with external criteria and receiver operating characteristics (ROC) curve].ResultsFifty patients with a mean age of 50.62 ± 13.8 years participated. The paired t-test showed significant changes in COMI-P scores (p < 0.001). The effect sizes for COMI-P were large (range 0.96–1.23). The score changes for the COMI-P revealed significant correlations with FRI-P (r = 0.67, p < 0.001), the VAS (r = 0.65, p < 0.001), and the GRCS (r = 0.34, p = 0.02). The COMI-P change scores showed excellent correlation with the dichotomized smallest detectable change (SDC) criterion (r = 0.83, p < 0.001). The ROC area under the curve for the COMI-P based on the dichotomized SDC criterion was perfect. The minimal clinically important change was estimated 2.15 points (sensitivity 94% and specificity 100%).ConclusionsThe COMI-P appears to have responsiveness and longitudinal validity in detecting changes after physiotherapy for non-specific chronic LBP. An improvement of 2.15 points in COMI-P total score is required to be interpreted as minimally clinically important change in individual patients.