Functional Assessment Of Chronic Illness Therapy Research Articles

Normalization of Hemoglobin, Lactate Dehydrogenase, and Fatigue in Patients with Paroxysmal Nocturnal Hemoglobinuria Treated with Pegcetacoplan.

We determined normalization rates for hemoglobin, lactate dehydrogenase (LDH), and fatigue in patients with paroxysmal nocturnal hemoglobinuria (PNH) treated with pegcetacoplan (PEG) in the PEGASUS (NCT03500549) and PRINCE (NCT04085601) phase III trials. Enrolled patients had PNH and hemoglobin <10.5 g/dL despite ≥3 months of eculizumab (ECU) [PEGASUS], or were complement component 5 (C5) inhibitor-naive, receiving supportive care only, with hemoglobin less than the lower limits of normal (LLN) [PRINCE]. Hematologic and fatigue normalization endpoints were hemoglobin greater than or equal to the LLN (females: 12 g/dL; males: 13.6 g/dL) in the absence of transfusion; LDH ≤226U/L in the absence of transfusion; and Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue ≥43.6, the general population norm. Safety was assessed by investigators using standardized terms and definitions for seriousness and severity. Hemoglobin normalization occurred in 34.1% (14/41) of PEG-treated patients at Week 16 (randomized controlled period) in PEGASUS (vs. 0% [0/39] of ECU-treated patients) and in 45.7% (16/35) of PEG-treated patients at Week 26 in PRINCE (vs. 0% [0/18] of supportive care-treated patients). At Week 48 (open-label period) in PEGASUS, 24.4% of PEG-treated patients (PEG-to-PEG) and 30.8% of patients treated with ECU through Week 16 who switched to PEG through Week 48 (ECU-to-PEG) had hemoglobin normalization. Rates of LDH normalization in PEGASUS were 70.7% (PEG-treated patients) and 15.4% (ECU-treated patients) at Week 16, and 56.1% (PEG-to-PEG) and 51.3% (ECU-to-PEG) at Week 48. In PRINCE, 67.5% of PEG-treated patients at Week 26 had normalized LDH concentrations. Rates of FACIT-Fatigue score normalization in PEGASUS were 48.8% and 10.3% in PEG- and ECU-treated patients, respectively, at Week 16, and 34.1% and 51.3% in PEG-to-PEG- and ECU-to-PEG-treated patients, respectively, at Week 48. In PRINCE, 68.6% of PEG-treated patients and 11.1% of supportive care patients had FACIT-Fatigue score normalization at Week 26. PEG was safe and well tolerated. Injection site reactions, mostly mild, were the most common adverse event of special interest in PEG-treated patients in the PEGASUS randomized controlled period (36.6%) and in PRINCE (30.4%). PEG is superior to ECU and supportive care in hemoglobin, LDH, and FACIT-Fatigue score normalization for patients with PNH and persistent anemia despite ≥3 months of treatment with ECU, and in C5 inhibitor-naive patients. The PEGASUS trial (NCT03500549) was registered on 18 August 2018, and the PRINCE trial (NCT04085601) was registered on 11 September 2019.

Advance Care Planning for Children With Rare Diseases: A Pilot RCT.

Pediatric rare diseases are often life-limiting conditions and/or require constant caregiving. Investigators assessed the initial efficacy of the FAmily CEntered (FACE) pediatric advance care planning (pACP), FACE-Rare, intervention on families' quality of life. A pilot-phase, single-blinded, intent-to-treat, randomized controlled clinical trial enrolled families from 1 pediatric quaternary hospital between 2021 and 2023. Intervention families received 3 weekly 60-minute (FACE-Rare pACP) sessions: (1) Carer Support Needs Assessment Tool or Action Plan, (2) Carer Support Needs Assessment Tol Action Plan Review, and (3) Pediatric Next Steps: Respecting Choices pACP. Controls received treatment as usual (TAU). Outcome measures were Beck Anxiety Inventory, Family Appraisal of Caregiving, Functional Assessment of Chronic Illness Therapy (FACIT)-Spirituality, and health care utilization. Generalized mixed effect models with γ response assessed the intervention effect at 3-month follow-up. Children (n = 21) were aged 1 to 10 years, 48% male, 24% Black; and 100% technology dependent. Primary family caregivers (n = 21) were aged 30 to 43 years, 19% male, 19% Black; and 27% household income below the Federal poverty level. Dyads underwent 1:1 randomization: 9 to FACE-Rare and 12 to TAU. TAU caregivers reported statistically lower meaning and peace than FACE-Rare caregivers (0.9, P = .03, confidence interval [CI]: 0.75-0.99). Black caregivers reported significantly less caregiver distress (0.7, P = .04, CI: 0.47-0.98) than non-Black caregivers. Poor families reported more anxiety (3.5, P = .002, CI: 1.62-7.94), more caregiver strain (1.2, P = .006, CI: 1.07-1.42); and less family well-being (0.8, P = .02, CI: 0.64-0.95). FACE®-Rare was feasible, acceptable, safe, and demonstrated initial efficacy, providing greater feelings of meaning and peace to caregivers. Poverty impacted well-being. A multisite trial is needed to determine generalizability.

Psychometric analysis of the modified COVID-19 Yorkshire Rehabilitation Scale (C19-YRSm) in a prospective multicentre study

BackgroundLong COVID (LC) is a novel multisystem clinical syndrome affecting millions of individuals worldwide. The modified COVID-19 Yorkshire Rehabilitation Scale (C19-YRSm) is a condition-specific patient-reported outcome measure designed for assessment...

Clinical significance of anti-mutated citrullinated vimentin antibodies in rheumatoid arthritis patients.

Anti-mutated citrullinated vimentin (MCV) antibodies have recently been recommended as a better arthritis diagnostic marker. To investigate the association between anti-MCV antibodies and the clinical, functional, and radiographic characteristics of rheumatoid arthritis (RA) patients. This case-control study was conducted on 40RApatients and 40healthy subjects. All patients were subjected to an assessment of disease using the 28-joint DAS (DAS28) and Clinical Disease Activity Index (CDAI), function by HAQ-DI, physical activity by International Physical Activity Questionnaire (IPAQ), fatigue by Functional Assessment of Chronic Illness Therapy (FACIT), serological tests as well as anti-MCV Abs measurement. A plain X-ray of both hands and wrists was done. The anti-MCV Abs level was significantly higher in RA patients than in healthy controls (P< 0.001). The anti-MCV Abs had a significant positive correlation with DAS, CDAI, HAQ, RF, Anti-CCP, and CRP (P= 0.006, 0.013, 0.005, < 0.001, < 0.001and 0.041respectively) and a significant negative correlation with FACIT (p= 0.007). Positive anti-MCV RA patients had significantly higher erosions, JSN, and a total sharp score. Anti-MCV Abs may contribute to poor physical activity and more fatigue in RA patients beyond their established role in disease activity and erosion.

Safety and Efficacy of Pegcetacoplan in Adult Patients with Paroxysmal Nocturnal Hemoglobinuria over 48Weeks: 307 Open-Label Extension Study.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening disease characterized by complement-mediated hemolysis and thrombosis. Pegcetacoplan, the first targeted complement component3 (C3) PNH therapy, was safe and efficacious in treatment-naive and pre-treated patients with PNH in five clinical trials. The 307 open-label extension (OLE) study (NCT03531255) is a non-randomized, multicenter extension study of long-term safety and efficacy of pegcetacoplan in adult patients with PNH who completed a pegcetacoplan parent study. All patients received pegcetacoplan. Outcomes at the 48-week data cutoff (week48 of 307-OLE or August 27, 2021, whichever was earlier) are reported. Hemoglobin concentrations, Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scores, and transfusion avoidance were measured. Hemoglobin > 12g/dL and sex-specific hemoglobin normalization (i.e., male, ≥ 13.6g/dL; female, ≥ 12g/dL) were assessed as percentage of patients with data available and no transfusions 60days before data cutoff. Treatment-emergent adverse events, including hemolysis, were reported. Data from 137 patients with at least one pegcetacoplan dose at data cutoff were analyzed. Mean (standard deviation [SD]) hemoglobin increased from 8.9 (1.22) g/dL at parent study baseline to 11.6 (2.17) g/dL at 307-OLE entry and 11.6 (1.94) g/dL at data cutoff. At parent study baseline, mean (SD) FACIT-Fatigue score of 34.1 (11.08) was below the general population norm of 43.6; scores improved to 42.8 (8.79) at 307-OLE entry and 42.4 (9.84) at data cutoff. In evaluable patients, hemoglobin > 12g/dL occurred in 40.2% (43 of 107) and sex-specific hemoglobin normalization occurred in 31.8% (34 of 107) at data cutoff. Transfusion was not required for 114 of 137 patients (83.2%). Hemolysis was reported in 23 patients (16.8%). No thrombotic events or meningococcal infections occurred. Pegcetacoplan sustained long-term improvements in hemoglobin concentrations, fatigue reduction, and transfusion burden. Long-term safety findings corroborate the favorable profile established for pegcetacoplan. ClinicalTrials.gov identifier, NCT03531255.

Patient Navigator Intervention to Improve Palliative Care Outcomes for Hispanic Patients With Serious Noncancer Illness

Disparities persist across the trajectory of serious illness, including at the end of life. Patient navigation has been shown to reduce disparities and improve outcomes for underserved populations. To determine the effectiveness of a lay patient navigator intervention, Apoyo con Cariño, in improving palliative care outcomes among Hispanic patients. This was a multicenter randomized clinical trial that took place across academic, nonprofit, safety-net, and community health care systems in urban, rural, and mountain/frontier regions of Colorado from January 2017 to January 2021. Self-identifying Hispanic adults with serious noncancer medical illness and limited prognosis were recruited. Data were collected and analyzed from July 2022 to July 2023. Participants randomized to the intervention group received 5 home visits from a bilingual, bicultural lay patient navigator; participants randomized to control received care as usual. Both groups received culturally tailored educational materials. Investigators/outcome accessors remained blinded to participant assignment. Change in score from baseline to 3 months on the Functional Assessment of Chronic Illness Therapy (FACIT) General quality of life (QOL) scale (primary outcome), Advance Care Planning (ACP) Engagement Survey, Brief Pain Inventory, Edmonton Symptom Assessment Scale, and FACIT Spiritual Well-Being subscale; at 6 months, advance directive (AD) documentation; and at 46 months or death, hospice utilization and length of stay, as well as aggressiveness of care at end of life. Of 209 patients enrolled (mean [SD] age, 63.6 [14.3] years; 108 [51.7%] male), 105 patients were randomized to control and 104 patients to the intervention. There were no statistically significant differences in the change in mean (SD) QOL score between the intervention and control groups (5.0 [16.5] vs 4.3 [15.5]; P = .75). Participants in the intervention group, compared with the control group, had statistically significant greater increases in mean (SD) ACP engagement (0.8 [1.3] vs 0.1 [1.4]; P < .001) and were more likely to have a documented AD (62 of 104 [59.6%] vs 28 of 105 [26.9%]; P < .001). There were no statistically significant differences in mean (SD) change in pain intensity score (0-10) between patients in the intervention group compared with control (-0.4 [2.6] vs -0.5 [2.8]; P = .79), nor pain interference (-0.2 [3.7] vs -0.4 [3.7]; P = .71). Patients receiving the intervention were more likely to be referred to hospice compared with patients receiving control (19 of 43 patients [44.2%] vs 7 of 33 patients [21.2%]; P = .04) and less likely to receive aggressive care at end of life (27 of 42 patients [64.3%] vs 28 of 33 patients [84.8%]; P = .046). In this randomized clinical trial, a culturally tailored patient navigator intervention did not improve QOL for patients. However, the intervention did increase ACP engagement, AD documentation, and hospice utilization in Hispanic persons with serious medical illness. ClinicalTrials.gov Identifier: NCT03181750.

Cross-Cultural Adaptation and Psychometric Properties of The Thai Versions of The Patient-Reported Outcomes Measurement Information System Short Form – Anxiety 8a and the Pain Anxiety Symptoms Scale-20 in Individuals with Chronic Low Back Pain

Objective: To translate and cross-culturally adapt the Patient-Reported Outcomes Measurement Information System Short Form v1.0–Anxiety 8a and the Pain Anxiety Symptoms Scale-20 into Thai versions (T-PROMIS-Anx8a and T-PASS-20, respectively) and evaluate their psychometric properties in individuals with chronic low back pain (CLBP).Material and Methods: The translations and cultural adaptations were performed using the Functional Assessment of Chronic Illness Therapy (FACIT) guidelines. Thai individuals with CLBP completed the T-PROMIS-Anx8a and T-PASS-20. Psychometric evaluation including: internal consistency, test-retest reliability, and dimensionality. Construct validity was evaluated by computing correlations among the scores on the T-PROMIS-Anx8a, T-PASS-20, Thai version of the Hospital Anxiety and Depression Scale–Anxiety (T-HADS-A), and Thai version of the Fear Avoidance Beliefs Questionnaire (T-FABQ).Results: A total of 269 individuals with CLBP were included in the analyses. The T-PROMIS-Anx8a showed unidimensionality and the T-PASS-20 evidenced a 4-factor structure. Both measures demonstrated good to excellent internal consistency (Cronbach’s alphas ranged from 0.85 to 0.95), good test-retest reliability (ICC(2,1) ranged from 0.79 to 0.88), and neither ceiling nor floor effects were observed for any of the scales. Both measures evidenced acceptable convergent and discriminant validity, based on their associations with the T-HADS-A and T-FABQ.Conclusion: The T-PROMIS-Anx8a and T-PASS-20 were culturally adapted and evidenced acceptable psychometric properties for assessing anxiety in Thai individuals with CLBP. 

Cross-Cultural Adaptation and Psychometric Properties of The Thai Versions of The Patient-Reported Outcomes Measurement Information System Short Form – Anxiety 8a and the Pain Anxiety Symptoms Scale-20 in Individuals with Chronic Low Back Pain

Objective: To translate and cross-culturally adapt the Patient-Reported Outcomes Measurement Information System Short Form v1.0–Anxiety 8a and the Pain Anxiety Symptoms Scale-20 into Thai versions (T-PROMIS-Anx8a and T-PASS-20, respectively) and evaluate their psychometric properties in individuals with chronic low back pain (CLBP).Material and Methods: The translations and cultural adaptations were performed using the Functional Assessment of Chronic Illness Therapy (FACIT) guidelines. Thai individuals with CLBP completed the T-PROMIS-Anx8a and T-PASS-20. Psychometric evaluation including: internal consistency, test-retest reliability, and dimensionality. Construct validity was evaluated by computing correlations among the scores on the T-PROMIS-Anx8a, T-PASS-20, Thai version of the Hospital Anxiety and Depression Scale–Anxiety (T-HADS-A), and Thai version of the Fear Avoidance Beliefs Questionnaire (T-FABQ).Results: A total of 269 individuals with CLBP were included in the analyses. The T-PROMIS-Anx8a showed unidimensionality and the T-PASS-20 evidenced a 4-factor structure. Both measures demonstrated good to excellent internal consistency (Cronbach’s alphas ranged from 0.85 to 0.95), good test-retest reliability (ICC(2,1) ranged from 0.79 to 0.88), and neither ceiling nor floor effects were observed for any of the scales. Both measures evidenced acceptable convergent and discriminant validity, based on their associations with the T-HADS-A and T-FABQ.Conclusion: The T-PROMIS-Anx8a and T-PASS-20 were culturally adapted and evidenced acceptable psychometric properties for assessing anxiety in Thai individuals with CLBP. 

Hematopoietic Stem Cell Transplantation Impact on Patients' Perceived Quality of Life: A Longitudinal Study.

The aim of this paper was to evaluate the quality of life of adult patients with onco-hematological disease treated with hematopoietic stem cell transplantation up to two years post-transplantation. A quantitative, observational, longitudinal, and analytical study was conducted with 121 participants diagnosed with onco-hematological cancer who underwent hematopoietic stem cell transplantation between October 2017 and September 2019, with a 2-year post-transplantation follow-up, of whom only 39 completed the study. The Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) questionnaire and its subscales, Functional Assessment of Cancer Therapy-General (FACT-BMT) and Functional Assessment of Cancer Therapy Trial Outcome Index (FACT-TOI), developed by the Functional Assessment of Chronic Illness Therapy (FACIT) and validated for Spain, were used to assess quality of life. The average age for hematopoietic stem cell transplantation was 54 years, with a majority of male participants. The evaluation of quality of life showed a decrease at the time of hospital discharge, followed by a progressive improvement up to one year after the transplantation. There was a significant difference in the quality of life questionnaire scores between both sexes during all stages of the research, with higher scores in male participants. The length of hospital stay significantly affected patients' physical and functional well-being, and marital status was related to differences in the perception of quality of life. Despite the initial decrease in quality of life for patients undergoing hematopoietic stem cell transplantation, levels of quality of life similar to baseline are regained one year after the transplantation. Sociodemographic variables are related to how these patients perceive their quality of life. However, further studies with a larger sample size are needed for more precise results.

Translation and Cultural Adaptation into Arabic of Patient-Reported Outcome Measurement Information System® Item Banks: Cognitive Function Abilities and Physical Function for Samples with Mobility Aid Users.

This study aimed to provide Arabic-speaking individuals with tools to assess their cognitive abilities and physical function and to contribute to a better understanding of these capabilities in this population. Thus, the specific objective was to translate into Arabic and culturally adapt two Patient-Reported Outcome Measurement Information System (PROMIS) item banks: the Adult Cognitive Function Abilities and the Physical Function for Samples with Mobility Aid Users item banks. This study employed the Functional Assessment of Chronic Illness Therapy (FACIT) multilingual translation methodology to ensure cultural and linguistic relevance. The translation process included forward and back translations, expert reviews, and finalisation by a language coordinator. Cognitive debriefing interviews were conducted with 30 native healthy Arabic speakers to assess the clarity and comprehension of translated items. Most items were well understood, but two items related to cognitive ability and four related to physical functions required revision to address participant confusion. The translations were refined based on the participants' feedback and expert recommendations. This study followed a rigorous translation process and included cognitive debriefing interviews to ensure linguistic and cultural equivalence. The availability of these tools in Arabic enhances cross-cultural research and practice in healthcare and contributes to a global understanding of cognitive and physical functions.

Abstract A093: Implementation of a financial hardship screening among Native American patients with cancer

Abstract Introduction: Financial hardship and financial hardship screening are emerging concerns in oncology. Native American patients may be at increased risk of financial hardship due to factors including poverty, medical comorbidities, and lack of private health insurance coverage. Financial hardship for Native American patients with cancer has only rarely been studied, and implementation of screening for financial hardship for these patients has never been reported. Methods: Guided by input from a stakeholder advisory board consisting of patient, provider, and staff members at a single cancer center in Oklahoma, we implemented a financial hardship screening tool, the COmprehensive Score for financial Toxicity (COST) – Functional Assessment of Chronic Illness Therapy (FACIT) among 42 Native American patients with cancer. We conducted key informant interviews with ten of these patients and four clinical staff involved in the implementation process. Patient interviews included questions about current financial hardship, experiences in discussing financial hardship with the cancer care and primary care team, and acceptability of the COST-FACIT tool. Clinician interviews focused on their experience with the project, including implementation of the COST-FACIT tool, barriers to implementation, and sustainability. Recorded interviews were transcribed and thematically analyzed using MAXQDA® software. COST-FACIT tool data were analyzed using SAS v. 9.4 Results: Three-quarters (76%, n=32) of participants who completed the COST-FACIT tool reported moderate or severe financial hardship (Score &amp;lt;25 out of max 44, with lower scores indicating more hardship). A higher percentage of patients experiencing financial hardship were younger, covered by Medicaid, unemployed, not married/cohabiting, had lower income, and lower education compared to those with no/mild hardship (Scores ≥25). Among patients and clinicians, we identified themes of 1) financial hardship screening perception and intervention experiences, 2) screening efficacy and opportunities for improvement, and 3) systematic and patient related themes of Native American health systems and culture. Conclusions: Financial hardship was reported by the majority of Native American patients with cancer included in our study. Patients expressed a positive experience with the screening tool, including identification of financial challenges though timing of the tool in regards to their cancer diagnosis varied across patients. Clinicians experienced challenges in implementation of the COST-FACIT tool related to logistics, the COVID-19 pandemic, and concerns for sustainability. However, clinicians reported a positive experience with the tool and interactions with patients and referrals that resulted from the screening. Citation Format: Amanda E. Janitz, Amber S. Anderson-Buettner, Stefani D. Madison, Mark P. Doescher, Dorothy A. Rhoades. Implementation of a financial hardship screening among Native American patients with cancer [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A093.

Dutch–Flemish translation and validation of the gastrointestinal symptom scales from the patient‑reported outcomes measurement information system (PROMIS)®

PurposeTo translate the eight PROMIS® GastrointestinaI Symptom Scales into Dutch–Flemish and to evaluate their psychometric properties.MethodsThis study consisted of two parts: (1) translation according to the Functional Assessment of Chronic Illness Therapy (FACIT) translation methodology and (2) evaluation of psychometric properties: structural validity, using confirmatory factor analysis; and construct validity using hypothesis testing.ResultsIn the first part of the study, in 19 out of the 77 items (24.7%) translation was challenging. After discussion between the translators, consensus could be achieved. In the cognitive debriefing interview phase, ten minor changes in the wording of items were made. A universal Dutch–Flemish translation for all 77 items was obtained. In de second part of the study a good fit was found for three DF-PROMIS GI Scales: Bowel Incontinence, Gas and Bloating, and Belly Pain. Four scales (Reflux, Disrupted Swallowing, Diarrhea, and Constipation) did not show sufficient fit and fit for the Nausea and Vomiting scale could not be assessed because of skewed responses. Construct validity was considered sufficient for six out of eight DF-PROMIS GI Scales. Less than 75% of hypothesis for de Constipation and Disrupted Swallowing scales could be confirmed.ConclusionThe PROMIS GI Symptom Scales were successfully translated into DutchFlemish. The findings suggest a sufficient structural validity for the PROMIS GI Scales. Bowel Incontinence, Gas and Bloating and Belly Pain. Construct validity was sufficient for the Scales Gas and Bloating, Incontinence, Nausea and Vomiting, Reflux, Belly Pain, and Diarrhea.

Patient-Reported Outcomes (PROs) in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) Treated with Crovalimab and Eculizumab: Results from the Phase III Randomized COMMODORE 2 and COMMODORE 1 Trials

Introduction COMMODORE 2 (NCT04434092) and COMMODORE 1 (NCT04432584) are global, randomized, open-label, multicenter Phase III trials evaluating crovalimab (crova) vs eculizumab (ecu) in patients (pts) with PNH. COMMODORE 2 tested the non-inferiority of crova vs ecu in C5i-naive pts and demonstrated that crova was non-inferior to ecu for hemolysis control, transfusion avoidance, breakthrough hemolysis, and hemoglobin stabilization (Röth EHA 2023; #S181). In both studies, crova was well tolerated for both C5i-naive and C5i-experienced pts (Röth EHA 2023; #S181, Scheinberg EHA 2023; #S183). To investigate the efficacy of crova vs ecu from a pt perspective, PRO tools were used to assess fatigue, PNH-related symptoms, functioning, and global health status/quality of life (GHS/QoL) among COMMODORE 2 and COMMODORE 1 pts. Methods In COMMODORE 2, C5i-naive pts were randomized 2:1 to receive crova or ecu during a 24-week primary treatment period. In COMMODORE 1, C5i-experienced pts receiving ecu at study start were randomized 1:1 to receive crova or ecu during a 24-week primary treatment period. Pts received crova as a weight-based tiered regimen (Liu ASH 2022; #293) that included loading doses followed by maintenance doses via subcutaneous injection every 4 weeks, or ecu via intravenous infusion every 2 weeks (900 mg per label). After completing 24 weeks of treatment, COMMODORE 1 and 2 pts randomized to crova continued crova, and those randomized to ecu switched to crova if continuing in the extension period. Paper PRO questionnaires were completed by adult pts at baseline (BL) and at Weeks 2, 5, 9, 17, and 25 during the primary treatment period (up to Week 25) and during the crova extension period (from Week 25 onwards). Fatigue was assessed with the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale (higher scores indicate lower fatigue severity). Additional PNH symptoms (dyspnea, dysphagia, headaches, abdominal pain, chest pain, and erectile dysfunction) were assessed using relevant questions selected from the European Organisation for Research and Treatment of Cancer (EORTC) Item Library (EORTC IL-40; higher scores indicate worse symptoms). Physical function, role function, and GHS/QoL were assessed with the EORTC Quality of Life Questionnaire Core 30 (EORTC QLQ-C30; higher scores indicate better functioning/quality of life). Results For the primary analysis, COMMODORE 1 randomized 45 pts to crova and 44 to ecu, and enrolled 38 pts in the descriptive arm; COMMODORE 2 randomized 135 pts to crova and 69 to ecu. In COMMODORE 2, C5i-naive pts in both arms showed rapid and sustained improvement across all PRO measures during the primary treatment period. Clinically meaningful improvement (≥5 points; Cella ASH 2021; #1952) in mean FACIT-Fatigue scores from BL occurred in both arms, with numerically higher improvement with crova (crova: 7.8, 95% CI: 6.5, 9.1; ecu: 5.2, 95% CI: 3.4, 6.9; Table 1). Mean fatigue levels of pts treated with crova improved by Week 2 and were similar to normative population values by Week 25. Analysis of the individual FACIT-Fatigue items was also conducted. Additionally, improvements were observed for both treatment arms in all EORTC IL-40 symptoms and in the functioning and GHS/QoL scales of the EORTC QLQ-C30, with numerically greater improvement with crova for most scales (Table 2). The improvements with crova treatment were maintained during the crova extension period. In COMMODORE 1, C5i-experienced pts randomized to receive crova or ecu maintained BL levels of fatigue, PNH symptoms, functioning, and GHS/QoL scores throughout the primary treatment period (Tables 1 and 2) and with crova treatment during the extension period. There was no meaningful change in the mean values of any PRO scores after pts switched from ecu to crova at Week 25. Conclusions C5i-naive pts inCOMMODORE 2 experienced rapid and sustained improvements from BL in fatigue, PNH symptoms, functioning, and GHS/QoL scores while on treatment with crova and ecu, with numerically greater improvement in fatigue and most GHS/QoL scales in the crova arm. C5i-experienced pts in COMMODORE 1 maintained BL levels during the first 24 weeks of treatment with crova or ecu. These trends were maintained after pts were switched from ecu to crova. These data provide supportive evidence for the treatment benefit of crovalimab for self-reported fatigue and quality of life.

Improvement of Patient-Reported Outcomes Among Heavily Pretreated Patients with Lower-Risk Myelodysplastic Syndromes and High Transfusion Burden Treated with Imetelstat on the IMerge Phase 3 Trial

CONCLUSIONS Transfusion-dependent anemia and related fatigue are commonly associated with lower-risk myelodysplastic syndromes (LR-MDS) and frequently not improved with therapy. Patients with symptoms associated with anemia have an impaired quality of life and inferior overall survival. In IMerge (NCT02598661), the phase 3, randomized, global trial of patients with LR-MDS and a red blood cell transfusion burden of ≥4 U, imetelstat-treated patients had a significantly higher transfusion independence rate than those treated with placebo and showed sustained improvement in patient-reported fatigue via the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue (Sekeres et al. EHA 2023. P732). Here, we assess the impact of imetelstat on several patient-reported outcomes (PROs) relevant to LR-MDS. Functional Assessment of Cancer Therapy-Anemia (FACT-An; 55 items) and Quality of Life in Myelodysplasia Scale (QUALMS; 38 items) were the main questionnaires used. Analyses included symptom-specific derived scores for the following parameters: dyspnea, measured by 1 FACT-An and 1 QUALMS item; physical function and systemic symptoms, by 3 FACT-An items each; pain, by 2 FACT-An items; and bleeding, by 1 QUALMS item. Higher scores indicated improvement. QUALMS total score and physical burden score were also analyzed. Psychometric analyses were conducted using blinded interim data to document the measurement properties of these item sets and define the scores that would be used to specify PRO end points in IMerge; all analyses were exploratory and were conducted in the intention-to-treat (ITT) population. The overall effect of imetelstat on each score was evaluated from the repeated measurement mixed model (RMMM) comparing the least-squares means (LSMs) of change in score estimated in the 2 treatment groups using all available data while on treatment up to cycle 30. A positive mean change in the dyspnea score was observed throughout the treatment, up to cycle 24, in the imetelstat group but not in the placebo group (Figure). The RMMM analysis showed an overall change in dyspnea score from baseline of 0.53 (by LSM with 95% CI, 0.241-0.825) with imetelstat versus −0.40 (by LSM with 95% CI, −0.794 to 0.003) with placebo, with a significant difference between the treatment groups (LSM difference, 0.93; 95% CI, 0.446-1.411; P &amp;lt; .001; Table). The model-based mean change estimates for each score showed that, despite having high transfusion burden at baseline, patients in the imetelstat group did not experience more deterioration in any of the other outcomes than those in the placebo group (Table). In addition, the QUALMS composite scores suggested significantly improved health outcomes with imetelstat versus placebo based on RMMM. LSM difference was 4.66 (95%CI, 0.862-8.461; P = .016) and 6.34 (95% CI, 1.771-10.913; P = .007) for QUALMS total and QUALMS physical burden, respectively (Table). Findings from multiple validated PRO questionnaires consistently show that patients with red blood cell transfusion-dependent LR-MDS enrolled into the IMerge randomized trial who were treated with imetelstat reported improved fatigue, dyspnea, and QUALMS composite scores (total and physical burden) compared with those in the placebo group. These data indicate that, in addition to improving transfusion burden in patients with LR-MDS, imetelstat targets multiple core symptoms of LR-MDS simultaneously, also improving PROs.

Efficacy and Safety Is Maintained in Adult Patients with Paroxysmal Nocturnal Hemoglobinuria Receiving Pegcetacoplan for up to 3 Years

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening disease characterized by complement-mediated hemolysis and thrombosis. Pegcetacoplan, the first complement component 3 (C3) inhibitor for PNH, increased hemoglobin (Hb) levels in complement component 5 inhibitor (C5i)-experienced and -naive adult patients with PNH in 2 phase 3 clinical trials (PEGASUS [NCT03500549] and PRINCE [NCT04085601], respectively). This integrated analysis of data from the pivotal phase 3 trials and the subsequent open-label extension (study 307; NCT03531255) evaluated the long-term efficacy and safety of pegcetacoplan for PNH treatment. Methods: For this integrated analysis, baseline was defined as the initiation of pegcetacoplan, regardless of when in the trials this occurred. Patients initially received pegcetacoplan 1080 mg subcutaneously twice weekly; dose escalations to once every 3 days or 3 times weekly were permitted. Efficacy was evaluated from baseline up to Weeks 132 (2.5 years, PRINCE) and 156 (3 years, PEGASUS) by Hb, lactate dehydrogenase (LDH; upper limit of normal [ULN] 226 IU/L), absolute reticulocyte count (ARC), and indirect bilirubin values; Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scores; and transfusion avoidance rates (percentages of patients who did not require a transfusion during treatment). Safety was assessed by incidence of adverse events (AEs) and serious AEs (SAEs) during pegcetacoplan monotherapy for up to 3 years. Results: Of the 133 patients in the phase 3 trials (PEGASUS, 80; PRINCE, 53), 114 enrolled in the extension study (PEGASUS, 64; PRINCE, 50). At least 75% had received a transfusion in the year before enrolling in PEGASUS or PRINCE. Prior to pegcetacoplan initiation, mean (SD) Hb levels were 8.95 (1.09) g/dL in PEGASUS, 9.27 (1.44) g/dL in PRINCE, and 9.08 (1.24) g/dL in the total population; median (interquartile range) LDH levels were 217.0 (184.8, 276.5) IU/L in PEGASUS, 1964.0 (1409.0, 2503.3) IU/L in PRINCE; and mean (SD) FACIT-Fatigue scores were 31.6 (11.7) in PEGASUS, 36.6 (10.0) in PRINCE, and 33.6 (11.3) in the total population. After pegcetacoplan initiation, mean Hb levels markedly improved from baseline and remained stable through Weeks 132 (2.5 years, PRINCE) and 156 (3 years, PEGASUS) ( Figure). Median LDH rapidly decreased and stabilized below the ULN ( Figure). Improvements in ARC and indirect bilirubin were similarly maintained. Average FACIT-Fatigue scores increased (indicating less fatigue) rapidly and were maintained near the general population norm of 43.6. Annual transfusion avoidance ranged from 71%-79% in PEGASUS and 80%-86% in PRINCE, with 52% of patients from PEGASUS avoiding transfusion for up to 3 years of pegcetacoplan treatment and 67% of patients from PRINCE avoiding transfusion for up to 2.5 years. Overall, &amp;gt;92% patients had compliance rates of at least 95%. Over 3 years, most patients experienced an AE; SAEs were reported in 50.0% of patients, with 4.5% experiencing a SAE deemed related to pegcetacoplan. Overall, 17 patients discontinued pegcetacoplan due to an AE; of those, 9 discontinued due to a hemolytic disorder, 7 of which discontinued within 1 year of starting pegcetacoplan. Over 3 years, 4 (3.0%) deaths occurred, none were deemed related to pegcetacoplan; 3 (2.3%) patients experienced a thrombotic event (in the context of multiple associated comorbidities or discontinuation of pegcetacoplan) and no cases of meningitis were reported. Overall, no new or unexpected safety findings were identified. Conclusions: Rapid improvements in Hb, LDH, ARC, indirect bilirubin, and FACIT-Fatigue values were observed and maintained up to 3 years in C5i-experienced patients and up to 2.5 years in C5i-naive patients. The transfusion burden was significantly reduced. No new safety findings were identified. This analysis demonstrates sustained efficacy and continued safety of long-term pegcetacoplan for patients with PNH, regardless of prior C5i treatment.

Efficacy and Safety of Subcutaneous Ravulizumab in Patients with Paroxysmal Nocturnal Hemoglobinuria Who Received Prior Intravenous Eculizumab: 2-Year Follow-up

Background : Subcutaneous (SUBQ) ravulizumab, administered weekly via an on-body delivery system, showed pharmacokinetic (PK) non-inferiority to intravenous (IV) ravulizumab over 71 days in adult patients with paroxysmal nocturnal hemoglobinuria (PNH) who were clinically stable on prior IV eculizumab treatment (NCT03748823). This analysis reports results through 2 years of SUBQ ravulizumab treatment during the extension period of a phase 3 randomized trial. The reporting period started at day 15 for patients who continued SUBQ ravulizumab during the extension period (SUBQ/SUBQ) and day 71 for patients who switched from IV ravulizumab to SUBQ ravulizumab (IV/SUBQ). Objectives: To evaluate the PK, pharmacodynamics (PD), efficacy, and safety of SUBQ ravulizumab through 2 years (day 743) of treatment in adult patients with PNH previously treated with IV eculizumab. Methods: Patients (≥ 18 years) who received IV eculizumab (once every 2 weeks) for at least 3 months prior to study entry with clinically stable PNH (lactate dehydrogenase [LDH] levels ≤ 1.5 × upper limit of normal [246 U/L]) were enrolled in the study, which consisted of a screening period (day −1 to day −30), a 10-week randomized treatment period, and an extension period of up to 172 weeks. During the randomized treatment period, patients were assigned (2:1) to receive either SUBQ ravulizumab (weekly) or IV ravulizumab (once every 8 weeks); all patients received SUBQ ravulizumab during the extension period. PK/PD endpoints through 2 years of treatment included serum ravulizumab and free C5 concentrations. Efficacy endpoints included change in LDH from baseline, incidence of breakthrough intravascular hemolysis (BTH), maintenance of transfusion avoidance, and maintenance of stabilized hemoglobin (avoidance of a ≥ 2 g/dL decrease in hemoglobin in the absence of transfusion). Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue subscale questionnaire. Safety outcomes, including adverse events (AEs), serious AEs (SAEs), and adverse device effects (ADEs), were also assessed up to the 2-year data cut-off. Results: In total, 128 patients received SUBQ ravulizumab (SUBQ/SUBQ: n = 84; IV/SUBQ: n = 44; mean [range] duration of SUBQ treatment: 839.4 [37 - 1108] days). During 2 years of SUBQ treatment, serum ravulizumab concentrations were maintained ≥ 175 μg/mL and serum free C5 concentrations &amp;lt; 0.5 μg/mL, the previously defined thresholds for achieving and sustaining complete terminal complement inhibition ( Figure). Efficacy endpoints remained consistent over time. Mean (standard deviation [SD]) percentage change in LDH from baseline to day 743 was +2.3% (21.6%; n = 108). BTH events were infrequent: 5/128 patients (3.9%). Transfusion avoidance was maintained in 74.2% of patients (n = 95/128) and 69.1% (n = 85/123) achieved stabilized hemoglobin. Mean (SD) change in FACIT-Fatigue subscale score from baseline to day 743 was +1.3 (9.09; n = 68). The most common AEs (excluding ADEs related to device product issues) during SUBQ treatment were COVID-19 (25.0%), headache (18.8%), and pyrexia (18.0%). Treatment-emergent SAEs were experienced by 29.7% of patients. No treatment-emergent anti-drug antibodies were observed. ADEs not related to a medical device issue were reported by 25.0% of patients. The most frequently reported ADEs unrelated to a medical device issue were injection site reaction (4.7%), medical device site erythema (4.7%), and injection site erythema (3.1%). Among 30,221 devices used in the study, full volume per device was delivered by 98.6% of devices. Complaints were reported in 1.6% of devices used: 0.1% had a confirmed technical defect, 0.8% had a use error, and 0.7% had other/unknown defects. Conclusions: The efficacy of ravulizumab was maintained following the switch from IV to SUBQ ravulizumab and no new safety signals were identified through 2 years of treatment in patients with PNH. SUBQ ravulizumab demonstrated a favorable benefit-risk profile and the types and incidences of AEs were comparable with those reported for IV eculizumab and IV ravulizumab in previous studies, except for local site reactions. The SUBQ method of administration provides an additional treatment choice for patients with PNH receiving ravulizumab treatment.

Cold Agglutinin Disease (CAD) Real-World Evidence (CADENCE) Registry: Update to the Study Design of the First International, Prospective CAD Registry

Cold agglutinin disease (CAD) is a rare chronic autoimmune hemolytic anemia (AIHA) characterized by classical complement pathway (CP)-mediated hemolysis. CAD is associated with a substantial disease burden negatively impacting quality of life (QoL), including severe fatigue, and increased risk of both thromboembolic events and early mortality. Due to the rarity of CAD, there is scarce information regarding its natural history, long-term impacts, and complications. Sutimlimab, a humanized monoclonal antibody that selectively inhibits the CP, is the first approved treatment for CAD. In the CARDINAL and CADENZA Phase 3 trials, sutimlimab reduced hemolysis, anemia, was generally well tolerated, and meaningfully improved QoL. The CADENCE Registry (NCT05791708) is a large international database of patients with CAD or cold agglutinin syndrome (CAS, a cold antibody-driven hemolytic anemia associated with an underlying condition). First launched in 2019, the first study patient was enrolled in 2022 following a COVID-19 pandemic-related hiatus. Presented here is an update on the current CADENCE protocol and study design. CADENCE is a multinational, multicenter, observational, prospective, longitudinal registry study enrolling patients ≥18 years of age diagnosed with CAD (diagnostic criteria: a monospecific direct antiglobulin test strongly positive for C3d and negative or weakly positive for immunoglobulin G and a cold agglutinin titer ≥1:64) or CAS (CAD diagnostic criteria, with causative infection, autoimmune disorder or overt malignancy). Exclusion criteria include patients with a diagnosis of warm or mixed AIHA and those actively participating in a CAD/CAS interventional trial. The main study objective is to better understand patient demographics, clinical characteristics, treatment patterns, healthcare resource utilization (HRU), natural history of disease, long-term clinical outcomes, and impact on patient QoL. A sutimlimab-treated cohort sub-study is ongoing to assess the real-world safety and effectiveness of sutimlimab in patients with CAD, fulfilling the regulatory commitment for a post-authorization safety study. The enrollment period is expected to last ~3 years and patients will be followed for 3 years after the last patient enrolled. Data collection will include both clinical assessments as per standard of care and patient-reported outcome (PRO) data collected at enrollment and at ~6-month interval follow-ups. Additional safety data will be collected for the sutimlimab cohort. The CADENCE Registry's first patient enrolled (after study restart) was in Q2 2022, with last patient's first visit expected in Q2 2025 and last patient's last visit expected in 2028 ( Figure). The registry will collect data on ~400 patients with CAD/CAS across ~90 sites in 8 countries: Austria, France, Germany, Italy, Japan, Spain, the UK, and the US. Among them, ≥30 patients with CAD treated with sutimlimab are expected to take part in the cohort study. Key data to be collected include clinical characteristics, disease complications, comorbidities, mortality, treatment regimens, HRU, and PROs. Biomarkers for hemolysis will be assessed, including lactate dehydrogenase, haptoglobin, total and indirect bilirubin. In the sutimlimab cohort, data will also be collected on adverse events (AEs), serious AEs, and AEs of special interest (serious infections, Raynaud's, arterial hypertension, autoimmune disorders, hypersensitivity/anaphylaxis, exposure in pregnancy, overdose). PRO measures include the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue, the 36-item Short Form Health Survey (SF-36), and the CAD symptoms and impact questionnaire (CAD-SIQ), a novel 11-item questionnaire specifically designed for CAD. Interim analyses will occur annually. Final analyses will be performed at study end both at regional and global levels. As of July 13, 2023, 47 of 82 targeted sites have been activated, and 113 of 405 targeted patients (CAD/CAS) have been enrolled, including 13 sutimlimab-treated patients. CADENCE is the first global registry for patients with CAD and will help advance understanding of the natural history and disease process of this rare condition. This registry will also assess the long-term safety and effectiveness of sutimlimab in patients with CAD in a real-world setting, providing clinicians with data that may help improve treatment practices.

Evaluation of the effects of somatotype profiles on pain, proprioception, isokinetic muscle strength and kinesiophobia in patients with meniscopathy.

Somatotype causes differentiation of physical, physiological and biochemical metabolisms in the body. To what extent meniscopathy (M) is affected by somatotype profiles has been an issue of concern. The aim of the study was to investigate whether somatotype profiles have an effect on kinesiophobia, pain, proprioception and isokinetic muscle strength in patients with an M diagnosis. 172 (85 female, 87 male) M patients between the ages of 18 and 65 were included in the study. The Heath-Carter method was used to determine somatotype components. Biodex Isokinetic system at 120∘/sec angular speed was used for muscle strength measurements, a digital inclinometer with goniometer was used for proprioception measurement, the Tampa Kinesiophobia Scale (TKS) was used for the assessment of kinesiophobia, the Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scale was used for the assessment of fatigue and pain, and the visual analogue scale (VAS) was used for pain assessment. Five somatotype profiles were found. When the right-left knee proprioception values were compared according to the somatotype profiles of patients, a significant difference was found in favor of balanced ectomorph at 15∘ and 30∘. No significant difference was found when TKS, FACIT, VAS values were compared in terms of somatotype profiles; while no significant difference was found in TKS, FACIT, VAS (REST-NIGHT) in terms of gender, a significant difference was found in VAS MOVE. Endomorph somatotype was dominant in the M patients. Individuals with M disease showed significant differences in terms of endomorph components. Obesity may also be one of the negative findings for M disease. Somatotype classification may represent a suitable tool for monitoring M.

Glucocorticoid Withdrawal Symptoms and Quality of Life in Patients with Systemic Lupus Erythematosus.

SLE patients whose prednisolone had been previously withdrawn or taken <5 mg/day were enrolled. Serum morning cortisol levels were collected after 72-hour GCS discontinuation, and low-dose ACTH stimulation test (LDST) was performed. Patient report outcomes (PROs) included SLE-specific quality of life questionnaire (SLEQoL), functional assessment of chronic illness therapy (FACIT), patient health questionnaire (PHQ-9), and Pittsburgh's sleep quality index (PSQI). Serum morning cortisol of 100 SLE patients was tested. Most patients were female (88%). Seventy-four patients showed remission. The mean ± SD of prednisolone was 0.73 ± 1.08 mg/day. Total SLEQoL and FACIT (mean ± SD) of all patients were 67.05 ± 26.15 and 13.7 ± 8.87, respectively. Eighteen percent of patients had moderate-severe depressive symptoms, and 49% were poor sleepers. Adrenal function was determined by LDST in only 39 patients; 5 patients (12.8%) were adrenal insufficiency (AI), and 34 patients were normal adrenal function. Compared to normal adrenal function patients, SLE patients with AI had higher proportion of moderate-severe depressive symptom (PHQ - 9 > 9), but not statistically significant (40% vs. 20.6%, p = 0.34). PROs were comparable between groups. Independent factors associated with SLEQoL were FACIT (adjusted β 1.31, 95% CI 0.76, 1.86, p < 0.001), PHQ-9 (adjusted β 5.21, 95% CI 4.32, 6.09, p < 0.001), and PSQI (adjusted β 4.23, 95% CI 3.01, 5.45, p < 0.001), but not with AI (adjusted β -5.2, 95% CI -33.26, 22.93, 0.71, p = 0.71). SLE patients with previous GCS exposure could experience AI and withdrawal symptoms such as sleep disturbance and depression during discontinuation of low-dose GCS. Fatigue, depression, and poor sleeper were significantly associated with poor SLEQoL.

Unraveling the connections between gut microbiota, stress, and quality of life for holistic care in newly diagnosed breast cancer patients

There is little research about the stress, quality of life (QOL) and gut microbiota in newly diagnosed breast cancer patients. In this study addressing the dearth of research on stress, quality of life (QOL), and gut microbiota in newly diagnosed breast cancer patients, 82 individuals were prospectively observed. Utilizing the Functional Assessment of Chronic Illness Therapy (FACT)-Breast questionnaire to assess health-related quality of life (HRQOL) and the Distress Thermometer (DT) to gauge distress levels, the findings revealed a mean FACT-B score of 104.5, underscoring HRQOL's varied impact. Significantly, 53.7% reported moderate to severe distress, with a mean DT score of 4.43. Further exploration uncovered compelling links between distress levels, FACT-B domains, and microbial composition. Notably, Alcaligenaceae and Sutterella were more abundant in individuals with higher DT scores at the family and genus levels (p = 0.017), while Streptococcaceae at the family level and Streptococcus at the genus level were prevalent in those with lower DT scores (p = 0.028 and p = 0.023, respectively). This study illuminates the intricate interplay of stress, QOL, and gut microbiota in newly diagnosed breast cancer patients, offering valuable insights for potential interventions of biomarker or probiotics aimed at alleviating stress and enhancing QOL in this patient cohort.