Functional Assessment Of Chronic Illness Therapy Research Articles

Melatonin supplementation for preventing cancer-related fatigue in patients receiving radiotherapy for early-stage breast cancer: A double-blind placebo-controlled phase III trial.

e24079 Background: Fatigue is common in patients undergoing radiotherapy (RT). Melatonin, an inexpensive natural supplement, may improve symptoms and attenuate the side effects of RT. The effect of melatonin for prevention of fatigue and other symptoms was evaluated in a double-blind placebo-controlled trial. Methods: Early-stage or ductal carcinoma in-situ breast cancer patients ≥ 18 years, female, Eastern Cooperative Oncology Group performance status (ECOG PS) < 3, hemoglobin ≥9 g/dL. RT with curative intent, randomized 1:1 to melatonin 20 mg or oral placebo, starting night before RT initiation until 2 weeks post-RT. Sample size of 142 evaluable patients in each arm for 80% power and interim analysis at mid recruitment using the unified family method rho = 0.3. Randomization stratified to RT duration (< 3 weeks, ≥3 weeks) and prior chemotherapy. Primary outcome : Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue subscale after completion of RT with additional scores measured at baseline, 2 and 8 weeks post-RT. Secondary outcomes : FACIT-F subscales, Edmonton Symptom Assessment System (ESAS) and Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue-Short Form 8a. Secondary analyses reported using an F-test at a 5% significance level. Results: For this interim analysis, 85 patients screened; 80 randomized; 39 received melatonin and 38 placebo. 72 included in the analysis as 5 patients had no post baseline FACIT score. Characteristics of age, race, and ECOG PS similar in both arms. Treatment X time for FACIT-Fatigue not significant for melatonin compared to placebo (p .83). FACIT physical, emotional, and functional well-being scores not significantly different (p .35, .62, and .71) but showing a trend for social well-being (p .06). PROMIS scores not changed over time (p .34). ESAS individual symptoms of anxiety, well-being, drowsiness, poor appetite, nausea, pain, shortness of breath, sleep and tiredness not significant, except for depression (p.04). However, a decrease of 0.01 unit in depression score is not considered clinically significant. No grade 3 or 4 adverse events. No participants died during study, 2 died after study completion from breast cancer recurrence. 16 withdrew prior to study completion because of adverse events, unrelated hospitalizations, RT discontinuation, and COVID-19 precautions. Trial was stopped based on statistical analysis demonstrating no difference for primary outcome and imminent expiry of available drug. Discontinuation was approved by Data Safety Monitoring Committee. Conclusions: Melatonin did not prevent fatigue in patients with early stage breast cancer undergoing RT. Melatonin also demonstrated no benefit for other symptoms, except depression. Analysis showed little evidence of an effect, and the trial was terminated early. Clinical trial information: NCT02332928.

Survivorship profile and post-treatment quality of life of oral cancer survivors in comparison with caregivers: An analysis of a real-world cohort of a developing country.

e18036 Background: Oral cavity cancer is the second most common cancer in India; India bears the most burden of oral cancer in the world. The most effective way to study the effectiveness of treatments is in clinical trials, but the quality of life (QOL) and post-treatment effects of those treatments are seldom studied in real-world settings. Methods: All oral cancer survivors treated with curative intent at our institute from September 2019 to January 2021, who were disease-free for a minimum of six months following treatment, were included in this study. The QOL of these cancer survivors was compared with that of their caregivers using the WHOQOL BREF questionnaire. The complete survivorship profile was evaluated using a Constant shoulder score for shoulder dysfunction, clinical oral dryness score (CODS) for xerostomia, Sydney Swallow Questionnaire (SSQ) for swallowing dysfunction, Patterson scale for lymphedema, Comprehensive Score for financial Toxicity (COST)‐Functional Assessment of Chronic Illness Therapy (FACIT) questionnaire for financial toxicity, Depression, Anxiety and Stress Scale - 21 Items (DASS-21) for psychological wellbeing. Results: A total of seventy-nine survivors were included. The median age was 49 years. Though both survivors and caregivers had similar QOL scores in the physical and environmental domains, survivors had poor scores in the social (M = 58.7,SD = 21.9) and psychological domains (M = 60.4,SD = 15.6). The T stage (p = 0.06), surgery (p = 0.008), and trismus (p = 0.03) were significant factors affecting swallowing. Those patients who had undergone selective neck dissection had better shoulder scores compared to those who had modified radical neck dissection (p = 0.006). 75% of people had xerostomia and 10.9% had severe xerostomia. Internal lymphedema was seen in 30.4% of people. Depression and anxiety were recorded in 46 (58.2%) and 33 (41.8%) patients respectively. Employment status (p = 0.04) and treatment modality (p = 0.05) were significant factors affecting financial toxicity. Conclusions: Oral cancer survivors had a poor psychosocial QOL compared to their caregivers. Treatment-related functional sequelae had a significant negative impact on quality of life across all domains. Clinical trial information: CTRI/2020/07/026848.

Impact of lung function and baseline clinical characteristics on patient-reported outcome measures in systemic sclerosis-associated interstitial lung disease.

The SENSCIS® trial demonstrated a significant reduction of lung function decline in patients with SSc-associated interstitial lung disease (SSc-ILD) treated with nintedanib, but no significant effect on health-related quality of life (HRQoL). To assess whether SSc/SSc-ILD severity and large changes in lung function correlate with HRQoL, a post-hoc analysis of SENSCIS®, aggregating treatment arms, was undertaken. Patient-reported outcome (PRO) measures [St. George's Respiratory Questionnaire (SGRQ), Functional Assessment of Chronic Illness Therapy (FACIT)-Dyspnoea, and HAQ-Disability Index (HAQ-DI), incorporating the Scleroderma HAQ visual analogue scale (SHAQ VAS)] at baseline and week 52 were assessed for associations to SSc-ILD severity. At baseline and at week 52, forced vital capacity (FVC) <70% predicted was associated with worse PRO measure scores compared with FVC ≥70% predicted [week 52: SGRQ 45.1 vs 34.0 (P < 0.0001); FACIT-Dyspnoea 48.9 vs 44.5 (P < 0.0001); HAQ-DI 0.7 vs 0.6 (P < 0.0228); SHAQ VAS breathing problems 3.6 vs 2.6 (P < 0.0001)]. Patients with diffuse cutaneous SSc and other characteristics associated with SSc-ILD severity had worse PRO measure scores. Patients requiring oxygen or with >30% fibrosis on high-resolution computed tomography at baseline demonstrated worse PRO measure scores at week 52. After 1 year, patients with a major (>10%) improvement/worsening in FVC demonstrated corresponding improvement/worsening in SGRQ and other PRO measures, significant for the SGRQ symptom domain (P < 0.001). Severe SSc-ILD and major deteriorations in lung function have important impacts on HRQoL. Treatments that slow lung function decline and prevent severe SSc-ILD are important to preserve HRQoL. clinicaltrials.gov, www.clinicaltrials.gov, NCT02597933.

Back Massage Relaxation Therapy Intervention and Measurement of Client Fatigue Score in Congested Heart Failure Clients with Activity Intolerance Disorder

Objective: Congestive heart failure is a condition where the heart is unable to pump adequate blood to meet the needs of the network. If the supply in the blood cannot flow to parts of the body, it can cause the body to experience weakness, lethargy, and usually tire easily, so that it will experience problems, namely activity intolerance. One of the non-pharmacological interventions that can be done is relaxation therapy, one of which is back massage therapy, and measuring fatigue scores. This study was conducted to present nursing care to congestive heart failure clients with activity intolerance problems with back massage interventions and to measure client fatigue scores in the Kenanga Room at Banjar City Hospital. Method: The method in this study is a descriptive case study and a subjective questionnaire that aims to describe the nursing care of congestive heart failure clients with activity intolerance disorders with back massage interventions and measure fatigue scores using FACIT (Functional Assessment of Chronic Illness Therapy) questionnaires for clients in the memory room of RSUD Kota Banjar. The approach used in this case study is the process of nursing care, which includes assessment, intervention, diagnosis, implementation, and evaluation of nursing. Data collection techniques include interviews, observation, physical examination, and documentation studies. Subjects in this study were patients who experienced congestive heart failure with activity intolerance problems. Result: At the assessment stage, it is known that the client complains that the body is tired easily. The intervention given is energy management according to the SIKI book, and adding back massage therapy and measuring the client's fatigue score are carried out for 3 days. After the intervention was carried out, the client said that he was tired, and the client's fatigue score had increased. Conclusion: Nursing care for clients who experience congestive heart failure with activity intolerance problems using back massage therapy is effective in overcoming client fatigue.

Impact of remission and low disease activity on health-related quality of life in patients with systemic lupus erythematosus.

To investigate the impact of remission and lupus low disease activity state (LLDAS) on health-related quality of life (HRQoL) in systemic lupus erythematosus. Short-Form 36 (SF-36), three-level EQ-5D (EQ-5D-3L)and Functional Assessment of Chronic Illness Therapy (FACIT)-Fatiguedata from the BLISS-52 (NCT00424476) and BLISS-76 (NCT00410384) trials were used. Duration in remission/LLDAS required to reach a HRQoL benefit ≥ minimal clinically important differences (MCIDs) during and post-treatment was determined using quantile regression and generalized estimating equations. Patients (n = 1684) were assessed every fourth week (15 visits). Four cumulative (β = 0.60) or four consecutive (β = 0.66) visits in remission were required to achieve a benefit ≥MCID in SF-36 physical component summary (PCS) scores, and six cumulative (β = 0.44) or five consecutive (β = 0.49) for a benefit ≥MCID in mental component summary (MCS) scores. Eight cumulative (β = 0.30 for both) or eight consecutive (β = 0.32 for both) visits in LLDAS were required for a benefit in PCS/MCS ≥MCID, respectively. For EQ-5D-3L index scores ≥MCID, six cumulative (β = 0.007) or five consecutive (β = 0.008) visits in remission were required, and eight cumulative (β = 0.005) or six consecutive (β = 0.006) visits in LLDAS. For FACIT-Fatigue scores ≥MCID, 12 cumulative (β = 0.34) or 10 consecutive (β = 0.39) visits in remission were required, and 17 cumulative (β = 0.24) or 16 consecutive (β = 0.25) visits in LLDAS. Remission and LLDAS contribute to a HRQoL benefit in a time-dependent manner. Shorter time in remission than in LLDAS was required for a clinically important benefit in HRQoL, and longer time in remission for a benefit in mental compared with physical HRQoL aspects. When remission/LLDAS was sustained, the same benefit was achieved in a shorter time.

Composite endpoint to evaluate complement inhibition therapy in patients with paroxysmal nocturnal hemoglobinuria.

This study developed and explored a novel composite endpoint to assess the overall impact that treatment can have on patients living with paroxysmal nocturnal hemoglobinuria (PNH). Candidate composite endpoint variables were selected by a group of experts and included: lactate dehydrogenase levels as a measure of intravascular hemolysis; complete terminal complement inhibition; absence of major adverse vascular events, including thrombosis; absence of any adverse events leading to death or discontinuation of study treatment; transfusion avoidance; and improvements in fatigue‐related quality of life as determined by the Functional Assessment of Chronic Illness Therapy (FACIT)‐Fatigue score. From these variables, a novel composite endpoint was constructed and explored using data collected in the ravulizumab PNH Study 301 (NCT02946463). Thresholds were defined and reported for each candidate variable. Five of the six candidate variables were included in the final composite endpoint; the FACIT‐Fatigue score was excluded. Composite endpoint criterion was defined as patients meeting all five selected individual component thresholds. All patients in the ravulizumab arm achieved complete terminal complement inhibition and a reduction in lactate dehydrogenase levels; 51.2% and 41.3% of patients in the ravulizumab arm and eculizumab arm, respectively, achieved all composite endpoint component thresholds (treatment difference: 9.4%; 95% confidence interval: −3.0, 21.5). The composite endpoint provided a single and simultaneous measurement of overall benefit for patients receiving treatment for PNH. Use of the composite endpoint in future PNH research is recommended to determine clinical benefit, and its use in health technology assessments should be evaluated.

Abstract PD5-11: Pilot study to assess prolonged nightly fasting in breast cancer survivors (LONGFAST)

Abstract Background: Prior, retrospective analysis of nightly fasting among women with breast cancer suggests that fasting less than 13 hours per night may be associated with higher risk of breast cancer recurrence. Small studies suggest that fasting duration can influence inflammation, obesity, sleep, and other potential mediators of breast cancer recurrence risk. Prolonged overnight fasting is a simple, nonpharmacological behavioral intervention strategy that may be doable for most patients. We designed this pilot study to prospectively evaluate the feasibility of prolonged overnight fasting among breast cancer survivors. Methods: We designed a single-arm, pilot study to evaluate the feasibility of fasting for 13 hours overnight for a 12-week period among women with a history of early stage breast cancer (I to III) who had completed initial cancer therapy at least 6 months prior. Baseline and end of study assessments included measurements of body mass index (BMI), quality of life (QOL) (Functional Assessment of Cancer Therapy - General (FACT-G)), mood (Hospital Anxiety and Depression Scale (HADS)), fatigue (Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue), levels of physical activity (Godin Leisure-Time Exercise Questionnaire), and blood biomarkers (expanded lipid profile, hemoglobin A1c, C-reactive protein, interleukin-6, tumor necrosis factor alpha, leptin, adiponectin). Patient-reported outcome (PRO) surveys were also administered at 6 weeks. Feasibility was defined as ≥ 60% of participants documenting fasting in the food diary for 13 hours on at least 70% of nights during the study period. Changes in study measures from baseline were evaluated using Wilcoxon signed-rank tests. Results: Between July 2020 and January 2021, we enrolled 40 women with a history of breast cancer. Participants had a median age of 59.9 (range 34.9-76.3) and median time since diagnosis was 4.5 years (range 0.8-20.7). At baseline, BMI was normal (18.5-24.9) in 40.0%, overweight (25-29.9) in 37.5%, and obese (≥30) in 22.5%. Forty-two and a half percent had Stage I cancer, 42.5% stage II, and 15.0% stage III. Sixty-five percent were on hormonal therapy. Ninety-five percent of participants fasted ≥ 13 hours for at least 70% of study days (95% CI 83%-99%). At 6 weeks, there was a statistically significant improvement in anxiety (p=.0007). No other significant changes were seen in PROs. At 12 weeks, there were statistically significant improvements in BMI (p=.0072), anxiety (p=.0141), depression (p=.0048), and fatigue (p=.0105). There was no association between change in BMI during the study and baseline BMI category, age, or endocrine therapy. There was no significant change in overall QOL, physical activity levels, or blood biomarkers at 12 weeks. Conclusions: Prolonged overnight fasting is feasible in the breast cancer population and may improve BMI, mood, and fatigue without a detrimental effect on overall QOL. The data from this study support the need for a larger, longer randomized study of prolonged overnight fasting in the breast cancer population to further evaluate the effects on body composition, mood, QOL, metabolic markers, and risk of recurrence. Table 1.Impact of Prolonged Overnight Fasting among Breast Cancer SurvivorsStudy AssessmentMedian at baselineMedian at 12 weeksMedian within-participant changep-valueBody Mass Index (kg/m2)26.4225.80-0.380.0072HADS - Depression1.001.00-1.000.0048HADS - Anxiety4.504.00-0.500.0141FACIT - Fatigue47.5049.821.000.0105FACT-G - Quality of Life95.2096.840.910.4933Physical Activity Level40.5039.000.000.3340Hemoglobin A1c (mg/dL)5.455.400.000.2758High-density lipoprotein (mg/dL)72.0073.00-2.000.4688Low-density lipoprotein (mg/dL)92.0099.001.000.5626Total Cholesterol (mg/dL)193.00192.003.000.6569C-reactive protein (mg/L)1.500.90-0.100.1043Interleukin-6 (pg/mL)2.001.90-0.300.1213Tumor Necrosis Factor α (pg/mL)0.740.74-0.050.2898Adiponectin (ug/mL)12.0012.000.000.0682Leptin (ng/mL)7.158.30-0.100.8418 Citation Format: Elizabeth K. O'Donnell, Yael N. Shapiro, Amy Comander, Steven J. Isakoff, Beverly Moy, Laura Spring, Seth Wander, Irene Kuter, Jennifer Shin, Jerry Younger, Michelle Specht, Chryssanthi Kourniotis, Carol Sullivan, Loren Winters, Nora Horick, Jeffrey Peppercorn. Pilot study to assess prolonged nightly fasting in breast cancer survivors (LONGFAST) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD5-11.

The burden of illness in patients with paroxysmal nocturnal hemoglobinuria receiving treatment with the C5-inhibitors eculizumab or ravulizumab: results from a US patient survey

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare and life-threatening disease with symptoms of hemolysis and thrombosis. Current therapies for this complement-mediated disease rely predominantly on inhibition of the C5 complement protein. However, data on treatment responses and quality of life in C5-inhibitor (C5i)-treated PNH patients are scarce. The objective of this study was to determine C5i treatment effects on clinical parameters, PNH symptoms, quality of life, and resource use for PNH patients. This cross-sectional study surveyed 122 individuals in the USA receiving treatment for PNH with C5-targeted monoclonal antibodies, eculizumab (ECU) or ravulizumab (RAV). Despite most patients receiving C5i therapy for ≥ 3 months (ECU 100%, n = 35; RAV 95.4%, n = 83), many patients remained anemic with hemoglobin levels ≤ 12 g/dL in 87.5% (n = 28/32) and 82.9% (n = 68/82) of ECU and RAV recipients, respectively. A majority of patients on ECU (88.6%; n = 31/35) and RAV (74.7%; n = 65/87) reported fatigue symptoms. Among PNH patients receiving C5i therapy for ≥ 12 months, some still reported thrombotic events (ECU, 10.0%, n = 1/10; RAV, 23.5%, n = 4/17) and required transfusions within the past year (ECU, 52.2%, n = 12/23; RAV, 22.6%, n = 7/31). Other patient-reported PNH symptoms included breakthrough hemolysis, shortness of breath, and headaches. Patients reported scores below the average population norms on the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) scales. Overall, this study found that PNH patients receiving ECU or RAV therapy demonstrated a significant burden of illness, highlighting the need for improved PNH therapies.

Categorized Hematologic Response to Pegcetacoplan and Correlations with Quality of Life in Patients with Paroxysmal Nocturnal Hemoglobinuria: Post Hoc Analysis of Data from Phase 1b, Phase 2a, and Phase 3 Trials

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a complement-mediated, hematologic disease characterized by hemolysis, anemia, and fatigue that impairs quality of life. Pegcetacoplan (PEG), a C3-inhibitor recently approved by the Food and Drug Administration for treatment of PNH, controls intravascular hemolysis (IVH) and prevents extravascular hemolysis (EVH). The PADDOCK and PALOMINO trials demonstrated PEG's improvement of key hematologic and clinical parameters, including hemoglobin (Hb) level and Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score. The PEGASUS trial demonstrated that PEG was more effective than eculizumab (ECU) in improving these parameters in PNH patients with suboptimal response to prior ECU treatment.Aims: This post hoc analysis categorized hematologic response to PEG in 3 trials: PADDOCK (phase 1b, open-label, two-cohort [NCT02588833]), PALOMINO (phase 2a, open-label, single-cohort [NCT03593200]), and PEGASUS (phase 3, randomized, open-label, active-comparator controlled [NCT03500549]).Methods: PADDOCK and PALOMINO included adult complement inhibitor-naïve patients, while PEGASUS included adult patients with Hb <10.5 g/dL despite ≥3 months of ECU treatment. PADDOCK was a multiple ascending dose pilot study of 2 cohorts: cohort 1 received a suboptimal PEG dose (180 mg/day subcutaneously [SQ]) for 28 days; cohort 2 received a PEG dose of 270-360 mg/day SQ for up to one year. Patients could be enrolled in both cohorts. PALOMINO patients received a PEG dose of 270-360 mg/day SQ for up to one year. PEGASUS comprised a 4-week run-in period where patients received both ECU (continued dosing regimen) and PEG (1080 mg SQ twice-weekly), 16-week randomized controlled period (PEG or ECU monotherapy), and 32-week open-label period (PEG monotherapy) including a 4-week run-in period for the ECU-to-PEG group.Hematologic response category was assessed at Days 113/337 for patients in the combined PADDOCK/PALOMINO trials (N=24) via manual categorization by two independent, blinded observers. Categorization was assessed at Weeks 16/48 for PEGASUS patients (N=80) using SAS 9.4M5. Statistical significance for hematologic response categories within arms at Week 16 vs. 48, and between arms at Week 48, was evaluated using Wilcoxon-Mann-Whitney and Chi-square testing. FACIT-Fatigue scores for PEGASUS patients, summarized using descriptive statistics, were also correlated to hematologic response category.Response categories were defined per the following criteria (Risitano A, et al., Front Immunol, 2019;10:1157): complete- no transfusions required, stable Hb (normal range), no evidence of hemolysis (lactate dehydrogenase [LDH]≤1.5×upper limit of normal [ULN] U/L, absolute reticulocyte count [ARC]≤150,000/µL); major- no transfusion, normal Hb, but with evidence of hemolysis (LDH>1.5×ULN U/L and/or ARC>150,000/µL); good- no transfusions, but with chronic mild anemia or evidence of hemolysis; partial- chronic moderate anemia and/or occasional transfusions (<3 units/6 months); minor- regular transfusions required (3-6 units/6 months); no response- regular and frequent transfusions required (>6 units/6 months).PADDOCK/PALOMINO patients missing data at an assessment timepoint, or PEGASUS patients missing data within 6 weeks prior to an assessment timepoint, were not evaluated.Results: Most PADDOCK/PALOMINO patients achieved at least a good hematologic response at Days 113 and 337 (Table 1). At Week 48, most patients in both PEGASUS arms achieved a good/major/complete hematologic response (inter-arm p=0.4390), with a significant increase in the percent of ECU-to-PEG patients achieving at least a good response after switching to PEG at Week 16 (Week 16 vs. 48: intra-arm p<0.0001; Table 1). In PEGASUS, patients with better response categories had higher FACIT-Fatigue scores when compared to the rest of the cohort (Week 16: p<0.001, Week 48: p=0.028; Table 2).Conclusions: In post hoc analyses of PADDOCK, PALOMINO, and PEGASUS trial data, a substantial proportion of patients achieved and maintained good, major, or complete hematologic responses to PEG, suggesting that PEG can lead to sustained improvements in hematologic parameters. PEGASUS data also demonstrated correlation of improved hematologic response category with clinically meaningful improvements in quality of life, as measured by FACIT-Fatigue. [Display omitted] DisclosuresRisitano: Jazz: Other: Lecture fees, Speakers Bureau; Achillion: Membership on an entity's Board of Directors or advisory committees, Other: Lecture fees; Biocryst: Membership on an entity's Board of Directors or advisory committees; RA Pharma: Research Funding; Amyndas: Consultancy; Samsung: Membership on an entity's Board of Directors or advisory committees; Alexion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Lecture fees, Research Funding, Speakers Bureau; Alnylam: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Lecture fees, Research Funding, Speakers Bureau; F. Hoffmann-La Roche Ltd.: Membership on an entity's Board of Directors or advisory committees; Pfizer: Other: Lecture fees, Speakers Bureau; Apellis Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Other: Lecture fees, Speakers Bureau. Wong: Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau; Apellis Pharmaceuticals: Research Funding, Speakers Bureau; Alexion: Consultancy, Honoraria, Research Funding, Speakers Bureau. Al-Adhami: Apellis Pharmaceuticals: Current Employment. Chen: Apellis Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Peffault De Latour: Swedish Orphan Biovitrum AB: Consultancy, Honoraria; Apellis Pharmaceuticals: Consultancy, Honoraria; Alexion Pharmaceuticals: Consultancy, Honoraria, Research Funding; Amgen: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding.

Dexamethasone 8 mg for Cancer-Related Fatigue in Inpatients with Advanced Cancer Undergoing Palliative Care: A Multicenter Phase II Trial.

Objective: No standard treatment for cancer-related fatigue (CRF) for inpatients in a palliative care setting exists. The aim of this study was to validate the previous study-derived efficacy of dexamethasone 8 mg for CRF among inpatients in a palliative care setting.Methods: Inpatients with moderate fatigue (≥4/10) were enrolled in a multicenter phase II trial. Dexamethasone 8 mg p.o. or 6.6 mg i.v. was administered for seven days and 4 mg p.o. or 3.3 mg i.v. for seven consecutive days. The primary endpoint was a threshold average change of Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue subscale score of 3. The secondary endpoints were evaluated with the anorexia-cachexia subscale (ACS), and the Edmonton symptom assessment scale-revised Japanese version.Results: A total of 32 patients were enrolled. On day 8, the mean change of FACIT-fatigue subscale from day 1 was 5.2 (95% confidence interval 0.8–10.0), in which the lower bound was above 0 but not above the prespecified threshold value of 3.0 (p = 0.72). Edmonton symptom assessment system (ESAS)-fatigue was significantly improved by day 3 (p = 0.02), but not on day 8 or day 15. ACS, physical well-being, and ESAS-lack of appetite significantly improved by day 8 and day 15. Adverse events were tolerable.Conclusion: This study showed that dexamethasone 8 mg failed to achieve the preset efficacy for CRF among inpatients in a palliative care setting. However, this treatment improved fatigue and would be an option for CRF.jRCT (jRCTs031180068).

Sarilumab monotherapy vs sarilumab and methotrexate combination therapy in patients with rheumatoid arthritis.

ObjectiveSarilumab, as monotherapy or in combination with conventional synthetic DMARDs, such as MTX, has demonstrated improvement in clinical outcomes in patients with RA. The primary objective of this post hoc analysis was to compare the efficacy of sarilumab (200 mg every 2 weeks) monotherapy (MONARCH study) with that of sarilumab and MTX combination therapy (MOBILITY study) at week 24.MethodsThe endpoints assessed were mean change from baseline in the Clinical Disease Activity Index (CDAI), 28-joint Disease Activity using CRP (DAS28-CRP), CRP, haemoglobin (Hb), pain visual analogue scale (VAS) and Functional Assessment of Chronic Illness Therapy (FACIT)–Fatigue. Least square (LS) mean change from baseline (95% CI) at week 24 for all endpoints was compared between the treatment arms for adjusted comparisons.ResultsThis analysis included 184 patients on sarilumab monotherapy and 399 patients on sarilumab plus MTX. Differences (P < 0.05) were observed in ethnicity, region, body mass index group, rheumatoid factor, anti-cyclic citrullinated peptide antibodies, swollen joint count, CRP, CDAI and oral glucocorticoid use between these treatment groups. After adjusting for these differences in a mixed-effect model repeated measure, LS mean change from baseline for all assessments was similar between the treatment groups with overlapping CIs: CDAI, −28.79 vs −26.21; DAS28-CRP, −2.95 vs −2.81; CRP, −18.31 vs −16.46; Hb, 6.59 vs 8.09; Pain VAS, −33.62 vs −31.66; FACIT-Fatigue, 9.90 vs 10.24.ConclusionThis analysis demonstrated that the efficacy of sarilumab monotherapy was similar to that of sarilumab and MTX combination therapy.

Impact of obesity on quality of life, psychological status, and disease activity in psoriatic arthritis: a multi‑center study.

This article aims to evaluate the possible effect of obesity on quality of life, psychological status, and other clinical variables in Psoriatic arthritis (PsA). PsA patients have been recruited by the Turkish League Against Rheumatism-Network from various centers in Turkey in this cross-sectional study. Patients with a body mass index (BMI) ≥ of 30kg/m2 were considered obese. Differences among patients with regard to obesity status were assessed with health-related quality of life measures (PsA Quality of Life Questionnaire [PsAQoL]), psychological status (Hospital Anxiety and Depression Scale [HADS]), and disease activity parameters (the Disease Activity index for PSoriatic Arthritis [DAPSA], Disease Activity Score 28-C-reactive protein [DAS28-CRP], Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], Psoriasis Area and Severity Index [PASI]), physical functions (Ankylosing Spondylitis Functional Index [BASFI], Health Assessment Questionnaire [HAQ], and Health Assessment Questionnaire for the spondyloarthropathies [HAQ-S]). Pain was assessed using visual analog scale of pain (VAS-P), and fatigue was evaluated using visual analog scale of fatigue (VAS-F) and Functional Assessment of Chronic Illness Therapy (FACIT). A total of 1033 patients with PsA, 650 (62.9%) non-obese and 383 (37.1%) obese were included in the study. The PsAQoL, HADS-Anxiety, HADS-Depression, DAPSA, DAS28-CRP, BASDAI, BASFI, HAQ and HAQ-S scores of the obese group were higher than the non-obese group (p < 0.05). VAS-P and PASI scores were similar between group of patients with and without obesity. Obese patients had higher median scores of VAS-F and FACIT than non-obese patients (p < 0.05). Linear regression analysis showed that BMI affects the quality of life, depression, and disease activity. Consequently, obesity has significant associations with higher disease activity, lower QoL, risk of anxiety, depression, and fatigue. Therefore, obesity should also be taken into account in the management of PsA patients.

Phase 2 study of danicopan in patients with paroxysmal nocturnal hemoglobinuria with an inadequate response to eculizumab

AbstractParoxysmal nocturnal hemoglobinuria (PNH) is characterized by uncontrolled terminal complement activation and subsequent intravascular hemolysis (IVH). C5 inhibitors prevent membrane attack complex formation, but patients may experience extravascular hemolysis (EVH) and continue to require blood transfusions. Danicopan, an oral proximal complement inhibitor of alternative pathway factor D (FD), is designed to control IVH and EVH. In a phase 2 dose-finding trial, eculizumab-treated transfusion-dependent patients with PNH (n = 12) received danicopan, 100 to 200 mg thrice daily, in addition to their eculizumab regimen for 24 weeks. End points included hemoglobin (Hgb) change vs baseline at week 24 (primary), reduction in blood transfusions, and patient-reported outcomes. Safety, tolerability, and pharmacokinetics/pharmacodynamics were measured. Twelve patients received ≥1 danicopan dose; 1 patients discontinued from a serious adverse event deemed unlikely related to danicopan. Eleven patients completed the 24-week treatment period. Addition of danicopan resulted in a mean Hgb increase of 2.4 g/dL at week 24. In the 24 weeks prior to danicopan, 10 patients received 31 transfusions (50 units) compared with 1 transfusion (2 units) in 1 patient during the 24-week treatment period. Mean Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score increased by 11 points from baseline to week 24. The most common adverse events were headache, cough, and nasopharyngitis. Addition of danicopan, a first-in-class FD inhibitor, led to a meaningful improvement in Hgb and reduced transfusion requirements in patients with PNH who were transfusion-dependent on eculizumab. These benefits were associated with improvement of FACIT-Fatigue. This trial was registered at www.clinicaltrials.gov as #NCT03472885.

Guselkumab demonstrated an independent treatment effect in reducing fatigue after adjustment for clinical response\u2014results from two phase 3 clinical trials of 1120 patients with active psoriatic arthritis

BackgroundThe interleukin-23p19-subunit inhibitor guselkumab effectively treats signs and symptoms of psoriatic arthritis (PsA). We evaluated the effect of guselkumab on fatigue.MethodsAcross two phase 3 trials of guselkumab (DISCOVER-1, DISCOVER-2), patients with active PsA despite standard therapy were randomized to subcutaneous injections of guselkumab 100 mg every 4 weeks (Q4W, N = 373); guselkumab 100 mg at week 0, week 4, and then Q8W (N = 375); or placebo (N = 372) through week 24, after which patients in the placebo group crossed over to guselkumab Q4W. Fatigue was measured as a secondary endpoint using the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue instrument (range 0–52, higher scores indicate less fatigue). Least-squares mean changes in FACIT-Fatigue scores were compared between treatments using a mixed-effect model for repeated measures. Mediation analysis was used to adjust for indirect effects on fatigue deriving from improvement in other outcomes, including ≥20% improvement in American College of Rheumatology criteria (ACR20; prespecified), minimal disease activity (MDA; post hoc), or C-reactive protein (CRP; post hoc).ResultsBaseline mean (SD) FACIT-Fatigue scores in DISCOVER-1 (N = 381) and DISCOVER-2 (N = 739), ranging from 29.1 (9.5) to 31.4 (10.1), indicated substantial levels of fatigue relative to the United States general population (43.6 [9.4]). Across studies, mean improvements, and proportions of patients with ≥4-point improvements, in FACIT-Fatigue scores at week 24 with guselkumab Q4W and Q8W (5.6–7.6 and 54–63%, respectively) were larger vs placebo (2.2–3.6 and 35–46%). Improvement in FACIT-Fatigue scores with guselkumab was sustained from week 24 to week 52, with moderate-to-large effect sizes (Cohen’s d = 0.52–0.81 at week 24; 0.66–0.91 at week 52). Mediation analyses demonstrated that substantial proportions of the effects of guselkumab vs placebo on fatigue were direct effect, after adjusting for achievement of ACR20 (Q4W 69–70%, Q8W 12–36% direct effect) or MDA (72–92% across dosing regimens) response or for change in serum CRP concentrations (82–88% across dosing regimens).ConclusionsIn patients with active PsA, guselkumab 100 mg Q4W or Q8W led to clinically meaningful and sustained improvements in fatigue through 1 year. A substantial portion of the improvement in FACIT-Fatigue scores induced by guselkumab was independent of effects on the achievement of other select outcomes.Trial registrationName of the registry: ClinicalTrials.govTrial registrations: DISCOVER-1, NCT03162796; DISCOVER-2, NCT03158285Date of registration: DISCOVER-1, May 22, 2017; DISCOVER-2, May 18, 2017URLs of the trial registry record:DISCOVER-1, https://clinicaltrials.gov/ct2/show/NCT03162796?term=NCT03162796&draw=1&rank=1DISCOVER-2, https://clinicaltrials.gov/ct2/show/NCT03158285?term=NCT03158285&draw=2&rank=1

Functional assessment of cancer therapy questionnaire for melanoma in the Serbian population: A factor analytic approach

The aim of this study was to examine the psychometric properties of the Functional Assessment Cancer Therapy—Melanoma (FACT-M) questionnaire in the Serbian language. The FACT-M was translated into Serbian using the standard methodology after obtaining the licence from the Functional Assessment of Chronic Illness Therapy (FACIT) translation project team. This version of FACT-M was distributed to a cohort of consecutive patients with histologically confirmed high-risk skin melanoma treated at the tertiary referral center. To examine construct validity of the FACT-M in Serbian, we performed exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). The FACT-General (FACT-G) did not fit the original 4-domain structure. Instead, we accepted a 7-domain structure which, aside from physical, emotional, social and functional well-being, had domains of ‘friends’ support’, ‘illness acceptance’ and ‘fear of death’. Melanoma scale (MS) and Melanoma surgery scale (MSS) did not fit the original one-dimensional structure. The MS was observed to have 4 domains: ‘pain’, ‘skin problems’, ‘abdominal metastases’ and ‘other problems’. The MSS was observed to have 2 domains: ‘having symptoms’ and ‘no symptoms’. It is suggested that the FACT-M questionnaire is analyzed using the newly extracted domains to examine quality of life of people with high-risk melanoma in Serbia.

Kanser Tedavisinin İşlevsel Değerlendirmesi Ölçeği FACT-G Türkçe Versiyonunun Geçerlik ve Güvenilirliği

Objective: Many of the cancer-specific quality of life (QOL) questionnaires improved over the last 20 years, can be contemplated as reference measures. The Functional Assessment of Chronic Illness Therapy (FACIT) system is an based and generic health-related quality of life measures. The aim of this study was conducted to test the reliability and construct validity of the Functional Assessment of Cancer Therapy General (FACT-G) for Turkish cancer patients. Material and Methods: This research is a methodological study. The data were obtained by using the sociodemographic and the FACT-G questionnaire. The sample comprised 148 cancer pa¬tients. Data were analysed by using the SPSS package program, descriptive statistics and to assess the reliability of the scales, cronbach alpha coefficient, item total score analysis, and, item total correlation coefficient (Pearson's correlation). For the construct validity of the instrument; exploratory factor analysis and confirmatory factor analysis were used. Results: The mean total score of FACT-G was 60.71±14.42, and for the physical, social/ family, emotional and functional well-being subscales 15.83±5.48, 13.91±4.90, 13.45±5.03 and 17.51± 5.04, respectively. The alpha coefficient was 0.88 for the global scale of the FACT-G questionnaire and ranged from 0.70 to 0.79 across subscales. A statistically significant positive correlation was found between FACT-G and test-retest scores of the four sub-dimensions (p=0.001). Conclusion: In this study, as a result of evaluating the psychometric properties of the FACT-G scale, the scale is a valid and reliable tool for use in Turkish patients with cancer.

Impact of Transfusion Dependency on Health-Related Quality of Life Outcomes in Newly Diagnosed Patients with Myelodysplastic Syndromes (MDS). Analysis on 669 Patients By Disease Risk

Background:There is some evidence indicating that transfusion dependency negatively impact health-related quality of life HRQOL of patients with myelodysplastic syndromes (MDS). However, there is paucity of evidence-based on this relationship across all different disease risk-group categories.Aims:The primary objective of this study is to examine whether transfusion dependency has a different impact on HRQOL outcomes (ie. functional wellbeing and symptom burden) by disease risk according to the International Prognostic Scoring System (IPSS).Methods:Analysis is based on 669 newly diagnosed MDS patients enrolled in ongoing international prospective observational study. Patients with any IPSS risk score category were consecutively enrolled in 37 centers from nine countries. Patients were invited to participate during one of the first consultations, after confirmed diagnosis of MDS. Multidimensional HRQOL and fatigue outcomes were assessed at baseline (i.e., before treatment) with the well validated European Organization for Research and treatment of Cancer (EORTC) QLQ-C30 and the Functional Assessment of Chronic Illness Therapy (FACIT)Fatigue questionnaires. Patients were classified as transfusion dependent (TD) or transfusion independent (TI) using the following definition of “transfusion dependency”: having received at least one red blood cell transfusion every 8 weeks over a period of 4 months (Malcovati L, et al, J Clin Oncol . 2007; 25: 3503-10). We used proportions, means and medians to describe data, by risk and transfusion-dependence groups. Possible statistically significant differences between groups were assessed by Fisher and Wilcoxon-Mann-Whitney tests according to the type of variable. We also investigated possible clinically meaningful differences according to previously published guidelines.Results:Median age of the entire cohort (N=669) was of 77 years (range 18-96 years) and there were 418 men (62%) and 251 (38%) women. Of the entire cohort, 364 (54%) were classified as IPSS intermediate-2 or high-risk (higher risk disease: HRD) and 305 (46% as IPSS low or intermediate-1 (lower risk disease: LRD). There were: 44(14%) and 261(86%) patients respectively classified TD and TI in the LRD group, while in the HRD group there were 78(21%) and 286 (79%) patients respectively classified as TD and TI. Within LRD and HRD groups, there were no statistically significant differences in age, gender, comorbidity and education level between TD and TI patients. In addition, there were no statistically significant imbalances in the distribution of IPSS risk categories, respectively low and int-1 in LRD patients and int-2 and high-risk in HRD patients, between TD and TI groups. Within LRD, median hemoglobin (Hb) level was 10.2 g/dl and 8.9 g/dl for TI and TD patients and within HRD, median Hb level was 9.5 g/dl and 8.2 g/dl for TI and TD patients respectively. HRQOL profile of TD patients was generally worse than that of TI patients in both LRD and HRD. However, statistically and clinically meaningful differences in key symptoms of fatigue (P=.001, mean difference of 11.1) and pain (P=.002, mean difference of 8.4) were only noted between TD and TI patients within the HRD group. The trend of a fatigue was also confirmed by the FACIT Fatigue scale. Details on mean differences in selected HRQOL scales by disease risk groups (LRD versus HRD) are provided in Figure 1.Conclusion:This study suggests that impact of transfusion dependency on HRQOL can be different depending on disease risk at diagnosis with some major impact in fatigue and pain for HRD patients. This data might help physicians to provide more targeted interventions. [Display omitted] DisclosuresEfficace:Incyte: Consultancy; Seattle Genetics: Consultancy; TEVA: Consultancy, Research Funding; Lundbeck: Research Funding; Amgen: Consultancy, Research Funding. Gaidano:AbbVie: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Breccia:TEVA: Speakers Bureau. Platzbecker:Acceleron: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Research Funding; Celgene: Consultancy, Honoraria, Research Funding.

Patient Experiences, Satisfaction, and Expectations with Current Systemic Lupus Erythematosus Treatment: Results of the SLE-UPDATE Survey.

ObjectivesTo provide information on systemic lupus erythematosus (SLE) patients’ experiences, satisfaction, and expectations with treatments and examine the association between treatment satisfaction and patient-reported outcomes (PRO).MethodsA cross-sectional, non-interventional, online survey of US adult patients with SLE was conducted in 2019. The survey consisted of 104 questions about SLE and the following PRO instruments: LupusPRO™, Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue, Work Productivity and Activity Impairment (WPAI), an 11-point Worst Pain Numerical Rating scale (NRS), and an 11-point Worst Joint Pain NRS.ResultsFive hundred participants (75% female, 76% White/Caucasian, mean age 42.6 ± 12.7 years, 63% with an associate degree or higher) completed the survey. Most participants were “completely” or “somewhat satisfied” with their treatments, although satisfaction rates were lower for corticosteroids (65%), immunosuppressants (71%), and anti-malarials (55%) than for belimumab (intravenous or subcutaneous) (86%) and rituximab (94%). Treatments were more often considered “burdensome” or “very burdensome” for belimumab (67%) and rituximab (63%) than for corticosteroids (48%), immunosuppressants (49%), and anti-malarials (30%). Pain and productivity assessments supported substantial impairment for the majority of participants, even those who indicated that they were completely satisfied with treatments. The treatment goals most commonly reported as “very important” were reducing fatigue, pain, and the frequency or severity of flares. Three-quarters of participants (76.6%) indicated that their physician’s goals for their therapy matched their own goals “very” or “somewhat closely.” Despite high levels of satisfaction, most participants (63.0%) indicated that their physicians had not asked about their treatment goals during the past 3 months.ConclusionSLE patients reported high rates of satisfaction with current therapies despite identifying substantial treatment burdens, residual pain, and fatigue. Reduced fatigue, pain, and flares were the most important treatment goals for these patients.

AB0704 TELEMEDICINE AT THE TIME OF COVID-19: THE EXPERIENCE WITH RA PATIENTS TREATED WITH JAK-INHIBITORS

Background:The spread of COVID-19, the lockdown, the limited access to care reevaluated the role of tele-consultation and self-assessment.Objectives:Our aim was to evaluate in a cohort of Rheumatoid Arthritis (RA) patients treated with JAK-inhibitors (JAKi): the self-assessed disease activity during lockdown, the lockdown impact on fatigue, anxiety, depression and the prevalence of Covid-19.Methods:We enrolled RA patients treated with baricitinib or tofacitinib. At baseline (BL) and follow-up we collected: patients’ demographic data, composite disease activity indices (CDAI, DAS28CRP), global assessment (PGA), pain visual analogue scale (VAS), FACIT (functional assessment of chronic illness therapy) and a self-rating scale for disease impact on anxiety and depression (Zung-A/D). Patients were instructed on how to perform self-assessment through video-material and fulfilled the online form of “Rheumatoid Arthritis Impact of Disease” (RAID)1 and “RA Disease Activity Index” (RADAI). To capture the pandemic effect, we compared patients in different status (remission, low, moderate and high-disease activity) at the last in-person visit (preCoV) through the DAS28CRP and CDAI, to the tele-health visit (THV), measured by the RAID. BL and pre-CoV ZUNG-A, ZUNG-D, FACIT questionnaires were compared with the online results during the pandemic. Exposure, tests and symptoms of Covid-19 were recorded. Data were expressed as mean±standard deviation or median(IQR) according to distribution.Results:Twenty patients (median age 58.2±11.9 and mean disease duration 153.5 ± 112.7 months) were treated with tofacitinib and 27 with baricitinib. The median time-lapse between the pre-CoV visit and the THV was 12 (IQR 4) weeks. DAS28CRP and CDAI significantly decreased from BL to pre-CoV visit. During the last in-person visit, 21 patients (48.83%) were in remission, 9 (20.93%) in low disease activity; according to the RAID, 15 (31.91%) and 7 (14.89%) patients were respectively in remission and low disease activity during the THV (Table A). PGA and pain significantly decreased from BL to pre-Cov visit but worsened during the lockdown (Table A). FACIT remaining stable during THV. At THV, we detected a significant improvement of anxiety from BL (Zung-A) and a tendency to lower depression scores compared to BL (Table A). JAKi showed a good safety profile considering Covid-19 symptoms, none of the patients was diagnosed with SarsCoV2 infection.Conclusion:This is the first study on virtual assessment in RA patients treated with JAKi. The unique social experiment of the pandemic impaired the clinical response already achieved before the lockdown, without a collateral worseling of FACIT, anxiety and depression.

Comparison of the Effects of the Somatotype on the Physical Activity, Kinesiophobia, and Fatigue Levels of Obstructive Sleep Apnea Syndrome Patients and Healthy Individuals.

Background:We aimed to compare the physical activity, kinesiophobia, and fatigue levels of obstructive sleep apnea syndrome (OSAS) patients and healthy individuals in terms their somatotypes.Methods:A total of 165 individuals were enrolled referred to the Department of Chest Diseases Sleep Disorders Center Outpatient Clinic of Inonu University, Malatya, Turkey in 2018. The somatotype analysis was conducted using the Heath-Carter method, the fatigue level was assessed using the Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scale, the kinesiophobia level was assessed using the Tampa Scale for Kinesiophobia (TSK), and the physical activity level was assessed using the International Physical Activity Questionnaire (IPAQ).Results:The results of the somatotype analysis revealed 3 different somatotypes in the healthy individuals and the OSAS patients’ mesomorph endomorph, endomorphic mesomorph, and mesomorphic endomorph. When comparing the somatotypes of the healthy individuals and the OSAS patients, statistically significant differences were found in the FACIT scores of the mesomorph endomorphs, the IPAQ and FACIT scores of the endomorphic mesomorphs, and the TSK and FACIT scores of the mesomorphic endomorphs (P<0.05).Conclusion:In all three somatotypes of the OSAS patients, the fatigue index scores were higher when compared to those of the healthy individuals. Moreover, when compared with the healthy individuals, the physical activity levels of the endomorphic mesomorphs with OSAS were low, while the kinesiophobia scores of the mesomorphic endomorphs with OSAS were high. Based on the results of this study, in OSAS patients, the endomorphic mesomorph somatotype could be a risk factor for reduced physical activity, while the mesomorphic endomorph somatotype could be a risk factor for increased kinesiophobia.