Functional Assessment Of Chronic Illness Therapy-Fatigue Research Articles

Home-based Exercise Influence On Circulating Cytokines, Functional Capacity And Quality Of Life In Men With Prostate Cancer Under Active Surveillance

PURPOSE: To investigate the impact of a home-based exercise program in men with PCa. METHODS: Fifteen men with PCa under active surveillance completed 24 weeks of home-based exercise (HBE), combining aerobic and body-weight based exercises. Aerobic exercise included 5 days of walking for 30 minutes at 40-60% of the participant’s heart rate reserve. Body-weight based exercises were performed 3 times per week consisting of 3 sets of 15 reps of bodyweight squats, inclined push-ups, and hip thrusts. Baseline and end of study assessments were done. Blood was collected to measure circulating eotaxin, IFNγ, IL-12, IL-1a, IL-5, IL-6, TNF-α, and VEGF (pg/mL; Millipore Sigma, Billerica, MA). A 6-minute walk test (6MWT) was done to measure physical function. The Short form 36 (SF-36) and Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) were used to quantify changes in quality of life (QoL). T-tests were performed with significance set to p < 0.05. RESULTS: Of the 15 men consented, 9 men completed the intervention (40% attrition due to COVID). Participants were 72.0 ± 8.52 yrs old, 85.31 ± 6.41 kg with BMI of 27.77 ± 2.93 kg/m2. A tendency was observed for improved 6MWT distance (Pre: 382.7 ± 108.1 m; Post: 466.7 ± 73.78; p = 0.08). Non-significant reductions were seen in circulating of IFNγ (Pre: 152.9 ± 312.7; Post: 118.9 ± 258.8; p = 0.08) and VEGF (Pre: 125.2 ± 198.7; Post: 80.29 ± 124.3; p = 0.06). Several other biomarkers showed relevant, though not significant, decreases as well, including IL-12 (Pre: 28.69 ± 32.06; Post: 23.92 ± 19.38; -16.6%), IL-1a (Pre: 78.76 ± 183.3; Post: 65.55 ± 147.6; -16.8%), IL-6 (Pre: 23.71 ± 45.64; Post: 21.24 ± 45.18; -10.4%), and TNF-α (Pre: 24.58 ± 35.4; Post: 19.71 ± 20.76; -19.8%). Significant differences were identified in the SF-36 for role limitation due to emotional problems (Pre: 85 ± 15.1; Post: 96.7 ± 7.0; p = 0.003) and the FACIT subscales for physical wellbeing (Pre: 3.7 ± 0.2; Post: 1.3 ± 1.5; p < 0.001) and emotional wellbeing (Pre: 3.7 ± 0.3; Post: 1.5 ± 0.9; p < 0.001). CONCLUSIONS: : Despite the loss of participants due to COVID-19 protocols limiting in person research visits, the results show promising indications that HBE can be effective in reducing cytokines, increasing functional capacity and promoting QoL in men with PCa. Further investigation is needed with a powered sample.

Impact of Rehabilitation on Fatigue in Post-COVID-19 Patients: A Systematic Review and Meta-Analysis

The post-COVID-19 syndrome may affect patients after the COVID-19 post-acute phase. In particular, the 69% of patients reported persistent fatigue at the discharge. To date, no clear data are available regarding the most effective rehabilitative approaches for the treatment of this condition. Thus, this systematic review aimed to evaluate the rehabilitation treatment’s efficacy on fatigue in post-COVID-19 patients. We systematically searched PubMed, Scopus, and Web of Science databases to find longitudinal study designs presenting: post-COVID-19 patients as participants; a rehabilitative approach aimed to reduce post-COVID-19 syndrome as intervention; and fatigue intensity assessed through an evaluation tool that quantified the perceived exertion (i.e., fatigue severity scale, FSS; Borg Scale (BS); Borg Category Ratio 10, CR10; Checklist Individual Strength (CIS) fatigue scale; FACIT (Functional Assessment of Chronic Illness Therapy) fatigue scale). The present systematic review protocol was registered on PROSPERO (registration number CRD42021284058). Out of 704 articles, 6 studies were included. Nearly all patients showed COVID-19-related fatigue, and after the rehabilitation treatment, only 17% of subjects reported the persistency of symptoms. The overall effect size reported a −1.40 decrease in Borg Category Ratio 10 with a SE of 0.05 and a 95% CI between −1.50 and −1.30 (p &lt; 0.001). The present systematic review and meta-analysis underlines the rehabilitation role in the fatigue reduction in patients affected by post-COVID-19 syndrome.

The Effect of Intradialytic Exercise on Fatigue-Related Chronic Kidney Disease: A Case Study of Patient Undergoing Hemodialysis

BACKGROUND: Fatigue is one of the most common problems experienced by chronic kidney disease (CKD) patients undergoing hemodialysis. The application of intradialytic exercises can be the best solutions to overcome fatigue related to CKD.&#x0D; CASE PRESENTATION: A 50-year-old male patient with CKD, who complained of severe fatigue, was selected in case study. The FACIT Fatigue Scale questionnaire and clinical indicators were measured before and after intervention. The intradialytic exercise was administered at 3rd hour of hemodialysis for 4 sessions in 2 weeks. Each session required 30 minutes, containing warming up, main exercise and cooling down. After two weeks intervention, there was an improvement of fatigue score (16 to 29) and reduction of weakness, tiredness, washout feeling, sleepy, and tiredness on eating. Moreover, the clinical indicators showed positive improvement after the intervention.&#x0D; CONCLUSION: Thus, intradialytic exercise is practically promising to minimize fatigue related to CKD among patients undergoing hemodialysis. Hemodialysis nurses or other health care providers could utilize this evidence as a program to reduce the fatigue related to CKD.

Serum 25-hydroxyvitamin D and cancer-related fatigue: associations and effects on depression, anxiety, functional capacity and health-related quality of Life in breast cancer survivors during adjuvant endocrine therapy

BackgroundThe adjuvant treatment with Aromatase Inhibitor (AI) is considered standard of care for postmenopausal breast cancer (BC) women with hormone receptor-positive (HR +), however, it often causes adverse effects such as cancer-related fatigue (CRF). The high prevalence of vitamin D deficiency in postmenopausal women who start adjuvant AI supports the hypothesis that hypovitaminosis D would be one of the biological explanations for toxicity of AI. This study aimed to identify the relationship between 25-hydroxyvitamin D [25(OH)D] and CRF, and to analyze their associations and effects on depression, anxiety, functional disability, muscle/joint aches and HRQL.MethodsThis prospective study included 89 postmenopausal women diagnosed with HR + early BC in adjuvant endocrine therapy with AI. Anthropometric and body composition assessments were performed, as well as dietary assessments by application of 24-h dietary recall, at three time points, totaling 24 months of follow-up. The women completed the Cervantes Scale (CS), Hospital Anxiety and Depression Scale (HADS) and Health Assessment Questionnaire (HAQ). The CRF was determined from the Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-F). The serum 25(OH)D was determined by electrochemiluminescence, with cut-off point above 75 nmol/L adopted as sufficiency. Generalized Linear Model (GLzM) and Generalized Mixed Model (GMM) analysis were used.ResultsAt baseline, 36% (n = 32) of the women presented CRF and 39.3% (n = 35) had 25(OH)D below 75 nmol/L. None of the women reached the Estimated Average Requirements (EAR) of vitamin D. The causality between 25(OH)D and CRF was not significant. Longitudinally, lower levels of 25(OH)D had a negative effect on anxiety (p = 0.020), Menopause and Health (p = 0.033) and Vasomotor scores (p = 0.007). Also, the CRF had a negative effect on anxiety (p = 0.028); depression (p = 0.027); functional disability (p = 0.022); HRQL (p = 0.007); Menopause and Health (p = 0.042), Psychological (p = 0.008) and Couple Relations (p = 0.008) domains; and on Health (p = 0.019) and Aging (p = 0.036) subdomains. Vasomotor subdomain (β = -2.279, p = 0.045) and muscle/joint aches (β = -0.779, p = 0.013) were significant with CRF only at baseline.ConclusionsThis study found negative effect of body adiposity on CRF. Still, the clinical relevance of 25(OH)D and CRF is highlighted, especially that of CRF, considering the consistent impact on several adverse effects reported by BC survivors during adjuvant endocrine therapy.

Generation of evidence supporting the content validity of SF-36, FACIT-F, and LupusQoL, and novel patient-reported symptom items for use in patients with systemic lupus erythematosus (SLE) and SLE with lupus nephritis (LN)

ObjectiveSLE and lupus nephritis (LN) have significant impacts on the health-related quality of life of patients living with the condition, which are important to capture from the patient’s perspective using...

Changes in hemoglobin and clinical outcomes drive improvements in fatigue, quality of life, and physical function in patients with paroxysmal nocturnal hemoglobinuria: post hoc analyses from the phase III PEGASUS study

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, chronic, acquired, hematologic, life-threatening disease characterized by thrombosis, impaired bone marrow function, and complement-mediated hemolysis. The PEGASUS phase III clinical trial demonstrated superiority of pegcetacoplan over eculizumab regarding improvements in hemoglobin levels in patients with suboptimal response to prior eculizumab treatment. The objective of this post hoc analysis was to compare the patient-reported outcome (PRO) response rates observed among PEGASUS participants and the relationships between their PRO scores with clinical and hematological parameters. Data from the 16-week randomized, controlled (1:1 to pegcetacoplan or eculizumab) period of the PEGASUS trial included comparisons of weekly PRO measurements taken using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) scales. A clinically meaningful FACIT-F response was defined as an increase from baseline of ≥5 points. Convergent validity was assessed using conventional threshold correlations between FACIT-F, EORTC QLQ-C30, and laboratory parameters. A clinically meaningful improvement in FACIT-F score was seen in 72.2% of pegcetacoplan-treated patients compared to 22.9% of eculizumab-treated patients. At week 16, the FACIT-F total score correlated with hemoglobin levels (r=0.47, p< 0.0001), absolute reticulocyte count (r=−0.37, p<0.01), and indirect bilirubin levels (r=−0.25, p<0.05). Clinically meaningful improvements in pegcetacoplan-treated patients were also observed for multiple EORTC scales. Fatigue and other self-reported outcomes were correlated with clinically meaningful improvements in clinical and hematological parameters. Clinical trial registration: NCT03500549

Postural balance and its association with functionality and quality of life in non-hospitalized patients with post-acute COVID-19 syndrome.

Background and ObjectivesThe neuromuscular system is responsible for performing adequate muscle activities to maintain postural balance. Since COVID‐19 can cause damage to this system, long‐term sequelae might alter control of postural stability. This study aimed to evaluate the postural balance of patients with post‐acute COVID‐19 syndrome (PCS) who were not hospitalized and to evaluate the correlations of changes in postural balance with general fatigue, muscle strength, and quality of life (QoL).MethodsThis was a cross‐sectional study in which 40 patients with PCS and 40 controls underwent balance assessment through the Berg Balance Scale (BBS) and Tinetti Balance Scale (TBS). They were evaluated for general fatigue by the Functional Assessment of Chronic Illness Therapy‐Fatigue (FACIT‐F) scale, handgrip strength (HGS), and quality of life (QoL) by the Short Form‐36 (SF‐36).ResultsWhen compared to controls, patients with PCS had lower BBS and TBS scores (p = 0.001 for both). The FACIT‐F score was lower in PCS patients (p = 0.0001). HGS was slightly lower in the PCS patients, but not statistically significant (p = 0.09). Regarding QoL, PCS patients showed worse evaluations in five dimensions of the SF‐36 (physical functioning, physical role limitations, bodily pain, general health perceptions, and mental health). Both the BBS and TBS scores had statistically significant positive correlations with the FACIT‐F score, HGS, and two SF‐36 dimensions (physical role limitations and emotional role limitations).ConclusionsPatients with PCS show worse postural balance than controls, which is associated with general fatigue, lower HGS, and poor QoL. Postural balance assessment should be considered in the follow‐up and rehabilitation of PCS.

Efficacy and safety of Janus kinase inhibitors in patients with ankylosing spondylitis: A systematic review and meta-analysis

ObjectivesTo assess the efficacy and safety of janus kinase (JAK) inhibitors in the treatment of ankylosing spondylitis (AS). MethodsWe searched the PubMed and Cochrane Central Register of Controlled Trials to Nov 1, 2021. We included all randomized controlled trials (RCTs) evaluating JAK inhibitors in the treatment of AS. Two reviewers independently selected studies, extracted data and assessed the risk of bias. ResultsFour RCT studies with 779 participants were included in the meta-analysis. Compared with placebo group, percentages of participants achieving responses of Assessment of spondyloarthritis international society(ASAS) 20, ASAS 40, ASAS 5/6, Bath AS disease activity index (BASDAI) 50 were significantly higher in JAK inhibitor group respectively; changes from baseline in AS disease activity score using C-reactive protein(ASDAS-CRP), Maastricht AS enthesitis score (MASES), AS Quality of Life (ASQoL) score, short-form-36 health survey physical component summary (SF-36 PCS) score, BASDAI, Bath AS functional index (BASFI), Bath AS metrology index (BASMI), Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-F) score, SPARCC joint score and Work Productivity and Activity Impairment (WPAI) Overall Work Impairment score showed significant improvements in JAK inhibitor group. The incidence of adverse events (AEs) and severe adverse events (SAEs) showed no significant differences between the JAK inhibitor and placebo groups. ConclusionsJAK inhibitors showed a satisfactory and promising efficacy in the treatment of active AS not only in mitigating disease activity, but also substantially improving patient's physical function, emotional well-being and social participation. The results of this meta-analysis provide solid evidence for JAK inhibitor as a novel therapeutic strategy for patients with active AS.

Fatigue is a systemic extraintestinal disease manifestation largely independent of disease activity, chronicity, and nutritional deficiencies in inflammatory bowel disease on biologics

Background Fatigue is a common symptom reported by patients with chronic immunoinflammatory diseases and with profound negative implications on health-related quality of life. This study aimed to delineate underlying components contributing to fatigue in patients with inflammatory bowel disease (IBD) receiving biologic therapy. Methods Cross-sectional questionnaire study of all patients with IBD receiving any biologic therapy at a tertiary IBD center. Fatigue was assessed by Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F). Disease activity and quality of life were evaluated by generic questionnaires. Principal component analysis (PCA) was used to identify components of variables explaining fatigue. Results Three hundred patients with IBD were included. Moderate-to-severe fatigue defined as FACIT-F ≤ 39 was present in half of the included patients. PCA condensed variables associated with fatigue into three main components contributing to 49% of observed fatigue. The first component, explaining 21% of fatigue, included factors related to disease chronicity, e.g., long disease duration, high number of previously used biologic therapies, presence of previous intestinal surgery, and increasing age. The second component explained 14% of fatigue and comprised disease activity-related aspects, e.g., disease activity indices and C-reactive protein. The third explained 14% of fatigue and comprised various nutritional deficiencies. Conclusion Fatigue can partly be explained by chronicity, disease activity, and nutritional deficits. However, the cause of fatigue is unexplained in approximately half of the patients with IBD supporting that fatigue can be an independent, systemic extraintestinal disease manifestation in IBD.

The impact of tofacitinib on fatigue, sleep, and health-related quality of life in patients with rheumatoid arthritis: a post hoc analysis of data from Phase 3 trials

BackgroundFatigue, a common symptom of rheumatoid arthritis (RA), is detrimental to health-related quality of life (HRQoL). We evaluated the impact of tofacitinib on fatigue, sleep, and HRQoL and explored associations between fatigue, related patient-reported outcomes (PROs), and disease activity in RA patients.MethodsThis post hoc analysis pooled data from three Phase 3 studies of tofacitinib (ORAL Scan; ORAL Standard; ORAL Sync) in RA patients. Patients received tofacitinib 5 or 10 mg twice daily, placebo, or adalimumab (active control; ORAL Standard only, not powered for superiority) with conventional synthetic disease-modifying antirheumatic drugs. Assessed through Month (M)12 were changes from baseline in disease activity, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Medical Outcomes Study Sleep scale (MOS-SS), and Short Form-36 Health Survey (SF-36) composite/domain scores, and proportions of patients reporting improvements from baseline in FACIT-F total and SF-36 domain scores ≥ minimum clinically important differences (MCIDs) or ≥ population normative values. Pearson correlations examined associations among PROs at M6. Treatment comparisons were exploratory, with p < 0.05 considered nominally significant.ResultsGenerally, active treatment led to significant improvements from baseline in FACIT-F total, and MOS-SS and SF-36 composite/domain scores vs placebo, observed by M1 and maintained through M6 (last placebo-controlled time point). Through M6, more patients achieved improvements from baseline ≥ MCID and achieved scores ≥ population normative values in FACIT-F total and SF-36 domain scores with tofacitinib vs placebo. Through M12, some nominally significant improvements with tofacitinib vs adalimumab were observed. With active treatment at M6, FACIT-F scores were moderately (0.40–0.59) to highly (≥ 0.60) correlated with SF-36 composite/domain scores (particularly vitality), moderately correlated with most MOS-SS domain scores, and highly correlated with MOS-SS Sleep Problems Index I scores. Disease activity correlations were moderate with FACIT-F scores and low (0.20–0.39) to moderate with SF-36 general health domain/composite scores.ConclusionTofacitinib and adalimumab generally conferred significant, clinically meaningful improvements in fatigue, sleep, and HRQoL (including vitality) vs placebo through M6, with improvements maintained to M12. M6 correlations between FACIT-F, PROs of sleep, HRQoL, and disease activity underscore the interrelatedness of multiple PROs and disease activity in RA.Trial registrationClinicalTrials.govNCT00847613 (registered: February 19, 2009); NCT00853385 (registered: March 2, 2009); NCT00856544 (registered: March 5, 2009).

Prevalence of self-reported fatigue in intensive care unit survivors 6\xa0months\u20135\xa0years after discharge

Prolonged stays in intensive care units (ICU) are responsible for long-lasting consequences, fatigue being one of the more debilitating. Yet, fatigue prevalence for patients that have experienced ICU stays remains poorly investigated. This study aimed to evaluate fatigue prevalence and the level of physical activity in ICU survivors from 6 months to 5 years after ICU discharge using the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) and Godin questionnaires, respectively. Data from 351 ICU survivors (out of 1583 contacted) showed that 199 (57%) and 152 (43%) were considered as fatigued and non-fatigued, respectively. The median FACIT-F scores for fatigued versus non-fatigued ICU survivors were 21 (14–27) and 45 (41–48), respectively (p < 0.001). Time from discharge had no significant effect on fatigue prevalence (p = 0.30) and fatigued ICU survivors are less active (p < 0.001). In multivariate analysis, the only risk factor of being fatigued that was identified was being female. We reported a high prevalence of fatigue among ICU survivors. Sex was the only independent risk factor of being fatigued, with females being more prone to this symptom. Further studies should consider experimental approaches that help us understand the objective causes of fatigue, and to build targeted fatigue management interventions.

Health-Related Quality of Life in Patients with Inflammatory Bowel Disease in Clinical Remission: What Should We Look For?

Background and Objectives: Inflammatory bowel diseases (IBD) are chronic conditions with an unpredictable evolution that can have a negative impact on patients’ quality of life (QoL). Even though patients in remission have a better QoL compared to patients with active disease, they still have a lower QoL compared to healthy people. The aim of this study is to identify the factors that are associated with a lower QoL in patients with IBD in clinical remission, in a tertiary IBD center in Romania. Materials and Methods: Ninety-seven adult patients with a current diagnosis of IBD for over 3 months who were in clinical remission were enrolled in this study. Pregnant women, patients with ostomy, perianal disease, extraintestinal manifestations or other significant comorbidities were excluded. Out of the 97 patients, 63.9% were men. The median age was 39 years (IQR 29–47), and the median disease duration was 5 years (IQR 2–10). Disease activity was assessed using the SCCAI score for ulcerative colitis and HBI score for Crohn’s disease. Remission was defined for SCCAI score ≤ 1 and HBI score ≤ 4. The health-related quality of life (HR-QoL) was assessed using the IBDQ32 score. FACIT-Fatigue was used to evaluate the level of fatigue. Patients with symptoms of anxiety or depression were identified with the HADS score. Symptoms of anxiety were considered when HADS-A >7 points and symptoms of depression when HADS-D >7 points. Results: Sixty-five patients (67%) were diagnosed with CD and the remaining 32 (33%) with UC. Ninety-three patients (95.9%) were on biological therapy. The mean IBDQ score (total score) was 190.54 points (SD +/− 8.2). The mean FACIT Fatigue score was 42.5 (SD +/− 8.2), with 6.2% of patients suffering from severe fatigue (FACIT Fatigue < 30 points). A total of 33% of patients had symptoms of anxiety and 16.5% of depression. Exposure to more than one biologic therapy (p = 0.02), fatigue (p < 0.001) and symptoms of anxiety (p < 0.001) were associated with a lower HR-QoL in the multivariate analysis. Female patients, patients with Crohn’s disease, patients with anemia and patients with symptoms of depression also had a lower HR-QoL, but this did not reach statistical significance in our study. Conclusions: Exposure to a higher number of biological agents (patients that switched multiple biologics), the presence of fatigue and symptoms of anxiety impair the HR-QoL of patients with IBD in clinical remission. Further studies should assess in a prospective manner whether early identification of these factors with prompt clinical interventions could lead to a better HR-QoL in these patients.

Genetic Variants of the BAFF Gene and Risk of Fatigue Among Patients With Primary Sjögren's Syndrome.

Background/PurposePrimary Sjögren’s Syndrome (SS) is characterized by B lymphocyte hyperactivity with B cell activating factor (BAFF) acting as an important regulator. Single Nucleotide Polymorphisms (SNPs) of the BAFF gene have been implicated in the pathogenesis of several autoimmune diseases characterized by heightened fatigue levels, including primary SS. We aimed to explore potential associations between BAFF SNPs and fatigue status of primary SS patients.MethodsFatigue status was assessed in 199 consecutive primary SS patients (Greek cohort) using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale. Clinical, histological, laboratory, psychometric and personality data were also collected. DNA extracted from peripheral blood of all patients underwent evaluation for the presence of five BAFF SNPs (rs9514827, rs1041569, rs9514828, rs1224141, rs12583006) by PCR. To confirm our findings, an independent replicative cohort of 62 primary SS patients (Dutch cohort) was implemented. Finally, 52 multiple sclerosis (MS) patients were served as disease controls (MS cohort). Analysis of BAFF SNPs in association with fatigue levels was performed by the online platforms SNPStats and SHEsis and the SPSS 26 and Graph Pad Prism 8.00 software.ResultsTT genotype of the rs9514828 BAFF polymorphism was significantly less frequent in the fatigued primary SS patients of the Greek cohort compared to the non-fatigued (14.1% vs 33.3%). The corresponding ORs [95%CI] in the dominant and overdominant models were 0.33 [0.15-0.72], p=0.003 and 0.42 [0.23-0.78], p=0.005 respectively. The association remained significant after adjustment for the variables contributing to fatigue in the univariate analysis (OR [95% CI]: 0.3 [0.1-0.9], p=0.026). Accordingly, in the Dutch cohort, there was a trend of lower mental fatigue among patients carrying the TT rs9514828 BAFF genotype compared to their CC counterparts (4.1 ± 2.4 vs 6.0 ± 2.2 respectively, p=0.06). The rs9514828 BAFF SNP was not significantly associated with fatigue in the MS cohort.ConclusionsWe report a novel association between genetic makeup and primary SS-associated fatigue with the rs9514828 TT genotype decreasing the likelihood of fatigue development among these patients. These findings need validation in multi-center studies.

The effect of secukinumab on patient-reported outcomes in patients with active psoriatic arthritis in a randomised phase 3 trial.

The phase 3 FUTURE 5 trial (NCT02404350) showed the clinical and radiographical efficacy of secukinumab in patients with psoriatic arthritis. This analysis aimed to assess the effect of secukinumab on patient-reported outcomes (PROs). FUTURE 5 was a phase 3, multicentre, parallel-group randomised trial in which patients who were 18 years old or older, met the classification criteria for psoriatic arthritis at screening, and had symptoms of moderate-to-severe psoriatic arthritis for at least 6 months were randomly assigned to receive secukinumab 300 mg, 150 mg, 150 mg no loading dose (NL), or placebo weekly from baseline to week 4 and every 4 weeks thereafter. The prespecified PROs of the FUTURE 5 trial were assessed first in the overall population. We report mean changes from baseline and the proportion of patients reporting improvements equal to or more than the minimum clinically important differences (MCIDs) and scores equal to or more than the normative values for patient global assessments (PtGA) of disease activity; psoriasis and arthritis visual analogue scale (VAS) scores; pain VAS; Health Assessment Questionnaire Disability Index (HAQ-DI); 36-item Short Form Health Survey (SF-36); Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F); and quality of life questionnaires. Patients were then stratified and assessed according to their tumour necrosis factor (TNF) inhibitor status (TNF-naive and TNF-inadequate responder [TNF-IR] populations) as a post-hoc analysis. Patients in all secukinumab groups reported significant least-squares mean changes from placebo at week 16 in all PROs except SF-36 mental component summary (MCS), irrespective of TNF inhibitor use. These included PtGA (300 mg difference vs placebo -12·2 [95% CI -16·3 to -8·1], 150 mg -8·22 [-12·4 to -4·1], 150 mg NL -8·3 [-12·5 to -4·2]; all p<0·0001), pain VAS (300 mg -14·3 [-18·3 to -10·2], 150 mg -11·5 [-15·6 to -7·5], 150 mg NL -11·3 [-15·3 to -7·2]; all p<0·0001), HAQ-DI (300 mg -0·33 [-0·42 to -0·24], 150 mg -0·23 [-0·32 to -0·14], 150 mg NL -0·24 [-0·33 to -0·15]; all p<0·0001), and FACIT-F (300 mg 4·8 [3·2 to 6·4], 150 mg 4·2 [2·6 to 5·8], 150 mg NL 3·5 [1·9 to 5·1]; all p<0·0001). Similarly, the proportion of patients with improvements equal to or better than MCID at week 16 was higher in the secukinumab group compared with the placebo group for most PROs except SF-36 (MCS), regardless of TNF inhibitor use. Secukinumab resulted in early, statistically significant, clinically meaningful, sustained improvements in PROs across all doses compared with placebo in patients with active psoriatic arthritis. These improvements were seen irrespective of previous TNF inhibitor use, in a post-hoc analysis. These results indicate that secukinumab provides comprehensive improvement for patients with psoriatic arthritis, regardless of previous therapy. Novartis.

Clinical meaningfulness of a British Isles Lupus Assessment Group-based Composite Lupus Assessment response in terms of patient-reported outcomes in moderate to severe systemic lupus erythematosus: a post-hoc analysis of the phase 3 TULIP-1 and TULIP-2 trials of anifrolumab

The British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) is a validated global measure of treatment response in systemic lupus erythematosus (SLE) clinical trials but does not include patient-reported outcomes. To evaluate the clinical meaningfulness of a BICLA response from the patient perspective, we aimed to analyse patient-reported outcomes by BICLA responses with anifrolumab or placebo in patients with moderate to severe SLE. We did a post-hoc analysis of pooled data from the phase 3 TULIP-1 (NCT02446912) and TULIP-2 (NCT02446899) trials of anifrolumab, which assessed health-related quality of life using the Short Form 36 Health Survey (SF-36; version 2) and Lupus Quality of Life, fatigue using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), pain using the Numerical Rating Scale, and disease activity using Patient Global Assessment. Changes from baseline and proportions of patients reporting improvements in patient-reported outcomes greater than or equal to the minimum clinically important differences and scores greater than or equal to the normative values were compared in BICLA responders and non-responders and by treatment group (intravenous anifrolumab 300 mg or placebo). 726 patients were included in the TULIP trials, of whom 366 received placebo (184 patients in TULIP-1 and 182 in TULIP-2) and 360 received anifrolumab 300 mg (180 patients in each trial). The mean patient age was 41·8 years (SD 11·9). 674 (93%) patients were female, 52 (7%) were male, and 479 (66%) were White; 283 (39%) were BICLA responders and 443 (61%) were BICLA non-responders. Compared with non-responders, BICLA responders reported greater mean improvements from baseline at week 52 in Patient Global Assessment, SF-36, Lupus Quality of Life, FACIT-F, and pain Numerical Rating Scale scores (all nominal p<0·0053). Compared with non-responders, a greater proportion of BICLA responders reported improvements greater than or equal to the minimum clinically important difference across all SF-36 domains; eg, Physical Component Summary (165 [60%] of 277 for responders vs 63 [15%] of 416 for non-responders), Mental Component Summary (140 [51%] of 276 vs 59 [15%] of 416), and role physical (184 [70%] of 264 vs 76 [19%] of 398); Lupus Quality of Life domains; eg, physical health (151 [58%] of 262 vs 60 [15%] of 396), and intimate relationships (77 [41%] of 187 vs 33 [11%] of 286), and FACIT-F (155 [56%] of 276 vs 66 [15%] of 439). Similarly, a greater proportion of BICLA responders had scores equal to or greater than the normative values across all SF-36 domains and FACIT-F compared with BICLA non-responders at week 52. Patients who received anifrolumab reported greater numerical improvements in Patient Global Assessment, SF-36, Lupus Quality of Life, FACIT-F, and pain Numerical Rating Scale scores than those who received placebo. BICLA responders reported significant and clinically meaningful improvements in Patient Global Assessment, health-related quality of life, fatigue, and pain compared with BICLA non-responders. More patients with moderate to severe SLE who received anifrolumab were BICLA responders and had improved health-related quality of life, fatigue, and pain than those who received placebo. AstraZeneca.

Yunpi Qufeng Chushi Formula for Pre-Rheumatoid Arthritis: Study Protocol for a Multiple-Center, Double-Blind, Placebo-Controlled Randomized Controlled Trial.

Introduction: Rheumatoid arthritis (RA) is an autoimmune disease characterized by progressive bone erosion on diarthrodial joints. RA patients usually experienced three stages before final diagnosis: the health period, the pre-clinical period (immune response exists without clinical symptoms), and the pre-RA period (immune response exists with mild inflammatory manifestation). Presently, there is seldom guidance referring to early intervention which is a benefit for stable disease conditions and low morbidity. Prophylactic treatment is a major feature of traditional Chinese medicine (TCM). In this present study, a multi-center, double-blind, placebo-controlled clinical trial is carried out to evaluate both efficacy and safety in preventing RA progression on Yunpi Qufeng Chushi formula (YQCF). Method: The multi-center, double-blind, placebo-controlled clinical trial is conducted in 13 hospitals nationwide. A total of 390 patients ages between 18 and 70 will be recruited in the trial. They will be randomly assigned to the intervention group (YQCF) and placebo group. The follow-up visit will be taken every 3 months from baseline to 1 year. Diagnosis, disease activity scores, clinical disease activity index (CDAI), simplified disease activity index (SDAI), TCM syndrome scores, and safety assessments will be recorded at every visit. Joint color doppler ultrasound, health assessment questionnaire-disability index (HAQ-DI), and functional assessment of chronic illness therapy-fatigue (FACIT-F) will be recorded at baseline and the last visit. Discussion: This work will provide evidence of YQCF in preventing RA progression. However, whether early intervention would benefit the controlling RA disease still needs a long-term follow-up. Ethics and dissemination: Protocol version 2 (201910-1). This research was approved by the medical ethics committee of Zhejiang Chinese Medical University (2019-045). Results will be published in a peer-reviewed academic journal. Trial registration numbers: http://www.chictr.org.cn/index.aspx, ChiCTR1900024166.

A Prospective Observational Pilot Study of Young Women Undergoing Initial Breast Cancer Treatment and Their Biopsychosocial Profile

Background: Breast cancer in young women can be a major challenge for those affected. To offer support, the establishment of a biopsychosocial profile may be beneficial. Methods: For this prospective observational pilot study, we collected data of 19 women with a mean age of 42.8 ± 5.4 years (30.0-49.0 year) before (T0) and after (T1) initial breast cancer treatment. The handgrip strength (HGS), 6-minute walk test (6MWT), and bioimpedance analysis for the detection of phase angle (PhA) and bioimpedance vector analysis (BIVA) were used. Assessments included the Hospital Anxiety and Depression Scale (HADS), Functional Assessment of Cancer Therapy-Breast (FACT-B), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). Results: Women (age &lt;50 years) with breast cancer showed impaired functional status (HGS, 6MWT, and PhA), abnormal physiologic findings (BIVA), decreased health-related quality of life (HRQoL), and cancer-related fatigue (CRF) after breast cancer diagnosis prior to the onset of cancer treatment with significant deterioration following cancer treatment. This was accompanied by a potentially higher risk of mortality and impaired function due to the prevalence of values below a critical threshold (PhA: T0 = 11%, T1 = 42%; HGS: T0 = 21%, T1 = 32%). In addition, there was evidence of anxiety (47%) and depression (32%) at T0. Conclusion: Routine assessment of biomarkers of physical function, mental health, HRQoL, and CRF may lead to individual risk stratification and multidisciplinary intervention in young patients with breast cancer, which could help to personalize and optimize survivorship care plans.

Evaluation of Physical Activity in Patients With Heart Failure and Its Relationship With Fatigue: A Cross-sectional Study

Background and Objectives: Disability and intolerance to exercise are common in heart failure and can lead to feelings of fatigue in patients and can change patients’ lifestyles; therefore, this study was performed to Evaluation of physical activity in patients with heart failure and its relationship with fatigue. Methods: In this descriptive cross-sectional study, 100 patients with heart failure referred to rehabilitation centers in southeastern Iran were selected by convenience sampling. Data collection tools were RAPA physical activity questionnaire and FACIT fatigue questionnaire. Data were analyzed using Spearman correlation coefficient and regression. Significance was considered 0.05. Results: The results showed that the mean±sd of physical activity was 2.59‌±1.33 and the mean±sd of fatigue in the samples was 20.27±6.11 and the majority of patients had below normal physical activity and fatigue was unfavorable in the majority of them. The total score of physical activity was inversely and significantly correlated with the total score of fatigue. The results showed that 30.6% of the changes in patients ‘fatigue were influenced by variables of drug use, history of heart surgery and the degree of disease and they were predictors of patients’ fatigue. Conclusion: The results of the present study showed that patients who were more physically active had less fatigue. Due to the fact that fatigue is very common in patients with heart failure, it is recommended to take the necessary interventions to increase patients’ knowledge and skills about physical activity, to reduce the fatigue of patients

Patient-reported outcomes of upadacitinib versus abatacept in patients with rheumatoid arthritis and an inadequate response to biologic disease-modifying antirheumatic drugs: 12- and 24-week results of a phase 3 trial

BackgroundIn previous clinical trials, patients with active rheumatoid arthritis (RA) treated with upadacitinib (UPA) have improved patient-reported outcomes (PROs). This post hoc analysis of SELECT-CHOICE, a phase 3 clinical trial, evaluated the impact of UPA vs abatacept (ABA) with background conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) on PROs in patients with RA with inadequate response or intolerance to biologic disease-modifying antirheumatic drugs (bDMARD-IR).MethodsPatients in SELECT-CHOICE received UPA (oral 15 mg/day) or ABA (intravenous). PROs evaluated included Patient Global Assessment of Disease Activity (PtGA) by visual analog scale (VAS), patient’s assessment of pain by VAS, Health Assessment Questionnaire Disability Index (HAQ-DI), morning stiffness duration and severity, 36-Item Short Form Health Survey (SF-36), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Work Productivity and Activity Impairment (WPAI), and EQ-5D 5-Level (EQ-5D-5L) index score. Least squares mean (LSM) changes from baseline to weeks 12 and 24 were based on an analysis of covariance model. Proportions of patients reporting improvements ≥ minimal clinically important differences (MCID) were compared using chi-square tests.ResultsData from 612 patients were analyzed (UPA, n=303; ABA, n=309). Mean age was 56 years and mean disease duration was 12 years. One-third received ≥2 prior bDMARDs and 72% received concomitant methotrexate at baseline. At week 12, UPA- vs ABA-treated patients had significantly greater improvements in PtGA, pain, HAQ-DI, morning stiffness severity, EQ-5D-5L, 2/4 WPAI domains, and 3/8 SF-36 domains and Physical Component Summary (PCS) scores (P<0.05); significant differences persisted at week 24 for HAQ-DI, morning stiffness severity, SF-36 PCS and bodily pain domain, and WPAI activity impairment domain. At week 12, significantly more UPA- vs ABA-treated patients reported improvements ≥MCID in HAQ-DI (74% vs 64%) and SF-36 PCS (79% vs 66%) and 4/8 domain scores (P<0.05).ConclusionsAt week 12, UPA vs ABA treatment elicited greater improvements in key domains of physical functioning, pain, and general health and earlier improvements in HAQ-DI. Overall, more UPA- vs ABA-treated patients achieved ≥MCID in most PROs at all timepoints; however, not all differences were statistically significant. These data, however, highlight the faster response to UPA treatment.Trial registrationNCT03086343, March 22, 2017.

Long-term safety and erythroid response with luspatercept treatment in patients with β-thalassemia.

β-thalassemia is a hereditary blood disorder resulting in ineffective erythropoiesis and anemia. Management of anemia with regular blood transfusions is associated with complications including iron overload. Here, we report long-term safety and efficacy results of the first clinical study of luspatercept in β-thalassemia, initiated in 2013, enrolling adults with both nontransfusion-dependent (NTD) and transfusion-dependent (TD) β-thalassemia. The objective was to report long-term safety data, for up to 5 years of treatment, for 64 patients with TD or NTD β-thalassemia, and long-term efficacy data for a subset of 63 patients with β-thalassemia who received high-dose luspatercept (0.6-1.25 mg/kg): 31 NTD and 32 TD patients. The study was a phase 2, noncontrolled, open-label trial comprising a dose-finding base phase and a 5-year extension phase. Endpoints include safety; erythroid response over a continuous 12-week period [NTD: hemoglobin increase from baseline ⩾1.0 or ⩾1.5 g/dl; TD: red blood cell (RBC) transfusion burden reduction, ⩾20%, ⩾33%, or ⩾50%]; and changes in biomarkers of ineffective erythropoiesis, iron metabolism parameters, Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) scores, and 6-min walking distance. Median duration of luspatercept exposure for NTD and TD patients was 910 days (range, 40-1850) and 433 days (range, 21-1790), respectively. Seventeen of 31 (54.8%) NTD patients achieved a mean hemoglobin increase of ⩾1.5 g/dl and 19 of 32 (59.4%) TD patients achieved ⩾50% reduction in RBC transfusion burden, during any continuous 12-week period. Median cumulative duration of response was 1126 days (range, 127-1790) for NTD patients and 909 days (range, 87-1734) for TD patients. The most common treatment-related adverse events of any grade were bone pain, headache, and myalgia. Long-term assessment of patients with β-thalassemia showed luspatercept was associated with sustained increases in hemoglobin levels in NTD patients and sustained transfusion burden reductions in TD patients. (ClinicalTrials.gov Identifiers: NCT01749540 and NCT02268409). Long-term safety and erythroid response with luspatercept treatment in patients with β-thalassemia Background: β-thalassemia is a genetic blood disorder caused by mutations in the β-globin gene, which encodes one of the proteins that comprise hemoglobin, a key constituent of red blood cells. Patients with β-thalassemia experience anemia, the main treatment for which is blood transfusions. Long-term repeated blood transfusions lower patients' quality of life, use hospital resources, and the resulting accumulation of excess iron can cause organ failure and decrease life expectancy. The severity of the anemia experienced by patients with β-thalassemia varies; patients with transfusion-dependent β-thalassemia require regular blood transfusions, compared with those with nontransfusion-dependent β-thalassemia who require infrequent transfusions, or even none at all, to manage their symptoms. Luspatercept (Reblozyl®) is an agent that stimulates the production of red blood cells and is used to treat anemia caused by β-thalassemia. However, the long-term effects of luspatercept treatment on patients with β-thalassemia are not known.Objective: In this study, we report the long-term safety of luspatercept in 64 adult patients with either transfusion-dependent or nontransfusion-dependent β-thalassemia, and the long-term efficacy of high-dose luspatercept (0.6-1.25 mg/kg) in a subset of 63 patients.Results: The average time period that patients were treated with luspatercept was 910 days for nontransfusion-dependent β-thalassemia and 433 days for transfusion-dependent β-thalassemia. We report that in patients with nontransfusion-dependent β-thalassemia, luspatercept treatment was associated with sustained increases, just over 3 years, in hemoglobin levels. Likewise, in transfusion-dependent β-thalassemia, luspatercept treatment was associated with a sustained reduction, 2.5 years, in the amount of blood transfusion required to manage their anemia. Long-term treatment with luspatercept was not associated with any new side effects compared with previous short-term treatment studies. The most common side effects were headache (27 patients), bone pain (20 patients), and muscle pain (14 patients) with more than 90% of these patients experiencing these side effects as mild severity.Conclusion: The results of this study show that in patients with either transfusion-dependent or nontransfusion-dependent β-thalassemia, luspatercept provides lasting reduction in anemia with mostly mild and predictable side effects.