Assessment Of Chronic Illness Therapy-Fatigue Research Articles

Assessment of fatigue in adult patients with sickle cell disease: Useof the functional assessment of chronic illness therapy-Fatigue (FACIT-fatigue) questionnaire.

Few studies have used validated scales to assess the intensity and determinants of fatigue, a major symptom of sickle cell disease (SCD). We aimed to assess the level of basal fatigue in adult patients with SCD, using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) questionnaire. We prospectively included 102 stable adult outpatients with SCD over 2 months, who answered the FACIT-Fatigue (ranging from 0 (worst imaginable fatigue) to 52 (no fatigue)) and reported on the intensity of fatigue and its impact on quality of life. The cut-off for significant fatigue was <34. The median [IQR] FACIT-Fatigue score was 29 [22-37], indicating moderate-to-severe fatigue. In a multivariate analysis, the FACIT-Fatigue score was significantly associated with female sex, high body mass index, high level of stress, poor sleep quality, and number of previous episodes of acute chest syndrome, but not with the genotype or the haemoglobin level. Most adult patients with SCD experience significant and sometimes intense fatigue; this is probably due to several factors, including disease activity. Fatigue should be evaluated systematically during consultations and in patient education programmes and as an end-point in therapeutic trials.

Enthesitis and Dactylitis Resolution with Risankizumab for Active Psoriatic Arthritis: Integrated Analysis of the Randomized KEEPsAKE 1 and 2 Trials.

The presence (vs absence) of enthesitis/dactylitis is associated with greater psoriatic arthritis (PsA) activity and reduced health-related quality of life. Risankizumab, an interleukin 23 antagonist, demonstrated superior treatment efficacy over placebo in patients with PsA, including enthesitis/dactylitis. Herein, we report the efficacy of risankizumab on complete resolution of enthesitis and/or dactylitis and improvements in patient-reported outcomes in patients with PsA. This integrated post hoc analysis of data from KEEPsAKE 1 and KEEPsAKE 2 included patients with baseline enthesitis (Leeds Enthesitis Index > 0) and/or dactylitis (Leeds Dactylitis Index > 0). Efficacy outcomes at weeks 24 and 52 included proportion of patients achieving enthesitis and/or dactylitis resolution and minimal clinically important differences (MCID) in pain, Health Assessment Questionnaire-Disability Index, and Functional Assessment of Chronic Illness Therapy-Fatigue. Of 1407 patients, approximately 63%, 28%, and 20% had baseline enthesitis, dactylitis, and both enthesitis/dactylitis, respectively. At week 24, higher response rates were observed for risankizumab vs placebo for resolution of enthesitis, dactylitis, and both enthesitis/dactylitis (differences of 13.9%, 16.9%, and 13.3%, respectively; p < 0.05). By week 52, risankizumab treatment resulted in complete resolution of enthesitis, dactylitis, and both enthesitis and dactylitis in 55.0%, 76.1%, and 52.3% of patients; similar resolution rates occurred among patients who switched from placebo to risankizumab. Among risankizumab-treated patients who achieved resolution of enthesitis and/or dactylitis, MCIDs were also attained in patient-reported pain, disability, and fatigue at week 24 (all p < 0.05; except fatigue in patients with resolution of both enthesitis/dactylitis); responses were sustained through week 52. Higher proportions of risankizumab-treated (vs placebo-treated) patients achieved enthesitis and/or dactylitis resolution and meaningful improvements in patient-reported outcomes at week 24 and generally sustained responses at week 52. Thus, risankizumab may result in sustained alleviation of PsA-related pathognomonic musculoskeletal lesions of enthesitis/dactylitis. NCT03675308, and NCT03671148.

Development of a Primary Biliary Cholangitis-specific Version of Chronic Liver Disease Questionnaire: CLDQ-PBC.

Primary biliary cholangitis (PBC) is a chronic liver disease leading to cirrhosis and impairment of patient-reported outcomes (PROs). We aimed to develop a PBC-specific version of the Chronic Liver Disease Questionnaire (CLDQ) instrument to assess health-related quality of life of patients with PBC. From our Liver Database, we included patients with PBC who had CLDQ, clinico-laboratory data, and completed Short Form-36 (SF-36) and The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). The 29 items of CLDQ were subjected to item reduction, exploratory factor analysis, and fed into a standard instrument validation pipeline. Data were available for 108 PBC patients: 57±11 years, 7% male, 58% cirrhosis, 24% decompensated cirrhosis (Child's B and C). Of 29 CLDQ items, none met the exclusion criteria. Exploratory factor analysis (95% of variance) returned 7 factors. Based on evaluation of factor loadings and face validity, those factors yielded 7 domains (Diet, Emotion, Fatigue, Itch, Symptoms, Sleep, Worry). Good to excellent internal consistency (Cronbach's alpha 0.85-0.93) was observed for 5/7 domains. For the remaining two domains (Diet, Itch), additional items obtained from patients, experts and review of the literature were included. For 5 domains, known-groups validity tests discriminated between PBC patients with and without cirrhosis, advanced cirrhosis, depression (p<0.05 for 3-5 domains). The CLDQ-PBC domains were correlated with relevant domains of SF-36, CLDQ-PBC Fatigue correlated with Fatigue Scale of FACIT-F (rho=+0.85) and CLDQ-PBC Worry domain negatively correlated with alkaline phosphatase (rho=-0.38, p=0.0082). The CLDQ-PBC has been developed based on the original CLDQ. The new instrument has evidence for internal consistency and validity, and is being fully validated using an external cohort.

Assessment of the Impact of RNase in Patients With Severe Fatigue Related to Post-Acute Sequelae of SARS-CoV-2 Infection (PASC): A Randomized Phase 2 Trial of RSLV-132.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and RNA debris persist in viral reservoirs for weeks to months following infection, potentially triggering interferon production and chronic inflammation. RSLV-132 is a biologic drug composed of catalytically active human RNase1 fused to human IgG1 Fc and is designed to remain in circulation and digest extracellular RNA. We hypothesized that removal of SARS-CoV-2 viral RNA from latent reservoirs may improve inflammation, neuroinflammation, and fatigue associated with post-acute sequelae of SARS-CoV-2 infection (PASC). This was a phase 2, double-blind, placebo-controlled randomized clinical trial in participants with a 24-week history of PASC and severe fatigue. The primary endpoint of the trial assessed the impact of 6 intravenous doses of RSLV-132 on the mean change from baseline at day 71 in the Patient-Reported Outcomes Measurement Information System Fatigue Short Form 7a (PROMIS Fatigue SF 7a). A statistically significant difference on day 71 was not observed with respect to the primary or secondary endpoints. This was likely due to a placebo response that increased during the trial. Statistically significant improvement in fatigue as measured by the PROMIS Fatigue SF 7a, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), and Physicians Global Assessment (PGA) instruments were observed earlier in the trial, with women demonstrating greater responses to RSLV-132 than men. While fatigue was not statistically significantly improved at Day 71, earlier timepoints revealed statistically significant improvement in fatigue and physician global assessment. The data suggest eliminating latent viral RNA by increasing serum RNase activity may improve fatigue in PASC patients. Women may respond better to this approach than men. Future studies will aim to confirm these findings.

Digital Therapeutic (Mika) Targeting Distress in Patients With Cancer: Results From a Nationwide Waitlist Randomized Controlled Trial.

Distress is highly prevalent among patients with cancer, but supportive care needs often go unmet. Digital therapeutics hold the potential to overcome barriers in cancer care and improve health outcomes. This study conducted a randomized controlled trial to investigate the efficacy of Mika, an app-based digital therapeutic designed to reduce distress across the cancer trajectory. This nationwide waitlist randomized controlled trial in Germany enrolled patients with cancer across all tumor entities diagnosed within the last 5 years. Participants were randomized into the intervention (Mika plus usual care) and control (usual care alone) groups. The participants completed web-based assessments at baseline and at 2, 6, and 12 weeks. The primary outcome was the change in distress from baseline to week 12, as measured by the National Comprehensive Cancer Network Distress Thermometer. Secondary outcomes included depression, anxiety (Hospital Anxiety and Depression Scale), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue), and quality of life (Clinical Global Impression-Improvement Scale). Intention-to-treat and per-protocol analyses were performed. Analyses of covariance were used to test for outcome changes over time between the groups, controlling for baseline. A total of 218 patients (intervention: n=99 and control: n=119) were included in the intention-to-treat analysis. Compared with the control group, the intervention group reported greater reductions in distress (P=.03; ηp²=0.02), depression (P<.001; ηp²=0.07), anxiety (P=.03; ηp²=0.02), and fatigue (P=.04; ηp²=0.02). Per-protocol analyses revealed more pronounced treatment effects, with the exception of fatigue. No group difference was found for quality of life. Mika effectively diminished distress in patients with cancer. As a digital therapeutic solution, Mika offers accessible, tailored psychosocial and self-management support to address the unmet needs in cancer care. German Clinical Trials Register (DRKS) DRKS00026038; https://drks.de/search/en/trial/DRKS00026038.

5-EPIFAT trial protocol: a multi-center, randomized, placebo-controlled trial of the efficacy of pharmacotherapy for fatigue using methylphenidate, bupropion, ginseng, and amantadine in advanced cancer patients on active treatment

BackgroundCancer-related fatigue (CRF) is still undertreated in most patients, as evidence for pharmacological treatments is limited and conflicting. Also, the efficacy of the pharmacological agents relative to each other is still unclear. Therefore, medications that may potentially contribute to improving CRF will be investigated in this head-to-head trial. Our main objective is to compare the efficacy of methylphenidate vs. bupropion vs. ginseng vs. amantadine vs. placebo in patients with advanced cancer.MethodsThe 5-EPIFAT study is a 5-arm, randomized, multi-blind, placebo-controlled, multicenter trial that will use a parallel-group design with an equal allocation ratio comparing the efficacy and safety of four medications (Methylphenidate vs. Bupropion vs. Ginseng vs. Amantadine) versus placebo for management of CRF. We will recruit 255 adult patients with advanced cancer who experience fatigue intensity ≥ 4 based on a 0–10 scale. The study period includes a 4-week intervention and a 4-week follow-up with repeated measurements over time. The primary outcome is the cancer-related fatigue level over time, which will be measured by the functional assessment of chronic illness therapy-fatigue (FACIT-F) scale. To evaluate safety, the secondary outcome is the symptomatic adverse events, which will be assessed using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events in cancer clinical trials (PRO-CTCAE). Also, a subgroup analysis based on a decision tree-based machine learning algorithm will be employed for the clinical prediction of different agents in homogeneous subgroups.DiscussionThe findings of the 5-EPIFAT trial could be helpful to guide clinical decision-making, personalization treatment approach, design of future trials, as well as the development of CRF management guidelines.Trial registrationIRCT.ir IRCT20150302021307N6. Registered on 13 May 2023.

Efficacy and safety of tofacitinib for chronic plaque psoriasis and psoriatic arthritis: a systematic review and meta-analysis of randomized controlled trials.

To summarize and analyze the results of published randomized controlled trials of tofacitinib for the treatment of chronic plaque psoriasis and psoriatic arthritis(PsA) and discuss its efficacy and safety. An exhaustive systematic search encompassing PubMed, Cochrane, Embase, and Web of Science databases was conducted up to July 2023. Studies eligible for inclusion were analyzed, organized using Review Manager version 5.4.1 (Cochrane Collaboration, Oxford, UK) and STATA 15.0 version (Stata Corp, College Station, TX, USA) software. A total of six articles, covering 1393 patients (844 treated with tofacitinib and 549 with placebo), were included. The foundational characteristics of tofacitinib and placebo group showed similarity, except for age and Dermatology Life Quality Index (DLQI) score, especially in the context of chronic plaque psoriasis. It is noteworthy that we discovered tofacitinib exhibited a significant impact on Psoriasis Area and Severity Index 75 (PASI75) response, Physician's Global Assessment (PGA) response, and adverse events (AEs) in cases of chronic plaque psoriasis. Similarly, tofacitinib demonstrated substantial influence on American College of Rheumatology 20/50 (ACR20/50) response, PASI75 response, as well as alterations in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score, Health Assessment Questionnaire-Disability Index (HAQ-DI) Score, Dactylitis Severity Score (DSS), and Leeds Enthesitis Index (LEI) Score in the context of psoriatic arthritis (PsA). Nevertheless, there was no statistically significant impact of tofacitinib on serious adverse events (SAEs) in chronic plaque psoriasis, as well as on both adverse events (AEs) and SAEs in psoriatic arthritis (PsA). A comprehensive analysis revealed that tofacitinib has a positive effect on addressing skin and joint symptoms, as well as improving the quality of life for patients with chronic plaque psoriasis and psoriatic arthritis (PsA). However, the safety of the drug's long-term usage even requires further validation. Key Points • In 6 analyses involving a total of 1393 patients, tofacitinib exhibits positive effect on the treatment of both chronic plaque psoriasis and psoriatic arthritis (PsA). • Although dose-based subgroup analyses have demonstrated effectiveness. Some studies indicate that the 5-mg dose (twice daily) may not show an effect due to the failure of non-inferiority trials comparing tofacitinib with placebo. Therefore, caution is required when interpreting its effectiveness. On the other hand, the 10-mg dose (BID) has been associated with an increase in adverse events and serious adverse events,and is recommended to be used with caution in patients with cardiovascular or uveitis risk factors. • Tofacitinib has efficacy in comorbid psychiatric disorders (depression, anxiety, or Alzheimer's disease) and inflammatory bowel disease (ulcerative colitis), but patients with comorbid renal insufficiency, hepatic dysfunction, osteoporosis, cardiovascular disease, or uveitis may need to be moderated or avoided with tofacitinib.

Association between enthesitis/dactylitis resolution and patient-reported outcomes in guselkumab-treated patients with psoriatic arthritis

ObjectivesTo evaluate the association between enthesitis resolution (ER) and dactylitis resolution (DR) and meaningful improvements in patient-reported outcomes (PROs) among biologic-naïve patients with PsA receiving guselkumab in the DISCOVER-2 study.MethodsEnthesitis and dactylitis, characteristic lesions of PsA, were evaluated by independent assessors using the Leeds Enthesitis Index (range, 0–6) and Dactylitis Severity Score (range, 0–60). Proportions of patients with ER or DR (score = 0) among those with score > 0 at baseline were determined at weeks 24, 52, and 100. PROs included: fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-Fatigue]), pain (0–100 visual analog scale), physical function (Health Assessment Questionnaire-Disability Index [HAQ-DI]), and health-related quality of life (36-item Short-Form Health Survey physical/mental component summary [SF-36 PCS/MCS]). Meaningful responses were defined as: improvements of ≥ 4 for FACIT-Fatigue, ≥ 0.35 for HAQ-DI, and ≥ 5 for SF-36 PCS/MCS and absolute scores of ≤ 15 for minimal pain and ≤ 0.5 for normalized HAQ-DI. Associations between ER/DR status and PRO response status were tested using a Chi-square test.ResultsGuselkumab-treated patients with ER were more likely than those without ER to achieve minimal pain (p < 0.001), normalized HAQ-DI (p < 0.001), and PCS response (p < 0.05) at weeks 24, 52, and 100. Patients with DR were more likely than those without DR to achieve FACIT-Fatigue response at week 24 and week 52 (both p ≤ 0.01) and minimal pain at week 24 and normalized HAQ-DI at week 52 (both p ≤ 0.03).ConclusionIn biologic-naïve patients with active PsA treated with guselkumab, achieving ER or DR was associated with durable improvements in selected PROs, including those of high importance to patients.Trial registrationClinicalTrials.gov (https://clinicaltrials.gov) NCT03158285; Registered: May 16, 2017.Key Points• At week 100, 65% and 76% of guselkumab-treated patients achieved enthesitis and dactylitis resolution (ER/DR).• Achieving ER was associated with achieving DR and vice versa through the end of study.• Achieving ER or DR was associated with durable and meaningful improvements in selected patient-reported outcomes.

Efficacy and Safety of Risankizumab in Patients with Psoriatic Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Currently, the cause of psoriatic arthritis (PsA) is unknown, and the effectiveness of current drug treatments is unsatisfactory. In March 2019, the US Food and Drug Administration (FDA) approved risankizumab, a humanized immunoglobulinG1 (IgG1) monoclonal antibody targeting the p19 subunit of interleukin (IL)-23, for the treatment of PsA in adults. This study aimed to conduct a meta-analysis of double-blind, randomized, placebo-controlled trials to evaluate the effectiveness and safety of risankizumab in moderate-to-severe PsA. We conducted a thorough search of relevant databases from the establishment of the databases to October 1, 2023. We conducted a meta-analysis using Stata 12.0 and utilized I2 and Egger tests to assess heterogeneity and publication bias among the studies. Bias assessment was performed using the risk bias map and bias risk summary diagram generated by Revman5.4 software. The review protocols were registered on PROSPERO (CRD42023451894) and adhered to the preferred reporting item of system evaluation (PRISMA) guideline. Six randomized controlled trials (RCTs) involving 5038 patients with PsA treated with either risankizumab or placebo were included in the analysis. At 24weeks, the risankizumab group demonstrated a significantly higher American College of Rheumatology-20 (ACR20) response rate compared to the placebo group (RR1.760, 95%CI 1.568-1.977, P < 0.001). Additionally, the risankizumab group showed a significantly higher Minimal Disease Activity (MDA) response rate compared to the placebo group (RR1.827, 95%CI 1.048-3.184, P < 0.05). The risankizumab group also exhibited improvement in Short Form 36 Questionnaire (SF-36) score (SMD 0.51, 95%CI 0.33-0.69, P < 0.001), with significantly lower Health Assessment Questionnaire Disability Index (HAQ-DI) score (SMD - 0.27, 95%CI - 0.37 to - 0.17, P < 0.001) and higher Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score (SMD 0.27, 95%CI 0.20-0.35, P < 0.001) compared to the placebo group. Moreover, the risankizumab group had a significantly lower Psoriasis Area and Severity Index (PASI) score (SMD - 6.12, 95%CI - 10.02 to 2.23, P < 0.001). A study by Mease et al. indicated that patients receiving risankizumab generally demonstrated numerical improvements in the Leeds Enthesitis Index (LEI), although the small sample size limits the evidence. Further research is necessary to provide evidence-based guidelines. There were no significant differences in the incidence of serious adverse events (SAE) and serious treatment-emergent adverse events (STEAE) between the risankizumab and placebo groups (RR0.76, 95%CI 0.45-1.28, P = 0.31; RR0.99, 95%CI 0.49-1.99, P = 0.97, respectively), and the overall incidence of adverse events (AE) was not comparable (RR1.10, 95%CI 0.63-1.94, P = 0.73). Risankizumab showed superior efficacy across multiple outcome measures compared to placebo, with no significant increase in adverse events. Our findings endorse risankizumab as an excellent treatment option for PsA, offering valuable insights for clinicians and patients when choosing appropriate therapeutic interventions. Retrospectively registered (CRD42023451894, 16 August 2023).

P862 Effects of induction and maintenance therapy with risankizumab on health-related quality of life outcomes in patients with moderately to severely active ulcerative colitis: A post-hoc analysis of Phase 2b/3 trials

Abstract Background Ulcerative colitis (UC) has a detrimental impact on patients’ health-related quality of life (HRQoL).1 Long-term treatment goals for patients with moderately to severely active UC include restoration of HRQoL. This post-hoc analysis evaluated the effect of induction and maintenance treatment with risankizumab (RZB) on HRQoL outcomes. Methods Data from two Phase 2b/3 clinical trials (INSPIRE induction: NCT03398148 and COMMAND maintenance: NCT03398135) were evaluated. Patients received RZB 1200 mg intravenous (IV) or placebo (PBO) induction treatment at weeks 0, 4, and 8. Patients with a clinical response per Adapted Mayo score to RZB IV were randomised 1:1:1 to subcutaneous (SC) RZB 180 or 360 mg, or placebo (PBO [RZB withdrawal] SC) every 8 weeks for 52 weeks of maintenance. The proportion of patients achieving a meaningful within-person change (MWPC) for each HRQoL outcome was reported. HRQoL outcomes included Functional Assessment of Chronic Illness Therapy-Fatigue, disease-specific instruments such as Inflammatory Bowel Disease Questionnaire (IBDQ) and Ulcerative Colitis Symptom Questionnaire (UCSQ), as well as generic quality-of-life questionnaires like Work Productivity and Activity Index-Ulcerative Colitis (WPAI-UC), 36-Item Short-Form Survey (SF-36), and EuroQoL 5 Dimensions 5 Levels. MWPCs were measured from baseline to induction Week 12 and to maintenance Week 52. Estimated differences in proportions with 95% confidence intervals and p-values between RZB and PBO were compared using the Cochran-Mantel-Haenszel test adjusting for baseline strata. Results For RZB 1200 mg IV (n=650) versus PBO IV-treated (n=325) patients, a greater proportion of patients achieved MWPC across all HRQoL outcomes at Week 12 of induction (p&amp;lt;0.01; Table). At Week 52 of maintenance, a greater proportion of patients treated with RZB 180 mg SC (N=179) versus PBO (withdrawal) SC (N=183) achieved MWPC across all HRQoL outcomes (p&amp;lt;0.05), except for absenteeism from WPAI-UC (p=0.33). For RZB 360 mg SC (N=186) versus PBO (withdrawal) SC, a greater proportion of patients achieved MWPC for UCSQ, IBDQ, and SF-36 physical component summary (all p&amp;lt;0.05). Conclusion In this analysis, a greater proportion of patients treated with RZB versus PBO achieved MWPC on various HRQoL outcomes after completing 12-week induction IV therapy. HRQoL improvements were sustained up to Week 52 of treatment. This suggests RZB has the potential to help patients achieve restoration of HRQoL as a long-term goal of treatment in patients with moderately to severely active UC. 1. Mavroudis G. Therap Adv Gastroenterol. 2022;15:17562848211062406.

OP12 Mirikizumab improves fatigue, bowel urgency, and quality of life in patients with moderately to severely active Crohn’s Disease: Results from a phase 3 clinical trial

Abstract Background Mirikizumab (miri), an anti-IL-23p19 antibody, is approved for the treatment of ulcerative colitis and under development for Crohn’s disease (CD). We investigated how miri impacted fatigue, bowel urgency, and health-related quality of life (HRQoL) through 52 weeks in patients with moderately to severely active CD in the Phase 3 VIVID-1 study. Methods In the treat-through VIVID-1 (NCT03926130) study, patients (N=1065) with moderately to severely active CD and a Simple Endoscopic Score for CD (SES-CD) score ≥7 (or ≥4 for patients with isolated ileal disease) and failure to biologic and/or conventional therapy were randomized in a 6:3:2 ratio to receive miri (N=579) (a single 900mg intravenous (IV) dose at W0, W4, and W8 followed by a subcutaneous (SC) dose of 300 mg at W12 and then every 4 weeks), ustekinumab (N=287) (6mg/kg IV at W0 and SC dose of 90mg at W8 and then every 8 weeks), or PBO (N=199). At W12 PBO responders continued PBO to W52; PBO-non-responders received the same blinded miri regimen as described above. This analysis focuses on results in patients randomized to either miri or PBO. The change from baseline for Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Urgency Numeric Rating Scale (UNRS), and Inflammatory Bowel Disease Questionnaire (IBDQ) total and domain scores (bowel symptoms, systemic symptoms, emotional function, social function) were analyzed through W52. IBDQ response (≥16-point improvement from baseline) and remission (total score ≥ 170) rates were also analyzed at W12 and W52. For binary variables, adjusted risk differences were compared between miri and PBO using the Cochran-Mantel-Haenszel (CMH) test. For continuous variables, least squares mean changes from baseline were compared between treatment groups using ANCOVA. Results Significant improvement in mean change from baseline to W12 and W52 were observed with miri for FACIT-F, UNRS, and IBDQ total and domain scores (all p&amp;lt;0.000001 at W52) (Figure 1&amp;2). Miri-treated patients showed improved UNRS scores versus PBO as early as W8 with statistical significance sustained to W52 (Figure 1B). At W12 and W52, a greater percentage of miri-treated patients achieved IBDQ response (W12: p&amp;lt;0.000001; W52: p&amp;lt;0.000001) and remission (W12: p&amp;lt;0.000001; W52: p&amp;lt;0.000001) compared to PBO (Figure 2A&amp;B). Conclusion Treatment with miri resulted in improvements in fatigue, bowel urgency, and HRQoL at W12 and W52 in patients with moderately to severely active CD.

P194 Health-related quality of life and fatigue in newly-diagnosed inflammatory bowel diseases: findings from a prospective population-based inception cohort, IBD Prognosis Study

Abstract Background Patients with inflammatory bowel diseases (IBD) often experience impaired quality of life (QoL) and fatigue. In the current study, we aimed to investigate QoL and fatigue at the time of IBD diagnosis and determine their association with the disease presentation. Methods Incident adult patients (≥18 years old) with newly diagnosed ulcerative colitis (UC) or Crohn’s disease (CD) according to the Copenhagen IBD Criteria were included in the IBD Prognosis Study, a prospective, population-based, inception cohort representing approximately 20% of the Danish population (1.1 million). QoL was assessed using EQ-5D-5L and Short inflammatory Bowel Disease Questionnaires (SIBDQ), while fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale. A severe disease presentation was defined by the need for glucocorticoids, immunomodulators, biologics, or surgery within three months of disease. Multivariable logistical regression analyses were conducted by adjusting for gender, age, and disease phenotype. Results Out of the original cohort, 203 (65.9%) and 116 (57.7%) patients with incident UC and CD, respectively, responded to the questionnaires without differences between responders and non-responders. The mean EQ-5D-5L index values were significantly lower in patients with UC (0.82, SD 0.17) and CD (0.79, SD 0.23), compared to the Danish background population (both p&amp;lt;0.001). The difference between UC and CD was also statistically significant (p&amp;lt;0.001). Further, more than every third of patients reported severely reduced SIBDQ (UC 29.6%, CD 43.1%, p=0.04). Severe fatigue was experienced frequently at the diagnosis (UC 26.1%, CD 30.2%, p=0.43), and was more common compared to the control group (means: UC 37.2 (SD 12.0), CD 35.3 (SD 11.5), control group: p&amp;lt;0.001). Female gender and extensive UC were independently associated with severely impaired SIBDQ and fatigue in patients with UC, while EIMs were associated with both outcomes in UC and CD (Table 1). Finally, severely reduced SIBDQ and severe fatigue were independently associated with a severe disease presentation, as well as IBD-related hospitalization specifically, in both UC and CD (Figure 1). Conclusion In this prospective population-based inception cohort of newly diagnosed IBD, we found a high proportion of patients with severely impaired generic QoL, SIBDQ, and fatigue compared to healthy controls. This study emphasizes the importance of addressing these negative symptoms in patients with IBD and their prognostic impact on the disease presentation. Ref: 1. Jensen MB et al., Scand J Public Health. 2023. doi: 10.1177/14034948211058060. 2. Montan I et al., Value Health. 2018. doi: 10.1016/j.jval.2018.03.013.

Meaningful score changes for SF-36v2, FACIT-fatigue, and RASIQ in rheumatoid arthritis

BackgroundInterpretation thresholds for patient-reported outcome (PRO) scores are of crucial importance, particularly when interpreting treatment benefit. This study was designed to determine the within-patient meaningful improvement (WPMI) thresholds for the Short-Form 36 Health Survey version 2 (SF-36v2), the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), and the novel Rheumatoid Arthritis Symptoms and Impact Questionnaire (RASIQ) among patients with rheumatoid arthritis (RA).MethodsIn this post-hoc analysis, anchor-based and supportive distribution-based methods were used to derive WPMI based on blinded data from all treatment arms in two Phase 2 RA trials with otilimab. Patient’s Global Assessment of Disease Activity (PtGA) was the general anchor for all SF-36v2 scales. SF-36 Patient’s Global Impression of Status (PGIS), PtGA, and VT03 (an SF-36v2 item) were used as anchors for FACIT-Fatigue. SF-36 PGIS, PtGA, and Patient’s Assessment of Arthritis Pain (PAIN) were anchors for RASIQ. Mean change was calculated for the anchor category associated with minimal meaningful improvement from baseline to Week 24 for SF-36v2 and FACIT-Fatigue, and to Week 12 for RASIQ. Sensitivity and specificity were used to evaluate the accuracy of estimated WPMI values.ResultsFor the SF-36v2 physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health domains, anchor-based estimates of WPMI based on 0–100 scores were 24.5, 24.5, 25.4, 13.6, 21.5, 20.5, 16.9, and 14.3, respectively. Anchor-based WPMI estimates were 9.7 for the Physical Component Summary score and 7.6 for the Mental Component Summary score (using norm-based T-score metric). For FACIT-Fatigue (range 0–52), WPMI estimates ranged from 9.7 to 11.3 points. For RASIQ (range 0–100), anchor-based WPMI was determined as a change between -32.7 and -21.7 points for the Joint Pain scale, -26.7 to -23.7 for the Joint Stiffness scale, and -21.1 to -17.4 for the Impact scale.ConclusionsThis study derived WPMI thresholds for SF-36v2, FACIT-Fatigue, and RASIQ among patients with RA, using multiple anchors. Derivation of WPMI thresholds for these PRO instruments will enable their broader use in evaluating and interpreting treatment benefit in future RA studies.

Bitter ginger (Zingiber zerumbet) for patients with solid tumors with no treatment options: A pilot clinical study

IntroductionZerumbone is a natural compound found in bitter ginger plants (Zingiber zerumbet) that shows antiproliferative, antioxidant, anti-inflammatory, and analgesic properties. We aimed to investigate the role of zerumbone in improving the quality of life and symptom control in cancer patients with no treatment options. MethodsWe conducted a pilot, non-randomized, single-center, open prospective, and systematic study on the use of 400 mg of zerumbone twice a day. ResultsThe study included 35 patients (mean age, 68 years; 64% men), of which 16 completed the eight-week study. The intention-to-treat population showed no significant changes in weight or sleep quality over the eight-week study. Assessments performed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) showed significant improvements in the quality of life in the global (p = 0.072), activity (p = 0.0393), social (p = 0.0001), and emotional (p = 0.0023) dimensions. The Hospital Anxiety and Depression Scale (HADS) questionnaire scores showed significant improvement in anxiety (p = 0.032) and depression (p = 0.021), while the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire scores also indicated a significant improvement (p = 0.001). Bitter ginger showed low toxicity. ConclusionsBitter ginger showed promising results in improving the quality of life and reducing symptoms of anxiety and depression in the study population. A randomized placebo-controlled study is necessary to confirm these results.This trial was registered under the number FMABC: CAAE – 93459418.00000082, at ISRCTN (BIOMED CENTRAL) NUMBER 4388 (03/07/23) and at Plataforma Brasil (https://plataformabrasil.saude.gov.br/login.jsf)

Fatigue Assessment Using FACIT-F Scale in Spondyloarthropathy Patients and its Correlation with BASDAI and BASFI Scores.

To measure fatigue in axial spondyloarthropathy patients and find its correlation with the disease activity measures. Cross-sectional, descriptive study. Place and Duration of the Study: Rheumatology Unit, Federal Government Polyclinic Hospital, from November 2021 to May 2022. This study included 45 patients fulfilling the ASAS criteria for spondyloarthropathy. Bathankylosing spondylitis disease activity (BASDAI), Bath ankylosing spondylitis functional index (BASFI), and functional assessment of chronic illness therapy- fatigue (FACIT-F) scores were measured for each patient. In this study, there were 9 (20%) female patients and 36 (80%) male patients. There were 39 (86.7%) patients who had ankylosing spondylitis, 4 (8.9%) had axial spondyloarthropathy with peripheral arthritis and 2 (4.4%) had enthesitis-related juvenile idiopathic arthritis. The mean duration of the disease was 5.45 ± 4.19 years. Active disease with a BASDAI score of ≥4 was found in 16 (35.6%) patients while 29 (64.4%) had a BASDAI score <4. Severe fatigue with a FACIT-F score of <30 was found in 31 (68.9%) of the patients while less fatigue with FACIT-F score >30 was found in 14 (31.1%). The mean BASFI score of the cohort was 3.23 ± 2.01. Spearman's rho correlation analysis showed a significant strong correlation between the FACIT-F score, BASDAI and BASFI scores (p<0.001). Patients with active disease and higher BASFI scores had a lower FACIT-F score suggesting more fatigue, thus correlating with the disease activity. Bath ankylosing spondylitis disease activity (BASDAI), Functional assessment of chronic illness therapy-fatigue (FACIT-F), Ankylosing spondylitis (AS), Bath ankylosing spondylitis functional index (BASFI), Assessment in ankylosing spondylitis (ASAS).

SLEEP quality in patients with psoriatic arthritis and its relationship with disease activity and comorbidities: a cross-sectional study

The assessment of psoriatic arthritis is complex and multidimensional. It is increasingly common to include the patient perspective using patient-reported outcomes. Although some research has explored sleep quality in patients with psoriatic arthritis, most studies have had small sample sizes, failed to assess sleep quality considering the inflammatory process together with the psychological well-being of patients, and have not described any use of sleep medication. Further, research to date has not provided data on the relationship of sleep quality with axial forms. In this context, the objective of this study was to assess sleep quality in patients with psoriatic arthritis and its relationship with clinical characteristics, disease activity, functioning, disease impact, fatigue and psychological status. A cross-sectional study was conducted including 247 consecutive patients with PsA recruited during 2021. Sleep quality was measured using the Pittsburgh Sleep Quality Index. We assessed correlations of Pittsburgh Sleep Quality Index score with peripheral disease activity (Disease Activity Index for PSoriatic Arthritis), axial disease activity (Ankylosing Spondylitis Disease Activity Score-C-reactive protein and Bath Ankylosing Spondylitis Disease Activity Index), functioning (Bath Ankylosing Spondylitis Functional Index and Health Assessment Questionnaire), impact (Psoriatic Arthritis Impact of Disease questionnaire), anxiety, depression (Hospital Anxiety and Depression Scale) and fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) scores. A multiple linear regression model was constructed with PSQI as the dependent variable and as independent variables those that could influence sleep quality. Nearly two-thirds (63.15%) of patients had poor sleep quality. Poorer sleep quality was associated with being female, higher joint counts, greater peripheral and axial disease activity, fatigue, anxiety and depression, functioning and disease impact (p < 0.001). Multiple linear regression analysis found that pain (β: 0.3; p < 0.007) and fatigue β: − 0.1; p < 0.001 contributed 40% to the sleep quality model. Poor sleep quality was common among patients with psoriatic arthritis. Emotional factors (fatigue, anxiety) seemed more important than inflammatory factors in sleep quality.

Biopsychosocial Late Effects After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Metastases from Colorectal and Appendiceal Cancer: A National Prospective Cohort Study.

Colorectal cancer with peritoneal metastases can be treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Treatment may result in biopsychosocial late effects (LEs). We explored the frequency and severity of the following biopsychosocial LEs: anxiety, depression, fear of cancer recurrence (FCR), insomnia, fatigue, cognitive impairment, and pain, and evaluated their impact on quality of life (QoL). This was a national prospective cohort study screening for LEs during the period January 2021-May 2023. Patients completed the following questionnaires: General Anxiety Disorder-7, Patient Health Questionnaire-9, FCR Inventory-Short Form, Insomnia Severity Index, Functional Assessment of Chronic Illness Therapy-Fatigue, cognitive impairment (six items from the European Organisation for Research and Treatment of Cancer Item Library), and the Rectal Cancer Pain Score. Preregistration was completed at ClinicalTrials.gov (NCT04956107). In total, 99 patients were included. The mean age was 61 years and 57% were women. At 3 months after surgery, the frequent LEs were fatigue (72%), FCR (58%), and pain (48%), and at 12 months after surgery, the frequent LEs were FCR (65%), fatigue (40%), and insomnia (33%). More than half of the patients (54%) reported at least two LEs after 12 months. Patients with moderate-to-severe LEs reported a lower QoL than patients with no/mild LEs. Patients with no/mild LEs had a similar QoL as the Danishnorm population. Biopsychosocial LEs were prevalent. The QoL of patients reporting LEs in the worst severity categories was negatively impacted. Screening and treatment for these LEs should be a focus in cancer survivor follow-up.

Which breathlessness dimensions associate most strongly with fatigue?-The population-based VASCOL study of elderly men.

Breathlessness and fatigue are common symptoms in older people. We aimed to evaluate how different breathlessness dimensions (overall intensity, unpleasantness, sensory descriptors, emotional responses) were associated with fatigue in elderly men. This was a cross-sectional analysis of the population-based VAScular disease and Chronic Obstructive Lung Disease (VASCOL) study of 73-year old men. Breathlessness dimensions were assessed using the Dyspnoea-12 (D-12), Multidimensional Dyspnoea Profile (MDP), and the modified Medical Research Council (mMRC) scale. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire. Clinically relevant fatigue was defined as FACIT-F≤ 30 units. Scores were compared standardized as z-scores and analysed using linear regression, adjusted for body mass index, smoking, depression, cancer, sleep apnoea, prior cardiac surgery, respiratory and cardiovascular disease. Of 677 participants, 11.7% had clinically relevant fatigue. Higher breathlessness scores were associated with having worse fatigue; for D-12 total, -0.35 ([95% CI] -0.41 to -0.30) and for MDP A1, -0.24 (-0.30 to -0.18). Associations were similar across all the evaluated breathlessness dimensions even when adjusting for the potential confounders. Breathlessness assessed using D-12 and MDP was associated with worse fatigue in elderly men, similarly across different breathlessness dimensions.

Assessment and personalised advice for fatigue in systemic lupus erythematosus using an innovative digital tool: the Lupus Expert system for the Assessment of Fatigue (LEAF) study

BackgroundFatigue is reported as the most prevalent symptom by patients with systemic lupus erythematosus (SLE). Fatigue management is complex due to its multifactorial nature. The aim of the study was...

Patient-Reported Outcomes: Danicopan As Add-on Therapy to Ravulizumab or Eculizumab Versus Placebo in Patients with Paroxysmal Nocturnal Hemoglobinuria and Clinically Significant Extravascular Hemolysis

Background Treatment with complement C5 inhibitors eculizumab (Ecu) and ravulizumab (Rav) inhibits terminal complement activity, improving hemoglobin (Hgb) levels and clinical outcomes for patients (pts) with paroxysmal nocturnal hemoglobinuria (PNH), including reduced morbidity and mortality by preventing intravascular hemolysis (IVH), thrombotic events, hospitalizations, and death. In an analysis using data from the International PNH Registry (NCT01374360), Ecu improved pt survival through 20 y of real-world follow-up. Rav demonstrated a 98.4% survival rate up to 6 y in an open-label study (NCT03056040). Approximately 10-20% of pts experienced ongoing anemia caused by clinically significant extravascular hemolysis (cs-EVH). The phase 3, international, randomized, double-blind, placebo (Pbo)-controlled ALPHA (NCT04469465) superiority clinical trial assessed the effectiveness and safety of danicopan (Dan) add-on therapy to Rav or Ecu in pts with PNH and cs-EVH. This current analysis examined patient-reported outcomes (PROs) through wk 24. Methods Pts (≥18 y) with PNH and cs-EVH (Hgb ≤9.5 g/dL; absolute reticulocyte count ≥120×10 9/L) on Rav/Ecu &amp;gt;6 mo were randomized 2:1 to Dan or Pbo add-on therapy to Rav/Ecu for 12 wks (treatment period [TP] 1). At wk 12, Pbo arm pts switched to Dan (Pbo-Dan) and Dan arm pts continued treatment (Dan-Dan) for another 12 wks (TP2). The initial Dan dose of 150 mg TID could be escalated to 200 mg TID based on clinical response at investigator's discretion. Endpoints included change from baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) score to wks 12 and 24 (key secondary) and changes in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Scale (EORTC-QLQ-C30) global health status/QoL and physical functioning subscales and fatigue, nausea/vomiting, appetite loss, constipation, and diarrhea symptom subscales, and EuroQoL-5-Dimensions, 3-level version (EQ-5D-3L) to wk 24 (exploratory). Results As of 20 September 2022, 86 pts were randomized; 60 had completed (n=60) TP2 (Dan n=40; Pbo n=20). Baseline characteristics were similar between arms. The study met its primary endpoint of significant improvement in Hgb and all key secondary endpoints, including FACIT-Fatigue at wk 12 (data previously presented). Clinically meaningful (&amp;gt;5 point) and statistically significant increases from baseline in FACIT-Fatigue score were observed for Dan vs Pbo at wk 12 (least square mean difference [SEM] 7.97 [1.13] vs 1.85 [1.58]; P=0.0021). At wk 24 ( Fig 1), outcomes were maintained in the Dan-Dan arm (40.32) and improved in Pbo-Dan arm (40.55) to levels similar to the general public score of 43.6. Significant improvements from baseline with Dan vs Pbo were demonstrated for EORTC-QLQ-C30 scores (physical function and social function within functional subscales, and fatigue within symptom subscales) at wk 12, maintained at wk 24 for the Dan-Dan arm, and demonstrated at wk 24 in Pbo-Dan arm ( Fig 2). Trends in changes from baseline in other EORTC-QLQ-C30 function subscale scores paralleled that of the physical function subscale. EQ-5D-3L scores (US Health State Index) were similar between arms at baseline (Dan, 0.83; Pbo, 0.80), wk 12 (Dan, 0.90; Pbo, 0.86), and wk 24 (Dan-Dan, 0.90; Pbo-Dan, 0.87); scores at all timepoints are comparable to the general public (0.855-0.958). Dan demonstrated favorable benefit-risk profile with no deaths, meningococcal infections, or discontinuations due to hemolysis; additional safety analyses including adverse events were previously presented. No new safety signals were demonstrated. Conclusions These data suggest that Dan plus Rav or Ecu improves QoL compared to Rav or Ecu alone for pts with PNH and cs-EVH. In this phase 3, randomized, controlled superiority trial, improvements in clinically relevant PROs were observed in the Dan vs Pbo arm in the first double-blind 12 wks of treatment, and FACIT-Fatigue and EORTC-QLQ-C30 scores were maintained during the open-label period to wk 24 in the Dan-Dan arm and improved at wk 24 in Pbo-Dan arm to levels similar to those of the general public. Comparable EQ-5D-3L scores were maintained between arms across the study.