Sex differences in adverse event reporting in SWOG chemotherapy, biologic/immunotherapy, and targeted agent cancer clinical trials.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11588-11588 ◽  
Author(s):  
Joseph M. Unger ◽  
Riha Vaidya ◽  
Kathy S. Albain ◽  
Michael Leo LeBlanc ◽  
Lori M. Minasian ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Sex Differences ◽  
Adverse Events ◽  
Targeted Therapies ◽  
Patient Reported Outcome ◽  
Adverse Event Reporting ◽  
Multiple Treatment ◽  
Increased Risk ◽  
Patient Reported ◽  
Grade 3

11588 Background: Women have more adverse events (AEs) from chemotherapy than men, but few studies have explored sex differences in biologic/immunotherapies (BIs) or targeted therapies. We examined subjective (symptomatic) and objective AEs by sex across different treatments. Methods: We analyzed drug-related severe (grade 3) or worse AEs by sex in SWOG phase II and III clinical trials conducted between 1980-2018, excluding sex-specific cancers. AE codes and grade were categorized using the Common Terminology Criteria for Adverse Events (CTCAE). Subjective or symptomatic toxicities were defined as those aligned with the NCI’s new Patient-Reported Outcome (PRO) CTCAE; lab-based or physician-determined AEs were designated as objective. Multivariable logistic regression was used, adjusting for age, race, and disease prognosis. Thirteen symptomatic and 19 objective AE categories were examined. Results: In total, 36,397 patients (women, 13,907 [38.2%]; men, 22,490 [61.8%]) experiencing 522,835 AEs on 297 trials with 385 treatment arms were analyzed. Overall, 29.1% (n = 10.860) had severe or worse toxicity. Women experienced an increased risk of severe symptomatic AEs for BIs (OR = 1.53, 95% CI: 1.32-1.78, p < .0001), chemotherapy (OR = 1.31, 95% CI: 1.24-1.39, p < .0001), and targeted therapies (OR = 1.23, 95% CI: 1.06-1.43, p = .008). Women also had an increased risk of severe objective AEs for BIs (OR = 1.53, 95% CI: 1.32-1.78, p < .0001), chemotherapy (OR = 1.35, 95% CI: 1.28-1.43, p < .0001), but not targeted therapies (OR = 1.08, 95% CI: 0.94-1.25, p = .28). Across all treatments, sex differences were greater for hematologic (OR = 1.29, 95% CI: 1.24-1.35, p < .0001) v. non-hematologic (OR = 1.13, 95% CI: 1.08-1.18, p < .0001) objective AEs. Conclusions: The greater severity of both symptomatic and objective – especially hematologic – AEs in women across multiple treatment paradigms indicates broad-based sex-differences exist. This could be due to AE reporting, pharmacogenomics of drug metabolism and disposition, total dose received, and/or adherence to therapy. Particularly large sex differences were observed for patients receiving BIs, suggesting studying AEs from these agents is a priority.

scholarly journals Achilles tendon ruptures during summer show the lowest incidence, but exhibit an increased risk of re-rupture

2020 ◽  
Vol 28 (12) ◽  
pp. 3978-3986
Author(s):  
I. A. Saarensilta ◽  
G. Edman ◽  
P. W. Ackermann
Keyword(s):  
Adverse Events ◽  
Achilles Tendon ◽  
Tendon Rupture ◽  
Achilles Tendon Rupture ◽  
Surgical Techniques ◽  
Patient Reported Outcome ◽  
Injury Mechanism ◽  
Increased Risk ◽  
Patient Reported ◽  
Operative Complications

Abstract Purpose Achilles tendon rupture (ATR) is a common injury. The knowledge of seasonal factors´ impact is incomplete, but may provide means for preventive approaches for Achilles tendon related morbidity. The aim of this study was to investigate seasonal variations in ATR incidence in relation to injury mechanism, adverse events including risk of re-rupture, and patient-reported outcome in adults in Stockholm, Sweden. Methods In total, 349 patients with unilateral acute Achilles tendon rupture, prospectively treated with standardized surgical techniques, were retrospectively assessed. Date of injury was assigned to one of the four internationally defined meteorological seasons in the northern hemisphere. Injury mechanism and the rate of adverse events; deep venous thrombosis, infection and re-rupture in relation to per-operative complications. Patient-reported outcome at 1 year was assessed with the validated Achilles tendon Total Rupture Score. Results ATR incidence was significantly highest during winter and spring, and lowest during summer (p < 0.05). The most common sporting activities associated with ATR were badminton, floorball and soccer (> 50%). The rate of soccer-related ATR was highest during summer (p < 0.05). Patients sustaining an ATR during summer, compared to other seasons, exhibited more per-operative complications (p < 0.05), a significantly higher risk of re-rupture (p < 0.05) and a lower rate of good outcome (n.s.). The risk of other adverse events after ATR did not differ between the seasons. Conclusion Winter and spring are the high risk seasons for sports-related ATR and the risk sports are badminton, soccer and floorball. The reason for the higher risk of re-rupture after ATR repair during summer should be further investigated. Level of evidence III.

Patient experience of early high grade symptomatic adverse events on early phase clinical trials using the PRO-CTCAE.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 12051-12051
Author(s):  
Geoffrey Alan Watson ◽  
Zachary William Neil Veitch ◽  
Daniel Shepshelovich ◽  
Zhihui (Amy) Liu ◽  
Anna Spreafico ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Phase I ◽  
Early Phase ◽  
Daily Life ◽  
High Grade ◽  
Negative Experience ◽  
Patient Reported ◽  
Grade 3 ◽  
Early Phase Clinical Trials

12051 Background: There are limited data describing the patients’ experience of symptomatic adverse events (syAEs) on early phase clinical trials. This information is critical to understand the tolerability of experimental agents. The patient reported outcome version of the CTCAE (PRO-CTCAE) evaluates syAE components such as severity and interference in daily life. The aim of this study was to correlate clinician reported early, high grade (grade 3-4) AEs with patients’ reported experience of these toxicities. Methods: Advanced solid tumor patients (pts) enrolled on early phase clinical trials at Princess Margaret Cancer Centre were surveyed electronically using the full library of 78 items for PRO-CTCAE v1.0, which was administered at baseline (prior to therapy), mid-cycle 1, and mid-cycle 2. AEs on study were recorded by physicians using the CTCAE v4.0. Worst responses for severity items are ‘severe’ and ‘very severe’ and for interference items are ‘quite a bit’ and ‘very much’. A logistic regression model was used to assess the association between CTCAE grade and PRO-CTCAE severity and interference. Results: A total of 292 pts were approached in phase 1 clinics from May 2017 to January 2019, and 219 pts were included in the analysis: median age 60 years (range 18-82), 111 (51%) were male; all were ECOG ≤1. A total of 140 pts (64%) received combination therapy (immunotherapy and targeted therapy), and 73 pts (33%) had received ≥3 previous lines of treatment. In terms of patient reported syAEs, a total of 114 pts (52%) reported a symptomatic AE as either severe or very severe at any timepoint and 79 pts (36%) reported a syAE with an interference that was either ‘quite a bit’ or ‘very much’. With regards to clinician reported AEs, a total of 82 pts (37%) had a clinician reported grade 3 or 4 syAE, and of these 34 pts (41%) reported these as either severe or very severe; and 26 pts (32%) found these AEs interfered with daily life either ‘quite a bit’ or ‘very much’. Additionally 137 pts (66%) had a clinician reported grade 1 or 2 syAE, and of these 39 pts (28%) reported these as either severe or very severe; and 19 (14%) found these AEs interfered with daily life either ‘quite a bit’ or ‘very much’. Higher grade clinician reported syAEs (CTCAE grade 3-4 vs 1-2) was associated with higher patient reported severity levels (odds ratio, OR = 1.78, 95% CI 1-3.16, p = 0.049), and was associated with higher patient reported interference levels (OR = 2.88, 95% CI 1.47-5.64, p = 0.002). Conclusions: A majority of patients had a very negative experience of syAEs on a phase I trial. Higher grades of clinician reported AEs correlated with greater severity and interference with daily living. Future phase I studies could incorporate the PRO-CTCAE and other PRO tools which could inform the tolerability of experimental regimens and enhance the description of symptomatic AEs.

Landscape review of the patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE) in oncology: Adoption and recent learnings.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18587-e18587
Author(s):  
Antoine Regnault ◽  
Stephane Quéré ◽  
Boris Gorsh ◽  
Sandhya Sapra ◽  
Angély Loubert ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Analytical Methods ◽  
Linear Models ◽  
Single Agent ◽  
Patient Reported Outcome ◽  
Item Selection ◽  
Antibody Drug Conjugate ◽  
Patient Reported ◽  
Over Time

e18587 Background: The PRO-CTCAE is a patient-reported outcome measure of symptomatic toxicity in oncology trials designed to complement CTCAE criteria (clinician’s measure of adverse events [AEs]). Items for evaluation are selected from 78 symptomatic toxicities in the CTCAE. PRO-CTCAE uptake and use has not been uniformly assessed; understanding how to best analyze and present PRO-CTCAE data is important. We reviewed literature on clinical trials reporting the PRO-CTCAE to ascertain its use and current analytical methods to inform future analyses. Methods: A review of the literature and ongoing oncology trials using PubMed, oncology and outcomes research conferences (ASCO, ASH, ISOQOL, ISPOR), and ClinicalTrials.gov was completed August 2019; updated November 2020. Selected literature included guidance on: item selection; analytical methods; PRO-CTCAE data/endpoint use in clinical trials. Analytical and visualization methods from the literature were used to inform the specification of PRO-CTCAE analyses conducted on data from the DREAMM-2 (NCT03525678) trial of single-agent belantamab mafodotin (belamaf; BLENREP), a B-cell maturation antigen–binding antibody–drug conjugate, in relapsed/refractory multiple myeloma. Results: After screening (n = 197), 45 articles were reviewed: 13 related to recommendations for use/analysis, 7 to item selection, and 25 to examples of PRO-CTCAE use. 118 completed/ongoing trials reported PRO-CTCAE use (17 [14%] Phase I or I/II; 73 [62%] Phase II, II/III, or III; 3 [3%] Phase IV; 25 had no phase reported). Most (92/118, 78%) trials included the PRO-CTCAE as a secondary endpoint. The number of trials using the PRO-CTCAE increased from 3 in 2015 to 30 in 2020. PRO-CTCAE data in the literature were reported descriptively using tables (maximum post-baseline ratings; mean change over time; ratings higher than a predefined cutoff) and graphs (line graphs; stacked bar charts; heatmaps). These and more sophisticated analyses were applied to DREAMM-2 data to best capture the dynamics of patient-reported AEs over time, or control for baseline PRO-CTCAE ratings (eg, Toxicity over Time approach; ordinal log-linear models). Conclusions: The importance of tolerability and symptomatic AEs for patients is increasingly recognized, particularly for new therapies. This landscape review demonstrates recent growth in interest and adoption of PRO-CTCAE. There are few existing standards for analysis; this research increases understanding of existing methods and further evaluates ways of analyzing and presenting PRO-CTCAE data over time. Additional research exploring innovative methods to analyze PRO-CTCAE data and address its challenges is needed. Funding Source: GlaxoSmithKline (212225). Drug linker technology licensed from Seagen Inc.; mAb produced using POTELLIGENT Technology licensed from BioWa.

scholarly journals Online monitoring of patient self-reported adverse events in early phase clinical trials: Views from patients, clinicians, and trial staff

2020 ◽  
pp. 174077452097212
Author(s):  
Fiona Kennedy ◽  
Leanne Shearsmith ◽  
Michael Ayres ◽  
Oana C Lindner ◽  
Lewis Marston ◽  
...  
Keyword(s):  
Adverse Event ◽  
Adverse Events ◽  
Early Phase ◽  
Patient Reported Outcome ◽  
Adverse Event Reporting ◽  
Event Reporting ◽  
Patient Reported ◽  
Trial Staff ◽  
Early Phase Trial ◽  
Early Phase Clinical Trials

Background/aims New classes of cancer drugs bring a range of unknown and undesirable adverse events. Adverse event monitoring is essential in phase I trials to assess toxicity and safety. In phase II, the focus is also on efficacy but robust data on adverse events continue to inform the safety and the adverse event profile. Standard, clinician-led monitoring has been shown to underestimate patients’ symptoms. Hence, patient-reported adverse event monitoring has been argued to complement and improve the information on adverse events in early phase clinical trials. With advances in information technology, real-time patient self-reported adverse events in trials are feasible. This study explored the experiences and procedures for reporting adverse events in early phase trials among patients, clinical staff, and trial staff, and their views on using an electronic patient-reported outcome adverse event system in this setting. Methods Qualitative interviews were conducted with patients, purposively sampled across ages, gender, and different phases of trials, and with clinical and trial-related staff involved in early phase trials (e.g. consultants, research nurses, hospital-based trial assistants/data managers, trial unit management staff). Interviews explored patient experiences and views on current adverse event reporting processes and electronic patient-reported outcome adverse event reporting. Framework analysis techniques were used to analyse the data. Results Interviewees were from two hospital trusts with early phase portfolios in England and a trial unit, and included sixteen patients, five consultants, four research nurses, five hospital-based trial staff, and two trial unit staff. Interviews identified three key themes (patient experiences, data flow, and views on electronic patient-reported outcome adverse event reporting). Stakeholders emphasised the intensity of trials for patients and the importance of extensive information provision within the uncertainty of early phase trial drugs. Regular face-to-face appointments for patients supplemented by telephone contact aimed to capture any adverse events. Delayed or under-reporting of mild- or low-severity symptoms was evident among patients. Hospital-based staff highlighted the challenges of current data collection including intense timescales, monitoring by trial sponsors, and high workload. Positive views on electronic patient-reported outcome adverse events highlighted that this could provide a more comprehensive and accurate view on the side effects of new drugs. Clinical staff emphasised patient safety and the need for clear responsibilities for monitoring. The need for careful decision-making about data flow and symptom attribution was highlighted; with trial unit staff emphasising the need for clinician review. Conclusion Technology advances mean it is timely to explore the benefits and challenges of electronic patient-reported outcome adverse event reporting. This is a complex area warranting further consideration within the trial community. We have developed an online patient self-reporting tool and a small pilot with early phase trial patients is underway.

scholarly journals ReCAP: Identifying Severe Adverse Event Clusters Using the National Cancer Institute’s Common Terminology Criteria for Adverse Events

2016 ◽  
Vol 12 (3) ◽  
pp. 245-246 ◽  
Author(s):  
Xiaobo Zhong ◽  
Emerson A. Lim ◽  
Dawn L. Hershman ◽  
Carol M. Moinpour ◽  
Joseph Unger ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Adverse Event ◽  
Adverse Events ◽  
Advanced Prostate Cancer ◽  
Patient Reported Outcomes ◽  
Symptom Cluster ◽  
Standard Practice ◽  
Patient Reported ◽  
Grade 3

CONTEXT & QUESTION ASKED: Exploring the relationship among adverse events is important because those that arise from a common mechanism are amenable to a common intervention, which can improve symptom management, quality of life, and treatment adherence. To date, symptom cluster studies have used patient-reported data, which are not always available in clinical trials. In this study, we proposed using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) to identify adverse event clusters because the CTCAE are collected as standard practice and can therefore be used when patient-reported outcomes are unavailable. Hence, is it feasible to identify severe adverse events clusters from data captured using the CTCAE in clinical trials? SUMMARY ANSWER: Six severe adverse events clusters were identified in patients with advanced prostate cancer. Identifying adverse events clusters using CTCAE data from clinical trials is feasible. METHODS: A variable-based hierarchical cluster analysis was conducted using the CTCAE data captured from 323 patients who experienced at least one grade 3 or higher adverse event in an advanced prostate cancer randomized clinical trial conducted by SWOG (S9916). BIAS, CONFOUNDING FACTOR(S), DRAWBACKS: The difficulty of using adverse event data from clinical trials is that often not all adverse events are recorded. In our study, only the highest severity grade for each adverse event type was recorded, and only grade 3 or higher adverse events were captured reliably. Moreover, in contrast to previous publications on symptom cluster that used patient-reported outcomes, the CTCAE is clinician reported and may not accurately reflect the presence of patient symptoms and the severity of these symptoms. REAL-LIFE IMPLICATIONS: Capturing adverse events using the CTCAE, which is standard practice in all clinical trials, can be used to understand the relationships among adverse events and to identify adverse events clusters when patient-reported outcomes are unavailable. [Figure: see text]

558 Programmed death (PD)-1 and PD-ligand-1 inhibitors in the treatment of non-small cell lung cancer: a systematic review of their efficacy and safety

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A592-A592
Author(s):  
Melissa Lingohr-Smith ◽  
Chelsea Deitelzweig ◽  
Grace Lin ◽  
Jay Lin
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Patient Outcomes ◽  
Nsclc Patient ◽  
Response Rates ◽  
Phase Iii ◽  
Combination Therapies ◽  
Phase Iii Clinical Trials ◽  
Programmed Death ◽  
Grade 3

BackgroundTreatment advances have been made in non-small cell lung cancer (NSCLC) with the development and approval of programmed death (PD)-1 and PD-ligand 1 (PD-L1) inhibitors. PD-1 and PD-L1 inhibitors may be used as monotherapies or in combination with other agents and have been shown to improve NSCLC patient outcomes in clinical trials. We conducted a systematic search to compare the efficacy and safety of PD-1/PD-L1 inhibitors in the treatment of NSCLC.MethodsA systematic literature search of PubMed was conducted to identify phase III clinical trials in which the efficacy of PD-1/PD-L1 inhibitors in the treatment of NSCLC was evaluated. PD-1 inhibitors included nivolumab and pembrolizumab; PD-L1 inhibitors included atezolizumab, avelumab, and durvalumab. Patient characteristics and efficacy data were extracted.ResultsSixteen phase III clinical trials were identified (nivolumab=4; pembrolizumab=5; atezolizumab=5; avelumab=1; durvalumab=1). Across the 3 nivolumab monotherapy trials (n=638; median ages: 61–63 years), median progression-free survival (PFS) ranged 2.3–4.2 months; response rates ranged 19%-26%; grade 3/4 adverse events occurred in 7%-18% of patients. Nivolumab in combination with iplimumab (n=583; median age: 64 years) had a median PFS of 5.1 months and response rate of 33%; grade 3/4 adverse events occurred in 33% of patients. Across the 3 pembrolizumab monotherapy trials (n=1,481; median ages: 63–64 years), median PFS ranged 3.9–10.3 months; response rates ranged 18%-45%; grade ≥3 adverse events occurred in 13%-27% of patients. In the 2 pembrolizumab combination therapy trials (n=688; median ages: 65 years), median PFS ranged 6.4–8.8 months; response rates ranged 48%-58%; grade ≥3 adverse events occurred in 67%-70% of patients. In the 4 atezolizumab combination therapy trials (n=1,486; median ages: 63–64 years), median PFS ranged 6.3–8.3 months; response rates ranged 47%-63.5%; grade 3/4 adverse events occurred in 54%-73% of patients. In the 3 monotherapy trials of atezolizumab (n=613; median age: 63 years), avelumab (n=396; median age: 64 years), and durvalumab (n=476; median age: 64 years), the median months of PFS were 2.7, 2.8, and 17.2, respectively; response rates were 14%, 15%, and 30%, respectively; grade ≥3 adverse events occurred in 15%, 10%, and 30.5% of patients, respectively.ConclusionsAlthough treatment responses varied, most of the evaluated PD-1/PD-L1 inhibitors were associated with a clinical benefit for NSCLC trial patients. Generally, treatment efficacy was greater with combination therapies, but adverse events occurred more frequently. Innovations in the targeting/personalization of PD-1/PD-L1 combination therapies will likely lead to improved NSCLC patient outcomes and further research is needed in this regard.

scholarly journals Measurement properties of patient-reported outcome measures (PROMs) in hyperhidrosis: a systematic review

2021 ◽  
Author(s):  
Michaela Gabes ◽  
Helge Knüttel ◽  
Gesina Kann ◽  
Christina Tischer ◽  
Christian J. Apfelbacher
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Patient Reported Outcome Measures ◽  
Patient Reported Outcome ◽  
Measurement Properties ◽  
High Quality ◽  
High Quality Evidence ◽  
Patient Reported ◽  
Quality Evidence

Abstract Purpose To critically appraise, compare and summarize the quality of all existing PROMs that have been validated in hyperhidrosis to at least some extend by applying the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology. Thereby, we aim to give a recommendation for the use of PROMs in future clinical trials in hyperhidrosis. Methods We considered studies evaluating, describing or comparing measurement properties of PROMs as eligible. A systematic literature search in three big databases (MEDLINE, EMBASE and Web of Science) was performed. We assessed the methodological quality of each included study using the COSMIN Risk of Bias checklist. Furthermore, we applied predefined quality criteria for good measurement properties and finally, graded the quality of the evidence. Results Twenty-four articles reporting on 13 patient-reported outcome measures were included. Three instruments can be further recommended for use. They showed evidence for sufficient content validity and moderate- to high-quality evidence for sufficient internal consistency. The methodological assessment showed existing evidence gaps for eight other PROMs, which therefore require further validation studies to make an adequate decision on their recommendation. The Hyperhidrosis Disease Severity Measure-Axillary (HDSM-Ax) and the short-form health survey with 36 items (SF-36) were the only questionnaires not recommended for use in patients with hyperhidrosis due to moderate- to high-quality evidence for insufficient measurement properties. Conclusion Three PROMs, the Hyperhidrosis Quality of Life Index (HidroQoL), the Hyperhidrosis Questionnaire (HQ) and the Sweating Cognitions Inventory (SCI), can be recommended for use in future clinical trials in hyperhidrosis. Results obtained with these three instruments can be seen as trustworthy. Nevertheless, further validation of all three PROMs is desirable. Systematic review registration PROSPERO CRD42020170247

scholarly journals Enabling patient-reported outcome measures in clinical trials, exemplified by cardiovascular trials

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Theresa M. Coles ◽  
Adrian F. Hernandez ◽  
Bryce B. Reeve ◽  
Karon Cook ◽  
Michael C. Edwards ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Outcome Measures ◽  
Contextual Factors ◽  
The United States ◽  
Patient Reported Outcome Measures ◽  
Patient Reported Outcome ◽  
Think Tank ◽  
Level Of Evidence ◽  
Patient Reported ◽  
Evidentiary Standards

Abstract Objectives There has been limited success in achieving integration of patient-reported outcomes (PROs) in clinical trials. We describe how stakeholders envision a solution to this challenge. Methods Stakeholders from academia, industry, non-profits, insurers, clinicians, and the Food and Drug Administration convened at a Think Tank meeting funded by the Duke Clinical Research Institute to discuss the challenges of incorporating PROs into clinical trials and how to address those challenges. Using examples from cardiovascular trials, this article describes a potential path forward with a focus on applications in the United States. Results Think Tank members identified one key challenge: a common understanding of the level of evidence that is necessary to support patient-reported outcome measures (PROMs) in trials. Think Tank participants discussed the possibility of creating general evidentiary standards depending upon contextual factors, but such guidelines could not be feasibly developed because many contextual factors are at play. The attendees posited that a more informative approach to PROM evidentiary standards would be to develop validity arguments akin to courtroom briefs, which would emphasize a compelling rationale (interpretation/use argument) to support a PROM within a specific context. Participants envisioned a future in which validity arguments would be publicly available via a repository, which would be indexed by contextual factors, clinical populations, and types of claims. Conclusions A publicly available repository would help stakeholders better understand what a community believes constitutes compelling support for a specific PROM in a trial. Our proposed strategy is expected to facilitate the incorporation of PROMs into cardiovascular clinical trials and trials in general.

scholarly journals EQ-5D-3L full health state discriminates between drug and placebo in clinical trials of systemic lupus erythematosus

Rheumatology ◽  
2021 ◽  
Author(s):  
Julius Lindblom ◽  
Alvaro Gomez ◽  
Alexander Borg ◽  
Sharzad Emamikia ◽  
Dimitris Ladakis ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Lupus Erythematosus ◽  
Damage Index ◽  
Patient Reported Outcome ◽  
Health State ◽  
Full Health ◽  
Chi Square ◽  
Discriminative Ability ◽  
Exact Test ◽  
Patient Reported

Abstract Objectives To investigate the discriminative ability of EQ-5D-3L full health state (FHS) in clinical trials of SLE, and identify factors associated with FHS after treatment. Methods Data from the BLISS-52 (NCT00424476) and BLISS-76 (NCT00410384) trials of belimumab (N = 1684) were utilised. FHS was defined as a response of no problems in all five EQ-5D-3L dimensions, yielding an index score of 1. The Pearson’s chi-square or Fisher’s exact test was employed for comparisons, and logistic regression for adjustments and assessment of independence. Results We demonstrated higher EQ-5D-3L FHS frequencies among patients given standard therapy (ST) plus the licensed belimumab dose versus ST alone (26.1% versus 19.4%; P = 0.001; week 52), and within SRI-4 responders versus non-responders (27.0% versus 19.8%; P &lt; 0.001; week 52) from week 36 to 52. In multivariable regression analysis, SLEDAI-2K (OR: 0.90; 95% CI: 0.87 − 0.94; P &lt; 0.001) and SLICC/ACR Damage Index (OR: 0.79; 95% CI: 0.69 − 0.91; P = 0.001) scores were independently associated with lower FHS frequencies at week 52, while adding monthly infusions of belimumab 10 mg/kg to ST favoured FHS perception (OR: 1.60; 95% CI: 1.15 − 2.24; P = 0.006). Add-on belimumab 10 mg/kg yielded higher FHS frequencies in antimalarial users versus non-users (29.9% versus 20.1%; P = 0.011), and in anti-dsDNA and anti-Sm positive versus negative patients (31.4% versus 13.4%; P &lt; 0.001 and 33.0% versus 22.6%; P = 0.010, respectively), whereas no significant differences were observed in patients given ST alone. Conclusion EQ-5D-3L FHS distinguished belimumab from placebo and responders from non-responders, and exhibited known-group validity in subgroup analysis. FHS may prove a useful patient-reported outcome in SLE studies.

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