How scoring limits the usability of minimal important differences (MIDs) as responder definition (RD): an exemplary demonstration using EORTC QLQ-C30 subscales.

PURPOSE: The recommended method for establishing a meaningful threshold for individual changes in patient-reported outcome (PRO) scores over time uses an anchor-based method. The patients assess their perceived level of change and this is used to define a threshold on the PRO score which may be considered meaningful to the patient. In practice, such an anchor may not be available. In the absence of alternative information often the meaningful change threshold for assessing between-group differences, the minimally important difference, is used to define meaningful change at the individual level too. This paper will highlight the issues with this, especially where the underlying measurement scale is not continuous. METHODS: Using the EORTC QLQ-C30 as an example, plausible score increments ("state changes") are calculated for each subscale highlighting why commonly used thresholds may be misleading, including leading to sensitivity analyses that are inadvertently testing the same underlying threshold. RESULTS: The minimal possible individual score change varies across subscales; 6.7 for Physical Functioning, 8.3 for Global Health Scale and Emotional Functioning, 11.1 for fatigue, 16.7 for role functioning, cognitive functioning, social functioning, nausea and vomiting, pain and 33.3 for single items. CONCLUSIONS: The determination of meaningful change for an individual patient requires input from the patients but being mindful of the underlying scale ensures that these thresholds are also guided by what is a plausible change for patients to achieve on the scale.

Efficacy of treatments tested in COVID-19 patients with cardiovascular disease. A meta-analysis.

BACKGROUND: The COVID-19 pandemic has spread globally infecting and killing millions. Those with cardiovascular disease (CVD) are at higher risk of increased disease severity and mortality. We performed a systematic review and meta-analysis to estimate the rate of in-hospital mortality following different treatments on COVID-19 in patients with CVD. METHODS: Pertinent articles were identified from the PubMed, Google Scholar, Ovid MEDLINE, and Ovid EMBASE databases. This study protocol was registered under PROSPERO with the identifier CRD42020183057. RESULTS: Of the 1673 papers scrutinized, 46 were included in the review. Of the 2553 patients (mean age 63.9 ± 2.7 years/o; 57.2% male), the most frequent CVDs were coronary artery disease (9.09%) and peripheral arterial disease (5.4%) and the most frequent cardiovascular risk factors were hypertension (86.7%) and diabetes (23.7%). Most patients were on multiple treatments. 14 COVID-19 treatments were compared with controls. The pooled event rate for in-hospital mortality was 20% (95% confidence interval (CI): 11-33%); certain heterogeneity was observed across studies. CONCLUSIONS: COVID-19 is associated with a high in-hospital mortality rate in patients with CVD. This study shows that previous CVD determines mortality, regardless of the type of COVID-19 administered therapy. Treatments for at-risk patients should be administered carefully and monitored closely until further data are available.

Trends in the multiple myeloma treatment landscape and survival: a U.S. analysis using 2011-2019 oncology clinic electronic health record data.

Multiple myeloma treatment has evolved with approvals of new immunomodulatory imide drugs (IMiDs), monoclonal antibodies (MoABs), and proteasome inhibitors (PIs). We characterized U.S. treatment trends and survival from 2011 to 2019 using Flatiron data from multiple myeloma patients followed from treatment index until death/end of data. Patients (n = 10,553) were primarily (88%) treated in community centers. Frontline PI-IMiD-dexamethasone use increased over time, while IMiD-dexamethasone and PI-dexamethasone use decreased. MoAB-IMiD-dexamethasone use increased in relapsed/refractory disease. In all lines, use of doublets decreased and triplets increased, with triplets becoming the most prescribed combination by 2018-2019, especially in first line (62%). Monotherapy use decreased in first line (19% to 10%) but remained steady in relapsed/refractory disease (∼20%). With each increasing line of therapy, median overall survival decreased (60, 48, 36, 29, 23 months). Survival increased with more recent diagnosis. Our results indicate that the multiple myeloma landscape has evolved significantly in the last decade.

Economic burden of disease progression among multiple myeloma patients who have received transplant and at least one line of therapy in the US.

Effects of disease progression on healthcare resource utilization (HRU) and costs among multiple myeloma (MM) patients with ≥1 line of therapy (LOT) who received their first stem cell transplant (SCT) within 1 year of initial MM diagnosis were estimated using a large US claims database. Disease progression was defined as advancement to the next LOT, bone metastasis, hypercalcemia, soft tissue plasmacytoma, skeletal related events, acute kidney disease, or death within 12 months of LOT initiation. Annual HRU and costs in the first three LOTs (L1-L3) were compared for patients with versus without disease progression using inverse probability of treatment weighting to adjust for differences between groups in baseline characteristics. In all LOTs, mean annual hospitalizations and healthcare costs were greater for patients with versus without progression. Total incremental annual costs among patients with versus without progression in L1-L3 were $18,359, $87,055, and $71,917, respectively, among LOTs initiated between 2006 and 2018. In LOTs initiated between 2013 and 2018, the figures were $46,024, $100,329, and $101,942 in L1-L3, respectively. The economic burden of disease progression is substantial in this population of MM patients who underwent SCT and received systemic anti-myeloma therapy.

Cost-effectiveness of denosumab for the prevention of skeletal-related events in patients with solid tumors and bone metastases in the United States.

Aims: Bone complications (also known as skeletal-related events [SREs]) pose significant health and financial burdens on patients with bone metastases. Denosumab demonstrated superiority over zoledronic acid in delaying the time to first SRE. This study examined the lifetime cost-effectiveness of denosumab vs zoledronic acid from both US payer and societal perspectives.Methods: This analysis used a lifetime Markov model and included patients with breast cancer, prostate cancer, and other solid tumors and bone metastases. The societal perspective included direct medical, direct non-medical, and indirect costs associated with denosumab and zoledronic acid; the payer perspective included direct medical costs only. Bone complication rates for each tumor type were estimated from three pivotal phase 3 studies and modified to reflect real-world incidence.Results: From a societal perspective, compared with zoledronic acid, denosumab use resulted in an incremental cost of $9,043, an incremental benefit of 0.128 quality-adjusted life-years (QALYs), a lifetime cost per QALY of $70,730, and a net monetary benefit (NMB) of $10,135 in favor of denosumab. Direct drug costs for denosumab ($28,352) were higher than zoledronic acid/untreated ($578), but were offset by reduced costs associated with bone complications. From a payer perspective, denosumab use was associated with an incremental cost of $13,396, and an incremental benefit of 0.128 QALYs, for a cost of $104,778 per QALY and an NMB of $5,782 in favor of denosumab.Limitations: Some model inputs had limited information and, given that the results may be sensitive to changes in these inputs, our findings should be interpreted within the context of the data inputs and modeling assumptions used in the analysis.Conclusions: Denosumab is a cost-effective option to prevent bone complications in patients with solid tumors when considering both payer and broader societal perspectives.

Cost effectiveness of golimumab for the treatment of active psoriatic arthritis.

BACKGROUND: Golimumab is a novel TNF-α inhibitor licensed to treat patients with active PsA. Although its clinical efficacy has been proven in clinical trials, its cost effectiveness is yet to be established. OBJECTIVES: To estimate the cost effectiveness of golimumab among patients with active PsA from the UK NHS perspective. METHODS: A decision analytic model was used to simulate progression of a hypothetical cohort of active PsA patients on golimumab and other TNF-α inhibitors as well as palliative care. The clinical evidence was derived from clinical trials of TNF-α inhibitors and compared using mixed treatment models. The primary outcome measure was quality-adjusted life years (QALYs) estimated based on change in Health Assessment Questionnaire (HAQ) and Psoriasis Area Severity Index (PASI) from baseline. The annual acquisition cost of golimumab was assumed to be identical to annual cost of other subcutaneous TNF-α inhibitors. The resource use costs and outcomes were discounted at 3.5% over a period of 40 years. The uncertainty surrounding important variables was further explored using probabilistic sensitivity analyses (PSA). RESULTS: TNF-α inhibitors were significantly superior to palliative care but comparable to each other on Psoriatic Arthritis Response Criteria (PsARC), HAQ and PASI response. The incremental cost effectiveness ratio (ICERs) for golimumab compared to palliative care was £16,811 for PsA patients and £16,245 for a subgroup of PsA patients with significant psoriasis. At an acceptability threshold of £30,000 per QALY, the probability of golimumab being cost effective is 89%. CONCLUSION: Once monthly, golimumab is a cost-effective treatment alternative for patients with active PsA. With its patient-focussed attributes, golimumab is likely to offer additional choice in PsA treatment.

Effect of golimumab on patient-reported outcomes in rheumatoid arthritis: results from the GO-FORWARD study.

OBJECTIVE: To evaluate the effect of golimumab on physical function, general health, and fatigue in patients with active rheumatoid arthritis (RA) despite methotrexate (MTX) therapy. METHODS: In the multicenter, randomized, placebo-controlled GO-FORWARD study, 444 adults with active RA despite MTX received subcutaneous placebo + MTX (crossover to golimumab 50 mg at Week 24), golimumab 100 mg + placebo, golimumab 50 mg + MTX, or golimumab 100 mg + MTX every 4 weeks. Physical function and general health were assessed using the Health Assessment Questionnaire-Disability Index (HAQ-DI) and Physical and Mental Component Summary (PCS, MCS) scores of the Medical Outcomes Study Short Form-36 questionnaire (SF-36), respectively, through Week 52. Fatigue was measured through Week 24 using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) questionnaire. RESULTS: Mean improvements from baseline in HAQ-DI, SF-36 PCS, and FACIT-Fatigue scores (Weeks 14 and 24) were significantly greater for golimumab 50 mg + MTX and 100 mg + MTX versus placebo + MTX. Significantly greater proportions of patients treated with golimumab + MTX achieved clinically meaningful improvements from baseline to Weeks 14 and 24 in HAQ-DI, PCS, and FACIT-Fatigue scores. Mean improvements in SF-36 PCS (Week 14), MCS (Week 24), and FACIT-Fatigue (Weeks 14 and 24) scores were significantly greater for golimumab 100 mg + placebo versus placebo + MTX. Mean improvements from baseline in HAQ-DI, SF-36 PCS, and MCS scores through Week 24 were sustained through Week 52. CONCLUSION: Patients with active RA despite MTX had significant improvement in physical function, general health, and fatigue following golimumab + MTX therapy; improvements in physical function and general health were maintained through Week 52. (Clinical Trials Registration NCT00264550).

Golimumab reduces sleep disturbance in patients with active ankylosing spondylitis: results from a randomized, placebo-controlled trial.

OBJECTIVE: To evaluate the effect of golimumab on sleep disturbance in patients with active ankylosing spondylitis (AS). METHODS: Golimumab was studied in a multicenter, randomized, placebo-controlled study (GO-RAISE). At baseline, 356 patients were randomly assigned in a 1.8:1.8:1 ratio to subcutaneous golimumab 50 mg, 100 mg, or placebo every 4 weeks. Sleep disturbance was assessed using the Jenkins Sleep Evaluation Questionnaire (JSEQ), which was administered at baseline, week 14, and week 24. Treatment effect was evaluated using analysis of variance on the van der Waerden normal scores. RESULTS: Median JSEQ scores at baseline were 9.0 in the placebo group, 10.0 in the 50-mg group, and 11.0 in the 100-mg group, indicating moderate to severe sleep disturbance. Patients who received golimumab showed significantly greater median improvement from baseline in JSEQ scores compared with placebo at week 14 (-3.0 versus 0.0; P < 0.001) and week 24 (-3.0 versus -1.0; P < 0.001). Changes from baseline in JSEQ scores significantly correlated with changes from baseline in Short Form 36 summary scores, Bath AS Functional Index scores, total back pain, night back pain, and Bath AS Disease Activity Index scores. Multiple regression analyses indicated that improvement in the night back pain score was the most consistent predictor of change in JSEQ score or reduction in sleep disturbance. CONCLUSION: Patients with active AS showed significant sleep disturbance at baseline due to underlying pain associated with AS. Treatment with subcutaneous golimumab every 4 weeks significantly reduced sleep disturbance and improved health-related quality of life.