Characteristics and outcomes of COVID-19 patients presumed to be treated with sotrovimab in NHS hospitals in England.

BACKGROUND: The impact of the constantly evolving severe acute respiratory syndrome coronavirus 2 on the effectiveness of early coronavirus disease 2019 (COVID-19) treatments is unclear. Here, we report characteristics and acute clinical outcomes of patients with COVID-19 treated with a monoclonal antibody (mAb; presumed to be sotrovimab) across six distinct periods covering the emergence and predominance of Omicron subvariants (BA.1, BA.2, and BA.5) in England. METHODS: Retrospective cohort study using data from the Hospital Episode Statistics database from January 1-July 31, 2022. Included patients received a mAb delivered by a National Health Service (NHS) hospital as a day-case, for which the primary diagnosis was COVID-19. Patients were presumed to have received sotrovimab based on NHS data showing that 99.98% of COVID-19-mAb-treated individuals received sotrovimab during the study period. COVID-19-attributable hospitalizations were reported overall and across six distinct periods of Omicron subvariant prevalence. Subgroup analyses were conducted in patients with severe renal disease and active cancer. RESULTS: Among a total of 10,096 patients, 1.0% (n = 96) had a COVID-19-attributable hospitalization, 4.6% (n = 465) had a hospital visit due to any cause, and 0.3% (n = 27) died due to any cause during the acute period. COVID-19-attributable hospitalization rates were consistent among subgroups, and no significant differences were observed across periods of Omicron subvariant predominance. CONCLUSIONS: Levels of COVID-19-attributable hospitalizations and deaths were low in mAb-treated patients and among subgroups. Similar hospitalization rates were observed whilst Omicron BA.1, BA.2, and BA.5 were predominant, despite reported reductions in in vitro neutralization activity of sotrovimab against BA.2 and BA.5.

Real-world effectiveness of sotrovimab for the treatment of SARS-CoV-2 infection during Omicron BA.2 subvariant predominance: a systematic literature review.

PURPOSE: Emerging SARS-CoV-2 variants have impacted the in vitro activity of sotrovimab, with variable fold changes in neutralization potency for the Omicron BA.2 sublineage and onward. The correlation between reduced in vitro activity and clinical efficacy outcomes is unknown. A systematic literature review (SLR) evaluated the effectiveness of sotrovimab on severe clinical outcomes during Omicron BA.2 predominance. METHODS: Electronic databases were searched for peer-reviewed journals, preprint articles, and conference abstracts published from January 1-November 3, 2022. RESULTS: Five studies were included, which displayed heterogeneity in study design and population. Two UK studies had large samples of patients during BA.2 predominance: one demonstrated clinical effectiveness vs molnupiravir during BA.1 (adjusted hazard ratio [aHR] 0.54, 95% CI 0.33-0.88; p = 0.014) and BA.2 (aHR 0.44, 95% CI 0.27-0.71; p = 0.001); the other reported no difference in the clinical outcomes of sotrovimab-treated patients when directly comparing sequencing-confirmed BA.1 and BA.2 cases (HR 1.17, 95% CI 0.74-1.86). One US study showed a lower risk of 30-day all-cause hospitalization/mortality for sotrovimab compared with no treatment during the BA.2 surge in March (adjusted relative risk [aRR] 0.41, 95% CI 0.27-0.62) and April 2022 (aRR 0.54, 95% CI 0.08-3.54). Two studies from Italy and Qatar reported low progression rates but were either single-arm descriptive or not sufficiently powered to draw conclusions on the effectiveness of sotrovimab. CONCLUSION: This SLR showed that the effectiveness of sotrovimab was maintained against Omicron BA.2 in both ecological and sequencing-confirmed studies, by demonstrating low/comparable clinical outcomes between BA.1 and BA.2 periods or comparing against an active/untreated comparator.

Suboptimal outcomes and treatment burden of anti-vascular endothelial growth factor treatment for diabetic macular oedema in phakic patients.

OBJECTIVES: In England and Wales, treatment options were limited for patients with diabetic macular oedema (DMO) with phakic eyes that failed anti-vascular endothelial growth factor (anti-VEGF) treatment pre-2022. This study aimed to quantify the response to, and treatment burden of, anti-VEGF treatment in phakic eyes. METHODS: Retrospective, cohort study using electronic patient record data from two UK centres between 2015 and 2020. Primary objective was proportion of phakic eyes with a suboptimal response after initial 6 months of anti-VEGF treatment. Data were available for 500 eyes from 399 patients. RESULTS: At 6 months significantly more eyes had a suboptimal response to anti-VEGF treatment: 65.8% (95% CI 61.5-70.0%) vs 34.2% (95% CI 30.0-38.5%), p < 0.0001. Baseline visual acuity (VA) predicted VA outcome, however, despite greater gains in eyes with poorer VA, such eyes did not achieve the same VA levels as those who started treatment with better VA. Only 53.6% of eyes had more than three injections in the first 6 months indicating difficulties in delivering high volume/high frequency treatment. Treatment and review burden were similar over the following years regardless of response to anti-VEGF treatment. CONCLUSIONS: Data confirm previous real world evidence around response to anti-VEGF treatment, importance of baseline VA and frequency of injections in predicting outcomes in a UK setting. Continuing treatment beyond 6 months in suboptimal responders imposes unnecessary treatment burden without significant change in VA. In suboptimal responders, consideration of early switch to longer acting steroid treatments may help to reduce treatment burden, whilst maintaining or improving vision.

Assessment of Metastatic Colorectal Cancer Patients' Preferences for Biologic Treatments in Germany Using a Discrete Choice Experiment.

BACKGROUND: Current treatment regimens for metastatic colorectal cancer (mCRC) include biologics such as epidermal growth factor receptor and vascular endothelial growth factor inhibitors, which have specific side-effect profiles. There is a lack of information on mCRC patient preference in Germany regarding biologics in combination with chemotherapy. This study aims to identify German mCRC patients' preference for these treatments PATIENTS AND METHODS: This was a multicenter cross-sectional discrete choice experiment (DCE). Data were collected using electronic case report forms and structured phone interviews. DCE attributes were related to efficacy, side effects, frequency of administration, and distance to treating physicians' practice. Patients' characteristics and choices were analyzed descriptively. Choice data was modeled using a random utility maximization framework. RESULTS: All attributes, except distance to treating physicians' practice, had a significant impact on patients' decision. The most important driver of patients' treatment decision was overall survival, followed by safety-related attributes and frequency of administration. Overall survival was the main driver in all subgroups analyzed. Risk of severe skin toxicities was more important to women, than men. In patients with prior experience of side effects, the risk of side effects accounted for 45% of a patient's decision, compared to 35% in those without prior experience. CONCLUSION: Overall survival remains the most important driver in mCRC patients' preferences for biologic treatment in combination with chemotherapy. Attributes related to safety were less important to patients when considering their treatment decision. These results indicate that understanding patient preferences may lead to increased treatment compliance.

Management of Patients with Relapsed and/or Refractory Multiple Myeloma Treated with Novel Combination Therapies in Routine Clinical Practice in Germany.

INTRODUCTION: Multiple myeloma remains an incurable plasma cell malignancy which, despite improvements in overall survival over the last decade, is characterized by recurrent relapse and is associated with a poor prognosis. This study investigates the use of novel agents in current real-world clinical practice in the management of relapsed and/or refractory multiple myeloma (RRMM) in Germany over different lines of therapy. METHODS: A retrospective chart review was conducted for patients with RRMM treated at multiple centers across Germany between May 2017 and June 2018. Variables included patient demographics and clinical characteristics, current and prior treatment regimens, treatment response, cytogenetic abnormalities, testing methodology, and resource utilization. RESULTS: Data were analyzed from 484 patients from 47 centers across Germany (60% male; average age over 70 years; majority at International Staging System stage 2 or 3). Bone pain and anemia were the most common symptoms at diagnosis, with 63% of patients receiving osteoprotective drugs. Approximately one-third (32%) of patients had received autologous stem cell transplantation and approximately 70% underwent cytogenetic testing. After failure to respond to first-line treatment, most patients received regimens containing second-generation proteasome inhibitors and monoclonal antibodies, with overall response rates greater than 90% in second line (95% and 90% for daratumumab-based and carfilzomib-based therapies, respectively). The incidence of unplanned hospitalization ranged from 11% to 16% across all treatment lines, with longer hospital stays required for treatment administration than for treatment-related toxicity. CONCLUSION: Although treatment patterns for RRMM in Germany differ by line of therapy and are adapted as disease progresses, patients mostly receive combination regimens with carfilzomib or daratumumab in second and third lines, with high overall response rates achieved in all lines.

Fractures in untreated patients with osteoporosis in Germany: an InGef healthcare insurance database analysis.

Osteoporosis is a skeletal disease that may result in low-trauma fracture if untreated. Among men and women ≥ 70 years untreated for osteoporosis, 30% (43,514) sustained at least one post-index fracture. Care for patients with osteoporosis diagnosis directly contributed to a cost burden of €786 million. INTRODUCTION: Osteoporosis is a skeletal disease that manifests as bone mineral density loss and low-trauma fractures. This database analysis describes the characteristics of untreated osteoporosis patients, and their rate of fractures, health resource utilization, and cost burden. METHODS: From the InGef database (2011-2016), eligible patients (≥ 70 years) untreated for osteoporosis were identified via a recorded diagnosis of osteoporosis (ICD-10 codes M80/M81) or an initial fragility fracture (index point). All patients were followed up for fractures post index. Direct costs included inpatient, outpatient, pharmacy, and ancillary care costs. RESULTS: A total of 144,752 patients (mean age 79 years; 73% female, median follow-up of 3.2 years) met the eligibility criteria; 23% had a history of fractures. Forty-eight percent of patients had cardiac diseases, 32% diabetes, and 27% cerebrovascular disease. Thirty percent (43,514) of patients had at least one post-index fracture; two or more post-index fractures were experienced in 7% (10,262) of patients. Median time from index date to first fracture was 145.5 days. Bisphosphonates were the most prescribed osteoporosis treatment following a first fracture post-index (n = 4102, 9.2%). There was a total of 107,055 patients (74.0%) who had at least one all-cause hospital stay. The total number of fracture-related admissions was 63,595 and that of outpatient visits was 323,460. A total of 34,764 (24%) patients died during follow-up. Costs for fracture-related care for patients directly contributed to a cost burden of €786 million. CONCLUSIONS: Osteoporosis patients and patients who sustain a fragility fracture remain undertreated for osteoporosis, increasing their risk of future fractures. Diagnosing and treating this group of patients should remain a priority to alleviate the clinical and economic burden of osteoporosis-related fractures.

Survival and treatment patterns of patients with relapsed or refractory multiple myeloma in France - a cohort study using the French National Healthcare database (SNDS).

Over the past decade, several drugs have been approved for the treatment of relapsed or refractory multiple myeloma (RRMM). This retrospective study, using the French National Healthcare database (SNDS), describes the treatment patterns and outcomes of patients with RRMM treated in real-world clinical practice in France. Patients were adults, with a diagnosis of multiple myeloma, who initiated second-line (2L) treatment approved for use in France between 2014 and 2018; this included bortezomib, carfilzomib, daratumumab, ixazomib, lenalidomide, or pomalidomide. Data were analyzed overall, by first-line (1L) autologous stem cell transplant (ASCT) status and by lenalidomide treatment status at 2L. In total, 12987 patients with RRMM were included in the study (mean age 69.5 years); 27% received an ASCT at 1L, and 30% received a lenalidomide-sparing regimen at 2L. Overall, and among the ASCT and non-ASCT subgroups, most patients received a bortezomib-based regimen at 1L, whereas lenalidomide-based regimens were most common at 2L. Among patients who received a lenalidomide-sparing regimen at 2L, this was most often a proteasome inhibitor-based regimen. Mortality rate was 26.1/100 person-years, and median (95% confidence interval) survival from 2L initiation was 32.4 (31.2-33.6) months. Survival differed by various factors, shorter survival was reported in the non-ASCT group, those receiving a lenalidomide-sparing regimen at 2L, older patients (≥ 70 years), and those with multiple comorbidities. This analysis provides insight into the real-world use of approved novel MM treatments and highlights an ongoing unmet need to improve outcomes, particularly for selected patient groups.

Healthcare resource utilization and costs among patients with relapsed and/or refractory multiple myeloma treated with proteasome inhibitors in real-world clinical practice in Germany.

AIMS: To assess the real-world healthcare resource utilization (HRU) and costs associated with different proteasome inhibitors (PIs) for the treatment of patients with relapsed and/or refractory multiple myeloma (RRMM) in Germany. METHODS: We conducted a retrospective medical chart review of treatment patterns, outcomes, and HRU for patients with RRMM treated with bortezomib, carfilzomib, or ixazomib in second- or third-line (2L or 3L) therapy in Germany. Data were collected between 1 January 2017 and 30 June 2017. Costs were calculated based on drug prices and unit costs in Germany. RESULTS: Physicians provided data on 302 patients. Mean monthly total direct costs per patient receiving PI-based therapy were €7,925 and €10,693 for 2L and 3L, respectively, of which approximately 90% was anti-myeloma drug costs. Overall, the highest costs were associated with patients receiving 3L therapy. Regardless of treatment line, costs were higher for patients who had received a stem cell transplant (SCT) in a previous treatment line than for those who had not; the data suggest that this reflects the use of triplet regimens following a SCT. Patients with a complete response (CR) experienced no unplanned hospitalizations during the study period, whereas patients with progressive disease experienced the highest number of unplanned and planned hospitalizations. In 2L therapy, the highest proportion of patients with a CR was observed in those receiving carfilzomib (12% carfilzomib; 4% bortezomib; 0% ixazomib). LIMITATIONS: Patients with missing or incomplete follow-up data were included in the study and were accounted for using monthly cost estimates. CONCLUSIONS: Anti-myeloma drugs were the main contributor to total HRU costs associated with RRMM in Germany. Improved treatment response was associated with lower costs and reduced hospitalizations.

Real-World Evaluation of Health-Related Quality of Life in Patients With Multiple Myeloma From Germany.

INTRODUCTION: Real-world health-related quality of life (HRQoL) data in patients with multiple myeloma (MM) are scarce. Here, we report HRQoL by line of therapy in adults with MM in clinical practice in Germany. PATIENTS AND METHODS: This descriptive, multicenter, observational study included patients receiving all lines of MM therapy or best supportive care (BSC). The primary endpoint was HRQoL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 global health status [GHS]) by line of therapy; secondary endpoints included patient/disease characteristics and treatments by line of therapy. RESULTS: Overall, 490 patients were included from 40 centers (mean age 71.0 years, 62% male); 59% had an Eastern Cooperative Oncology Group performance status of 0 or 1% and 35% had undergone stem cell transplantation. First-line therapy included proteasome inhibitors in 81% of patients; subsequent treatments varied. The mean overall GHS/QoL score was 49.5; HRQoL decreased by therapy line (P < .001) and was lowest in those receiving BSC. Functional and symptoms scores worsened with increasing treatment line. The largest HRQoL reduction occurred when patients switched from active treatment to BSC. Compared with those on active treatment, patients in a treatment-free interval generally had better GHS/QoL, functioning, and fewer symptoms (P < .05). GHS/QoL also generally improved and symptoms lessened in those with ≥1 versus <1 year of ongoing treatment (P < .05). Worse GHS/QoL was observed in patients with ≥1 grade 3/4 toxicity versus those with none (P = .012). Eastern Cooperative Oncology Group performance status was the strongest determinant of HRQoL. CONCLUSIONS: This real-world study shows that patients with MM have impaired HRQoL and that HRQoL deteriorates with increasing lines of therapy.

Patient Characteristics and Outcomes of Relapsed/Refractory Multiple Myeloma in Patients Treated with Proteasome Inhibitors in Germany.

INTRODUCTION: Real-world data reflects treatments and outcomes in clinical practice in contrast with controlled clinical trials. This study evaluates real-life multiple myeloma (MM) patients receiving proteasome inhibitor (PI)-based treatments in the second or third therapy line in 2017 in Germany. METHODS: This is a retrospective chart review on adult relapsed/refractory MM patients treated with ≥1 dose of a PI-based regimen in either the second or the third line of therapy. Participating physicians had ≥3 years of clinical experience in treating symptomatic MM patients and used PI according to the label. RESULTS: Distinct patient profiles for each PI-based regimen emerged. Younger, fitter, transplant-eligible patients received novel PI triplets such as carfilzomib in combination with lenalidomide and dexamethasone (KRd) or IRd. Patients receiving lenalidomide in first-line therapy mostly received lenalidomide-free regimens in second-line therapy. In high-risk patients, no clear treatment patterns could be ascertained. The complete response rates were highest with KRd (13.0%), followed by carfilzomib in combination with dexamethasone (Kd) (5.7%) and bortezomib (4.8%). The very good partial response rates were highest with IRd (76.9%), followed by KRd (53.7%), Kd (25.7%), and bortezomib (20.5%). None of the KRd- or IRd-treated patients responded below a partial response. DISCUSSION/CONCLUSION: Clear patient profiles for each PI type were observed. In second-line therapy, younger, fitter, transplant-eligible patients received novel-PI-based triplets, e.g., KRd or IRd. Patients treated with lenalidomide in first-line therapy mostly received lenalidomide-sparing regimens in second-line therapy. In high-risk patients no clear treatment patterns could be ascertained due to the limited sample size.

Impact of novel agents on patient-relevant outcomes in patients with previously untreated chronic lymphocytic leukemia who are not eligible for fludarabine-based therapy.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is an orphan disease that primarily affects the elderly. The majority of symptomatic patients eligible for frontline treatment are unfit for fludarabine based chemoimmunotherapy. Historical treatment includes chlorambucil (Chl), bendamustine/rituximab (BR), and chlorambucil/rituximab/ChlR combination. Clinical guidelines now recommend the use of novel agents, such as ibrutinib (Ibr), in both frontline and relapse settings and other novel agents, such as idelalisib (with rituximab), in relapse settings. Despite compelling clinical results for novel agents, follow-up in clinical trials is relatively short and, thus, the comparative long-term benefits are still unknown. MATERIALS AND METHODS: The authors developed a simulation model to generate treatment specific lifetime estimates of Overall Survival (OS) and Quality Adjusted Life Years (QALYs) for treatment with BR, Chl, ChlR, and Ibr. Two potential clinical scenarios were modelled: with and without novel agents for treating CLL. The model was based on health states relating to first- and second-line progression-free survival (PFS), post-progression survival, and death. RESULTS: Where novel agents were assumed unavailable, mean OS ranged from 5.4-8.5 years and QALYs from 3.5-6.1. Where novel agents were available, the mean OS increased to 10.0 years, with a corresponding increase in QALYs to 7.6. Frontline Ibr use followed by Physician's Choice, including novel agents at relapse, resulted in projected increase in OS of between 18% (1.5 years) and 85% (4.6 years), corresponding to a 25-117% increase in QALYs, compared with currently available traditional therapies. LIMITATIONS: The limitations of this analysis include immature OS data and the assumption of equivalent efficacy across all novel agents in terms of their impact on PFS and OS. CONCLUSIONS: The use of novel agents is predicted to yield substantive gains in predicted lifetime OS and QALY improvements compared to traditional therapies in CLL patients who are ineligible for fludarabine-based chemoimmunotherapy.

EVEREST II high risk study based UK cost-effectiveness analysis of MitraClip® in patients with severe mitral regurgitation ineligible for conventional repair/replacement surgery.

OBJECTIVES: To evaluate the cost-effectiveness of MitraClip, an interventional procedure for patients with chronic severe mitral regurgitation. METHODS: A decision analytic model with a lifetime horizon was developed to assess the cost-effectiveness of MitraClip vs conventional medical management in patients with severe mitral regurgitation, ineligible for surgery. The analysis was performed from a UK NHS perspective and the estimates for mortality, adverse events, and cross-sectional NYHA class were obtained from the EVEREST II High Risk Study (HRS). Utility decrements were obtained from a heath technology assessment on Cardiac Resynchronization Therapy, while unit costs were obtained from national databases. The concept model was clinically validated. Costs (2011 £UK) and benefits were discounted at an annual rate of 3.5%. RESULTS: Compared to medical management, over 2- and 10-year periods MitraClip had incremental Quality Adjusted Life Year (QALY) gains of 0.48 and 2.04, respectively. The Incremental Cost-Effectiveness Ratios for MitraClip at 2 and 10 years are £52,947 and £14,800 per QALY gained. Overall, the model was most sensitive to the choice of time horizon, the discount rate applied to benefits, the starting age of cohort, the utility decrement associated with NYHA II, and cost of the MitraClip procedure. The model was insensitive to changes in all other parameters. MitraClip was also found to be cost-effective, regardless of the modelling approach, and insensitive to the key assumptions of the procedure cost. STUDY LIMITATIONS: The primary limitation of the analysis is the reliance on aggregate data from a modestly sized non-randomized study with a short-term follow-up period. Aligned to this was the need to extrapolate survival well beyond the study period in order to generate meaningful results. The impact of both of these limitations was explored via extensive sensitivity analyses. CONCLUSION: Compared to medical management, MitraClip is a cost-effective interventional procedure at conventional threshold values.