Introduction: Multiple myeloma (MM) is an incurable disease characterized by the proliferation of malignant plasma cells within the bone marrow, causing a wide range of burdensome symptoms. Patients initiating treatment typically receive a combination of drugs across various classes with or without autologous stem cell transplantation (ASCT). However, patients will invariably relapse following initial treatment, and often require many lines of drug treatment over the course of their disease. Real-word data showed that a significant proportion of newly diagnosed MM patients that receive frontline (FL) treatment did not receive subsequent treatment. These high attrition rates suggest that using the best treatment upfront is crucial in delaying disease progression. The CASSIOPEIA (transplant-eligible [TE] setting), MAIA and ALCYONE (transplant-ineligible [TIE] setting) trials demonstrate that the addition of daratumumab (DARA) to standard of care treatments in FL significantly improves patient outcomes. Based on data from these trials, the European marketing authorization for DARA has been extended to the FL setting. To ensure the best possible long-term patient outcomes in clinical practice, the availability of new FL treatment options requires a redefinition of treatment patterns. Thus, we aim to investigate whether the adoption of DARA as a FL, as opposed to later-line, treatment of MM leads to better outcomes and improved clinical practice. Methods: In the absence of real-world sequencing data, we developed a clinical sequencing simulation using individual patient data from the DARA trials and indirect comparative evidence, across all indications in MM. We used progression-free survival curves to simulate health state transition probabilities across four lines of active treatment, to capture the efficacy of treatment sequences in MM. Patients start with initiation of FL treatment, and ASCT eligibility determines the sequences patients receive. Clinical expert opinion was sought to determine 1) the full range of meaningful treatment sequences and 2) which of these are used most in Italian clinical practice. Based on the clinical simulation outcomes, we calculated average time spent in each line of treatment, percentage of patients alive at different timepoints, and the total survival for patients initiating a sequence. This analysis included conservative attrition rates from trial data, 14% for TE (CASSIOPEIA) and 24% for TIE (MAIA/ALCYONE), assumed as similar across regimens in each setting. Results: In the TE setting, the best outcomes were achieved when using the DARA-based regimen (DVTd) as FL treatment, followed by either a LEN-based regimen (KRd) or a BOR-based regimen (PVd), resulting in a total survival of 14.2 and 14.1 years, respectively. In the TIE setting, the best outcomes were achieved when DRd or DVMP were used as FL treatment, followed by either a BOR-based regimen (PVd, for DRd) or a LEN-based regimen (KRd, for DVMP), resulting in a total survival of 11.7 and 10.9 years, respectively. In both the FL and second line (2L) settings, there was a clear survival benefit of using DARA. When comparing the DARA-based sequence with the current FL TE benchmark sequence (DVTd + KRd + Pd + Vd versus VTd + DRd + Kd + Pd), an additional survival of 1.5 years was observed in TE patients. When DARA was added to the current FL TIE benchmark sequence (DRd + PVd + Kd + Vd versus VMP + DRd + Kd + Pd), TIE patients lived on average 2.8 years longer. For TE patients, time spent progression-free ranged from an average of 4.83 to 7.99 years at FL, 1.42 to 5.40 years in 2L, 0.23 to 2.24 years in 3L and 0.17 to 1.53 years on 4L. For TIE patients, the variation was higher, leaving more room for optimization: 1.97 to 7.31 years at FL, 0.68 to 4.76 years in 2L, 0.17 to 3.25 years in 3L and 0.19 to 0.51 years in 4L. Conclusion: To our knowledge, this is the first sequencing simulation to consider optimal patient outcomes across several lines of MM treatment. The results show that the longest time in remission is achieved with the use of DARA-based regimens as FL treatment, significantly improving patient outcomes. Time spent progression free decreases with each subsequent line of treatment and the magnitude of the effect seen in the third and fourth treatment lines is not as significant as that of the effect seen in earlier treatment lines. Therefore, patients should be treated with the most effective treatment upfront. Disclosures Petrucci: Celgene: Honoraria, Other: Advisory Board; Janssen-Cilag: Honoraria, Other: Advisory Board; BMS: Honoraria, Other: Advisory Board; Takeda: Honoraria, Other: Advisory Board; Amgen: Honoraria, Other: Advisory Board; GSK: Honoraria, Other: Advisory Board; Karyopharm: Honoraria, Other: Advisory Board. Mendes: Janssen-Cilag Farmacêutica: Current Employment. Boer: Janssen: Consultancy. Casamassima: Janssen: Current Employment. Willis: Janssen: Consultancy. Wadlund: Janssen: Current Employment. Matthijsse: Janssen: Consultancy. Armeni: Astrazeneca: Consultancy; Boehringer Ingelheim: Consultancy; Novartis: Consultancy; Sanofi: Consultancy; Johnson & Johnson: Consultancy; Amgen: Consultancy; Janssen: Consultancy.

model with incremental cost-effectiveness ratios or quality-adjusted life-years as outcome measures. Specific information on the decision-analytic models, including the modeling approach, perspective, population studied, interventions and data sources were extracted from each article. RESULTS: 1834 citations were screened and 68 full-text articles retrieved. Overall, 31 model-based studies were identified for extraction: 29 cohort-based state-transition models, one decision tree model, and one other cost-effectiveness model. Comparators included drugs such as dopamine agonists, entacapone, and rasagaline, as well as surgically implanted devices such as deep brain stimulation and levodopa-carbidopa intestinal gel. Overall, 10 modeled only early PD, 7 focused on advanced PD, 10 included early and late stage PD, and 4 did not specify stage. The most commonly modeled health outcomes were Hoehn and Yahr stage progression and % off-time. Other outcomes include motor complications, fluctuations, dyskinesia, falls, and dementia. CONCLUSIONS: The models identified typically had simple frameworks. Many projected disease progression from short-term clinical trial data alone and did not leverage real world observational data now available with longer longitudinal follow-up. Clinical efficacy was often applied by affecting only the initial distribution across health states, which likely does not fully capture the benefits of a treatment. Future studies should explore developing individual patient simulations to be able to more realistically represent the heterogeneity observed in the clinical manifestations and progression rates of the disease, as well as capture the potential benefits and risks of symptomatic or disease modifying treatments.

compared to TAU was performed using within-trial costs and outcomes data adopting the NHS perspective. Costs were calculated in 2017UK£ and include the cost of the COTiD-UK training for occupational therapists, the COTiD-UK intervention to person with dementia and supporters, the cost of NHS resource use (e.g. A&E and hospital admissions, GP consultations, etc.), medications, adaptations and equipment costs and changes in accommodation. The effectiveness of the intervention, captured using EQ5D-5L and DEMQOL questionnaires in both arms, were converted into QALYs, both for the person with dementia and the supporters. Extensive sensitivity analysis has been performed to control for uncertainty in the parameter values used. RESULTS: The preliminary results of the analysis show that at 26 weeks there is some evidence that NHS costs are significantly higher in the COTiD-UK arm for person with dementia alone and for the person with dementia and supporters combined: this is mainly due to the cost of the COTiD-UK intervention. There is some evidence that in the intervention arm QALYs are higher in the person with dementia, but the findings are not statistically significant. Further work is currently exploring the broader societal costs and also modelling the long-term results beyond the trial. CONCLUSIONS: The preliminary results of this analysis seem to suggest that COTiD-UK is effective for the person with dementia, but the ICER is exceeding the recommended threshold of £20,000 per QALY. However these results do not take into account the societal costs (private costs, transport costs, productivity losses) for person with dementia and supporters, that may provide better results.

The primary outcome was the discontinuation rate of treatment (for any cause). The secondary outcome was the "increased disease activity" rate as measured by the scores (SDAI, BASDAI and CASPAR). It was as "increased disease activity", any measure higher than the initial, and that was above the remission limit of the disease. The reference values for "increased disease activity" were the historical measures. The economic impact measured by a cost minimization analysis. RESULTS: In September 2017, 5 (6%) patients who switched from REMICADE to REMSIMA, discontinued therapy (04 due to failure and 01 loss of follow-up). The reference discontinuation rate (REMICADE) was 11% (9% failure and 2% loss of follow-up). Subgroup analyzes (discontinuation of therapy by type of pathology) were equivalent. The rate of "increased disease activity" occurred in 42% of patients for REMSIMA, and 46% for REMICADE. Subgroup analyzes (by type of pathology) also showed that rates of increase in disease activity were similar between groups. The economic analysis showed that the change from REMICADE to REMSIMA

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