Roberto Di Virgilio

Background: Multiple myeloma remains an incurable malignancy in which patients ultimately experience relapses and refractory disease despite therapeutic advances. Triple-class exposed relapsed/refractory MM (TCE/RRMM) patients represent both a population with high unmet clinical needs and a substantial economic burden for the Italian National Health Service (NHS). Recently, BCMA-CD3 bispecific antibodies, including elranatamab and teclistamab, have expanded the treatment options for these patients. This study aimed to evaluate the cost-effectiveness of elranatamab versus teclistamab in adults with TCE/RRMM from the Italian NHS perspective. Methods: A partitioned survival model with three health states—progression-free survival, post-progression survival, and death—was developed over a 25-year lifetime horizon, adopting weekly cycles and a 3% annual discount rate. Clinical data for elranatamab were derived from the MagnetisMM-3 trial, while teclistamab outcomes were estimated through matching-adjusted indirect comparisons using MajesTEC-1 data. Direct medical costs included those associated with drug acquisition and administration, disease management, adverse event management, and end-of-life care. Utility values were obtained from EQ-5D-based assessments in MagnetisMM-3. Deterministic and probabilistic sensitivity analyses were performed to test model robustness. Results: Elranatamab yielded 3.31 life-years and 2.33 QALYs per patient, compared with 1.83 life-years and 1.27 QALYs for teclistamab. Total lifetime costs were lower for elranatamab (EUR 153,337) versus teclistamab (EUR 224,610), generating EUR 71,273 in savings. Thus, elranatamab is considered to be dominant, due to its higher efficacy and lower cost. Furthermore, the robustness of these findings was confirmed through sensitivity analyses. Conclusions: From the Italian NHS perspective, elranatamab represents a clinically superior and economically favorable option for patients with TCE/RRMM. The obtained results support its value and sustainability within the national treatment landscape.

The availability of a new 20-valent pneumococcal conjugate vaccine (PCV) makes it appropriate to assess its cost-effectiveness. This was evaluated by adopting the Italian National Health Service perspective, using a cost consequences Markovian model. The expected effects of vaccination with 20-valent PCV were compared with the administration of 13-valent PCV and 15-valent PCV. Assuming a 100% vaccination of cohorts aged 65–74 years, in the (lifetime) comparison between 20-valent PCV and 13-valent PCV, the former is dominant (lower cost for a better health outcome). A reduction in disease events was estimated: −1208 deaths; −1171 cases of bacteraemia; −227 of meningitis; −9845 hospitalised all-cause nonbacteremic pneumonia cases (NBP) and −21,058 non-hospitalised. Overall, in the Italian population, a total gain of 6581.6 life years and of 4734.0 QALY was estimated. On the cost side, against an increase in vaccinations costs (EUR +40.568 million), other direct health costs are reduced by EUR 48.032 million, with a net saving of EUR +7.464 million. The comparison between 20-valent PCV and 15-valent PCV results in an Incremental Cost-Effectiveness Ratio (ICER) of EUR 66 per life year gained and EUR 91 per QALY gained. The sensitivity analyses confirm the robustness of the results. We can conclude that the switch to 20-valent PCV is a sustainable and efficient investment.

Background: Invasive and non-invasive pneumococcal diseases are significant health and economic burdens, especially in children and the elderly. Italy included the 7-valent (PCV7) and 13-valent pneumococcal conjugate vaccine (PCV13) in the National Immunization Program in 2007 and 2010, respectively, allowing a dramatic reduction in the burden of pneumococcal disease. In the era of budget constraints, decision-makers may consider switching from the higher-valent, more costly PCV13, to the lower-cost PCV10. This study estimated the potential public health and economic impact of changing vaccine programs from PCV13 to PCV10 in Italy. Methods: A decision-analytic forecasting model estimated the impact of PCV programs. Real-world surveillance data were used to forecast serotype distribution and disease incidence among children and the elderly over a specified 5-year time horizon. Costs and outcomes included estimates of cases and deaths avoided, quality-adjusted life years (QALYs) gained, and total costs from a payer perspective, discounted at an assumed rate of 3.0%, and robustness validated through several scenarios and sensitivity analyses. Results: A switch from PCV13 to PCV10 would increase invasive pneumococcal disease (IPD) cases by 59.3% (4317 cases) over a 5-year horizon, primarily due to serotypes 3 and 19A. Pneumonia increased by 8.3% and acute otitis media (AOM) by 96.1%. Maintaining a PCV13 program would prevent a total incremental 531,435 disease cases (1.02M over a 10-year time horizon) and 641 deaths due to invasive pneumococcal disease (IPD), with €23,642 per QALY gained over 5 years versus PCV10. One-way and probabilistic sensitivity analyses showed that a PCV13-based program remained cost-effective in 99.7% of the simulations in Italy as parameters varied within their plausible range; percent vaccinated had the most impact. Conclusions: Maintaining the PCV13 strategy would provide substantial public health and economic benefits in Italy and is cost-effective. Switching from PCV13 to PCV10 would increase the incidence of pneumococcal disease primarily linked to re-emergence of serotypes 3 and 19A.

Background: The rising incidence of resistance to currently available antibiotics among pathogens, particularly Gram-negative pathogens, in complicated intra-abdominal infections (cIAIs) has become a challenge for clinicians. Ceftazidime/avibactam (CAZ-AVI) is a fixed-dose antibiotic approved in Europe and the United States for treating (in combination with metronidazole) cIAI in adult hospitalised patients who have limited or no alternative treatment options. The approval was based on the results of RECLAIM, a Phase III, parallel-group, comparative study (RECLAIM 1 [NCT01499290] and RECLAIM 2 [NCT01500239]). The objective of our study was to assess the cost-effectiveness of CAZ-AVI plus metronidazole compared with 1) ceftolozane/tazobactam plus metronidazole and 2) meropenem, as an empiric treatment for the management of cIAI in Italy. Methods: A sequential, patient-level simulation model, with a 5-year time horizon and 3% annual discount rate (applied to both costs and health benefits), was developed using Microsoft Excel® to demonstrate the clinical course of the disease. The impact of resistant pathogens was included as an additional factor. Results: In the base-case analysis, the CAZ-AVI sequence (CAZ-AVI plus metronidazole followed by a colistin + tigecycline + high-dose meropenem combination after treatment failure), when compared to sequences for ceftolozane/tazobactam (ceftolozane/tazobactam plus metronidazole followed by colistin + tigecycline + high-dose meropenem after treatment failure) and meropenem (meropenem followed by colistin + tigecycline + high-dose meropenem after treatment failure), had better clinical outcomes with higher cure rates (93.04% vs. 91.52%; 92.98% vs. 90.24%, respectively), shorter hospital stays (∆ = − 0.38 and ∆ = − 1.24 days per patient, respectively), and higher quality-adjusted life years (QALYs) gained per patient (4.021 vs. 3.982; 4.019 vs. 3.960, respectively). The incremental cost effectiveness ratio in the CAZ-AVI sequence was €4099 and €15,574 per QALY gained versus each comparator sequence, respectively, well below the willingness-to-pay threshold of €30,000 per QALY accepted in Italy. Conclusions: The model results demonstrated that CAZ-AVI plus metronidazole could be a cost-effective alternative when compared with other antibiotic treatment options, as it is expected to provide better clinical benefits in hospitalised patients with cIAI in Italy.

Pneumococcal conjugate vaccines (PCV) have significantly reduced the burden of invasive (IPD) and non-invasive pneumococcal disease, globally. In Italy, after 11 years of PCV use (PCV7, 2007-PCV13, 2010), we aimed to evaluate the future clinical and economic value of continuing the current PCV13 national immunization program (NIP) compared with a switch to PCV10.