RESUMEN
(1) Background: Data on combination or sequential treatment of spinal muscular atrophy (SMA) with disease-modifying drugs (DMDs) are missing and the latter field is poorly understood. The currently available data of patients on risdiplam previously treated with nusinersen are coming from exploratory research mainly focused on safety. Our aim was to investigate the real-world effectiveness (hypothesising non-inferiority) and safety profile of risdiplam in a paediatric-and-adult nusinersen-risdiplam spinal muscular atrophy switch cohort. (2) Methods: A retrospective and anonymous collection of relevant demographic and clinical data for all Croatian SMA patients switched from nusinersen to risdiplam up to September 2023 (reimbursed by Croatian Health Insurance Fund-CHIF) was performed using the CHIF database and associated reimbursement documentation. Patients were included in effectiveness and safety analysis if they met the following inclusion criteria: (i) risdiplam was reimbursed by the CHIF; (ii) the patient received at least six doses of nusinersen before the switch to risdiplam; (iii) there was no relevant pause between the latter disease-modifying drugs; (iv) availability of all prespecified studied data and parameters. (3) Results: In total, 17 patients met the inclusion criteria (58.9% female; median age 12.75 (3.0-44.5) years). In our 'switch' cohort, we demonstrated a non-inferiority of risdiplam to nusinersen in the SMA 1 (+1.0 in CHOP INTEND; p = 0.067), SMA 3p (+0.7 in HFMSE; p = 0.897), and SMA 3a (+0.8 in RHS; p = 0.463) subpopulations, during a one-year follow-up period. There were no reports on respiratory function worsening, feeding worsening, and no lethal events. No new safety concerns were identified, except for the weight gain that arose as a new potential adverse drug reaction 'signal' in two patients. (4) Conclusions: We have reported pivotal real-world findings on switching SMA patients from nusinersen to risdiplam and demonstrated its effectiveness (non-inferiority), safety, and tolerability in a heterogenous paediatric-and-adult 'switch' cohort; this will further increase the quality and standards of care as well as safety of a notable portion of SMA patients, especially for those who demand the switch from nusinersen to other DMDs for clinical or personal reasons.
RESUMEN
(1) Background: To investigate the real-world effectiveness and safety profile of nusinersen in Croatian paediatric and adult spinal muscular atrophy (SMA) patients. (2) Methods: A retrospective and anonymous collection of relevant demographic and clinical data for all Croatian SMA patients treated with nusinersen and reimbursed by the Croatian Health Insurance Fund (CHIF) between April 2018 and February 2022 was performed through searching the CHIF database and studying the associated reimbursement documentation. All patients who received at least one dose of nusinersen were included in the baseline clinical-demographic overview and safety analysis, whereas only subjects who had completed six doses were included in the effectiveness analysis. (3) Results: Fifty-two patients [61.5% male; median age 13.4 (0.1-51.1) yr.] received nusinersen treatment. In SMA type 1 and type 3 paediatric patients, statistically significant motor function improvement (CHOP INTEND 10.8 ± 10.3 vs. 20.0 ± 15.8, p = 0.003; HFMSE 49.6 ± 7.9 vs. 53.1 ± 7.7, p = 0.008; respectively) was achieved immediately after 4 loading doses of nusinersen and remained statistically significant onwards. Average improvements in HFMSE motor performance in SMA type 2 patients after four, five, and six doses of nusinersen were +6.0, +10.5, and +11.0 points, respectively. In SMA type 3 adult patients, no significant improvement in RHS motor performance or the 6-Minute Walk Test (MWT) was demonstrated. During the study period, 437 doses were administered without any new safety concerns appearing. (4) Conclusions: Our RWD findings indicate that nusinersen is an effective and safe treatment in a heterogeneous group of paediatric patients with all types of SMA; however, no significant benefit (but only RHS and 6MWT maintenance) was demonstrated in SMA type 3 patients who started nusinersen after >18 years of age.
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The need for innovative payment models for health technologies with high upfront costs has emerged due to affordability concerns across the world. Early technology adopter countries have been experimenting with delayed payment schemes. Our objective included listing potential barriers for implementing delayed payment models and recommendations on how to address these barriers in lower income countries of Central and Eastern Europe (CEE) and the Middle East (ME). We conducted a survey, an exploratory literature review and an iterative brainstorming about potential barriers and solutions to implement delayed payment models in these two regions. A draft list of recommendations was validated in a virtual workshop with payer experts from the two regions. Eight barriers were identified in 4 areas, including transaction costs and administrative burden, payment schedule, information technology and data infrastructure, and governance. Fifteen practical recommendations were prepared to address these barriers, including recommendations that are specific to lower income countries, and recommendations that can be applied more universally, but are more crucial in countries with severe budget constraints. Conclusions of this policy research can be considered as an initial step in a multistakeholder dialogue about implementing delayed payment schemes in CEE and ME countries.
RESUMEN
BACKGROUND: Efficiency and transparency of pricing and reimbursement (P&R) rules and procedures as well as their implementation in South-eastern Europe (SEE) lag substantially behind Western European practice. Nevertheless, P&R systems in SEE are rarely critically assessed, warranting a detailed and wider-encompassing exploration. OBJECTIVE: Our study provides a comparative assessment of P&R processes for patent-protected medicines in ten SEE countries-EU member states: Croatia, Slovenia, Hungary, Romania and Bulgaria; and non-EU countries: Albania, Montenegro, Serbia, North Maceodina, Bosnia and Herzegovina. P&R systems are compared and evaluated through a research framework that focuses on: (1) public financing of patent-protected medicines, (2) definition of benefit packages, (3) requirements for the submission of reimbursement dossiers, (4) assessment and appraisal processes, (5) reimbursement decision making, (6) processes that occur post reimbursement, and (7) pricing. The study aims to contribute to the discussion on improving the efficiency and quality of P&R of patent-protected medicines in the region. METHODS: We conducted a non-systematic literature review of published literature, as well as policy briefs and reports on healthcare systems in the SEE region along with legal documents framing the P&R procedures in local languages. The information gathered from these various sources was then discussed and clarified through structured telephone interviews with relevant national experts from each SEE country, mainly current and former senior officials and/or executives of the funding and assessment/ appraisal bodies (total of 20 interviews conducted in late 2019). RESULTS: Capacity building through sharing knowledge and information on successful reforms across borders is an opportunity for SEE countries to further develop their P&R policies and increase (equitable) access to patent-protected medicines (especially expensive medicines), increasing affordability and containing costs. Simple yet robust and systematic decision-making frameworks that rely on international health technology assessment (HTA) procedures and are based on the pursuit of transparency seem to be the most cost-effective approach to strengthening P&R systems in SEE. CONCLUSIONS: Further reforms aiming to develop transparent and robust national decision-making frameworks (including oversight) and build institutional HTA-related and decision-making capacity are awaited in most of SEE countries, especially the non-EU members. In non-EU SEE countries, these efforts could increase access to patent-protected medicines, which is-at the moment-very limited. The EU-member SEE countries operate more developed P&R systems but could further benefit from developing their procedures, oversight and value-for-money assessment toolbox and capacity, hence further improving the transparency and efficiency of procedures that regulate access to patent-protected medicines.
