Real-world patient characteristics, treatment patterns and costs in relapsing multiple sclerosis patients treated with glatiramer acetate, dimethyl fumarate or teriflunomide in Germany

Aim: To evaluate adherence, healthcare resource utilization (HRU) and costs for glatiramer acetate (GA; injectable), dimethyl fumarate (oral) and teriflunomide (oral) in relapsing multiple sclerosis. Patients & methods: Retrospective analyses of a claims database. Results: Teriflunomide patients were older with more co-morbidities and fewer relapses versus GA and dimethyl fumarate. GA patients were mostly disease-modifying therapies (DMTs)-treatment naive. Treatment adherence was 61–70%. All DMTs reduced HRU versus pre-index. Costs were comparable across cohorts. High adherence reduced hospitalizations and several costs versus low adherers. Conclusion: Adherence rates were high and comparable with all DMTs. Similar (and high) reductions in HRU and costs occurred with all DMTs. High adherence improved economic outcomes versus low adherence. Thus, investing in adherence improvement is beneficial to improve outcomes in relapsing multiple sclerosis.

Effect of ofatumumab versus placebo in relapsing multiple sclerosis patients from Japan and Russia: Phase 2 APOLITOS study

Background: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, has been developed as a treatment for relapsing multiple sclerosis (RMS) which can be self-administered at home. Objective: To investigate the efficacy and safety of ofatumumab in RMS patients from Japan and Russia. Methods: APOLITOS included a 24-week, double-blind, placebo-controlled core-part followed by an open-label extension-part. Patients were randomized (2:1) to subcutaneous ofatumumab 20 mg or placebo. Primary outcome was the number of gadolinium-enhancing (Gd+) T1 lesions per scan over 24 weeks. Results: Sixty-four patients were randomized (ofatumumab, n = 43; placebo, n = 21). Primary endpoint was met; ofatumumab reduced Gd + T1 lesions versus placebo by 93.6% ( p < 0.001) and the results were consistent across regions (Japan/Russia). Ofatumumab reduced annualized T2 lesion and relapse rate versus placebo by week 24. Both groups showed benefit from ofatumumab in the extension-part. Incidence of adverse events was lower with ofatumumab versus placebo (69.8% vs 81.0%); injection-related reactions were most common. No deaths, opportunistic infections, or malignancies were reported. Conclusion: Ofatumumab demonstrated superior efficacy versus placebo, with sustained effect through 48 weeks in RMS patients from Japan/Russia. Switching to ofatumumab after 24 weeks led to rapid radiological and clinical benefits. Safety findings were consistent with pivotal trials.

Long-Term Safety and Efficacy of Subcutaneous Cladribine Used in Increased Dosage in Patients with Relapsing Multiple Sclerosis: 20-Year Observational Study

Cladribine is currently registered as a 10-milligram tablet formulation with a fixed cumulative dosage of 3.5 mg/kg over 2 years. It is important to investigate if an increased dosage may lead to further clinical stability with preserved safety. This study used an off-label subcutaneous (s.c.) formulation of cladribine and compared outcomes (Expanded Disability Status Scale (EDSS) scores and disease progression) between 52 relapsing multiple sclerosis (RMS) patients receiving different s.c. dosing regimens with up to 20 years of follow-up. The study group received induction therapy with s.c. cladribine (1.8 mg/kg cumulative dose; consistent with 3.5 mg/kg of cladribine tablets). Patients were subsequently offered maintenance therapy (repeated courses of 0.3 mg/kg s.c. cladribine during 5–20-year follow-up). Forty-one patients received an increased cumulative dose (higher than the induction dose of 1.8 mg/kg); 11 received the standard induction dose. Risk of progression on the EDSS correlated with lower cumulative dose (p < 0.05) and more advanced disability at treatment initiation (p < 0.05) as assessed by EDSS change between year 1 and years 5 and 10 as the last follow-up. Maintenance treatment was safe and well-tolerated, based on limited source data. Subcutaneous cladribine with increased cumulative maintenance dosage was associated with disease stability and favorable safety over a prolonged period of follow-up (up to 20 years) in RMS patients.

Cladribine tablets are a cost-effective strategy in high-disease activity relapsing multiple sclerosis patients in Iran

Background: Cladribine tablets are the foremost oral immune-reconstitution therapy for high disease activity relapsing multiple sclerosis (HDA-RMS). We aimed to assess the cost-effectiveness of cladribine tablets compared to natalizumab in patients with HDA-RMS in Iran. Methods: A 5-year cohort-based Markov model was developed with 11 expanded disability status score (EDSS) health states, including patients with HDA-RMS as on and off-treatment. All costs were identified from the literature and expert opinion and were measured in Iranian Rial rates, changed to the 2020 USD rate and were discounted by 7.2%. Quality adjusted life years (QALY), discounted by 3.5%, and life years gained (LYG) were adopted to measure efficacy. The final results were presented as incremental cost-effectiveness ratio that was compared to a national willingness to pay (WTP) threshold of 1 to 3 gross domestic product (GDP) per capita. Deterministic and probabilistic sensitivity analyses (D/PSA) were employed to evaluate uncertainty. Results: Cladribine tablets dominated natalizumab and yielded 6,607 USD cost-saving and 0.003 additional QALYs per patient. LYG was comparable. The main cost component was drug acquisition cost in both arms. DSA indicated the sensitivity of the results to the cost discount rates and also the patients’ body weight; while they were less sensitive to the main clinical variables. PSA indicated that cladribine tablets were cost-effective in Iran, with a probability of 57.5% and 58.6% at lower and higher limits of threshold, respectively. Conclusion: Cladribine tablets yielded higher QALYs and lower costs compared to natalizumab, in patients with HDA-RMS in Iran.

Cost-effectiveness of ocrelizumab for treatment of Iranian patients with relapsing multiple sclerosis

Background: The current study desired to conduct an economic analysis on ocrelizumab (OCR), a new relapsing multiple sclerosis (RMS) treatment strategy, in comparison to natalizumab (NTL), as one of the mostly-used disease-modifying therapies (DMTs) in Iran. Methods: A 31-health-state Markov model, based on Expanded Disability Status Scale (EDSS), containing patients on- and off-treatment with annual cycles was developed. Baseline demographics and utility scores were extracted from OPERA 1 and 2 trials. Confirmed disability progression (CDP) and annualized relapse rates (ARR) were extracted from the literature. Mortality was calculated based on age, sex, and disease state. Quality-adjusted life years (QALYs) and life years gained (LYG) were measurements of efficacy. Direct and indirect costs were identified and calculated based on the national book of tariffs in Iranian Rial (IRR) rates, then converted to the 2020 United States Dollar (USD). Final results were reported in terms of incremental cost-effectiveness ratio (ICER), which showed extra costs required for one additional QALY. Robustness of the model was analyzed through deterministic sensitivity analysis (DSA) and probabilistic sensitivity analysis (PSA). Results: OCR dominated NTL and was associated with cost-savings of 6971 USD, longer LYG (0.004), and higher QALYs (0.27). Although OCR had higher acquisition costs, which was the main component in both comparator arms, it was associated with lower total costs, due to lower disability progression and productivity loss. Results remained robust in DSA and PSA (93.5% cost-effectiveness in Iran’s pharmacoeconomic threshold, 2709 USD). Conclusion: Results suggested that OCR was a more cost-effective option than NTL for the treatment of patients with RMS in Iran.

Acid Treatments Attenuate the Progression and Prevent the Onset of Experimental Autoimmune Encephalomyelitis

Preprint Remitting-relapsing multiple sclerosis is now considered a treatable disease thanks to disease modifying treatments with good efficacy of reducing relapses. In contrast, effective treatment of progressive multiple sclerosis remains elusive. Using a murine experimental autoimmune encephalomyelitis (EAE) model, this study showed that acid treatments at early stages of EAE attenuated disability progression to advanced stages. When acid treatments were initiated prior to the onset of disease, onset of EAE was prevented or delayed. Histological analysis showed that the acid treatments cleared inflammation in the spinal cords. These results suggest that all forms of multiple sclerosis could be effectively prevented or treated with pH modifiers such as acids.