Clinical and economic evaluations of natalizumab, rituximab, and ocrelizumab for the management of relapsing-remitting multiple sclerosis in Saudi Arabia

Abstract

Introduction The advent of new disease-modifying therapies (DMTs), such as monoclonal antibodies (mAbs), resulted in significant changes in the treatment guidelines for Multiple sclerosis (MS) and improvement in the clinical outcomes. However, mAbs, such as rituximab, natalizumab, and ocrelizumab, are expensive with variable effectiveness rates. Thus, the present study aimed to compare the direct medical cost and consequences (e.g., clinical relapse, disability progression, and new MRI lesions) between rituximab and natalizumab in managing relapsing-remitting multiple sclerosis (RRMS) in Saudi Arabia. Also, the study aimed to explore the cost and consequence of ocrelizumab in managing RRMS as a second-choice treatment. Methods The electronic medical records (EMRs) of patients with RRMS were retrospectively reviewed to retrieve the patients’ baseline characteristics and disease progression from two tertiary care centers in Riyadh, Saudi Arabia. Biologic–naïve patients treated with rituximab or natalizumab or those switched to ocrelizumab and treated for at least six months were included in the study. The effectiveness rate was defined as no evidence of disease activity (NEDA-3) (i.e., absence of new T2 or T1 gadolinium (Gd) lesions as demonstrated by the Magnetic Resonance Imaging (MRI), disability progression, and clinical relapses), while the direct medical costs were estimated based on the utilization of healthcare resources. In addition, bootstrapping with 10,000 replications and inverse probability weighting based on propensity score were conducted. Results Ninety–three patients met the inclusion criteria and were included in the analysis (natalizumab (n = 50), rituximab (n = 26), ocrelizumab (n = 17)). Most of the patients were otherwise healthy (81.72%), under 35 years of age (76.34%), females (61.29%), and on the same mAb for more than one year (83.87%). The mean effectiveness rates for natalizumab, rituximab, and ocrelizumab were 72.00%, 76.92%, and 58.83%, respectively. Natalizumab mean incremental cost compared to rituximab was $35,383 (95% CI: $25,401.09– $49,717.92), and its mean effectiveness rate was 4.92% lower than rituximab (95% CI: -30–27.5) with 59.41% confidence level that rituximab will be dominant. Conclusions Rituximab seems to be more effective and is less costly than natalizumab in the management of RRMS. Ocrelizumab does not seem to slow the rates of disease progression among patients previously treated with natalizumab.

Real‐World Healthcare Cost Savings and Reduced Relapse Rate with Off‐Label Rituximab versus Disease‐Modifying Treatments Approved for Relapsing–Remitting Multiple Sclerosis: A Nationwide Cost‐Effectiveness Study

“…The only previous cost-effectiveness studies of rituximab in MS were two smaller observational studies from Saudi Arabia (including 146 and 93 patients, of which 12 and 26 were treated with rituximab, respectively) and 2 simulation studies from Iran and Thailand, respectively. [28][29][30][31] Although severely limited by their size or use of simulation instead of real-world data, the results were broadly in line with our findings. Additionally, a study by a US healthcare provider indirectly assessed the cost-effectiveness of rituximab as part of the evaluation of their MS treatment optimization program.…”

Cost-utility and cost-effectiveness analysis of disease-modifying drugs of relapsing–remitting multiple sclerosis: a systematic review

“…In this review, 3 studies evaluated the cost-effectiveness of rituximab and showed RRMS patients receiving rituximab had lower costs and more QALYs when compared with natalizumab [29,62]. Smet et al in the Netherlands suggested rituximab would already be the most cost-effective anti-CD20 mAb if its efficacy on 6-month CDP is comparable to traditional first-line therapies such as interferon-beta but there are no accurate estimates of rituximab's effect on disability progression [53].…”

“…In two studies, symptom management [63] and BSC [22] strategies were analyzed in addition to these two forms of medications. Three study analyzed only intravenous infusions DMDs for RMS [29,43,61,62] (Table 2).…”