Long-term outcome and predictors of long-term disease activity in natalizumab-treated patients with multiple sclerosis: real life data from the Austrian MS Treatment Registry

Abstract

Objectives To evaluate long-term effectiveness of natalizumab (NTZ) and to determine demographic, clinical, and radiological predictors regarding long-term disease activity (≥ 7 years) in a nationwide observational cohort, using data collected prospectively in a real-life setting. Materials and methods We analysed data from 230 patients from the Austrian Multiple Sclerosis Treatment Registry (AMSTR), who had started treatment with NTZ at any time since 2006 and stayed on NTZ for at least 7 years without treatment gap of more than three months. Results Estimated mean annualised relapse rates (ARR) over a mean treatment period of 9.3 years were 0.07 for NTZ. Sustained EDSS progression for 12 weeks was observed in 36 (19%) patients and for 24 weeks in 31 (16.3%) cases. Sustained EDSS regression for 12 and 24 weeks was seen in 45 (23.7%) and 42 (22.1%) cases. The baseline parameters ≥ 1 Gadolinium-enhancing MRI lesion(s) [incidence rate ratio (IRR) of 0.409 (95% CI 0.283–0.593), p = 0.001], ARR ≤ 1 in the prior 12 month before treatment initiation with NTZ [IRR of 0.353 (95% CI 0.200–0.623), p = 0.001] and EDSS ≤ 1 [incidence rate ratio (IRR) of 0.081 (95% CI 0.011–0.581), p = 0.012] were significantly associated with a reduced relapse risk, whereas a disease duration ≤ 5 years increased significantly the ARR [IRR of 1.851 (95% CI 1.249–2.743), p = 0.002]. The only predictive baseline parameter for experiencing EDSS progression (sustained for 12 and 24 weeks) was age > 35 years [HR of 2.482 (95% CI 1.110–5.549), p = 0.027, and HR of 2.492 (95% CI 1.039–5.978), p = 0.041, respectively]. Conclusions These real-life data show a stable disease course regarding relapse activity and disease progression under NTZ treatment for more than 7 years. The main predictors for disease activity were higher relapse rate before treatment initiation, higher disability, shorter disease duration and absence of Gadolinium-enhancing MRI lesions at baseline. Older age at NTZ start was the only significant risk factor for disease progression over long-term.

Use of natalizumab in persons with multiple sclerosis: 2022 update

“…The long-term studies (Boziki et al, 2021;Butzkueven et al, 2020a;Guger et al, 2021;Prosperini et al, 2017) confirm that natalizumab is a highly effective treatment option for PwMS. Risk stratification for PML and risk management strategies that include patient education and close monitoring have improved outcomes and reduced the number of natalizumab-associated PML incidences (Vivekanandan et al, 2021;Vukusic et al, 2020).…”

“…When initiated early in the disease course, natalizumab was associated with fewer relapses and reduced disability worsening (Butzkueven et al, 2020a;Wiendl et al, 2021). The long-term effectiveness of natalizumab was also described in other real-world studies (Boziki et al, 2021;Davidescu et al, 2021;Efthimios et al, 2021;Guger et al, 2021;Horakova et al, 2020;Prosperini et al, 2017). Results from these studies indicate that, when administered long-term, natalizumab is effective and has an adequate safety profile, provided subjects are closely monitored.…”

“…Anti-JCV antibody seropositivity and increased risk for PML is the most common reason for natalizumab discontinuation (Boziki et al, 2021;Chisari et al, 2021;Coerver et al, 2021;Guger et al, 2021;Hersh et al, 2020;Karanasios et al, 2021). If JCV index is > 1.5, management options include extending the dosing interval of natalizumab or switching to an alternative DMT.…”

Monoclonal Antibodies in the Treatment of Relapsing Multiple Sclerosis: an Overview with Emphasis on Pregnancy, Vaccination, and Risk Management

“…Long-term data of natalizumab effectiveness from the Austrian MS Treatment Registry show a stable disease course regarding relapse activity and disease progression under natalizumab treatment for more than 7 years, with older age at natalizumab start (> 35 years) being the only significant risk factor for disease progression over long-term [ 24 ].…”

Real-World Effectiveness of Natalizumab in Korean Patients With Multiple Sclerosis

“…After two pivotal phase 3 clinical studies (AFFIRM and SENTINEL), natalizumab was approved for relapsing-remitting MS (RRMS) in 2004 by the US Food and Drug Administration and in 2015 by the Korea Food and Drug Administration (4)(5)(6). Observational studies demonstrated the long-term effectiveness and well-established safety profile of natalizumab (7,8). However, the predominant concern with the use of natalizumab is its association with the development of progressive multifocal leukoencephalopathy (PML), a rare serious opportunistic infection caused by the John Cunningham virus (JCV), which can cause severe disability or even death.…”