Patients with multiple sclerosis who received natalizumab therapy had lower relapse rates and reduced inflammation.
Natalizumab (NTZ) was found to be an effective treatment for reducing inflammation and relapse rates in patients with multiple sclerosis (MS), according to a study in Russia published by PLOS ONE.
Researchers sought to characterize patients receiving NTZ in Russia and evaluate the efficacy and safety of NTZ treatment. They conducted an observational cross-sectional study with retrospective data analysis. Data were collected in 2018 from 7 MS centers throughout Russia. A total of 334 patients who received at least 1 infusion of NTZ were included in the study.
"Even though NTZ has been registered in Russia in 2010, no multi-center observational studies investigating the effect of NTZ in a routine clinical practice have been conducted," the authors wrote. "The real profile of patients, receiving NTZ in Russia is currently unknown."
Researchers performed efficacy analysis with information regarding the number of relapses during 24 months prior to NTZ initiation and every year they received treatment. They divided relapses prior to NTZ treatment into 24 to 12 months and 12 to 0 months. Relapses were registered and included into analysis when acute or subacute new or worsening neurological symptoms that lasted longer than 24 hours appeared.
Brain magnetic resonance imaging (MRI) scans were performed using standard protocols on 1.5T and 3.0T machines. Lesions that had grown were considered to be new. MRI data for the number of new T2 and T1 gadolinium enhancing (Gd+) lesions were analyzed for 12 months before NTZ initiation and every 6 months while patients received treatment. Expanded Disability Status Scale (EDSS) scores were analyzed every 6 months. No evidence of disease activity (NEDA-3) was assessed at year 2 in cases with data on 3 criteria: the number of relapses, EDSS progression, and new lesions on MRI.
A year prior to NTZ treatment, 7.19% of patients had no relapses, 26.05% patients had 1 relapse, 30.24% patients had 2 relapses, and 36.52% had 3 or more relapses. MRIs were also conducted for 217 patients a year prior to NTZ treatment. A total of 57.6% of patients had at least 1 new T2 brain lesion and 81.57% had 1 or more T1 Gd+ lesions. The number of patients who demonstrated active disease at baseline with both relapses and new T2 or T1 brain lesions on MRI was 62.13%.
The median duration of NTZ therapy, recorded for 332 patients with available data, was 17.10 months. Of the 334 patients at baseline, 2 didn’t have certain information regarding the end date of therapy. A total of 42.17% of patients received NTZ treatment for less than a year, 30.42% received it for 12 to 23 months, 19.88% of patients received it for 24 to 35 months, and 7.53% received it for more than 36 months. The maximal duration of treatment was 79.03 months. In total, all patients received 4611 infusions throughout the study.
The relapse rate of NTZ therapy was analyzed for 57.49% patients after 1 year and for 23.05% of patients who received it for at least 2 years and had available data. MRI dynamic data were available for 41.15% of patients after 1 year and for 32.47% of patients after 2 years who received NTZ and had available data.
Researchers assessed EDSS progression at 2 years. For the analysis of disability progression, they included 98 patients who received NTZ therapy for 24 months and those who didn’t but reached disease progression earlier than 2 years. At 24 months, 8 out of 98 (8.16%) of patients reached 6-months confirmed disability progression (6-m CDP), 2 out of 98 (2.04%) progressed during the first 12 months, and 6 out of 98 (6.12%) progressed 12 to 24 months after switching to NTZ treatment.
NEDA status was assessed for patients who received NTZ for no less than 2 years. Analysis was conducted for 22 out of 77 patients (28.57%) with all data available at the 24 months. NEDA-3 was reached by 18 out of 22 (81.82%) of those patients.
Researchers found that NTZ treatment had a great impact on MS activity. NTZ therapy led to a significant decrease of inflammatory activity, according to relapse rate and MRI activity. Patients had significantly lower relapse rates after 2 years of NTZ therapy—the median number of relapses during first and second years of therapy tended to be zero. MRI activity was nearly completely suppressed, proving NTZ treatment was strongly effective for highly-active patients, according to the authors. EDSS scores were mostly stable during 2 years of therapy, with only 8 patients having 6m-CDP. NEDA-3 was reached by 82% of patients.
High EDSS scores at the time of NTZ initiation was shown to be the only factor that predicted 6-m CDP after 2 years. Researchers stated their data confirms previous findings that patients with low EDSS who received NTZ have lower relapses and subsequently have lower chances for disability progression. Researchers recommended that NTZ treatment should be initiated as early as possible in patients with active disease in order to prevent disability progression.
Researchers also mentioned that risk management plan (RMP) compliance was only 36%. They stated that NTZ therapy requires a better reimbursement strategy and stronger attention of all participants involved, including neurologists, healthcare regulators, and manufacturers, to provide patients with better disease control and safety follow-up. They stated that more resources are needed to provide patients with timely MRIs to implement the RMP, which they believe may decrease the number of patients who stop therapy due to the fear of progressive multifocal leukoencephalopathy. They suggested many patients may be able to continue to receive the treatment with a greater frequency of MRI monitoring.
“NTZ is a highly efficacious [disease-modifying therapies] for active MS. Taking into consideration complex issues of therapy management, NTZ should be administered only in specialized MS centers where the physicians have enough resources, experience and knowledge,” researchers concluded.
Evdoshenko E, Stepanova A, Shumilina M, et al. Real-world study of efficacy, risk management and reasons for discontinuation of natalizumab for treatment of multiple sclerosis in Russia. PLoS ONE. 2019;14(5). doi: 10.1371/journal.pone.0217303.