Real-world study of efficacy, risk management and reasons for discontinuation of natalizumab for treatment of multiple sclerosis in Russia

Abstract

Background NTZ is approved in Russia for the treatment of highly active relapsing remitting multiple sclerosis and is reimbursed via federal budget program. However, no data about NTZ treatment in Russia and the effect of federal reimbursement have been performed so far. Objective To characterize the population of patients receiving natalizumab and assess the efficacy and risk-management plan (RMP) implementation of NTZ therapy in routine clinical practice in Russia. Methods We analyzed data for 334 patients, who received at least one infusion of NTZ. Relapse rate, MRI activity, NEDA-3 status after 2 years were assessed. Anti-JC virus antibodies status and RMP implementation were evaluated. Drop-out rate and reasons for therapy discontinuation were analyzed. Results Patients switched to natalizumab in Russia are mainly female (63%), with median EDSS score of 3.5 and high disease activity: 93% had at least 1 relapse and 58% had both T1Gd+ and new T2 lesion a year before therapy initiation. Introduction of federal reimbursement allowed patients with less relapses to start therapy with natalizumab. The only predictor of 6-month progression was EDSS score at the baseline of therapy (HR = 2.1375, 95%CI 1.0026–4.5570, p = 0.0492). 82% patients reached NEDA-3 at 24 month of therapy. 25% of patients discontinued NTZ for reasons: tolerability (14.5%), JCV antibody status (61%), and patient’s decision (17%). RMP was implemented in only 36% patients. Conclusion Natalizumab appeared to have high efficacy in Russian clinical practice. Federal reimbursement allowed less active patients to start natalizumab. More efforts should be done to improve RMP implementation.

Patient and treatment characteristics and safety outcomes of patients with relapsing-remitting multiple sclerosis treated with natalizumab in Greece: Results from the multicenter, 5-year prospective observational study ‘TOPICS greece’

“…The 50.7% overall treatment discontinuation rate in TOPICS Greece is within the range of 17.78-52.2% reported in other observational studies of natalizumab in RRMS. 14 , 15 , 17 , 21 , 22 The treatment discontinuation rate due to AE occurrence (including PML and cancer) was 5.2%.…”

Adherence to self-administering interferon-β1a using RebiSmart® device in Mexican patients with relapsing multiple sclerosis

“…aimed to control MS activity is still challenging. The most frequent causes for discontinuation of medications are disease progression, patient-perceived lack of efficacy, injection anxiety, and adverse effects including injection-site reactions, flu-like symptoms, reversible cognitive impairment, and fatigue [6][7][8][9]. Also, financial aspects, such as cost of therapies, co-payments to medical insurers, and other societal factors, are essential for the decision to leave medications, especially in low-to middle-income countries.…”

“…According to data from the European Multiple Sclerosis Therapy Consensus Group, patients usually discontinue treatment after three years [6]. Adherence rates to DMTs range from 41% to 88%; in retrospective studies, weighted mean adherence is 53.1% versus…”

“…As a consequence, no adherence is defined as the "failing to fill prescriptions, delaying prescription fills, reducing the strength of the dose taken, and or reducing the frequency of administration. It can also include the failure to keep appointments or to follow the recommended lifestyle or dietary changes [5,6]." The availability of DMTs in low-to middle-income countries and adherence of MS patients to a medication that is not curing their disease are two critical challenges nowadays.…”

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

“…In previous studies, longer disease duration, older age, lower pre-treatment relapse activity and higher Expanded Disability Status Scale (EDSS) scores at NTZ initiation have been defined as unfavourable predictors for disease progression [7][8][9], NTZ discontinuation due to lack of efficacy [10,11] and experiencing a relapse [12]; whereas, higher ARR at baseline, lower baseline EDSS, younger age and shorter disease duration were favourable predictors for no evidence of disease progression [7] and disease improvement [12][13][14]. In contrast, a lower baseline ARR showed a higher chance maintaining no further inflammatory disease activity in other studies [3,12,15]. Nevertheless, the observation periods were so far limited.…”