Background

Cladribine is a selective and oral immunological reconstitution treatment, approved in Europe in 2017 and in Portugal in 2018 for very active multiple sclerosis (MS) with relapses. Its safety and efficacy profile were assessed in phase III CLARITY (2005-2009) trial. Post-commercialization studies in real life conditions, are essential to confirm this profile.

Objectives

To assess the efectiveness of cladribine in multiple sclerosis patients a real-world clinical setting, during treatment follow-up.

Methods

Observational, multicentric, prospective study. Consecutive MS patients treated with cladribine were included in two tertiary hospitals in Lisbon and followed during treatment. Demographic and clinical aspects, EDSS, previous disease-modifying drugs (DMD) and annual relapse rate (ARR) were recorded, as well as laboratory and imaging monitoring during treatment

Results

Eighty-five included patients, 54 (63.5%) female, mean age 42±12 years old, mean disease duration 9±7 years. Seventy-seven (90.6%) had relapsing-remitting MS, and the remaining had secondary progressive MS. Median pre-treatment EDSS was 2,0 (1,5-4,0), and 40 (47.1%) patients had at least one relapse in previous year. Most (65.9%) patients had been submitted to more than one DMD before, 43 (51.2%) with first-line therapies and 9 (10.7%) were naïve. Cladribine was started in 57 (68.7%) patients due to inefficacy of previous drug. Mean follow-up time was 13±6 months, and 54 (63.5%) completed first year of treatment. Second year of treatment was delayed in some patients due to global COVID-19 pandemic. Fifteen relapses were registered in 12 patients. Five (5.9%) stopped treatment because of disease activity in the first year. After 12 months of follow-up (n=54), no difference was found between previous and 12-month EDSS medians (2 (IQR 1,5-4,0) vs 2 (IQR 1,25-4) p=0.606). Mean 12-month ARR (0,1±0,4) was significantly inferior to previous year ARR (0,6±1,0), p<0.001.

Conclusions

At pivot trial, the efficacy of cladribine was proved after two annual treatment cycles. In this population, short follow-up period is a limitation, but after mean follow-up of one year, clinical estabilization was found in MS patients treated with cladribine.

Background

Cladribine is a selective and oral immunological reconstitution treatment, approved in Europe in 2017 and in Portugal in 2018 for very active multiple sclerosis (MS) with relapses. Its safety and efficacy profile were assessed in phase III CLARITY (2005-2009) trial. Post-commercialization studies in real life conditions, are essential to confirm this profile.

Objectives

To assess the safety and tolerability of cladribine in MS patients a real-world clinical setting, during treatment follow-up.

Methods

Observational, multicentric, prospective study. Consecutive MS patients treated with cladribine were included in two tertiary hospitals in Lisbon and followed during treatment. Demographic and clinical aspects, EDSS, previous disease-modifying drugs (DMD) and annual relapse rate (ARR) were recorded, as well as laboratory, imaging monitoring and adverse reactions during treatment.

Results

Eighty-five included patients, 54 (63.5%) female, mean age 42±12 years old, mean disease duration 9±7 years. Seventy-seven (90.6%) had relapsing-remitting MS, and the remaining had secondary progressive MS. Median pre-treatment EDSS was 2,0 (1,5-4,0). Most (65.9%) patients had been submitted to more than one DMD before, 43 (51.2%) with first-line therapies and 9 (10.7%) were naïve. Cladribine was started in 57 (68.7%) patients due to inefficacy of previous drug. Mean follow-up time was 13±6 months, and 54 (63.5%) completed first year of treatment. Second year of treatment was delayed in some patients due to global COVID-19 pandemic. Most frequent adverse reactions were lymphocytopenia (43,5%), infections (20,8%) and fatigue (18,1%). After two months of first dose, CD19+ lymphocyte count showed greater reduction compared with CD4+ and CD8+. There were no grade 4 lymphocytopenia cases registered. Four (5.5%) serious adverse reactions were recorded. There were no cases of cladribine withdrawal because of adverse reactions.

Conclusions

This cohort has similar characteristics to the CLARITY trial study population. Registered adverse reactions were comparable to previously described, showing higher incidence of fatigue and lower incidence of infections. This study confirms the short-term tolerability and safety profile of cladribine in real life scenarios.

Background

The use of progressively more powerful disease-modifying therapies (DMTs) in multiple sclerosis (MS) has increased the risk of severe infection of vaccine-preventable diseases, as hepatitis B (HBV). Considering the low risk of vaccination and the potential complication of acute infection by HBV in patients undergoing immunomodulating therapies, vaccination is considered in seronegative patients.

Objectives

We aimed to evaluate if immunosenescence and DMT-treatment influenced the seroconversion rate following HBV vaccination.

Methods

We selected all seronegative MS patients submitted to HBV vaccination in our institution between January 2016 - May 2020. In our center, an accelerated HBV vaccination regimen is administrated with a 3 dose protocol (Day 0, 7, and 21). The antibody anti-HBs is reevaluated 4 weeks after the last dose and a fourth dose might be administrated if necessary.

Seroconversion status was defined as the outcome variable. To evaluate if immunosenescence influenced seroconversion, we compared the seroconversion rate of patients 50-years-old or younger and older than 50; to evaluate if DMTs were determinant in seroconversion rates we compared the following groups of patients: treatment-naïve, under BRACE and non-BRACE DMTs.

Results

We included 101 patients, 58 (57.4%) female, mean age 45.7 ± 13.5 years. At the time of vaccination 33 (32.7%) patients were treatment-naïve, while the remaining 68 (67.3%) were under the following DMTs: 27.7% BRACE, 8.9% teriflunomide, 12.9% dimethyl fumarate, 7.9% fingolimod and 9.9% natalizumab.

Seroconversion was observed in 69.3% of patients following vaccination. The seroconversion rate was similar between different age groups: 74.1% vs 69.2% in patients 50-years-old or younger and older than 50, respectively (p=0.65). The seroconversion rates were similar between BRACE-treated and treatment-naïve patients (85.2% vs 81.8%, p=1) but lower in the group of patients under non-BRACE DMTs comparing to BRACE- treated patients (54.1% vs 85.2%, p=0.014) and treatment-naïve patients (54.1% vs 81.8%, p=0.021).

Conclusions

Seroconversion following HBV vaccination was not influenced by age in our sample; however, treatment with DMTs other than BRACE was associated with a lower seroconversion rate following vaccination. Vaccination should then be considered at an early stage of MS treatment, preferably in naïve-RRMS or patients under BRACE DMTs.

Background

Recently, the growing number of first-line Disease Modifying Therapies (DMTs) available in clinical practice increased the complexity of treatment choices in naive Relapsing Remitting Multiple Sclerosis (RRMS).

Objectives

We aimed to evaluate if baseline factors such as older age, being a childbearing-aged woman and having comorbidities influenced the choice of the first-line DMT and to analyze switching patterns between different first-line DMTs in a real-world sample.

Methods

We included all consecutive RRMS patients diagnosed between 2016-2020 with a minimum follow-up of 6 months, proposed to an EMA-approved first-line DMT. The DMTs were dichotomized as injectable (BRACE) vs oral DMTs (dimethyl fumarate, teriflunomide). We performed a binary regression to assess if age ≥ 55 years, being a childbearing-aged woman and having comorbidities influenced DMT choice.

The risk of DMT switch at follow-up was evaluated using a Kaplan-Meyer survival analysis with a log-rank test.

Results

107 patients were included in the analysis, 71 (66.4%) female, mean age 35.7±12.1 years. The majority of patients starting a first-line treatment (58.9%) started an oral DMT.

Childbearing-aged women were almost 3 times more likely to be proposed to injectable treatment (OR 2.860, 95%CI 1.191-6.864, p=0.019), while older age and the presence of comorbidities did not influence DMT choice (p>0.05).

During a mean follow-up of 23.6 months, 34 (31.8%) patients switched treatment, the majority (61.8%) due to treatment failure. The survival analysis revealed a higher risk of treatment switch during follow-up in patients starting injectable DMTs (HR 0.475, 95%CI 0.240-0.943, log rank p=0.029).

Conclusions

The oral DMTs have become the most common first-line treatment in the contemporary management of naive-RRMS. Being a childbearing-aged woman, however, seemed determinant in the proposal for an injectable DMT, probably due to the higher safety of these drugs during pregnancy.

The oral DMTs were associated with a lower risk of treatment switch and might be considered from early stages on to enhance treatment persistence.