Study: Mavenclad Shows Long-term Effectiveness at Preventing MS Relapses, Disease Progression

Mavenclad (cladribine) prevents relapses and disease progression in more than half of patients with relapsing forms of multiple sclerosis (MS) for at least five years after the last dose, according to a real-life study from Italy.

These findings, based on real-world data from Italian MS patients previously treated with Mavenclad in clinical trials, support the therapy’s long-term effectiveness.

While some patients switched to another treatment after a median of three years, this was not necessarily associated with relapse or disability progression, the researchers noted.

The study, “Long-term effectiveness in patients previously treated with cladribine tablets: a real-world analysis of the Italian multiple sclerosis registry (CLARINET-MS),” was published in the journal Therapeutic Advances in Neurological Disorders.

Mavenclad, developed and marketed by EMD Serono (known as Merck KGaA outside North America), is an oral, short-course therapy approved for relapsing forms of MS in more than 50 countries, including those in the European Union, the U.S., Australia, and Canada.

Given in two treatment courses of two weeks each, separated by approximately one year, Mavenclad works by lowering the number of immune cells in the bloodstream, which are the cause of neurodegeneration in MS.

While results from clinical trials showed that Mavenclad led to sustained effectiveness up to four years after the last dose, longer-term data has to rely on patient registries and real-world studies.

Mavenclad’s longer-term safety was reported previously in the observational PREMIERE registry (NCT01013350).

Now, researchers have reported data from the CLARINET-MS study, which is evaluating the therapy’s long-term effectiveness in Italian MS patients who were treated with Mavenclad in clinical trials.

They had received at least one full course of Mavenclad during the clinical studies CLARITY (NCT00213135), the CLARITY extension (NCT00641537), ORACLE-MS (NCT00725985), or ONWARD (NCT00436826).

Patients’ real-world data were obtained from the Italian MS registry, which merges data from more than 65,000 Italian MS patients at 155 Italian MS centers, spanning from the last Mavenclad dose during the trial to the last visit date in the registry.

CLARINET-MS included 80 eligible patients (46 women and 34 men) with relapsing forms of MS from 17 Italian MS centers. Ten had clinically isolated syndrome (CIS), 60 had relapsing-remitting MS (RRMS), and 10 had secondary progressive MS (SPMS). Their mean age at the start of the observation period was 38.7 years and most did not need assistance to walk or work.

Researchers analyzed the time until patients experienced disease relapse, disease progression — defined as an increase of at least one point in the Expanded Disability Status Scale (EDSS) for at least 12 weeks — and switch to another disease-modifying therapy (DMT).

The proportion of patients free of DMT switch and of those who converted from CIS to clinically definite MS also was assessed.

Patients were followed for a median of 80.3 months (over six-and-a-half years), with more than 75% of them having follow-up data for more than 60 months (five years).

Results showed that more than half of the patients were free from relapses (57.2%) or disease progression (63.7%) five years after the last Mavenclad dose. In terms of MS type, those with CIS were more likely to have relapses but less likely to have disability progression, while SPMS patients showed the opposite trend.

Notably, patients who participated in the ORACLE-MS study tended to show better outcomes than those previously enrolled in the other trials. This discrepancy may be associated with the fact that ORACLE-MS included patients with milder disease in terms of inflammatory activity and disability, the researchers noted.

During follow-up, 54 patients (67.5%) initiated treatment with another DMT — the most common being interferon beta — after a median of 32.1 months (nearly three years). The likelihood of not having switched to another DMT after five years was 28.1% overall, 15% for CIS patients, 30.1% for RRMS patients, and 29.6% for SPMS patients.

While the reasons for treatment switching were not recorded in the registry, the researchers noted it did not appear to be necessarily linked to relapse or disability progression, since there was a discrepancy between the proportion of patients experiencing disease progression and those switching DMTs.

Also, changes to alternative DMTs were included in the protocol of some of these trials for specific situations.

Moreover, 40% of patients diagnosed with CIS had not converted to definite MS five years after the last dose of Mavenclad, conversions occurring between one and 41 months after last dose.

“Over half of patients analyzed did not relapse or experience disability progression, demonstrating that further treatment was not required for most patients to prevent disease progression,” the researchers wrote.

“Overall, study results confirmed the effectiveness of [Mavenclad] tablets demonstrated in previous clinical studies, but over a longer observable period and in a real-world setting,” the team concluded.