The benefits of Mavenclad (cladribine) have continued for up to 15 years after its last course of treatment in people with relapsing-remitting multiple sclerosis (MS), according to real-world data from the CLASSIC-MS study.
More than half of those who received oral therapy in clinical trials that supported its approval no longer needed further disease-modifying therapies (DMTs) and went on to be twice as likely to not relapse over 10.9 years compared with those who were never given.
realistic study,”Long-term follow-up of patients with relapsing-remitting multiple sclerosis from the CLARITY/CLARITY extension group of CLASSIC-MS: an ambiguous study.“in Multiple Sclerosis Journal.
Mavenclad, marketed by EMD Serono, is a short-course oral DMT approved for relapsing forms of MS, including relapsing-remitting MS (RRMS) and active secondary advanced multiple sclerosis (SPMS). It works by decreasing the number of immune cells circulating in the bloodstream that cause inflammation and nerve damage in MS.
Its approval is supported by data from three Phase III clinical trials – CLARITY (NCT00213135), CLARITY Extension Study (NCT00641537), and ORACLE-MS (NCT00725985), all of which showed Mavenclad’s efficacy compared to placebo.
Long lasting results with Mavenclad
The Phase 4 Pilot CLASSIC-MS Trial (NCT03961204) – conducted post-approval in a real setting – assessing the long-term durability of Mavenclad for up to 15 years was completed after the two-year regimen of three Phase 3 trials.
The analysis focused on the long-term outcomes of 435 CLASSIC-MS patients, ages 32 to 79, who had previously participated in CLARITY with or without enrollment in the expanded study. All eligible CLASSIC-MS participants had received at least one course of Mavenclad tablets or placebo in previous studies.
A total of 394 (90.6%) patients had been previously treated with Mavenclad and 160 of them completed the two-year treatment regimen. The time period since the last Mavenclad dose ranged from 9.3 to 14.9 years, with an average of 10.9 years.
In achieving the long-term primary mobility goal, CLASSIC-MS demonstrated that significantly more patients treated with Mavenclad did not use a wheelchair or were not confined to bed compared with those treated with placebo in CLARITY (90% vs 77.8%). Compared to those not treated with Mavenclad, those who received the full two years of treatment were 48% less likely to need a wheelchair or be bedridden when they entered CLASSIC-MS.
The trial also met the secondary long-term disability goal by showing that patients who received treatment were more likely to not need assistance with walking compared to those treated with placebo (81.2% vs. 75.6%).
Mavenclad reduces the need for subsequent DMTs
In a four-year responder analysis, more patients treated with Mavenclad did not need subsequent DMTs compared to placebo (66.2% vs. 36.6%). No disease reactivation was observed in more patients exposed than placebo (50.3% vs. 26.8%).
The team also noted that participants with high relapse activity responded well to Mavenclad treatment.
During the follow-up period of 10.9 years, more than half (53.1%) of the CLASSIC-MS patients did not use DMT medications. Most of those who used other DMTs were treated with immunomodulatory interferon (68.6%).
Compared with placebo, treatment with Mavenclad during CLARITY reduced the likelihood of using DMT after the last dose of CLARITY, with 55.8% of patients exposed to Mavenclad versus 26.8% in the never-exposed group who did not receive DMTs later.
Similarly, fewer patients exposed to Mavenclad received a second dose of DMT than patients never exposed (14.2% vs 29.2%), as did those given a third DMT (4.6% vs 7.3%). The estimated median time until the first subsequent DMT dose after the last CLARITY dose was longer with Mavenclad than with placebo (12 vs 2.8 years).
Of the 200 patients who had not experienced a relapse since the last dose, about twice as many patients treated with Mavenclad were relapse-free than those given placebo (48.0% vs. 26.8%). This result was reflected in the annual relapse rate for Mavenclad versus placebo (0.12 vs 0.23 relapses per year).
Finally, at the onset of CLASSIC-MS, the proportion of patients in active function was higher among those exposed to Mavenclad in CLARITY than in the never-exposed group (51% vs 27.5%).
Together, these findings support previous studies reporting the sustained efficacy of [Mavenclad] “Tablets after treatment,” the researchers said.