A post-hoc analysis from the 2-year study CLARITY has demonstrated that cladribine, also known as Mavenclad, reduced the risk of six-month EDSS progression by 47% vs placebo, as well as having a greater treatment effect (82%) on patients with highly active multiple sclerosis (MS).
In this post-hoc analysis, two clinically relevant definitions of high disease activity were selected to effectively identify patients more likely to experience disease progression. Patients from the CLARITY study with high disease activity were categorised by fulfilling one of two overlapping criteria, which reflect those included in the EU SmPC (summery of product characteristics) for MAVENCLAD:
High Relapse Activity (HRA): Patients with two or more relapses during the year prior to study entry, whether on disease-modifying drug (DMD) treatment or not.
High Relapse Activity plus Disease Activity on Treatment (HRA + DAT): patients with one or more relapse and one or more T1 Gadolinium-enhancing (Gd) + or nine or more T2 lesions during the year prior to study entry while on therapy with other DMDs, plus patients with two or more relapses during the year prior to study entry, whether on DMD treatment or not.
HRA and HRA + DAT patients showed clinical and MRI responses to cladribine that were generally better than, or at least comparable with, the outcomes previously seen in the overall CLARITY study population.
In both high disease subgroups, cladribine was shown to reduce the risk of six-month EDSS progression by 82% vs placebo, compared to a 47% reduction in the overall CLARITY study population.
The newly published analysis also evaluated disease-free status, showing that in the HRA + DAT subgroup, treatment with cladribine was significantly more likely to result in no evidence of disease activity (NEDA) when compared with the non-HRA + DAT subgroup. The HRA subgroup was also more likely to achieve NEDA, but a statistically significant difference was not observed when compared to the non-HRA group.
The relative risk of cumulative new T1 Gd+ lesions for patients in both high-disease subgroups treated with cladribine was low, with strong effects observed in each treatment subgroup. Overall, the subgroup-specific safety analysis for patients with HRA and HRA+DAT did not reveal evidence for new safety findings compared with those previously described for the overall CLARITY population.
“This analysis provides valuable insights on the effect of Mavenclad on patients with ongoing disease activity despite treatment with platform therapy, as well as naïve patients with more relapses at baseline, who tend to do worse over time,” said Professor Gavin Giovannoni, a lead investigator in the CLARITY studies and Chair of Neurology, Barts and The London School of Medicine and Dentistry. “The efficacy data presented in this publication show an even greater risk reduction on expanded disability status scale (EDSS) progression with Mavenclad in patients with highly active MS.”