The main concerns of patients, regarding their treatment, include disease control and safety, but they also want to make sure that their day-to-day life remains as close to normal as possible. In his presentation at the ECTRIMS 2021 meeting, Mathias Mäurer, Head of the Clinic for Neurology and Neurological Early Rehabilitation at the Stiftung Juliusspital, Würzburg, Germany, explained how data from Phase 4 studies such as CLARIFY-MS, can help to improve our understanding of the impact of a treatment on quality of life (QoL) of patients with multiple sclerosis (MS). Prof. Mäurer also discussed long-term efficacy data from the phase 4 CLASSIC-MS trial and data from the Essen-Munster cohort, before going on to talk about how long-term response influences treatment decisions.
The primary objective of the open-label CLARIFY-MS study was to assess health-related QoL (HRQoL) in patients with active relapsing multiple sclerosis (MS) treated with cladribine tablets. An interim analysis after a 1-year treatment course reported significant improvements from baseline in Multiple Sclerosis QoL (MSQoL) physical and mental health composite scores (estimated changes were 4.5 and 4.3 points, respectively, on a 10-point scale). These improvements were meaningful, e.g. reflecting a change whereby a patient goes from having no energy to being able to participate in daily activities and enjoy their hobbies again.
Prof. Mäurer went on to talk about the CLASSIC-MS trial. This Phase 4 study evaluated the long-term efficacy and durability of cladribine tablets beyond the two annual treatment courses in patients previously enrolled in the Phase 3 trials CLARITY/CLARITY-EXT (relapsing-remitting MS patients) and ORACLE MS (patients with their first clinical demyelinating event). In patients who took part in the CLARITY trial, with or without subsequent participation in the extension trial, efficacy (in terms of long-term mobility and disability status) was sustained over a median of 10.9 years of follow up since the last dose in the parent study. Patients exposed to cladribine tablets during the parent studies were also less likely to receive further treatment with disease-modifying therapies (DMTs).
Data from the Essen-Münster cohort
For patients going beyond Year 2 of their treatment, Prof. Mäurer discussed recently published data from the Essen-Münster cohort, in Germany.1 Based on 270 patients treated with cladribine tablets, the relapse rate substantially decreased following treatment, compared to the 6 months prior to treatment (the relapse rate also remained low over the entire observational period). Expanded Disability Status Scale (EDSS) scores continued to be stable in most patients up to Month 36, mirroring Prof. Mäurer’s own clinical experience with cladribine tablets.
Long-term treatment response: Management scenarios
Various scenarios can be envisaged in terms of long-term response to cladribine tablets: (1) optimal/complete control, (2) breakthrough disease (i.e. new disease activity that may be even higher than at start of treatment), and (3) onset of disease activity after the full treatment course. The second scenario would require switching to a new therapy; however, Prof. Mäurer emphasized that this is completely different to someone experiencing some disease activity during the first treatment course (e.g. this may be a balance between onset of action of cladribine tablets and events carried over from the previous treatment) – these patients have not yet received the full therapeutic dose and should definitely continue their treatment. Options in the third scenario (for example, disease reactivation at Year 5) include further treatment with cladribine tablets (especially if the patient has responded so far to the treatment) or switching to another DMT. Prof. Mäurer noted that if a patient has maintained optimal response up to Year 5, options include no further treatment (while still monitoring for reappearance of disease activity), or a further treatment course (on the premise that sustained efficacy has not yet been studied in comparative trials beyond an observational period of 4 years).
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- Pfeuffer S, et al. Mult Scler. 2021. doi: 10.1177/13524585211012227. Online ahead of print.