Australian cladribine experience

Background: In 2011, 144 patients with multiple sclerosis (MS) were treated with cladribine through the Australian patient familiarisation program (PFP).

Objective: To characterise the Australian MSBase cladribine cohort.

Methods: Longitudinal data from 90 patients who received oral cladribine (1mg per kg, initial treatment consisting of 2 courses completed in 2 weeks) were captured in MSBase, including 66 patients with disability information before and after cladribine. Descriptive evaluation of the demographic and clinical information was carried out.

Results: Characteristics of the MSBase cladribine PFP cohort: 72% female, mean age 47 years (SD 12), mean MS duration 13 years (SD 9), 77% relapsing-remitting, 20% secondary progressive and 3% active primary progressive MS, median baseline EDSS 5 (quartiles 3-6), EDSS trajectory +0.3 step per year (quartiles 0.2-0.6) and annualised relapse rate 1 (quartiles 0.5-1.9). In 62 (69%) patients exposure to another disease modifying therapy (DMT) was recorded after cladribine, including 16 patients treated within a year of commencing cladribine. Most commonly, these included fingolimod (42%), dimethyl fumarate (23%) and natalizumab (15%). Seventeen patients experienced relapses prior to starting the subsequent DMT.
Mean on-cladribine relapse rate reached 0.6-0.75 per year (quartiles 0-1). Median time to the first post-cladribine relapse was 3.3 years. The proportions of patients reaching 6-month confirmed EDSS progression were 12% and 20% at years 1 and 2, respectively. EDSS trajectory post-cladribine was increasing at +0.1 step per year (quartiles 0-0.2). In contrast to the pre-cladribine EDSS trajectory, the post-cladribine trajetory stabilised for approximately 18 months, after which the EDSS has resumed its ascending trajectory.
Nineteen adverse events (of which 6 were reported as unrelated to cladribine) were recorded in 15 patients (17%). These included
moderate cephalalgia that was likely retated to cladribine, and severe gastrointestinal symptoms and moderate arterial hypertension in which the relationship to cladribine was not suggested. During the treatment with the subsequent DMTs, 12 adverse events in 10 (11%) patients were recorded. It should be noted that the records of adverse events in MSBase are likely to be incomplete.

Conclusion: The Australian cladrbine PFP suggested temporary amelioration of disability accrual in a cohort that was enriched for patients with progressive MS forms.