Cladribine Associated With Long-Term Sustained NEDA-3 Status in MS

Stuart Cook, MD, professor emeritus at Rutgers New Jersey Medical School

Stuart Cook, MD

Patients with multiple sclerosis (MS) treated with 10-mg cladribine tablets have been shown to sustain annual No Evidence of Disease Activity-3 (NEDA-3) status through 4 years.¹

In a post-hoc analysis of the CLARITY study, presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) 2019 Forum in Dallas, Texas, patients with MS) who were treated with 10-mg cladribine tablets (cumulative dose of 3.5 mg/kg over 2 years) in years 1 and 2 (n = 186) sustained annual No Evidence of Disease Activity-3 (NEDA-3) status up to the end of year 4.

Additionally, those who were treated with cladribine in years 1 and 2 but switched to placebo during the 2-year extension period (n = 98) also sustained NEDA-3 status up to year 4.

Notably, NEDA-3 status, determined using 6-month Expanded Disability Status Scale (EDSS) progression, was achieved in significantly more patients receiving cladribine (47%) compared to placebo (17%; P <.0001).

"The efficacy of cladribine tablets was evaluated in the CLARITY, CLARITY EXT, and ORACLE-MS trials that included patients with [relapsing] MS," said Stuart Cook, MD, professor emeritus at Rutgers New Jersey Medical School, in a statement.² "Building on existing clinical evidence, I am pleased to present an updated safety analysis on cladribine tablets at ACTRIMS, which includes up to 10 years of follow-up data in some patients."

The confirmed NEDA-3 status group in the first year of the CLARITY extension for year 3 (n = 152) included by 54 patients in the group that switched to placebo and 98 patients in the group that continued on cladribine through the extension period. In year 4, the number of patients from each subgroup included in the NEDA-3 status group was 40 and 77, respectively (n = 117).

In the year 3 group, annual NEDA-3 was achieved in 25 of 54 of patients (46%) treated with cladribine who switched to placebo compared to 47 of 98 of patients (48%) who continued on cladribine. The authors noted that there was a numerical trend for a lower rate of annual NEDA-3 status for those who switched to placebo (14 of 40 patients; 35%) compared to those who continued on cladribine (37 of 77 patients; 48%).

When adjusting for the length of the bridging interval, the investigators noted that there was no significant difference (P = .31) between the annual NEDA-3 status in the switched group (41.5%; 95% CI, 32.4 to 60.0) and the continuation group (48%; 95% CI, 40.2 to 64.4). “Similar patterns were observed when proportions of patients' annual relapse-free and annual 6-month EDSS progression-free were examined,” they wrote.

Also presented at ACTRIMS was an updated safety analysis of cladribine, pooled from the CLARITY, CLARITY Extension, and ORACLE-MS trials, as well as the PREMIERE registry, which further established the known safety profile of the 10-mg dose. The authors of that assessment, including Cook, noted that no new major safety findings were identified.³

The adjusted adverse events (AEs) incidences per 100 patient-years for experiencing ≥1 serious treatment-emergent AEs were 3.88 for the cladribine group (n = 923) and 3.24 for the placebo group (n = 641). Likewise, for serious lymphopenia was 0.11 for those treated with cladribine, with no serious lymphopenia being observed with placebo.

Serious infections and infestations occurred at a rate of 0.63 adjusted AEs incidences per 100 patient-years with cladribine and 0.44 with placebo. Serious herpes zoster was 0.05 with cladribine while no serious herpes zoster was observed with placebo. For serious neoplasms, benign, malignant and unspecified, adjusted AEs incidences per 100 patient-years were 0.65 and 0.35, respectively. With regard to post-marketing data, 47 serious adverse drug reactions were reported, though none were new to cladribine's known profile.

"We are proud to participate in the important scientific exchange at ACTRIMS as it aligns with our commitment to advancing MS science to address patient needs with our research programs and investigational MS treatments," said John Walsh, MD, the vice president of Neurology and Immunology, US Medical Affairs, EMD Serono, in a statement.²

REFERENCES

1.

Giovanonni

G, Keller B, Jack D. Durability of NEDA-3 status in patients with relapsing multiple sclerosis receiving cladribine tablets: CLARITY extension. Presented at: ACTRIMS Forum; February 28 to March 2, 2019; Dallas, TX. Poster #3658. actrims.confex.com/actrims/2019/meetingapp.cgi/Paper/3658. Accessed March 1, 2019.

2. EMD Serono to Present Multiple Sclerosis Data on Cladribine Tablets and Evobrutinib at ACTRIMS 2019 [press release]. Rockland, MA; EMD Serono; Published February 28, 2019. prnewswire.com/news-releases/emd-serono-to-present-multiple-sclerosis-data-on-cladribine-tablets-and-evobrutinib-at-actrims-2019-300804421.html. Accessed March 1, 2019.

3. Cook SD, Giovannoni G, Leist TP, et al. Updated safety analysis of cladribine tablets in the treatment of patients with multiple sclerosis. Presented at: ACTRIMS Forum; February 28 to March 2, 2019; Dallas, TX. Poster #3948. actrims.confex.com/actrims/2019/meetingapp.cgi/Paper/3948. Accessed March 1, 2019.