Efficacy of Cladribine Tablets Continues After Conversion to MS

LONDON—Significant treatment effect versus placebo of cladribine tablets given to patients with clinically isolated syndrome during the initial treatment period continues to be observed in patients who convert to clinically definite multiple sclerosis (MS) and switch to treatment with a different disease-modifying drug (ie, subcutaneous interferon beta-1a), according to data presented at the 32nd Congress of the European Committee for Treatment and Research in MS (ECTRIMS).

Giancarlo Comi, MD, Professor of Neurology and Chairman of the Department of Neurology at Vita-Salute San Raffaele University in Milan, and colleagues reported that patients with clinically isolated syndrome who had been treated with cladribine tablets and who had converted to MS during the Oral Cladribine in Early MS (ORACLE-MS) initial treatment period had lower annualized relapse rates during the open-label maintenance period, relative to those patients who had received placebo during the ORACLE-MS initial treatment period.

Giancarlo Comi, MD

The CLARITY (CLAdRIbine Tablets treating MS orallY) study in patients with active MS showed that annualized relapse rates and sustained disability worsening were reduced in patients treated with cladribine tablets annually for two years in short-duration courses, compared with placebo. The efficacy observed in the CLARITY study was maintained without further active treatment during the CLARITY extension study. In the ORACLE-MS study in patients with a first demyelinating event, cladribine tablets (3.5 mg/kg and 5.25 mg/kg) significantly reduced the risk of conversion to clinically definite MS, compared with placebo. If clinically definite MS occurred in the double-blinded, initial treatment period, patients were treated with subcutaneous interferon beta-1a in an open-label maintenance period.

The present study was designed to assess the annualized relapse rate during the ORACLE-MS open-label maintenance period in patients randomized to cladribine (3.5 mg/kg and 5.25 mg/kg) or placebo in the initial treatment period.

Similar to previous trials, participation in the ORACLE-MS open-label maintenance period was dependent upon the clinical course of the patient’s disease in the initial treatment period. Patients in ORACLE-MS who converted to clinically definite MS (according to Poser criteria) during the initial treatment period entered the open-label maintenance period and were treated with subcutaneous interferon beta-1a (titrated over four weeks up to the dose of 44 μg) administered three times per week.

A total of 109 patients in ORACLE-MS converted to clinically definite MS in the initial treatment period and received at least one dose of interferon beta-1a. The median time on interferon beta-1a was 56.0 weeks. Estimated annualized relapse rates in the open-label maintenance period were 0.14 for patients originally treated with cladribine 3.5 mg/kg (n = 25), 0.24 for patients originally treated with cladribine 5.25 mg/kg (n = 24), and 0.42 for patients who originally received placebo in the initial treatment period (n = 60).

According to the researchers, durable efficacy of cladribine tablets in ORACLE-MS into the open-label maintenance period is consistent with results of the CLARITY and CLARITY extension studies.

This study was sponsored by EMD Serono.

—Glenn S. Williams

Suggested Reading

Cook S, Vermersch P, Comi G, et al. Safety and tolerability of cladribine tablets in multiple sclerosis: the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study. Mult Scler. 2011;17(5):578-593.

Leist TP, Comi G, Cree BA, et al. Effect of oral cladribine on time to conversion to clinically definite multiple sclerosis in patients with a first demyelinating event (ORACLE MS): a phase 3 randomised trial. Lancet Neurol. 2014;13(3):257-267.