Long-term effectiveness in patients previously treated with cladribine tablets: a real-world analysis of the Italian multiple sclerosis registry (CLARINET-MS).Patti F, Visconti A, Capacchione A, Roy S, Trojano M; CLARINET-MS Study Group.Ther Adv Neurol Disord. 2020 Jun 10;13:1756286420922685
Background: The CLARINET-MS study assessed the long-term effectiveness of cladribine tablets by following patients with multiple sclerosis (MS) in Italy, using data from the Italian MS Registry.
Methods: Real-world data (RWD) from Italian MS patients who participated in cladribine tablets randomised clinical trials (RCTs; CLARITY, CLARITY Extension, ONWARD or ORACLE-MS) across 17 MS centres were obtained from the Italian MS Registry. RWD were collected during a set observation period, spanning from the last dose of cladribine tablets during the RCT (defined as baseline) to the last visit date in the registry, treatment switch to other disease-modifying drugs, date of last Expanded Disability Status Scale recording or date of the last relapse (whichever occurred last). Time-to-event analysis was completed using the Kaplan-Meier (KM) method. Median duration and associated 95% confidence intervals (CI) were estimated from the model.
Results: Time span under observation in the Italian MS Registry was 1-137 (median 80.3) months. In the total Italian patient population (n = 80), the KM estimates for the probability of being relapse-free at 12, 36 and 60 months after the last dose of cladribine tablets were 84.8%, 66.2% and 57.2%, respectively. The corresponding probability of being progression-free at 60 months after the last dose was 63.7%. The KM estimate for the probability of not initiating another disease-modifying treatment at 60 months after the last dose of cladribine tablets was 28.1%, and the median time-to-treatment change was 32.1 (95% CI 15.5-39.5) months.
Conclusion: CLARINET-MS provides an indirect measure of the long-term effectiveness of cladribine tablets. Over half of MS patients analysed did not relapse or experience disability progression during 60 months of follow-up from the last dose, suggesting that cladribine tablets remain effective in years 3 and 4 after short courses at the beginning of years 1 and 2.
Keywords: cladribine tablets; clinically isolated syndrome; effectiveness; long-term data; multiple sclerosis; real-world data; real-world evidence; registry; relapsing-remitting MS; secondary progressive MS.
Cladribine is given for 1 year (0-1 and 12-13 months) and then you do nothing for 4 years and the question is then what?
Now I’m not a neurologists so I will keep my mouth shut. But because the CLARITY programme was delay there isn information hole. But what happened in the real world?
The effect didn’t last for ever in about 40% of the people at 5 years and 35% of people at 3 years but at one year only about 15% of people failed. Remember, this could be better than that occurring after anti-CD52 depletion where 50-60% of treatment fails but they get another dose and as you saw recently about 75% of people get long-term treatment benefit
Now if we looked at the alemtuzumab data and there was about 50% failure rate after the first year, but as we heard the other day if you get a third dose then about 75% of people went in to get long-term remission. But in this study the people were switched to something else in about 75% of the time and within about 2-3 years.