No this is not a call for ProfK to become the next Prime Minister,but I am sure he would have done a better job. However, as German with a knowledge of oral Cladribine what are his Expert Thoughts?
You will note there are nine german neurologists….PofK can be the tenth one
Stangel M, Becker V, Elias-Hamp B, Havla J, Grothe C, Pul R, Rau D, Richter S, Schmidt S. Oral pulsed therapy of relapsing multiple sclerosis with cladribine tablets – expert opinion on issues in clinical practice. Mult Scler Relat Disord. 2021 Jun 7;54:103075. doi: 10.1016/j.msard.2021.103075. Epub ahead of print. PMID: 34261026.
Q1 Should oral cladribine be used early in the course of MS to increase the likelihood of a maximum therapeutic benefit?.…….Duh
Clinical studies indicate that oral cladribine is effective in the early phase of MS. However, there is insufficient evidence to decide whether long-term efficacy is improved if oral cladribine is used early, as suggested by data available for other highly effective treatment options. (Consensus 70%)
Q2 Is oral cladribine an effective treatment after a first demyelinating event (i.e. at clinical onset of MS)?….Duh
Oral cladribine is highly effective in patients presenting with a first demyelinating event according to the ORACLE trial. (Consensus 100%)
Q3 Is oral cladribine an effective treatment option for RMS patients in transition to SPMS (i.e. secondary progression with relapses and/or MRI activity)?
Oral cladribine is an effective treatment option for patients in the transition phase from RRMS to SPMS (i.e. secondary progression with relapses and/or MRI activity) (Consensus 80%)
Q4 Is oral cladribine a suitable treatment option for RMS patients requiring a rapid onset of the disease-modifying effect?
The treatment effect of cladribine tablets starts within the first 24 weeks after initiating treatment. Available evidence is insufficient to further narrow down the exact time of onset (Consensus 89%). Em I think the MAGNIFY shows it start to work within 8 weeks.https://multiplesclerosisnewstoday.com/news-posts/2021/04/29/aanam-ms-mavenclad-presentation-immune-cell/
Q5 Is the second cycle of cladribine tablets in year 2 important for long-term efficacy?
There is good evidence for the long-term efficacy of oral cladribine after completing the two licensed treatment cycles (Consensus 100%). There is insufficient evidence for adequate long-term efficacy after completing only one treatment cycle of oral cladribine (100%).
Q6 Will patients with disease activity in year 1 benefit from a second course of cladribine tablets in year 2?
There is low-grade evidence for a benefit of the second oral cladribine treatment cycle in terms of disease activity in patients with a relapse during the first year after treatment initiation (Consensus 67%).
Q7 How should patients be managed after completing the 2-year treatment period with oral cladribine?
If there is evidence of breakthrough disease after the second year of treatment with oral cladribine, all disease-modifying drugs licensed for RMS patients may be used, in accordance with an individualized risk-benefit analysis including the lymphocyte status. (Consensus 40%)
Q8 What is the risk of infection in patients treated with oral cladribine, which infections have been observed and how are they managed?
With the exception of a moderately increased risk of herpes zoster episodes, the overall risk of infections is not increased on treatment with oral cladribine (Consensus 78%).
Q9 What is the approach to vaccination in RMS patients before and on treatment with oral cladribine?
Immunizations with live-attenuated vaccines are possible 4 to 6 weeks before starting therapy with cladribine tablets. Vaccinations with live-attenuated vaccines should be avoided during the active treatment phase and afterwards until the lymphocyte counts have returned to the normal range. (Consensus 89%),
Q10 Is there a relevant risk of malignancies associated with oral cladribine?
There is currently no evidence of an increased risk of malignant disease in MS patients treated with oral cladribine. (Consensus 100%) – Comment ProfK: This is quite remarkable given a key reason for rejecting cladribine by the EMA in 2010/11 was the perceived cancer risk. Our meta-analysis had a significant impact on the EMA’s positive decision the second time around nearly seven years later.
Q11. At which time after treatment initiation with oral cladribine can female patients envisage a pregnancy?
Women can become pregnant 6 months after the last dose in the second year of therapy with cladribine tablets. Consensus : 89%.)
Q12 What are the monitoring requirements in patients before and on therapy with oral cladribine?
The monitoring requirements for patients treated with oral cladribine are low. Consensus 67%.
Q13 Does oral cladribine reduce the burden of therapy in RMS patients versus other highly effective treatment options?
Pulsed therapy with cladribine tablets is associated with a low treatment burden on RMS patients (Consensus 78%).
Q14. What is the impact of treatment with oral cladribine on the quality of life in RMS patients?
The quality of life of patients treated with cladribine tablets is improved as compared to placebo (Consensus: 89%) Comment ProfK: Fortunately, we decided to publish the respective data from the CLARITY data vault.
If you have any questions about cladribine we will try to answer but please read CHARIOTMS (NCT04695080)
Disclaimer: Please note that the opinions expressed here are those of the author and do not reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust or Queen Mary Univeristy of London.