Table 6.
Treatment switching to and from cladribine tablets and monitoring considerations.
| Consensus recommendations | Strength of recommendation‡ | Level of consensus¶ |
|---|---|---|
| Q10. When switching to cladribine tablets, what are the washout periods/baseline requirements for different DMDs? Are there any specific treatment classes that preclude cladribine tablets as a next switch?* (Level of evidence: very low) | ||
| Switch decisions should be made after a thorough risk/benefit analysis.19,29 | 9 (8.8) | 100% (31/31) |
| Due to a lack of clinical evidence for treatment switches in MS, caution should be taken in a patient who is switching from a prior treatment due to adverse events that may also occur with cladribine tablets. | 9 (8.1) | 90% (28/31) |
| *Due to a lack of clinical evidence for treatment switches in MS, recommendations are based on individual treatment risks or carry-over risks. | ||
| Glatiramer acetate/Interferon-beta • Possible treatment effects on blood (e.g. lymphopenia, leukopenia, thrombopenia), and/or liver and kidney parameters should have subsided • Recommended safety interval: none generally required |
9 (8.7) | 100% (31/31) |
| Dimethyl fumarate • Possible treatment effects on the differential blood count, should have subsided following the last dose of dimethyl fumarate • Possible additional treatment effects on blood (e.g. severe lymphopenia), liver/kidney parameters should have subsided • Recommended safety interval: none generally required |
9 (8.4) | 93.5% (29/31) |
| Teriflunomide • Possible treatment effects on the immune system and liver values should have subsided • Washout necessary – it must be documented that teriflunomide is no longer detectable in the blood • Recommended safety interval: normally around 4 weeks |
8 (7.9) | 90.3% (28/31) |
| Fingolimod • Possible treatment effects on the differential blood count, should have subsided following the last dose of fingolimod. There should be no cytopenia. • Possible treatment effects on other blood parameters and liver values, as well as vital signs, should have subsided • Recommended safety interval: normally around 4 weeks |
8 (7.7) | 80% (25/31) |
| Natalizumab • Possible effects on the immune system (e.g. lymphocytosis, cytopenia) should have subsided • PML should be excluded (e.g. MRI including FLAIR sequence immediately before start of treatment). A CSF examination including a JCV-PCR should be considered beforehand in patients with positive JCV antibody status and a treatment duration of >12 months) • Recommended safety interval: normally around 4–8 weeks |
8 (7.8) | 90.3% (28/31) |
| Alemtuzumab • Possible treatment effects on the immune system (e.g. cytopenia) should have subsided (lymphocyte typing is optional e.g. T and B cells) • Clinical and laboratory monitoring (including platelets, creatinine, TSH and urine sediment) must be continued for 4 years following the last alemtuzumab infusion • Recommended safety interval: normally around 6–12 months |
8 (8.3) | 96.8% (30/31) |
| Ocrelizumab • Differential blood count must be ascertained before treatment initiation (lymphocyte typing is optional e.g. • CD19+ B cells) • Any treatment effects on the immune system (e.g. cytopenia) should have subsided • Recommended safety interval: normally around 6–12 months |
8 (8.0) | 93.1% (27/29) |
| Q11. How do you switch from cladribine tablets? What DMDs can patients use after cladribine tablets? If the patient’s lymphocyte counts have not recovered to LLN but a treatment switch is required, what is the recommended course of action? (Level of evidence: very low) | ||
| Potential additive effects on the immune system should be considered when choosing subsequent DMDs following treatment with cladribine tablets. | 9 (8.5) | 93.5% (29/31) |
| Treatment-specific effects on lymphocyte counts should have ideally subsided before switching from cladribine tablets. | 8 (8.4) | 100% (31/31) |
| The waiting time is defined by the clinical need to switch. Cases of treatment non-response should be decided on an individual risk/benefit analysis. | 9 (8.6) | 100% (31/31) |
| Caution is recommended in switching from cladribine tablets to natalizumab in any patient who is JCV antibody positive. | 9 (8.4) | 93.5% (29/31) |
‡
Median score on a 1–9 scale (mean score in brackets).
¶
percentage of votes with 7–9 on a 9-point scale.
CSF, cerebrospinal fluid; DMD, disease modifying drug; FLAIR, fluid-attenuated inversion recovery; JCV, John Cunningham virus; LLN, lower limit of normal; MRI, magnetic resonance imagining; MS, multiple sclerosis; PCR, polymerase chain reaction; PML, progressive multifocal leukoencephalopathy; TSH, thyroid stimulating hormone.