receiving a live or attenuated live vaccine because of a risk of active infection. vaccination with live or attenuated live vaccines should also be avoided during and after treatment, but can be considered when lymphocyte counts have recovered to ≥1000 cells/mm3. following completion of the two treatment courses, no further treatment or additional monitoring is required. the use of cladribine tablets is contraindicated in pregnant women, and women of childbearing potential must use effective contraception to prevent pregnancy during treatment and 6 months after receiving the last dose. efficacy of cladribine tablets in multiple sclerosis clinical trial results have shown that cladribine tablets can be an effective treatment for highly active, relapsing forms of multiple sclerosis, with significant clinical benefits in relapse rate, disability progression, and radiological measures. compared with placebo, patients who received cladribine tablets (3.5 mg/kg) in the clarity study had a 58% reduction in annualized relapse rate and 47% of patients showed no evidence of disease activity at 2 years. clinical improvements can be observed at week 24 of treatment, and benefits may be sustained up to 4 years, beyond the 2-year dosing period and recovery of total lymphocytes. post-hoc analyses of clinical trial data showed that 89% of patients remained free from disability progression two years after treatment. further analyses of a subgroup of patients in the clarity study who had very active multiple sclerosis showed a 67% reduction in relapse rates and an 82% reduction in disability progression in those treated with cladribine tablets. similarly, clinical improvements were seen in lesion burden on mri scans in this population. studies evaluating the treatment effects of cladribine tablets across a spectrum of baseline demographics and disease characteristics showed that the relative risk of relapse was significantly reduced compared with placebo, irrespective of previous treatment experience. furthermore, treatment with cladribine tablets has been shown to significantly reduce the rate of brain atrophy in patients with highly active relapsing-remitting multiple sclerosis. this reduction correlated with a reduced risk in disability progression in a retrospective analysis. in clinical trials, higher cumulative doses of cladribine tablets did not result in further improvement in efficacy nor did additional courses after the 2-year treatment period, but was associated with a higher incidence of grade 3 and grade 4 lymphopenia. safety profile of cladribine tablets in multiple sclerosis cladribine tablets target the cells of the adaptive immune system with minimal impact on innate immune cells. although the exact mechanism by which cladribine exerts its therapeutic effect is not fully elucidated, it is proposed to have a transient effect on b and t lymphocyte depletion, interrupting the cascade of immune events central to multiple sclerosis. as a result, a reduction in lymphocyte count (lymphopenia) may be reported following treatment. in clinical trials, lymphocyte levels above grade 0 (≥1000 cells/mm3) and grade 1 (<1000–800 cells/mm3) were maintained in most patients, with levels continuing to improve after the 2-year dosing period. less than 1% of patients developed grade 4 lymphopenia (<200 cells/mm3). it is important that patients with lymphocyte counts below 500 cells/mm3 should be actively monitored for signs suggestive of infection and that anti-infective treatments are given to at-risk patients. despite the initial reduction in lymphocyte counts following treatment, studies showed the overall risk of infection in patients receiving cladribine tablets was comparable to those who received placebo, except for herpes zoster infection. due to this increased risk, it is recommended that patients are screened for varicella zoster virus and antibody-negative patients are vaccinated prior to receiving treatment. in an analysis of post-approval data, as of 2020, no new infection safety signals were observed in over 18,000 patients. progressive multifocal leukoencephalopathy has been reported in patients with hairy cell leukemia treated with parenteral cladribine. however, in up to 10 years of follow-up of patients receiving cladribine tablets for multiple sclerosis, no cases of progressive multifocal leukoencephalopathy have been observed; baseline mri must be performed prior to initiating treatment. in clinical trials, malignancies were observed more frequently in patients treated with cladribine tablets compared with patients who received placebo. compared with a matched reference population from the global cancer observatory database, cladribine tablets had no increased risk of malignancy in long-term real-world evidence data. research directions cladribine has been studied as part of a multidrug chemotherapy regimen for drug-resistant t-cell prolymphocytic leukaemia.