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Cladribine tablets (CladT), like alemtuzumab, acts as an immune reconstitution therapy. However, CladT is administered orally (alemtuzumab is given by infusion) and without the potential for serious side effects that limit the therapeutic use of alemtuzumab in multiple sclerosis (MS). Treatment with CladT, given initially as short courses of treatment 1 year apart, provides years of freedom from MS disease activity in responders to treatment. The appearance of mild or moderate MS disease activity after the initial 2 years of treatment may prompt careful follow-up or a further course of CladT, depending on the nature of the activity and individual circumstances. The appearance of severe MS disease activity requires a switch to an alternative high-efficacy disease-modifying treatment (DMT). The accumulating data from CladT-treated people with MS in real-world studies, including those with follow-up durations extending for years beyond the initial treatment, have demonstrated long-term freedom from MS disease activity in a good proportion of patients. This clinical experience has also confirmed that treatment with CladT is generally safe and well tolerated. The best time to prescribe a high-efficacy DMT is the subject of debate, with evidence that earlier versus later use of such agents may provide more effective long-term protection from disability progression. High-efficacy DMTs have traditionally been reserved for use in people with MS and high disease activity on presentation or breakthrough disease on one or more DMTs, as per the current product labels. The latest evidence from real-world studies suggests that CladT is effective and safe in DMT-naïve patients, including those with shorter disease duration., (© 2024. The Author(s).)

Introduction: Inconvenient administration and side effects of some disease-modifying therapies (DMTs) for relapsing multiple sclerosis (RMS) can deter adherence. We evaluated treatment satisfaction with cladribine tablets (CladT) for RMS in the Arabian Gulf., Methods: This was a non-interventional, multicentre, prospective observational study in non-pregnant/lactating adults (aged ≥ 18 years) with RMS eligible for 1st treatment with CladT (EU labelling). The primary outcome was overall treatment satisfaction at 6 months (Treatment Satisfaction Questionnaire for Medication [TSQM]-14, v. 1.4), Global Satisfaction subscale. Secondary endpoints were TSQM-14 scores for convenience, satisfaction with side effects and satisfaction with effectiveness. Patients provided written informed consent., Results: Of 63 patients screened, 58 received CladT and 55 completed the study. Mean age was 33 ± 9 years; mean weight 73 ± 17 kg; 31% male/69% female; mostly from the United Arab Emirates (52%) or Kuwait (30%). All had RMS (mean 0.9 ± 1.1 relapses in the past year), mean Expanded Disability Status Scale (EDSS) 1.4 ± 1.2; 36% were DMT-naïve. Mean [95% CI] score was high for overall treatment satisfaction (77.8 [73.0-82.6]), ease of use (87.4 [83.7-91.0]), tolerability (94.2 [91.0-97.3]) and effectiveness (76.2 [71.6-80.7]). Scores were similar irrespective of DMT history, age, gender, relapse history or EDSS. No relapses or serious treatment-emergent adverse events (TEAE) occurred. Two severe TEAE occurred (fatigue, headache) and 16% reported lymphopenia (two cases of grade 3 lymphopenia). Absolute lymphocyte counts at baseline and 6 months were 2.2 ± 0.8 × 10 9 /L and 1.3 ± 0.3 × 10 9 /L, respectively., Conclusions: Treatment satisfaction, ease of use, tolerability and patient-perceived effectiveness for CladT were high, irrespective of baseline demographics, disease characteristics and prior treatment., (© 2023. The Author(s).)

This article describes consensus recommendations from an expert group of neurologists from the Arabian Gulf region on the management of relapsing multiple sclerosis (RMS) in the COVID-19 era. MS appears not to be a risk factor for severe adverse COVID-19 outcomes (though patients with advanced disability or a progressive phenotype are at higher risk). Disease-modifying therapy (DMT)-based care appears generally safe for patients with MS who develop COVID-19 (although there may be an increased risk of adverse outcomes with anti-CD20 therapy). Interferon-β, teriflunomide, dimethyl fumarate, glatiramer acetate, natalizumab and cladribine tablets are unlikely to increase the risk of infection; fingolimod, anti-CD20 agents and alemtuzumab may confer an intermediate risk. Existing DMT therapy should be continued at this time. For patients requiring initiation of a DMT, all currently available DMTs except alemtuzumab can be started safely at this time; initiate alemtuzumab subject to careful individual risk-benefit considerations. Patients should receive vaccination against COVID-19 where possible, with no interruption of existing DMT-based care. There is no need to alter the administration of interferon-β, teriflunomide, dimethyl fumarate, glatiramer acetate, natalizumab, fingolimod or cladribine tablets for vaccination; new starts on other DMTs should be delayed for up to 6 weeks after completion of vaccination to allow the immune response to develop. Doses of the Oxford University/AstraZeneca vaccine may be scheduled around doses of anti-CD20 or alemtuzumab. Where white cell counts are suppressed by treatment, these should be allowed to recover before vaccination., (© 2021. The Author(s).)

This article describes consensus recommendations from an expert group of neurologists from the Arabian Gulf region on the management of relapsing multiple sclerosis (RMS) in the COVID-19 era. MS appears not to be a risk factor for severe adverse COVID-19 outcomes (though patients with advanced disability or a progressive phenotype are at higher risk). Disease-modifying therapy (DMT)-based care appears generally safe for patients with MS who develop COVID-19 (although there may be an increased risk of adverse outcomes with anti-CD20 therapy). Interferon-β, teriflunomide, dimethyl fumarate, glatiramer acetate, natalizumab and cladribine tablets are unlikely to increase the risk of infection; fingolimod, anti-CD20 agents and alemtuzumab may confer an intermediate risk. Existing DMT therapy should be continued at this time. For patients requiring initiation of a DMT, all currently available DMTs except alemtuzumab can be started safely at this time; initiate alemtuzumab subject to careful individual risk-benefit considerations. Patients should receive vaccination against COVID-19 where possible, with no interruption of existing DMT-based care. There is no need to alter the administration of interferon-β, teriflunomide, dimethyl fumarate, glatiramer acetate, natalizumab, fingolimod or cladribine tablets for vaccination; new starts on other DMTs should be delayed for up to 6 weeks after completion of vaccination to allow the immune response to develop. Doses of the Oxford University/AstraZeneca vaccine may be scheduled around doses of anti-CD20 or alemtuzumab. Where white cell counts are suppressed by treatment, these should be allowed to recover before vaccination., (© The Author(s) 2021.)

Most disease-modifying drugs (DMDs) are contraindicated in pregnancy. Management of MS is especially challenging for pregnant patients, as withdrawal of DMDs leave the patient at risk of increased disease activity. We, a group of experts in MS care from countries in the Arab Gulf, present our consensus recommendations on the management of MS in these patients. Where possible, a patient planning pregnancy can be switched to a DMD considered safe in this setting. Interferon β now can be used during pregnancy, where there is a clinical need to maintain treatment, in addition to glatiramer acetate. Natalizumab (usually to 30 weeks' gestation for patients with high disease activity at high risk of relapse and disability progression) may also be continued into pregnancy. Cladribine tablets and alemtuzumab have been hypothesised to act as immune reconstitution therapies (IRTs). These drugs provide a period of prolonged freedom from relapses for many patients, but the patient must be prepared to wait for up to 20 months from initiation of therapy before becoming pregnant. If a patient becomes pregnant while taking fingolimod, and requires continued DMD treatment, a switch to interferon β or natalizumab after a variable washout period may be prescribed, depending on the level of disease activity. Women who wish to breastfeed should be encouraged to do so, and interferon β may also be used during breastfeeding. There is a lack of data regarding the safety of using other DMDs during breastfeeding.

The majority of disease-modifying drugs (DMDs) available for the management of active relapsing-remitting multiple sclerosis (RMS) depend on continuous drug intake for maintained efficacy, with escalation to a more active drug when an unacceptable level of disease activity returns. Among continuously applied regimens, interferons and glatiramer acetate act as immunomodulators, while dimethyl fumarate, fingolimod, ocrelizumab, natalizumab and teriflunomide are associated with continuous immunosuppression. By contrast, immune reconstitution therapy (IRT) provides efficacy that outlasts a short course of treatment. Autologous hemopoietic stem cell transplantation is perhaps the classic example of IRT, but this invasive and intensive therapy has challenging side-effects. A short treatment course of a pharmacologic agent hypothesized to act as an IRT, such as Cladribine Tablets 3.5 mg/kg or alemtuzumab, can provide long-term suppression of MS disease activity, without need for continuous treatment (the anti-CD20 mechanism of ocrelizumab has the potential to act as an IRT, but is administered continuously, at 6-monthly intervals). Cladribine Tablets 3.5 mg/kg shows some selectivity in targeting adaptive immunity with a lesser effect on innate immunity. The introduction of IRT-like disease-modifying drugs (DMDs) challenges the traditional maintenance/escalation mode of treatment and raises new questions about how disease activity is measured. In this review, we consider a modern classification of DMDs for MS and its implications for the care of patients in the IRT era.