Practical Guidance on the Use of Cladribine Tablets in the Management or Relapsing Multiple Sclerosis: Expert Opinion from Qatar.

The increasing availability of high-efficacy disease-modifying therapies (DMT) for the management of relapsing multiple sclerosis (RMS) has increased the potential for individualised patient management but has added complexity to the design of treatment regimens. The long-term application of immune reconstitution therapy (IRT) is supported by an increasing database of real world studies that have added important information on the long-term safety and efficacy of this approach. Cladribine tablets (CladT) is an IRT given as two annual short courses of treatment, following which a majority of patients then demonstrate no significant MS disease activity over a period of years. Whether, and how, to treat patients beyond the first two years of treatment remains a matter for debate, as clinical evidence accumulates. We, a group of neurologists who manage people with RMS in Qatar, provide our expert consensus recommendations on the application and long-term management of CladT therapy based on our experience with treatment in the last 5 years. These include pragmatic recommendations for people with MS disease activity in years 3 and 4 (ie up to four years following first dose of CladT), and for people with or without MS disease activity in subsequent years. We believe our recommendations will help to ensure the optimal application of CladT-based IRT, with the potential benefit for the patient of achieving prolonged periods free of both MS disease symptoms and the burden of regular applications of immunosuppressive DMT.

Multicentre Observational Study of Treatment Satisfaction with Cladribine Tablets in the Management of Relapsing Multiple Sclerosis in the Arabian Gulf: The CLUE Study.

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 × 109/L and 1.3 ± 0.3 × 109/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.

Expert Consensus and Narrative Review on the Management of Multiple Sclerosis in the Arabian Gulf in the COVID-19 Era: Focus on Disease-Modifying Therapies and Vaccination Against COVID-19.

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-ß, 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-ß, 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.

Expert Consensus and Narrative Review on the Management of Multiple Sclerosis in the Arabian Gulf in the COVID-19 Era: Focus on Disease-Modifying Therapies and Vaccination Against COVID-19.

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-ß, 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-ß, 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.

Position of Cladribine Tablets in the Management of Relapsing-Remitting Multiple Sclerosis: An Expert Narrative Review From the United Arab Emirates.

The use of immune reconstitution therapies (IRT) in patients with relapsing-remitting multiple sclerosis (RRMS) is associated with a prolonged period of freedom from relapses in the absence of continuously applied therapy. Cladribine tablets is a disease-modifying treatment (DMT) indicated for highly active relapsing multiple sclerosis (MS) as defined by clinical or imaging features. Treatment with cladribine tablets is effective and well tolerated in patients with active MS disease and have a low burden of monitoring during and following treatment. In this article, an expert group of specialist neurologists involved in the care of patients with MS in the United Arab Emirates provides their consensus recommendations for the practical use of cladribine tablets according to the presenting phenotype of patients with RRMS. The IRT approach may be especially useful for patients with highly active MS insufficiently responsive to treatment with a first-line DMT, those who are likely to adhere poorly to a continuous therapeutic regimen, treatment-naïve patients with high disease activity at first presentation, or patients planning a family who are prepared to wait until at least 6 months after the end of treatment. Information available to date does not suggest an adverse interaction between cladribine tablets and COVID-19 infection. Data are unavailable at this time regarding the efficacy of COVID-19 vaccination in patients treated with cladribine tablets. Robust immunological responses to COVID-19 infection or to other vaccines have been observed in patients receiving this treatment, and treatment with cladribine tablets per se should not represent a barrier to this vaccination.

Disease-Modifying Drugs and Family Planning in People with Multiple Sclerosis: A Consensus Narrative Review from the Gulf Region.

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 ß 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 ß 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 ß may also be used during breastfeeding. There is a lack of data regarding the safety of using other DMDs during breastfeeding.

High-efficacy therapies for relapsing-remitting multiple sclerosis: implications for adherence. An expert opinion from the United Arab Emirates.

The number of disease-modifying treatments (DMDs) for relapsing-remitting multiple sclerosis has increased. DMDs differ not only in their efficacy and safety/tolerability, but also in the treatment burden of, associated with their initiation, route/frequency of administration, maintenance treatment and monitoring. High-efficacy DMDs bring the prospect of improved suppression of relapses and progression of disability, but may have serious safety issues, and burdensome long-term monitoring. Studies of patient preferences in this area have focused on side effects, efficacy and route of administration. Adherence to DMDs is often suboptimal in relapsing-remitting multiple sclerosis and there is a need to understand more about how the complex therapeutic and administration profiles of newer DMDs interact with these barriers to support optimal adherence to therapy.

Expert consensus from the Arabian Gulf on selecting disease-modifying treatment for people with multiple sclerosis according to disease activity.

Recent research has expanded our understanding of the natural history and clinical course of multiple sclerosis (MS) in the Arabian Gulf region. In addition, the number of available therapies for MS has increased greatly in recent years, which complicates considerably the design of therapeutic regimens. We, an expert group of physicians practising in Arabian Gulf countries, present pragmatic consensus recommendations for the use of disease-modifying therapy, according to the level of MS disease activity, according to objective criteria, and prior treatment (if any) received by a given patient.

Management of relapsing-remitting multiple sclerosis in Qatar: an expert consensus.

Healthcare systems vary greatly between countries. International, evidence-based guidelines for the management of multiple sclerosis (MS) may need to be adapted for use in particular countries. Two years ago, the authors published a comprehensive consensus guideline for the management of MS in Qatar. Since that time, the availability of disease-modifying treatments for relapsing-remitting MS (RRMS), and our understanding of how to apply those treatments, has increased. The authors present an update to our guidance, focussing on the management of relapsing-remitting RRMS. In particular, the authors consider the optimal use of different DMTs in patients presenting with mild, medium or high disease activity.

An Overview of High-Efficacy Drugs for Multiple Sclerosis: Gulf Region Expert Opinion.

This article discusses the opinions of the multiple sclerosis (MS) experts in the Gulf region on the use of high-efficacy disease-modifying drugs (DMDs; natalizumab, fingolimod, alemtuzumab, cladribine tablets, and ocrelizumab) in clinical practice. The experts reviewed the current literature including pivotal clinical trials and meta-analyses for high-efficacy DMDs, supplemented by the expert opinions on the usage of these DMDs in clinical practice. Several criteria were discussed by the panel based on different efficacy, safety, and convenience attributes. The panel concluded that all the DMDs available for the treatment of MS have benefits and risks, which should be considered while discussing the treatment plan with the patient. It is important to have a personalized approach based on the risk-benefit assessment for each case. Common considerations while choosing treatments include effectiveness, side effects/safety, and convenience/route of administration.Funding: Merck Serono Middle East FZ LTD.