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Prosperini, Luca; Haggiag, Shalom; Ruggieri, Serena; Tortorella, Carla; Gasperini, Claudio
2023 CNS Drugs
doi: 10.1007/s40263-023-01038-zpmid: 37740822
BackgroundThe question of whether multiple sclerosis requires life-long disease-modifying treatments (DMTs) remains unanswered. Some studies suggest that older patients with stable disease may safely discontinue their DMTs, yet comprehensive evidence-based data are scarce and real-world studies have provided mixed results.ObjectiveThe aim of this study was to assess the rate of disease reactivation and associated risk factors after discontinuation of DMTs in patients with multiple sclerosis.MethodsWe searched scientific databases (PubMed/MEDLINE, Scopus and Google Scholar) to identify real-world studies published until 31 July, 2023 that reported the number of patients who experienced relapses and/or disability accrual (outcomes of interest) following a therapy discontinuation longer than 12 months. Magnetic resonance activity and treatment re-start after DMT discontinuation were also considered as additional outcomes. We excluded studies where therapy discontinuation was explicitly related to an unintended or planned pregnancy or preceded a treatment switch. We ran random-effects meta-analyses, subgroup analyses and meta-regression models to provide pooled estimates of post-discontinuation relapse and disability events, and to identify their potential moderators (predictors).ResultsAfter an independent screening, 22 articles met the eligibility criteria, yielding a pooled sample size of 2942 patients followed for 1–7 years after discontinuation (11,689 patient-years). The pooled rates for relapse and disability events were 6.7 and 5.8 per 100 patient-years, respectively. However, available data did not allow us to disentangle isolated disability accrual from relapse-associated worsening. Studies including older patients (β = −0.65, p = 0.006), patients with a longer exposure to DMTs (β = −2.22, p = 0.001) and patients with a longer period of disease stability (β = −2.74, p = 0.002) showed a lower risk of relapse events. According to meta-regression equations, the risk of relapse events after DMT discontinuation became negligible (arbitrarily set at < 1% per year) at approximately 60 years of age, and after either 10 years of DMT exposure, or 8 years of disease stability. Additional analyses showed pooled rates for magnetic resonance imaging activity and re-start events of 16.7 and 17.5 per 100 patient-years, respectively.ConclusionsBased on our quantitative synthesis of real-world data, in the absence of definitive answers from clinical trials, DMT discontinuation appears feasible with a high degree of certainty in selected patients. While our findings are robust regarding relapse events, future efforts are warranted to determine if DMT discontinuation is associated with isolated disability accrual.
Sparaco, Maddalena; Carbone, Luigi; Landi, Doriana; Ingrasciotta, Ylenia; Di Girolamo, Raffaella; Vitturi, Giacomo; Marfia, Girolama Alessandra; Alviggi, Carlo; Bonavita, Simona
2023 CNS Drugs
doi: 10.1007/s40263-023-01036-1pmid: 37679579
Multiple sclerosis (MS) predominantly affects women of fertile age. Various aspects of MS could impact on fertility, such as sexual dysfunction, endocrine alterations, autoimmune imbalances, and disease-modifying therapies (DMTs). The proportion of women with MS (wMS) requesting infertility management and assisted reproductive technology (ART) is increasing over time. In this review, we report on data regarding ART in wMS and address safety issues. We also discuss the clinical aspects to consider when planning a course of treatment for infertility, and provide updated recommendations to guide neurologists in the management of wMS undergoing ART, with the goal of reducing the risk of disease activation after this procedure. According to most studies, there is an increase in relapse rate and magnetic resonance imaging activity after ART. Therefore, to reduce the risk of relapse, ART should be considered in wMS with stable disease. In wMS, especially those with high disease activity, fertility issues should be discussed early as the choice of DMT, and fertility preservation strategies might be proposed in selected cases to ensure both disease control and a safe pregnancy. For patients with stable disease taking DMTs compatible with pregnancy, treatment should not be interrupted before ART. If the ongoing therapy is contraindicated in pregnancy, then it should be switched to a compatible therapy. Prior to beginning fertility treatments in wMS, it would be reasonable to assess vitamin D serum levels, thyroid function and its antibody serum levels; start folic acid supplementation; and ensure smoking and alcohol cessation, adequate sleep, and food hygiene. Cervico-vaginal swabs for Ureaplasma urealyticum, Mycoplasma hominis, and Chlamydia trachomatis, as well as serology for viral hepatitis, HIV, syphilis, and cytomegalovirus, should be performed. Steroids could be administered under specific indications. Although the available data do not clearly show a definite raised relapse risk associated with a specific ART protocol, it seems reasonably safe to prefer the use of gonadotropin-releasing hormone (GnRH) antagonists for ovarian stimulation. Close clinical and radiological monitoring is reasonably recommended, particularly after hormonal stimulation and in case of pregnancy failure.