RESUMO
BACKGROUND: Epidemiological data reveal that 45% of persons with multiple sclerosis (PwMS) in France are more than 50 years. This population more than 50 is more susceptible to cancer, and this risk may be increased by frequent use of immunosuppressive drugs. Consequently, concerns have arisen about the potential increased risk of cancer in PwMS and how patients should be screened and managed in terms of cancer risk. OBJECTIVE: To develop evidence-based recommendations to manage the coexistence of cancer and multiple sclerosis (MS). METHODS: The French Group for Recommendations in MS collected articles from PubMed and university databases covering the period January 1975 through June 2022. The RAND/UCLA method was employed to achieve formal consensus. MS experts comprehensively reviewed the full-text articles and developed the initial recommendations. A group of multidisciplinary health care specialists then validated the final proposal. RESULTS: Five key questions were addressed, encompassing various topics such as cancer screening before or after initiating a disease-modifying therapy (DMT), appropriate management of MS in the context of cancer, recommended follow-up for cancer in patients receiving a DMT, and the potential reintroduction of a DMT after initial cancer treatment. A strong consensus was reached for all 31 recommendations. CONCLUSION: These recommendations propose a strategic approach to managing cancer risk in PwMS.
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Esclerose Múltipla , Neoplasias , Humanos , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/terapia , Neoplasias/epidemiologia , França/epidemiologia , Imunossupressores/uso terapêuticoRESUMO
BACKGROUND: In relapsing-remitting multiple sclerosis (RRMS), early identification of suboptimal responders can prevent disability progression. OBJECTIVE: We aimed to develop and validate a dynamic score to guide the early decision to switch from first- to second-line therapy. METHODS: Using time-dependent propensity scores (PS) from a French cohort of 12,823 patients with RRMS, we constructed one training and two validation PS-matched cohorts to compare the switched patients to second-line treatment and the maintained patients. We used a frailty Cox model for predicting individual hazard ratios (iHRs). RESULTS: From the validation PS-matched cohort of 348 independent patients with iHR ⩽ 0.69, we reported the 5-year relapse-free survival at 0.14 (95% confidence interval (CI) 0.09-0.22) for the waiting group and 0.40 (95% CI 0.32-0.51) for the switched group. From the validation PS-matched cohort of 518 independent patients with iHR > 0.69, these values were 0.37 (95% CI 0.30-0.46) and 0.44 (95% CI 0.37-0.52), respectively. CONCLUSIONS: By using the proposed dynamic score, we estimated that at least one-third of patients could benefit from an earlier switch to prevent relapse.
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Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , Fatores Imunológicos , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológicoRESUMO
BACKGROUND: In 2020, the French Multiple Sclerosis (MS) Society (SFSEP) decided to develop a national evidence-based consensus on pregnancy in MS. As neuromyelitis optica spectrum disorders (NMOSD) shares a series of commonalities with MS, but also some significant differences, specific recommendations had to be developed. OBJECTIVES: To establish recommendations on pregnancy in women with NMOSD. METHODS: The French Group for Recommendations in Multiple Sclerosis (France4MS) reviewed PubMed and universities databases (January 1975 through June 2021). The RAND/UCLA appropriateness method, which was developed to synthesise the scientific literature and expert opinions on health care topics, was used to reach a formal agreement. Fifty-six MS experts worked on the full-text review and initial wording of recommendations. A sub-group of nine NMOSD experts was dedicated to analysing available data on NMOSD. A group of 62 multidisciplinary healthcare specialists validated the final proposal of summarised evidence. RESULTS: A strong agreement was reached for all 66 proposed recommendations. They cover diverse topics, such as pregnancy planning, follow-up during pregnancy and postpartum, delivery routes, loco-regional analgesia or anaesthesia, prevention of postpartum relapses, breastfeeding, vaccinations, reproductive assistance, management of relapses, and disease-modifying treatments. CONCLUSION: Physicians and patients should be aware of the new and specific evidence-based recommendations of the French MS Society for pregnancy in women with NMOSD. They should help harmonise counselling and treatment practise, allowing for better individualised choices.
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Esclerose Múltipla , Neuromielite Óptica , Gravidez , Humanos , Feminino , Neuromielite Óptica/diagnóstico , Neuromielite Óptica/terapia , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/terapia , Vacinação , Período Pós-Parto , RecidivaRESUMO
OBJECTIVE: The objective of this study was to develop evidence-based recommendations on pregnancy management for persons with multiple sclerosis (MS). BACKGROUND: MS typically affects young women in their childbearing years. Increasing evidence is available to inform questions raised by MS patients and health professionals about pregnancy issues. METHODS: The French Group for Recommendations in Multiple Sclerosis (France4MS) reviewed PubMed and university databases (January 1975 through June 2021). The RAND/UCLA appropriateness method was developed to synthesise the scientific literature and expert opinions on healthcare topics; it was used to reach a formal agreement. Fifty-six MS experts worked on the full-text review and initial wording of recommendations. A group of 62 multidisciplinary healthcare specialists validated the final proposal of summarised evidence. RESULTS: A strong agreement was reached for all 104 proposed recommendations. They cover diverse topics, such as pregnancy planning, follow-up during pregnancy and postpartum, delivery routes, locoregional analgesia or anaesthesia, prevention of postpartum relapses, breastfeeding, vaccinations, reproductive assistance, management of relapses and disease-modifying treatments. CONCLUSION: The 2022 recommendations of the French MS society should be helpful to harmonise counselling and treatment practice for pregnancy in persons with MS, allowing for better and individualised choices.
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Esclerose Múltipla , Complicações na Gravidez , Gravidez , Humanos , Feminino , Esclerose Múltipla/terapia , Período Pós-Parto , Vacinação , Complicações na Gravidez/terapia , RecidivaRESUMO
BACKGROUND: In multiple sclerosis (MS) studies, the most appropriate model for the distribution of the number of relapses was shown to be the negative binomial (NB) distribution. OBJECTIVE: To determine whether the sample-size estimation (SSE) and the analysis of annualized relapse rates (ARRs) in randomized controlled trials (RCTs) were aligned and compare the SSE between normal and NB distributions. METHODS: Systematic review of phase 3 and 4 RCTs for which the primary endpoint was ARR in relapsing remitting MS published since 2008 in pre-selected major medical journals. A PubMed search was performed on 30 November 2020. We checked whether the SSE and ARR analyses were congruent. We also performed standardized (fixed α/ß, number of arms and overdispersion) SSEs using data collected from the studies. RESULTS: Twenty articles (22 studies) were selected. NB distribution (or quasi-Poisson) was used for SSE in only 7/22 studies, whereas 21/22 used it for ARR analyses. SSE relying on NB regression necessitated a smaller sample size in 21/22 of our calculations. CONCLUSION: SSE was rarely performed using the most appropriate model. However, the use of an NB model is recommended to optimize the number of included patients and to be congruent with the final analysis.
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Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Doença Crônica , Humanos , Esclerose Múltipla/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Projetos de Pesquisa , Tamanho da AmostraRESUMO
INTRODUCTION: Recent studies suggested that anti-CD20 and fingolimod may be associated with lower anti-spike protein-based immunoglobulin-G response following COVID-19 vaccination. We evaluated if COVID-19 occurred despite vaccination among patients with multiple sclerosis (MS) and neuromyelitis optica (NMO), using the COVISEP registry. CASE SERIES: We report 18 cases of COVID-19 after two doses of BNT162b2-vaccination, 13 of which treated with anti-CD20 and four with fingolimod. COVID-19 severity was mild. DISCUSSION: These results reinforce the recommendation for a third COVID-19 vaccine dose among anti-CD20 treated patients and stress the need for a prospective clinical and biological study on COVID-19 vaccine efficacy among MS and NMO patients.
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Vacina BNT162 , COVID-19 , Esclerose Múltipla , Neuromielite Óptica , Vacina BNT162/administração & dosagem , COVID-19/diagnóstico , Cloridrato de Fingolimode/uso terapêutico , Humanos , Esclerose Múltipla/complicações , Neuromielite Óptica/complicações , SARS-CoV-2RESUMO
BACKGROUND AND PURPOSE: Disease-modifying therapies (DMTs) have an impact on relapses and disease progression. Nonetheless, many patients with multiple sclerosis (MS) remain untreated. The objectives of the present study were to determine the proportion of untreated patients with MS followed in expert centers in France and to determine the predictive factors of nontreatment. METHODS: We conducted a retrospective cohort study. Data were extracted from the 38 centers participating in the European Database for Multiple Sclerosis (EDMUS) on December 15, 2018, and patients with MS seen at least once during the study period (from June 15, 2016 to June 14, 2017) were included. RESULTS: Of the 21,189 patients with MS (age 47.1 ± 13.1 years; Expanded Disability Status Scale (EDSS) score 3.4 ± 2.4), 6,631 (31.3%; 95% confidence interval [CI] 30.7-31.9) were not receiving any DMT. Although patients with a relapsing-remitting course (n = 11,693) were the most likely to receive DMT, 14.8% (95% CI 14.2-15.4) were still untreated (6.8% never treated). After multivariate analysis among patients with relapsing-remitting MS, the main factors explaining never having been treated were: not having ≥9 lesions on brain magnetic resonance imaging (odds ratio [OR] 0.52 [95% CI 0.44-0.61]) and lower EDSS score (OR 0.78 [95% CI 0.74-0.82]). Most patients with progressive MS (50.4% for secondary and 64.2% for primary progressive MS) did not receive any DMT during the study period, while 11.6% of patients with secondary and 34.0% of patients with primary progressive MS had never received any DMT. CONCLUSION: A significant proportion of patients with MS did not receive any DMT, even though such treatments are reimbursed by the healthcare system for French patients. This result highlights the unmet need for current DMTs for a large subgroup of patients with MS.
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Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Adulto , Humanos , Pessoa de Meia-Idade , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/terapia , Recidiva Local de Neoplasia , Estudos RetrospectivosRESUMO
OBJECTIVES: To evaluate the safety and efficacy of ketamine-magnesium combination to reduce attacks in a series of patients with refractory chronic cluster headache (rCCH). BACKGROUND: Refractory chronic cluster headache (CCH) is a rare but highly debilitating condition that needs new treatment options. A previous publication reported that a single infusion of ketamine-magnesium combination was effective in 2 patients with rCCH. METHODS: The treatment was proposed to consecutive patients with rCCH seen in 2 French hospitals between November 2015 and February 2020 and who were resistant to at least 3 preventive treatments. They received a single ketamine infusion (0.5 mg/kg over 2 hours) combined with magnesium sulfate (3000 mg). The main outcome was a comparison of the number of daily attacks 2 weeks prior to the ketamine-magnesium infusion and 1 week after (on days 7 and 8). The second outcome was the percentage of responders (patients with ≥50% reduction in the frequency of daily attacks). Safety was assessed by the recording of adverse events during infusion. Descriptive statistics are presented as mean ± standard deviation. RESULTS: Seventeen patients (14 men), with an age of 35.2 ± 8.1 years, were included. They presented with CCH for 6.6 ± 4.3 years. The number of daily attacks decreased from 4.3 ± 2.4 before treatment to 1.3 ± 1.0 after treatment (difference: -3.1 (95% CI: -4.5 to -1.6), P < .001). Seventy six percent (13/17) were responders. Transient and mild sedation was reported by 7/17 patients (41.2%). CONCLUSIONS: The ketamine-magnesium combination seems an effective and well-tolerated therapy for rCCH. Placebo-controlled studies should be conducted to further confirm these findings.
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Analgésicos/farmacologia , Ketamina/farmacologia , Sulfato de Magnésio/farmacologia , Adulto , Analgésicos/administração & dosagem , Analgésicos/efeitos adversos , Doença Crônica , Cefaleia Histamínica , Quimioterapia Combinada , Feminino , Humanos , Infusões Intravenosas , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Sulfato de Magnésio/administração & dosagem , Sulfato de Magnésio/efeitos adversos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Estudos RetrospectivosRESUMO
OBJECTIVES: To document the prevalence of new headaches in patients with Covid-19 infection and the potential association with other neuro-sensorial symptoms (anosmia and ageusia). The persistence of these symptoms 1 month after recovery was also documented. BACKGROUND: Headaches are a very common symptom of viral infections. Surprisingly, early Chinese studies reported a relatively low prevalence (12-15%) of headaches associated with Covid-19. METHODS: All the patients with laboratory-confirmed or chest-CT-confirmed Covid-19 infection, diagnosed between February 27th and April 15th , 2020 in the dedicated laboratory of Clermont-Ferrand University Hospital were followed for 1 month after recovery. RESULTS: A total of 139 consecutive patients (mean [SD] age, 48.5 [15.3] years; 87 women [62.6%]) were interviewed 1 month after disappearance of fever and dyspnea (semi-structured phone interview). Overall, 59.0% (82/139) of people with Covid-19 had mild disease, 36.7% (51/139) had severe disease, and 4.3% (6/139) had critical illness. Eighty-two (59.0%; 95% CI: 50.3 to 67.3) reported new headaches during the acute phase and 3.6% (5/139) had persistent headaches 1 month after fever and dyspnea remission. Anosmia and ageusia were also very common, occurring in 60.4% (84/139) and 58.3% (81/139) of the patients, respectively. These 2 symptoms persisted in 14.4% (20/139) and 11.5% (16/139) of Covid-19 patients 1 month after recovery. Headaches were neither clearly associated with anosmia, nor with ageusia, and were not associated with disease severity (ie, requiring hospitalization or intensive care unit). CONCLUSION: This specific study highlights the high prevalence of new headaches during Covid-19 infection in French patients. Further studies are needed to refine the characterization of patients with Covid-19-associated headaches.
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COVID-19/complicações , Cefaleia/epidemiologia , Idoso , Estudos de Coortes , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , SARS-CoV-2RESUMO
BACKGROUND: Several neuromodulation methods exists for migraine treatment. The aim of the present study was to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) focusing on migraine treatment using neurostimulation methods. METHODS: We searched Medline and Embase up to July 1, 2020 for RCTs reporting acute or preventive treatment of migraine with either non-invasive or invasive neurostimulation methods. Two researchers independently assessed the eligibility of the retrieved studies and extracted data. Outcomes for the quantitative synthesis were 2 h pain free for acute treatment and headache days per month for preventive treatment. We performed subgroup analyses by treatment (stimulation method and site of application). Estimates were pooled using random-effects meta-analysis. RESULTS: Thirty-eight articles were included in the qualitative analysis (7 acute, 31 preventive) and 34 in the quantitative evaluation (6 acute, 28 preventive). Remote electrical neuromodulation (REN) was effective for acute treatment. Data were insufficient to draw conclusions for any other techniques (single studies). Invasive occipital nerve stimulation (ONS) was effective for migraine prevention, with a large effect size but considerable heterogeneity, whereas supra-orbital transcutaneous electrical nerve stimulation (TENS), percutaneous electrical nerve stimulation (PENS), and high-frequency repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) were effective, with small to medium effect sizes. Vagus-nerve stimulation, left prefrontal cortex rTMS, and cathodal transcranial direct current stimulation (tDCS) over the M1 had no significant effect and heterogeneity was high. CONCLUSION: Several neuromodulation methods are of potential interest for migraine management, but the quality of the evidence is very poor. Future large and well-conducted studies are needed and could improve on the present results.
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Transtornos de Enxaqueca , Estimulação Transcraniana por Corrente Contínua , Estimulação Elétrica Nervosa Transcutânea , Humanos , Transtornos de Enxaqueca/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Estimulação Magnética TranscranianaRESUMO
BACKGROUND: Chronic cluster headache (CH) is a rare, highly disabling primary headache condition. As NMDA receptors are possibly overactive in CH, NMDA receptor antagonists, such as ketamine, could be of interest in patients with intractable CH. CASE REPORTS: Two Caucasian males, 28 and 45 years-old, with chronic intractable CH, received a single ketamine infusion (0.5 mg/kg over 2 h) combined with magnesium sulfate (3000 mg over 30 min) in an outpatient setting. This treatment led to a complete relief from symptoms (attack frequency and pain intensity) for one patient and partial relief (50%) for the other patient, for 6 weeks in both cases. CONCLUSION: The NMDA receptor is a potential target for the treatment of chronic CH. Randomized, placebo-controlled studies are warranted to establish both safety and efficacy of such treatment.
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Cefaleia Histamínica/tratamento farmacológico , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Ketamina/administração & dosagem , Sulfato de Magnésio/administração & dosagem , Adulto , Assistência Ambulatorial , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Receptores de N-Metil-D-Aspartato/antagonistas & inibidoresRESUMO
BACKGROUND: Amyotrophic lateral sclerosis is a progressive debilitating and lethal disorder, characterized by degeneration of motor neurons that warrant palliative care. Pain is frequent in patients with amyotrophic lateral sclerosis and significantly impacts on quality of life. AIM: To describe pain and assess the prevalence of pain with neuropathic characteristics in patients with amyotrophic lateral sclerosis. DESIGN: Cross-sectional survey from March 2009 to October 2013. SETTING/PARTICIPANTS: Amyotrophic lateral sclerosis patients underwent multidisciplinary assessment and completed questionnaires measuring the severity and impact of pain and anxiety. The Douleur Neuropathique-4 questionnaire was used to look for pain with neuropathic characteristics. RESULTS: Of 96 clinical evaluations, 93 were usable for analysis (age at onset: 62 ± 12.5 years; disease duration: 34 ± 33 months). The overall pain prevalence was 66%, with 9% experiencing pain with neuropathic characteristics. Pain was most often located in the neck and shoulders (38% of pain patients). Neck and shoulder pain was associated with neck (p = 0.04) and proximal upper limb muscular weakness (p = 0.02), respectively. Pain was not associated with disease duration, respiratory or nutritional parameters, but with higher anxiety scores (p = 0.01). Patients with neuropathic characteristics pain did not differ significantly from patients with or without pain, except that they had higher minimal pain intensity score (p < 0.05). Neuropathic characteristics pain was frequently spontaneous (rarely evoked) and described as numbness, burning, electric shock, tingling, and pins-and-needle. CONCLUSION: Even if amyotrophic lateral sclerosis is a disease of the motor system, pain is frequent and can rarely have neuropathic characteristics. Pain must be always sought and appropriately treated to limit quality of life impairment.
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Esclerose Lateral Amiotrófica/complicações , Esclerose Lateral Amiotrófica/fisiopatologia , Neuralgia/epidemiologia , Neuralgia/etiologia , Idoso , Estudos Transversais , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Medicina Paliativa , Prevalência , Qualidade de VidaRESUMO
BACKGROUND: The number and indications of lumbar punctures (LPs) performed nowadays are unknown. The primary aim of this work was to report the number of LPs performed in each of the departments of 2 French university hospitals, their indications and the prevalence of atraumatic spinal needles used. METHODS: We carried out a retrospective study of all the LPs performed in 2014. The clinical department in which the intervention was performed and the final diagnosis was made from the Medical Information Department. The type of needles (cutting or atraumatic) used during the study period was also available. RESULTS: In 2014, 6,594 LPs were performed. Overall, 80% were performed for diagnostic purposes. Twenty percent of these LPs were performed in the Neurology Department and were usually carried out at routine check-ups. Overall, atraumatic needles were used in 8.0% of cases. Overall, 1.4 LPs per 100 hospital stays were performed and 0.8 LP for 100 Emergency department admissions. CONCLUSION: LP is a routine procedure for many clinicians and although neurologists perform the largest number of LPs, they are doing only one fifth of all procedures. Atraumatic needles are underused.
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Agulhas , Punção Espinal/estatística & dados numéricos , Humanos , Neurologistas , Cefaleia Pós-Punção Dural , Estudos RetrospectivosRESUMO
Neuropathic pain continues to be a significant problem that lacks effective solutions for every single patient. In 2015, international guidelines (NeuPSIG) were published, while the French recommendations were updated in 2020. The purpose of this minireview is to provide an update on the process of developing evidence-based recommendations and explore potential changes to the current recommendations. Primary treatments for neuropathic pain include selective serotonin-norepinephrine reuptake inhibitors (SNRIs) such as duloxetine and venlafaxine, gabapentin, tricyclic antidepressants, as well as topical lidocaine and transcutaneous electrical nerve stimulation, which are specifically suggested for focal peripheral neuropathic pain. Pregabalin is a first line treatment according to international guidelines but second-line in the more recent French guidelines, due to lower efficacy seen in more recent studies and misuse risk. Additionally, tramadol, combination therapies, and psychotherapy as adjuncts are proposed second line; high-concentration capsaicin patches, and botulinum toxin A are proposed specifically for focal peripheral neuropathic pain. In cases where primary and secondary treatments prove insufficient, third-line options come into play. These include high-frequency repetitive transcranial magnetic stimulation (rTMS) targeting the motor cortex, spinal cord stimulation, and the use of strong opioids when no alternative is available. To ensure optimal management of neuropathic pain in real-life situations, it is imperative to disseminate these recommendations widely and secure the acceptance of practitioners. By doing so, we can bridge the gap between theory and practice, and enhance the overall care and treatment of individuals suffering from neuropathic pain.
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Medicina Baseada em Evidências , Neuralgia , Guias de Prática Clínica como Assunto , Humanos , Neuralgia/terapia , Neuralgia/tratamento farmacológico , Analgésicos/uso terapêuticoRESUMO
BACKGROUND AND OBJECTIVES: People with multiple sclerosis (MS) have an increased risk of severe coronavirus infection due to their level of motor disability or exposure to certain immunosuppressive treatments. Thus, patients with MS have had priority access to coronavirus disease 2019 (COVID-19) vaccination. However, relapses after vaccination have been reported, leading some patients to not seek the recommended booster doses. The main objective was to estimate the risk of severe relapse after 1, 2, and 3 (booster) doses of COVID-19 vaccination in patients with MS. The secondary objectives were to assess the risk of relapse in clinically meaningful subgroups according to the type of vaccine, the characteristics of the patients, and the use of disease-modifying treatments (DMTs). METHODS: We conducted a nationwide study using data from the French National Health Data System. Patients with MS were identified according to ICD codes, specific treatments, and reimbursement data up to March 31, 2022. Relapses requiring treatment with high-dose corticosteroids were identified. A self-controlled case series method was used to evaluate the risk of relapse associated with COVID-19 vaccines in the 45 days after vaccination. The associated risk was evaluated after 1, 2, or 3 (booster) doses and is expressed as overall incidence rate ratios (IRRs) and in subgroups of interest. RESULTS: Overall, 124,545 patients with MS were identified on January 1, 2021, and 82% received at least 1 dose of a COVID-19 vaccine (n = 102,524) until December 31, 2021, for a total of 259,880 doses. The combined IRR for MS relapse was 0.97 (0.91-1.03, p = 0.30). The same absence of risk was confirmed in various subgroups (age younger than 50 years, duration of MS < 10 years, use of DMT). A small increase in the relapse risk cannot be excluded after a booster dose (IRR 1.39 [1.08-1.80]) for patients with high MS activity, especially when not treated. DISCUSSION: There is no increased risk of relapse requiring corticosteroid therapy after COVID-19 vaccination for almost all patients. We cannot exclude an increased risk after the booster dose for patients who have had at least 2 relapses in the previous 2 years. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that COVID-19 vaccination does not increase the risk of severe relapse in patients with MS.
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Vacinas contra COVID-19 , COVID-19 , Esclerose Múltipla , Recidiva , Humanos , França/epidemiologia , Feminino , Masculino , Vacinas contra COVID-19/administração & dosagem , COVID-19/prevenção & controle , COVID-19/epidemiologia , Adulto , Pessoa de Meia-Idade , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/epidemiologia , Vacinação , SARS-CoV-2RESUMO
PURPOSE: To report a case of uveitis associated with multiple sclerosis (MS) that was refractory to multiple lines of therapy but achieved remission with tocilizumab. METHODS: We conducted a retrospective analysis of the patient's medical record including clinical, biological and imaging data. RESULTS: A 33-year-old female patient with a history of MS inactive for 5 years on teriflunomide, and no significant medical or ophthalmological history, presented with bilateral granulomatous panuveitis. Initial examination revealed a visual acuity of 0.4 logMAR and 1.3 logMAR in the right eye and the left eye, respectively, along with a significant anterior chamber flare in both eyes, posterior synechiae, large granulomatous keratic precipitates, bilateral vitritis, bilateral macular edema with foveolar pigment epithelial detachment, and significant bilateral venous and arterial vasculitis. The patient underwent several lines of treatment, all of which proved unsuccessful, including corticosteroids alone or in combination with azathioprine, methotrexate, and mycophenolate mofetil. As a final therapeutic option, tocilizumab was initiated, leading to the remission of uveitis. One year later, the uveitis remained inactive under a 5 mg/day prednisone regimen. CONCLUSIONS: Tocilizumab appears to be an efficient option for managing uveitis associated with MS and may be a valuable choice for clinicians dealing with such cases.
RESUMO
BACKGROUND AND OBJECTIVES: Progressive multifocal leukoencephalopathy (PML) is a severe neurologic disease resulting from JC virus reactivation in immunocompromised patients. Certain multiple sclerosis (MS) disease-modifying therapies (DMTs) are associated with PML risk, such as natalizumab and, more rarely, sphingosine-1-phosphate receptor modulators (S1P-RMs). Although natalizumab-associated PML is well documented, information on S1P-RM-associated PML is limited. The aim of this study is to compare clinical presentations and outcomes between the 2 groups. METHODS: A retrospective multicenter cohort study included patients with PML from 2009 to 2022 treated with S1P-RMs or natalizumab. Data on clinical and radiologic presentation, outcomes, immune reconstitution inflammatory syndrome (IRIS), survival, disability (using the modified Ranking scale-mRS), and MS relapses post-PML were analyzed. RESULTS: Of 88 patients, 84 were analyzed (20 S1P-RM, 64 natalizumab). S1P-RM-associated PML was diagnosed in older patients (median age 52 vs 44 years, p < 0.001) and after longer treatment duration (median 63.9 vs 40 months, p < 0.001). Similarly, S1P-RM patients were more prone to show symptoms at diagnosis (100 vs 80.6%, p = 0.035), had more disseminated lesions (80% vs 34.9%, p = 0.002), and had higher gadolinium enhancement (65% vs 39.1%, p = 0.042). Natalizumab patients had a higher IRIS development rate (OR: 8.3 [1.92-33.3]). Overall, the outcome (mRS) at 12 months was similar in the 2 groups (OR: 0.81 [0.32-2.0]). Yet, post-treatment MS activity was higher in S1P-RM cases (OR: 5.7 [1.4-22.2]). DISCUSSION: S1P-RM-associated PML shows reduced IRIS risk but higher post-treatment MS activity. Clinicians should tailor post-PML treatment based on pre-PML medication.
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Leucoencefalopatia Multifocal Progressiva , Natalizumab , Moduladores do Receptor de Esfingosina 1 Fosfato , Humanos , Leucoencefalopatia Multifocal Progressiva/induzido quimicamente , Natalizumab/efeitos adversos , Masculino , Pessoa de Meia-Idade , Feminino , Adulto , Estudos Retrospectivos , Moduladores do Receptor de Esfingosina 1 Fosfato/farmacologia , Moduladores do Receptor de Esfingosina 1 Fosfato/efeitos adversos , Esclerose Múltipla/tratamento farmacológico , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/farmacologia , Fatores Imunológicos/administração & dosagem , Estudos de Coortes , Idoso , Síndrome Inflamatória da Reconstituição Imune/induzido quimicamenteRESUMO
ANTI-CALCITONIN GENE-RELATED PEPTIDE (CGRP) THERAPIES FOR MIGRAINE. Currently, four monoclonal antibodies targeting the CGRP (calcitonin gene-related peptide) pathway have been shown to be effective as migraine prophylactics: eptinezumab, erenumab, fremanezumab and galcanezumab. Unlike the usual preventive treatments, they are administered parenterally: subcutaneously (monthly or quarterly) or by quarterly IV infusion for eptinezumab. They reduce the frequency of attacks by at least 50% in 50 to 60% of migraine patients, even in cases of failure of several conventional preventive treatments, in cases of chronic migraine and medication overuse. Their tolerance is better than that of conventional oral treatments and the discontinuation rates are very low. They can be proposed after failure of at least two conventional prophylactic treatments, in patients with at least 8 migraine days per month and without cardiovascular pathology. Indeed, these drugs present a risk in case of cardiovascular disease, by inhibiting vasodilation, and are therefore contraindicated in this population. The main limitation to the use of these treatments in France at present is the lack of reimbursement, the cheapest molecule being available at a price of 245 per injection.
ANTICORPS ANTI-CGRP ET MIGRAINE. Actuellement, quatre anticorps monoclonaux ciblant la voie du CGRP (calcitonin gene-related peptide) ont démontré une efficacité en tant que traitement prophylactique de la migraine : l'eptinézumab, l'érénumab, le frémanézumab et le galcanézumab. À la différence des traitements préventifs habituels, ils sont administrés par voie parentérale : voie sous-cutanée (mensuelle ou trimestrielle) ou perfusion intraveineuse trimestrielle pour l'eptinézumab. Ils permettent de réduire la fréquence des crises d'au moins 50 % chez 50 à 60 % des patients migraineux, même en cas d'échec de plusieurs traitements de fond classiques, en cas de migraine chronique et d'abus médicamenteux. Leur tolérance est meilleure que celle des traitements oraux classiques et les taux d'arrêt sont très faibles. Ils peuvent être proposés après échec d'au moins deux traitements prophylactiques classiques chez des patients ayant au moins huit jours de migraine par mois et sans pathologie cardiovasculaire. En effet, ces médicaments inhibent la vasodilatation et présentent donc un risque en cas de maladie cardiovasculaire ; ils sont ainsi contre-indiqués dans cette situation. La principale limite à leur utilisation à l'heure actuelle en France est l'absence de remboursement, la molécule la moins chère étant disponible au prix de 245 par injection.