Alemtuzumab Treatment For Multiple Sclerosis Research Articles

Alemtuzumab treatment for multiple sclerosis in Austria: An observational long-term outcome study.

Observational real-world study to analyze the clinical effects of alemtuzumab (ALEM) and subsequent disease-modifying therapy (DMT) usage in multiple sclerosis (MS). Data retrieved from the Austrian MS treatment registry (AMSTR) included baseline (BL) characteristics (at ALEM start), annualized relapse rate (ARR), 6-month confirmed progression independent of relapse activity (PIRA; ≥ 0.5-point Expanded Disability Status Scale (EDSS) score increase), 6-month confirmed disability improvement (CDI; ≥ 0.5-point EDSS decrease), and safety outcomes until initiation of a subsequent DMT. The EDSS was re-baselined at 30 days from ALEM start (BL EDSS). Eighty-seven ALEM-treated patients (median age: 32 years, 72% female, 14% treatment-naïve) were followed for a median of 55 (interquartile range 31-68) months. We found significant reductions in the ARR from 1.16 before ALEM to 0.15 throughout Years 1-9 (p < 0.001). Subsequent DMTs were initiated in 19 patients (22%, 74% anti-CD20 monoclonal antibodies). At Year 5 (n = 53), more patients achieved CDI (58%, 95% confidence interval (CI) 45%-71%) than had experienced PIRA (14%, CI 7.5%-24%), and 58% remained relapse-free. Shorter MS duration (p < 0.001, hazard ratio (HR) 0.86 (CI 0.80-0.93)) and no previous high-efficacy treatment (p < 0.001, HR 5.16 (CI 2.66-10.0)) were the best predictors of CDI, while PIRA was associated with a higher number of previous DMTs (p = 0.04, HR 3.06, CI 1.05-8.89). We found no new safety signals. ALEM had long-lasting beneficial effects on the ARR and disability improvement, especially when initiated early in the course of the disease. Only a subset of patients received subsequent DMTs.

Primary Central Nervous System Vasculitis Following Alemtuzumab Treatment for Multiple Sclerosis: A Case Report and Literature Review.

Cerebral vasculitides are often devastating conditions that require immediate diagnosis and treatment. We report a pathologically proven clinical case of primary central nervous system vasculitis in a 50-year-old man with a diagnosis of relapsing-remitting multiple sclerosis after alemtuzumab therapy, which required additional immunosuppression to control this life-threatening condition. In patients presenting subacute neurological deterioration after alemtuzumab therapy, primary central nervous system vasculitis should be considered as a differential diagnosis among other autoimmune conditions.

BH14 Multiple sclerosis and alopecia areata: drug-induced alopecia areata or coexisting autoimmune phenomena?

Abstract Alopecia areata (AA) is an autoimmune condition characterized by well-demarcated patches of nonscarring alopecia. AA shares multiple gene loci with other autoimmune conditions, including multiple sclerosis (MS). There are limited data on drug-induced alopecia areata (DIAA); however, the literature is expanding, with several targeted therapies implicated including dupilumab, nivolumab and multiple disease-modifying MS treatments, namely, alemtuzumab and ocrelizumab. Alemtuzumab is monoclonal antibody against CD52, which is expressed on T and B lymphocytes, natural killer (NK) cells, monocytes and macrophages. It is considered a highly efficacious treatment; however, there are increasing reports of secondary autoimmunity in up to 40% of patients (Tuohy O, Costellow L, Hill-Cawthorne G et al. Alemtuzumab treatment of MS: long-term safety and efficacy. J Neurol Neurosurg Psychiatry 2015; 86:208–15). A 35-year-old man was referred by his neurologist with concerns of alemtuzumab-induced alopecia universalis (AU). He has relapsing-remitting MS, diagnosed in 2018. His first alemtuzumab course was in 2018 and the second in June 2019, which achieved remission. He reported AU approximately 10 months after this second course with complete spontaneous regrowth. A further episode of AU occurred 6 months later with only minimal eyebrow regrowth. He had no previous history of alopecia or thyroid disease. He had vitamin D insufficiency. There are 12 cases of alemtuzumab-induced AA reported in the literature with variable timeframes of onset, ranging between weeks to over 6–9 months postinfusion. The majority of patients received more than one infusion prior to the onset of AA. Our case echoes other case reports, including one case of AU manifesting 9 months post-alemtuzumab (Zimmermann J. Buhl T, Muller M. AU following alemtuzumab treatment in MS: a barely recognized manifestation of secondary autoimmunity – case report and review of literature. Front Neurol 2017; 8:569). AA pathogenesis, like MS, is hypothesized to be multifactorial with genetic, environmental and autoimmune aspects. It is believed that AA hair follicle cells have increased major histocompatibility complex class I and II activity, presenting autoantigens to CD8+ T cells, CD4+ T cells and NK cells. Interferon (IFN)-γ is considered key in AA pathogenesis. Patients with AA are found to have raised serum levels, along with reports of raised interleukin (IL)-6 levels. Alemtuzumab-induced immunosuppression precedes a phase of immune reconstitution. Cytokines are released post-treatment, including IFN-γ, tumour necrosis factor-α, IL-6 and IL-2. It is plausible that alemtuzumab could trigger AA as a sequela of the immune reconstitution. However, DIAA has been poorly described and the genetic overlap raises the question of both conditions occurring spontaneously. Accurate phenotyping and a multidisciplinary approach will enable us to gain greater clarity, inform our decision-making in the management of these complex patients and provide insights into pathogenic AA pathways.

Motor Evoked Potential-A Pilot Study Looking at Reliability and Clinical Correlations in Multiple Sclerosis.

Multiple sclerosis (MS) is a clinically heterogeneous disease. Biomarkers that can assess pathological processes that are unseen with conventional imaging remain an unmet need in MS disease management. Motor evoked potentials (MEPs) could be such a biomarker. To determine and follow longitudinal MEP reliability and correlations with clinical measures in MS patients. This is a single-center study in alemtuzumab-treated MS patients to evaluate temporal reliability of MEPs, identify MEP minimum detectible differences, and explore correlations with existing clinical scales. Ten MS patients recently treated with alemtuzumab were evaluated every 6 months over 3 years. Clinical evaluations consisted of expanded disability status scale, timed 25-foot walk, 6-minute walk, and nine-hole peg test. MEPs were measured twice, 2 weeks apart, every 6 months. Eight patients completed all 3 years of study. The intraclass correlation coefficient for MEP parameters ranged from 0.76 to 0.98. TA latency and amplitude with facilitation significantly and strongly correlated with all clinical measures, whereas the MEP duration modestly correlated. Biceps latency with facilitation significantly and moderately correlated with 9-hole peg test. Longitudinal correlations demonstrated good predictive values for either clinical deterioration or improvement. MEPs have excellent intrapatient and intrarater reliability, and TA MEPs significantly and strongly correlated with expanded disability status scale, 6-minute walk, and timed 25-foot walk, whereas biceps MEPs significantly and moderately correlated with nine-hole peg test. Further studies using larger cohorts of MS patients are indicated. ClinicalTrials.gov, Identifier: NCT02623946.

Objectively assessed physiological, physical, and cognitive function along with patient-reported outcomes during the first 2 years of Alemtuzumab treatment in multiple sclerosis: a prospective observational study.

In persons with multiple sclerosis (pwMS), little evidence exist on the effects of Alemtuzumab on physiological, physical, and cognitive function along with patient-reported outcomes, despite these domains are being rated as highly important. Therefore, our purpose was to perform a prospective observational study to examine these outlined outcomes during the first two years of Alemtuzumab treatment in pwMS. In n = 17 relapsing-remitting pwMS, physiological function [body composition; bone mineral content; muscle strength; aerobic capacity], physical function [6-min walk test (6MWT, primary outcome); timed 25 ft walk test (T25FWT); six spot step test (SSST); 9-step stair ascend (9SSA); timed up and go test (TUG); 5 × sit to stand test (5STS)], cognitive function [selective reminding test (SRT); symbol digit modalities test (SDMT)], and patient-reported outcomes [multiple sclerosis impact scale-29 (MSIS29); 12-item multiple sclerosis walking scale (MSWS12); modified fatigue impact scale (MFIS); hospital anxiety and depression scale (HADS)] were assessed prior to Alemtuzumab treatment initiation as well as 3, 6, 12, and 24months into the treatment. Improvements were observed at 24-month follow-up in T25FWT (+ 8%), SSST (+ 10%), SDMT (+ 5.2 points, 53% improved more than the clinical cut-off score) and SRT, whereas the primary outcome 6MWT, and all other remaining outcomes, remained stable throughout the Alemtuzumab treatment period. The present findings suggest that Alemtuzumab treatment in relapsing-remitting pwMS can improve certain domains of physical function (short distance walking) and cognitive function (processing speed, memory), and furthermore stabilize physiological and physical function along with patient-reported outcomes. Registered at clinicaltrials.gov: NCT03806387.

Low vitamin D levels do not predict risk of autoimmune disease following alemtuzumab treatment for multiple sclerosis

Alemtuzumab is a highly effective treatment for multiple sclerosis (MS) and the treatment strategy of two cycles 12 months apart has a lot of appeal to patients. Widespread use of alemtuzumab has been tempered by treatment emergent autoimmunity which is seen in approximately one-third of patients in the 5 years after treatment. It has been postulated that relative vitamin D deficiency may be a causative factor in this setting. We have conducted a retrospective case-control study looking at the association of vitamin D and other potentially relevant clinical factors on the likelihood of treatment emergent autoimmune disease following alemtuzumab. Occurrence of autoimmunity was monitored for clinically and through the Bloodwatch® monitoring program. Clinical data and vitamin D levels obtained as part of routine clinical practice were recorded. Vitamin D levels were seasonally adjusted. Only cases with complete data were included. Univariable and multivariable Cox proportional hazards analyses were performed. There were 113 patients treated with alemtuzumab for whom there was complete data. Median follow up was 4.4 years. Risk of autoimmune disease was not associated with lower vitamin D levels. Risk of autoimmune disease was associated with female sex (HR 3.5) and with higher EDSS score at treatment. The association with EDSS was lost when analysis was restricted to those with 4 or more years of follow up. These data do not support a role for vitamin D supplementation in the prevention of autoimmune disease following alemtuzumab. Males have a lower risk of autoimmunity following alemtuzumab.

IgG4-related autoimmune manifestations in Alemtuzumab-treated multiple sclerosis patients

We aimed to determine whether Alemtuzumab-induced immune reconstitution affects immunoglobulin and complement levels in the serum of Relapsing-Remitting Multiple Sclerosis (RRMS) patients. IgG4-levels were increased 24-months after treatment initiation compared to baseline levels in twenty-nine patients. Alemtuzumab-treated patients with the highest IgG4-levels were more prone to thyroid-related autoimmune manifestations and specific autoimmune adverse events such as Crohn's disease, Graves' disease, and hemolytic anemia. Compared to baseline, total IgG-levels showed a trend towards reduced levels following two-courses of Alemtuzumab, but no significant change of C3 and/or C4-levels was observed. In conclusion, monitoring of IgG4-levels can serve as a marker for secondary autoimmunity risk in multiple sclerosis patients treated with Alemtuzumab.

Graves’ disease and concurrent immune thrombocytopenia in a patient with albinism following alemtuzumab treatment for multiple sclerosis: a rare case report

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Thyroid Autoimmunity Following Alemtuzumab Treatment in Multiple Sclerosis Patients

Alemtuzumab, a humanized anti-CD52 monoclonal antibody, is approved for the treatment of highly active relapsing-remitting multiple sclerosis (MS). The principal adverse effect is the development of secondary autoimmune disorders during the immune reconstitution period after alemtuzumab, with autoimmune thyroid disease (AITD) being the most common. To define the type, timing and course of AITD after alemtuzumab treatment for MS we analyzed clinical and serologic data from 31 patients (follow-up range 8 to 58 months). Hashimoto thyroiditis (HT) with positive anti-TPO and/or anti-Tg antibodies was present at baseline in four patients. Of note, one of them 13 months after the first dose developed mild hyperthyroidism [stimulating TRAbs: 1,8U/L, normal range:<0,1] with subsequent spontaneous shift to hypothyroidism within two months. Of 26 patients without previous history of thyroid dysfunction, 17 (65,3%) developed adverse thyroid events, principally Graves’ disease (GD) with positive stimulating TRAbs (n=10, 58,8%) after a mean of 22,4 months following the first alemtuzumab course. Half of the GD cases exhibited fluctuating thyroid status, transitioning from hyperthyroidism to hypothyroidism and vice versa. Most of them were started on block and replace antithyroid drug (ATD) treatment. Three GD patients are currently under treatment with ATD in a dose-reducing regimen. Two patients developed Graves’ ophthalmopathy. One of them underwent total thyroidectomy and 27 months post-surgery TRAbs are still positive. One patient developed hypothyroidism associated with surprisingly high stimulating TRAbs (>40 U/L) as well as anti-Tg antibodies. Seven cases of HT with positive anti-TPO/anti-Tg antibodies were documented, of which one developed hypothyroidism. During follow-up, two successful pregnancies were recorded. The first, a 32-year-old woman, developed HT with hypothyroidism 12 months after the first cycle of alemtuzumab and gave birth to a healthy boy 22 months following last dose. The second, a 31-year-old woman, developed GD hyperthyroidism during the first trimester of pregnancy and was started on PTU that was stopped in the beginning of the second trimester. TRAbs titer declined and a healthy girl was delivered. Contrary to published literature, we recorded frequent occurrence of GD with fluctuating and unpredictable course requiring block and replace ATD regimen. This is suggestive of alternating stimulating and inhibitory TRAbs, while further studies are needed to understand the underlying mechanisms responsible for Th1-Th2 balance and cytokine pathways towards AITD. Pretreatment screening and careful follow-up allow for early diagnosis and treatment. Finally, concerning future pregnancies post-alemtuzumab it is important to address the risk for secondary AITD in women of childbearing age in conjunction with their treating obstetrician.

Potential Clues to the Pathogenesis of Acquired Hemophilia.

There have been several recent reports of the development of acquired hemophilia in patients who received alemtuzumab treatment for multiple sclerosis.[1] [2] [3] [4] [5] [6] [7] This monoclonal antibody is increasingly noted to be associated with secondary autoimmune disorders since its approval for use in multiple sclerosis a decade ago.[8] Common autoimmune disorders developing after alemtuzumab therapy are thyroid diseases and immune thrombocytopenia (ITP).[8] With the addition of acquired hemophilia to this list, it may be useful to examine whether this unusual complication may shed some light on the pathogenesis of acquired hemophilia.

Two case reports of acquired haemophilia A as complications of alemtuzumab treatment for multiple sclerosis.

ObjectiveTo describe the case histories of two patients who developed acquired haemophilia A following treatment with alemtuzumab for multiple sclerosis.ResultsTwo patients, a 48-year-old woman and a 31-year-old woman, developed acquired haemophilia A 21 months after their second doses of alemtuzumab. Both presented with spontaneous bruising, and the second case reported menorrhagia. One patient required treatment to control bleeding. Both patients responded to treatment with prednisolone and cyclophosphamide to eliminate the inhibitor.ConclusionsAcquired haemophilia A is a rare complication following treatment with alemtuzumab. Activated partial thromboplastin time and prothrombin time should be performed in cases of abnormal bleeding in which the platelet count is normal, to facilitate timely diagnosis and prevention of major bleeding complications.

Development of Autoimmune Thyroid Disease in Multiple Sclerosis Patients Post-Alemtuzumab Improves Treatment Response.

Alemtuzumab is an anti-CD52 monoclonal antibody used in the treatment of relapsing-remitting multiple sclerosis (MS). Between 20% and 40% of alemtuzumab-treated MS patients develop autoimmune thyroid disease (AITD) as a side effect. The objective of this work is to determine whether MS disease progression following alemtuzumab treatment differs in patients who develop AITD compared to those who do not. A retrospective analysis of 126 patients with relapsing-remitting MS receiving alemtuzumab from 2012 to 2017 was conducted at a tertiary referral center. Thyroid status, new relapses, Expanded Disability Status Scale (EDSS) score change, and disability progression following alemtuzumab were evaluated. Twenty-six percent (33 out of 126, 25 female, 8 male) of alemtuzumab-treated patients developed AITD, 55% of which was Graves disease. EDSS score following alemtuzumab was reduced in patients who developed AITD compared to those who did not (median [interquartile range]; AITD: -0.25 [-1 to 0.5] vs non-AITD: 0 [1-0]. P = .007]. Multivariable regression analysis confirmed that the development of AITD was independently associated with EDSS score improvement (P = .011). Moreover, AITD patients had higher relapse-free survival following alemtuzumab (P = .023). There was no difference in the number of new focal T2 lesions and contrast-enhancing magnetic resonance imaging lesions developed following alemtuzumab between the 2 groups. Graves disease was the most common form of AITD developed by MS patients following alemtuzumab. This study suggests that MS patients who develop AITD may have an improved response to alemtuzumab, as measured by reduced disability and lower relapse rate.

Quality of Life Improves with Alemtuzumab Over 6Years in Relapsing-Remitting Multiple Sclerosis Patients with or without Autoimmune Thyroid Adverse Events: Post Hoc Analysis of the CARE-MS Studies.

IntroductionIn clinical trials of alemtuzumab, autoimmune thyroid adverse events (AEs) were frequent. Here, we assess the impact of thyroid AEs on health-related quality of life (HRQL) in alemtuzumab-treated patients with relapsing-remitting multiple sclerosis (RRMS).MethodsIn phase 3 CARE-MS I (NCT00530348) and II (NCT00548405) trials, patients with RRMS were administered alemtuzumab 12 mg/day on 5 consecutive days at baseline and on 3 consecutive days 12 months later. Patients could participate in an extension study (NCT00930553) through year 6. HRQL was assessed at baseline and annually using the Functional Assessment of Multiple Sclerosis (FAMS), EuroQoL-5 Dimension Visual Analog Scale (EQ-5D VAS), and 36-Item Short-Form Survey (SF-36) questionnaires. Outcomes were analyzed in patients with or without thyroid AEs (nonserious or serious). A subset of patients with thyroid AEs was analyzed to assess HRQL before and during the onset of thyroid AEs.ResultsA total of 811 CARE-MS patients were treated with alemtuzumab. Of these, 342 (42%) patients experienced thyroid AEs over 6 years; serious thyroid AEs occurred in 44 (5%) patients. At year 6, HRQL outcomes generally remained slightly improved or similar to core study baseline in alemtuzumab-treated patients with or without thyroid AEs: FAMS (least-squares mean change from baseline without thyroid AEs, 0.7; with nonserious thyroid AEs, 5.1; with serious thyroid AEs, − 5.3), EQ-5D VAS (2.0; 3.0; − 6.8), SF-36 mental component summary (MCS [0.6; 1.6; − 2.8]), SF-36 physical component summary (PCS [0.8; 1.0; 1.1]). Over 6 years, 63–82% of patients in each group had improved/stable SF-36 MCS and PCS scores. Among patients with thyroid AE onset in year 3 (peak incidence), there were minimal differences between HRQL outcomes before onset (year 2) and after onset (year 3).ConclusionAutoimmune thyroid AEs (serious and nonserious) had minimal impact on HRQL in alemtuzumab-treated patients. These data may aid therapeutic decisions in patients with relapsing MS.Electronic supplementary materialThe online version of this article (10.1007/s40120-020-00191-7) contains supplementary material, which is available to authorized users.

Alemtuzumab and prescription medication use in the MS population

Medications are indicated to minimize adverse reactions with alemtuzumab treatment for multiple sclerosis, but polypharmacy can be problematic. We characterized prescriptions filled by 160 individuals before, during and after first infusion of alemtuzumab (Dec/2013-Jun/2017). Ninety-five percent of individuals filled ≥1 prescription(s) before alemtuzumab across 87 unique drug classes, averaging 5.3 prescriptions/person over 47 weeks. During the infusion period, 90% filled ≥1 prescription(s) for 40 new drug classes, averaging 2.2 prescriptions/person over 5 weeks. Twenty-four percent refilled ≥1 of these prescription(s) after alemtuzumab across 17 drug classes, averaging 0.3 refills/person over 24 weeks. There was substantial medication burden throughout the study.

Alemtuzumab treatment of multiple sclerosis in real-world clinical practice: A report from a single Italian center

BackgroundAlemtuzumab, is a compound approved for highly active MS, and, in Europe, employed after the use of other disease-modifying treatments (DMTs) with an escalation approach or used as a first therapeutic option. The occurrence of secondary autoimmune adverse events and or infections can differ depending on the employed approach. ObjectiveTo evaluate the efficacy and safety of alemtuzumab in real-world MS population that encompassed patients previously treated with other DMTs. Methods35 patients, treated with alemtuzumab in a single MS Center, were followed for at least 36 months. The study investigated the prevalence of patients reaching the phase of the non-active disease (NEDA-3). All the adverse events were also reported, and correlations assessed. ResultsAt the 36-month follow-up, 66,7% of patients achieved the NEDA-3 status, 90,5% of the patients were relapse-free, 85,7% showed no signs of disability progression, nor signs of MRI activity. Adverse events were observed in 45,7% of the patients and ranked as severe in 23% of them. Cases of autoimmune hemolytic anemia (AIHA), pancytopenia, viral hepatitis E, and noninfectious meningo-encephalomyelitis were found and reported. For these complications, the post hoc analysis showed possible interactive factors and causality related to previous DMT treatments. ConclusionsIn a real-world MS population like the one investigated in our study, alemtuzumab was found to be an effective treatment when employed as an escalation or rescue therapy. The compound exhibits a variable safety profile and frequent adverse events that are likely depending on previous treatments and their impact on the immune system.

Alemtuzumab a léčba roztroušené sklerózy v současné klinické praxi

Alemtuzumab (Lemtrada®) je humanizovana monoklonalni protilatka urcena k lecbě vysoce aktivni relaps-remitentni formy roztrousene sklerozy (RR-RS), selektivně namiřena proti glykoproteinu CD52 přitomnem na povrchu imunitnich buněk, zejmena T a B lymfocytech. Po specificke vazbě alemtuzumabu na povrchový znak CD52 dochazi k depleci cirkulujicich autoagresivnich lymfocytů a nově vznikle repopulace buněk nasledně vedou k rekonstituci imunitniho systemu. Ucinnost alemtuzumabu byla ověřena v několika kontrolovaných klinických studiich, ktere rovněž popisovaly i rizika rozvoje možných nežadoucich ucinků vyplývajicich z mechanizmu působeni leku. V praci prezentujeme kazuistiku prvniho a uspěsně alemtuzumabem leceneho pacienta na nasem pracovisti.

133 B cell depletion therapy resulting in sustained remission of severe autoimmune complications following alemtuzumab treatment of multiple sclerosis

IntroductionAlemtuzumab is a pan-lymphocyte ablating anti CD-52 monoclonal antibody licensed for the treatment of relapsing remitting multiple sclerosis (RRMS). Despite being classified as a high efficacy therapy, clinical application of alemtuzumab has been hampered by the frequent occurrence of secondary autoimmune disease (AID), with clinical trials and single-centre follow up cohorts estimating an incidence of up to 50% at seven years post treatment. Despite the establishment of pharmacovigilance programs to monitor for common complications of alemtuzumab, management guidelines for these conditions are lacking.MethodsHere, we report a series of cases of female patients treated with alemtuzumab for RRMS who developed treatment refractory secondary AID complications; specifically acquired haemophilia A (AHA) and an autoimmune encephalitis (AIE).ResultsWe report the sustained remission of these severe autoimmune disorders following administration of anti-CD20 therapy. This supports the current understanding of alemtuzumab associated AIDs, which occur in a time frame in which B-cell hyperpopulation and peripheral expansion occurs following initial lymphoablation.ConclusionsThus, we suggest that B-cell depletion should be initiated early in patients with severe, refractory complications of alemtuzumab. Furthermore, we suggest vigilant monitoring of patients with a preceding history of autoimmune thyroid disease following alemtuzumab treatment, as our experience suggests these patients have already demonstrated the potential to develop secondary AID.

Thyroid dysfunction after Alemtuzumab treatment for multiple sclerosis: diagnostic and therapeutic modalities

Thyroid dysfunction after Alemtuzumab treatment for multiple sclerosis: diagnostic and therapeutic modalities

Incidence, management, and outcomes of autoimmune nephropathies following alemtuzumab treatment in patients with multiple sclerosis

Background: Autoimmune disorders including nephropathies have been reported more frequently in alemtuzumab-treated multiple sclerosis (MS) patients than in the general population. Objective: Describe instances of autoimmune nephropathy in alemtuzumab-treated MS patients. Methods: Cases were identified from safety monitoring within the alemtuzumab relapsing-remitting multiple sclerosis (RRMS) clinical development program (CDP) or post-marketing, or following off-label use. Results: As of 16 June 2017, 16 autoimmune nephropathies have occurred following alemtuzumab treatment for MS. The incidence of autoimmune nephropathies was 0.34% within the CDP (5/1485 patients). The five CDP cases (one of anti-glomerular basement membrane (anti-GBM) disease, two of membranous glomerulonephropathy, and two of serum anti-GBM antibody without typical anti-GBM disease) were identified early, responded to conventional therapy (where needed), and had favorable outcomes. Three of 11 cases outside the CDP occurred following off-label alemtuzumab use prior to approval for RRMS and were all anti-GBM disease. Diagnosis was delayed in one of these three cases and another did not receive appropriate treatment; all three cases resulted in end-stage renal failure. All anti-GBM disease cases with documented urinalysis demonstrated prior microscopic hematuria. Conclusion: Close monitoring of alemtuzumab-treated MS patients facilitates diagnosis and treatment early in the nephropathy course when preservation of renal function is more likely.

Best Practices for Long-Term Monitoring and Follow-Up of Alemtuzumab-Treated MS Patients in Real-World Clinical Settings.

Multiple sclerosis (MS) is a chronic autoimmune neurological disease that typically affects young adults, causing irreversible physical disability and cognitive impairment. Alemtuzumab, administered intravenously as 2 initial courses of 12 mg/day (5 consecutive days at baseline, and 3 consecutive days 12 months later), resulted in significantly greater improvements in clinical and MRI outcomes vs. subcutaneous interferon beta-1a over 2 years in patients with active relapsing-remitting MS (RRMS) who were either treatment-naive (CARE-MS I; NCT00530348) or had an inadequate response to prior therapy (CARE-MS II; NCT00548405). Efficacy with alemtuzumab was maintained over 7 years in subsequent extension studies (NCT00930553; NCT02255656), in the absence of continuous treatment and with a consistent safety profile. There is an increased incidence of autoimmune events in patients treated with alemtuzumab (mainly thyroid events, but also immune thrombocytopenia and nephropathy), which imparts a need for mandatory safety monitoring for 4 years following the last treatment. The risk management strategy for alemtuzumab-treated patients includes laboratory monitoring and a comprehensive patient education and support program that enables early detection and effective management of autoimmune events, yielding optimal outcomes for MS patients. Here we provide an overview of tools and techniques that have been implemented in real-world clinical settings to reduce the burden of monitoring for both patients and healthcare providers, including customized educational materials, the use of social media, and interactive online databases for managing healthcare data. Many practices are also enhancing patient outreach efforts through coordination with specialized nursing services and ancillary caregivers. The best practice recommendations for safety monitoring described in this article, based on experiences in real-world clinical settings, may enable early detection and management of autoimmune events, and help with implementation of monitoring requirements while maximizing the benefits of alemtuzumab treatment for MS patients.