Author Of 9 Presentations
P0100 - Italian prospective multicentric observational real-life study of aggressive Relapsing Remitting Multiple Sclerosis treated with alemtuzumab (ID 1730)
- L. Moiola
- M. Di Cristinzi
- A. Sultana
- C. Zanetta
- F. Rinaldi
- L. Brambilla
- J. Frau
- S. Malucchi
- P. Annovazzi
- G. Puorro
- A. Bianco
- G. Lus
- P. Cavalla
- F. Sangalli
- M. Romeo
- G. Marfia
- A. Gallo
- V. Barcella
- S. Bucello
- M. Ferrò
- C. Lapucci
- L. Chiveri
- C. Chisari
- E. Baldi
- R. Clerici
- P. Banfi
- C. Tortorella
- R. Totaro
- R. Cerqua
- S. Tonietti
- V. Mantero
- G. Santuccio
- M. Filippi
Abstract
Background
Alemtuzumab(ALEM) is an anti-CD52 monoclonal antibody approved for the treatment of active Multiple Sclerosis(MS) which showed an overall high efficacy in clinical trials, also in the highly active subgroup of patients.
Objectives
The aim of this multicenter obervational study is to evaluate efficacy and safety of ALEM-treatment in a population of aggressive MS naïve-patients at year 2 and 3 after a complete cycle of treatment.
Methods
We conducted a multicenter prospective observational study in a cohort of ALEM-naïve MS patients. Clinical and neuroradiological parameters were collected from patients’ clinical records in 26 Italian MS Centers from October 2015 to May 2020.
Results
133 naïve patients were treated with ALEM: 60,2% females, mean age 31,4(± 8,9) years, mean disease duration 18,5(± 22,7) months, mean follow-up(FU) 34,2(± 12,1) months, median EDSS 3(0-6,5), ARR in the year preceding treatment 1,8 (± 0,9), mean number of brain T2/FLAIR-hyperintense lesions 29,8 (± 20,8) and mean number of Gd-enhancing lesions 3,4(± 5,1). Regarding ALEM efficacy, we report data obtained after the first complete cycle of treatment (2 ALEM-courses) because the occurrence of disease activity between the first and second course is not indicative of a therapeutic failure. 99 and 61 over 133 patients have at least 24 and 36 months FU respectively: 97% and 82% were relapse-free, ARR was 0,02 and 0,1, 92.9% and 82% were MRI activity-free and 97,7% and 91,8% progression-free with median EDSS of 2,0 and 1,5 (IQR 1 – 2,5) at year 2 and 3. The mean time to first relapse was 27,6(± 6,4) months 89,2% and 69,4% of patients reached NEDA-3 at year 2 and year 3 respectively. 5,3% of patients needed a third cycle of therapy. Overall 74,4% of patients had adverse events. Infusion-reaction and infections occurred respectively in 70,1% and 9,8% of patients; regarding secondary autoimmune disease the most frequent was thyroid dysfunction (15,8%).
Conclusions
In our very active MS-population after ALEM-treatment a strong reduction of both relapse rate and MRI activity was achieved. These results strengthen the assumption that aggressive naïve patient is an ideal candidate for immune system resetting, likely due to young age, short disease duration and low disability. Furthermore, absence of previous immunomodulating/immunosuppressant drugs altering the immune system could play a key role in determining effectiveness of this powerful drug. However, longer FU is needed to confirm our data and evaluate whether an early induction therapy could be worthy in this specific population, balancing benefit-risk ratio.
P0161 - Short-term evaluation of alemtuzumab to ocrelizumab switch in MS patients with disease activity after alemtuzumab: an Italian multicentric study. (ID 1603)
Abstract
Background
the management of MS patients (pts) who show disease activity after 2 alemtuzumab (ALM) courses represents an unsolved issue. No real-life data about the switch to ocrelizumab (OCR) have been reported yet.
Objectives
To describe efficacy and safety outcome of OCR patients switching from ALM due to persistence of disease activity after ALM
Methods
MS pts who switched from ALM to OCR from March 2019 to March 2020 were retro- and prospectively recruited from different Italian MS Centers. Clinical, immunological and neuroradiological data about ALM treatment period, ALM-OCR interval and OCR treatment period were collected.
Results
we recruited 23 MS pts [mean age: 35.7(SD±6.8); female, 40.1%; Relapsing Remitting, (RR): 75.8%, active Secondary progressive, (aSP): 24.2%; mean time interval (days) from II ALM course: 87.4(SD±108); cumulative number of relapses: 21; mean number of new T2 and Gd+ lesions: 4.1(SD±4.5) and 1.6(SD±3.1); median EDSS:3(range 1-7)]. The mean follow-up (FU) from OCR start was 7.9±7.4 months. Efficacy: 4 (17.4%) pts had a relapse after OCR start (1 pt relapsed between the first and the second OCR infusion and 3 pts after 3, 11 and 15 months from OCR start respectively), with complete recovery after steroid treatment. 4 (17.4%) pts showed radiological activity with no clinical correlates at 3 months (n=2), 4 months (n=1) and 9 months (n=1). EDSS was stable except for 1 aSP patient who showed 1-year disability progression. Safety: I) Infusion Associated Reactions (IARs) occurrence was significantly lower with respect to alemtuzumab courses (p<0.05); (ii) infections: mild upper airways (n=1), urinary infections (n=1), appendicectomy (n=1) and fever due to probable Sars-Cov2 infection (n=1). For 12 pts, data about immunophenotype were available. Of them, no pts showed T CD4+ cell count decrease <200 cell/mm3 at 3, 6-months and 1-year FU; complete B CD19+ cell depletion (<5 cell/mm3) was confirmed at 3, 6-months and 1-year FU. 10 (43.4%) pts developed hypogammaglobulinemia without developing associated infectious events. C) Autoimmunity: no alemtuzumab-related new complications occurred.
Conclusions
short-term FU seems to suggest that the switch to OCR in MS patients who showed disease activity after 2 ALM courses is characterized by a good safety and efficacy profile, although clinical and neuroradiological activity can be detected both in an early and in a later phase of treatment. Longer follow-up is warranted and recruitment is still ongoing.
P0262 - Searching for Fabry disease in previously diagnosed CIS and defined MS patients: a cohort study. (ID 1693)
Abstract
Background
Fabry disease (FD) is a rare panethnic x-linked lysosomal storage disorder that can mimic MS, and thus must be considered in differential diagnosis. While clinical profile and MRI studies can overlap, some other considerations help distinguish them, like presence of CSF oligoclonal bands and medullary demyelinating lesions for MS and multi-organ involvement and positive familiar history for FD. In our center a patient was diagnosed with MS in 2004, and with FD in 2015, due to in depth-analysis following the clue of a positive family history.
Objectives
To identify the possible presence of unacknowledged FD in a cohort of Italian patients previously diagnosed with CIS or MS.
Methods
We enrolled consecutive CIS and MS patient that fulfilled McDonald revised criteria referred to our center. In female subjects, the GLA gene was analyzed by PCR and sequencing of the entire coding region. In male subjects the concentration of the alpha-galactosidase enzyme in dry blood spot was measured with fluorescence spectroscopy. For these purposes we used Centogene diagnostic kit for Fabry disease.
Results
411 patients (300 females) were enrolled, 21 with a diagnosis of CIS and 390 with definite MS, mean age 45.5 years (SD:12.0), mean disease duration 15.3 years (SD:10.1), mean EDSS 2.5 (SD:1.9). No one of them presented pathogenic mutations of GLA gene or alpha-galactosidase deficiencies.
Conclusions
Although the diagnosis of FD must be ruled out when studying a patient with suspected MS, the systematic genetic or enzymatic analysis of every patient doesn’t appear necessary in everyday clinical practice. The analysis of GLA gene and of alpha-galactosidase activity should be reserved for patients with elements suspicious for FD, like a positive family history and multi organ involvement (especially renal impairment and angiokeratomas). Our patient with both the diagnosis, other than positive family history, later developed proteinuria as systemic dysfunction; she also showed demyelinating lesions on brain and spinal cord MRI, sometimes with Gadolinium enhancement, and intrathecal synthesis of oligoclonal bands (type 3). Clarifying the correct diagnosis is of fundamental importance due to the different therapeutic approaches.
P0273 - A multicentre, real-life study on the risk of lymphopenia and infections discloses a favourable safety profile of cladribine in MS patients. (ID 1086)
Abstract
Background
Background. Lymphopenia monitoring during treatment with disease modifying drugs for MS is relevant because of the potential increased risk of infections. Lymphopenia is an anticipated effect of cladribine (CLD) treatment, given its mechanism of action.
Objectives
Objectives. We aimed to i) characterize the absolute lymphocyte count (ALC) changes, and ii) evaluate the risk of infections in CLD-treated RRMS patients. ALCs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE v5.0).
Methods
Materials and methods. In this observational multicentre study, demographic, clinical and MRI data of the patients included in the Free Of Charge CLD program were collected. ALC was also collected at baseline (before therapy initiation) and at month 3, 7, 12, 15, 19 and 24.
Results
Results. 236 patients were enrolled in 56 Italian MS Centres (71% F; mean age: 39+11.5 years; mean disease duration: 10+8.5 years). The median baseline EDSS was 3.0 (quartiles 1.5-3.5; range 0-6.5). 53 patients (22.5%) were treatment naïve, 107 (45.3%) switched to CLD from first line DMDs (for inefficacy), 76 (32.2%) switched to CLD after a second line therapy (33/76 for safety reason, 43/76 for inefficacy). Mean follow up was 12.2+5 months. At baseline, median ALC was 1615.0 cell/mm3 (quartiles, 1300.0-2200.0). At month 3, ALC was available in 190/236 and 101/190 had lymphopenia: 12 (6.3%) grade 3, 47 (24.7%) grade 2 and 42 (22.1%) grade 1. Among patients presenting grade 3 at month 3, only one had persistent ALC <500 cell/mm3 at month 7. At month 7, ALC was available in 180/236 and 77/180 had lymphopenia: 1 (0.6%) grade 4, 1 (0.6%) grade 3, 43 (23.9%) grade 2 and 32 (17.8%) grade 1. Up to date, 159/236 patients were re-treated. No retreatment was delayed because of grade 4 lymphopenia. No patient presented grade 4 lymphopenia at month 15, 6/89 (6.6%) experienced grade 3, 37/89 (40.7%) grade 2, 17/89 (18.7%) grade 1. At month 19, 1/38 (2.6%) presented grade 3 lymphopenia, 11/38 (29.0%) grade 2 and 9/38 (23.7%) grade 1. At month 24, 1/9 (11.1%) patient presented grade 3 and 1/9 (11.1%) presented grade 4 lymphopenia. During treatment course, 15 patients experienced infections (1 VZV, 3 HSV), none occurring in grade 3 or 4 lymphopenia.
Conclusions
Conclusions. In our study, the risk of grade 3 and 4 lymphopenia was lower compared to that observed in RCT. Moreover, grade 3 lymphopenia was transient in the majority of the patients. Compared to RTC, a more favourable CLD safety profile emerged in our study.
P0773 - Variation of RNFL thickness in MS patients and DMTs: a longitudinal study. (ID 1184)
Abstract
Background
The measure of retinal nerve fiber layer (RNFL) thickness by OCT is a marker of neurodegeneration. It is known that RNFL, especially in the temporal sector, is thinner in MS patients than in healthy controls and this process occurs over time. No study has explored the possible relation between RNFL thickness and the use of DMTs to date.
Objectives
To evaluate the variation of RNFL over a follow-up of 2 years and its relation with DMTs in a group of relapsing MS patients.
Methods
Patients with relapsing-remitting MS were included and underwent a spectral-domain OCT at baseline, after 6, 12 and 24 months. In patients taking DMTs, the baseline was the time of DMT initiation. Global (G), temporal (T), and papillo-macular bundle (PMB) sectors of RNFL have been measured. Age, gender, EDSS, age at onset, and DMTs taken during the study have been collected. DMTs were divided in first (interferon beta, glatiramer acetate, dimetilfumarate, teriflunomide) and second line (natalizumab, ocrelizumab, alemtuzumab, fingolimod). The variation of RNLF during the follow-up was studied by ANOVA. By linear regression we analysed the G sector variation using as variables: DMT taken for longer time during the study by each patient, demographic and clinical features.
Results
One-hundred-one patients were included (78.2%: females; mean age and mean age at onset: 41.3 years (SD:9.7) and 30.5 (SD:9.4), respectively). Seven patients did not take any DMT during the study, and one patients started interferon beta 17 month after the baseline. At baseline: 21 subjects started with a second line DMT; 72 started with a first line DMT, and 9 of them shifted to a second line after a mean time of 17.3 months (SD:7.1). An over-time reduction of all the RNFL sectors has been found both in right (G: p<0.001; T: p<0.001; PMB: p=0.041) and in left eye (G: p<0.001; T: p<0.001; PMB: p=0.002). No relation has been found between the G sector thinning and clinical and demographic features, but a trend versus less thinning in patients with second line DMT has been shown.
Conclusions
We confirmed an over-time thinning of RNFL in patients with MS, also in a short follow-up of 2 years. No clinical and demographic variables seem to influence this phenomenon. Otherwise, even if our result is only a trend, the DMTs with more impact on the inflammation appear to slow down the thinning. A wider cohort with more patients taking second line DMTs is needed to better clarify this point.
P0910 - Relapse-free and NEDA status with Cladribine in a real life population: a multicentre study (ID 1484)
Abstract
Background
Trials leading to Cladribine (CLD) approval for the treatment of Multiple Sclerosis (MS) were conducted over a decade ago: there is a need of proof of CLD efficacy and safety profile in the present MS therapeutic landscape.
Objectives
To evaluate CLD efficacy and safety profile in the current MS population, and to identify early predictors of response.
Methods
Before the drug was marketed under the national healthcare system, in Italy CLD was available through a Free Of Charge (FOC) program. We asked all participating MS centres to contribute to the present study, collecting demographic, clinical and MRI data of the patients who received CLD in the FOC program.
Results
56 MS centres participated to the study, for a total of 236 patients (71% F) (mean age: 39 + 11,5 years; mean disease duration: 10 + 8,5 years). Mean Annualized Relapse Rate (ARR) in the two years before CLD was 0,7 + 0,6; median baseline EDSS was 3 (quartiles 1,5-3,5; range 0-6,5). 53 patients (22,5%) were treatment naïve, 107 (45,3%) switched to CLD from first-line DMDs (for inefficacy), 76 (32,2%) switched to CLD from a second line therapy (33/76 for safety or loss of tolerability, 43/76 for inefficacy). Mean follow up was 12,2 + 5 months. 84,7% of the patients were relapse-free at follow-up. Mean ARR at follow-up was 0,2 + 0,6. Patients taking CLD as first therapy were less likely to experience a relapse (HR 0,6; 95% CI: 0,2-0,8; p = 0,04) while a higher baseline ARR was a predictor of clinical activity (HR 2,7, 95% CI: 1,4-5,6; p = 0,004). Median EDSS at follow up was 2 (quartiles 1-3,5). EDSS was stable in 73.7%, improved of at least 1 point in 21,6% and worsened of at least 1 point in 4,7% of the patients. 157/236 patients completed one year of follow up. Of these 92 (59,7%) reached No Evidence of Disease Activity (NEDA-3); NEDA-3 was achieved more frequently by naive patients (70%) than switchers from a first (57%) or a second line (50%) (HR 2,3; 95% CI: 1,01-5,3; p = 0,04). 33/236 patients reported at least one adverse event (AE), most frequently infections (15 cases); other AEs included gastrointestinal side effects, cutaneous rash, aphthous stomatitis and headache. Two severe AEs were reported (one pneumonia, one melanoma).
Conclusions
Even with the limitations of a retrospective study, our data confirm CLD safety and efficacy profile. Consistently with previous studies on patients with a first demyelinating event, CLD efficacy is maximized when used early in the course of MS.
P1003 - A cohort analysis of MS patients exposed to high-dose corticosteroids (ID 768)
Abstract
Background
Corticosteroids in high dose (HDC) is the recommended treatment for multiple sclerosis (MS) relapses. Most common first line treatment consists of three to five days courses of 1 g of intravenous methylprednisolone. The choice of HDC duration varies due to different clinical considerations.
Objectives
Our aim was to determine which demographic factors, comorbidities and MS clinical considerations led to the choice of a longer or shorter HDC course duration, also exploring the possible effect on clinical benefit reported by treated patients after one month.
Methods
MS subjects with a clinical relapse of MS or with MRI activity who underwent a treatment with HDC were enrolled. Demographics (sex and age), clinical features (type of relapse and EDSS) and medical history (occurrence of metabolic, immune and psychiatric comorbidities) were collected prior to HDC. After a month, subjective clinical benefit was also evaluated. Regression models were used to evaluate the relationships of HDC duration and clinical benefits after 1 month with demographic and medical variables.
Results
101 MS patients were enrolled (mean age 44 years, male 24.8%, mean EDSS 3.1). Most of them (92.1%) had a clinical relapse (31.1% with multisystem involvement), 7.9% only had brain MRI activity. 66.3% were on DMDs. 36.6% had comorbidities (autoimmune comorbidities 16.8%) and 45.8% had mood disorder. Linear regression showed that older age (p 0.039) and psychiatric comorbidities (p 0.019) correlate with the choice of shorter HDC treatment (3 days). Conversely, multisystem deficit relapses correlate with the choice of longer treatment (5 days) (p 0.001). Subjective clinical benefit after one month was only associated with EDSS score pre HCD treatment (p 0.004), while no association was reported with number of days of treatment.
Conclusions
Data suggests that some clinical factors, such as severity of relapse, age and comorbidities can affect the choice of HDC course duration. Shorter HDC treatments in selected patients appear to be an appropriate treatment option that does not affect the reported clinical benefit.
P1011 - Complications after lumbar puncture: a preliminary comparative analysis on the use of atraumatic vs standard needle (ID 805)
Abstract
Background
Lumbar puncture (LP) is a frequently used procedure in Multiple Sclerosis (MS) diagnosis. Atraumatic needles have been proposed to reduce complication rates after lumbar puncture (LP), despite this, many clinicians prefer to continue using standard needles.
Objectives
The study aimed to evaluate the frequency of post procedural headache, low back pain and other complications in a cohort of multiple sclerosis (MS) patients underwent LP by using atraumatic or standard needle.
Methods
The study included patients underwent the procedure of LP. Demographic (gender, age, BMI) and clinical features (disease duration) were collected for each patient. In addition, information on chronic headache and its treatment were also recorded. For each patient, it was indicated whether the LP was performed with the use of standard or atraumatic needle. Then, the occurrence of post-procedural complications (headache, low back pain and nausea) and the possible relationships with the type of needle used was investigated.
Results
The study included 100 patients (28% male; mean age 42.3±11.9 years). 21% of these had a history of chronic headache with use of medications for 5%. Regression analysis showed that lower body mass index (p 0.032) and younger age (p 0.002) were associated with the use of atraumatic needles, while no association was reported with gender. A lower frequency of post-procedural headache (31% vs 50.7%) and low back pain (34.5% vs 40.8%) were reported respectively by using atraumatic vs standard needles (p<0.05). Multivariate analyses showed that post-procedural headache, with a tendency toward statistical significance (p=0.058), but not low back pain and nausea were associated to the use of standard needles after controlling for other demographic variables. Finally, an association between lower back pain and female gender (p=0.018), and between nausea and lower BMI (p=0.032) were also reported.
Conclusions
Our data seem to suggest the usefulness of the atraumatic needle for PL to prevent post procedural headache. Further investigations into larger cohorts are needed.
P1134 - Recovery of menstrual cycle in women with multiple sclerosis treated with autologous haematopoietic stem cell transplantation. (ID 1633)
Abstract
Background
Autologous haematopoietic stem cell transplantation (aHSCT) is increasingly taken into consideration as a treatment strategy for patients with aggressive multiple sclerosis (MS). The chemotherapies used in the conditioning regimens for aHSCT are known to be responsible of amenorrhea in fertile women. Therefore, concerns on successful family planning in women with aggressive MS treated with aHSCT might rise.
Objectives
To assess fertility outcomes in women treated with aHSCT for aggressive MS considering different conditioning regimens.
Methods
We collected disease- and treatment-related characteristics from consecutive women with MS treated with aHSCT at the Italian MS centers of Genoa, Barletta and Cagliari. ANCOVA analyses and binary logistic regression were performed to assess the effects of baseline characteristics on fertility outcomes.
Results
We included 38 women [25(67%) with relapsing-remitting MS] with a mean age at aHSCT of 31.7(±6.7) years and a mean disease duration of 10.9(±6.0) years. Mean age of menarche was 12.3(±1.9) years. 31(82%) patients underwent transplant with a myeloablative cconditioning regimen while 7(18%) patients were transplanted with a low-intensity lymphoablative regimen. 26(68.4%) patients recovered menstrual cycle after a mean time of 5.7(5.2) months. Among these, 10(38%) patients had irregular periods (<21days;>35days apart) and 11(42%) had changes in the menstrual flow. Patients who recovered menstrual cycle were younger at the time of transplant (28.8vs37.7 years;p<0.0001) and had lower EDSS scores 1 year before aHSCT (4.7vs5.8;p=0.024). No significant differences were noted in terms of clinical phenotypes, age of menarche, body mass index, number of previous therapies, previous exposure to cyclophosphamide, mitoxantrone and the conditioning regimen used within aHSCT. A younger age was independently associated with a higher probability of recovery of menstrual cycle (OR=0.78;p=0.006). 3/27 patients (11%) with ≤35 years had persistent amenorrhea after aHSCT. We recorded 4 pregnancy after aHSCT (3 uncomplicated pregnancies and 1 spontaneous abortion). One patient repeatedly tried to conceive, both naturally and artificially, without success.
Conclusions
Younger age is independently associated with the recovery of menstrual cycle in women with MS treated with aHSCT, which is obtained in 89% of women under 35 years old. The use of a myeloablative conditioning regimen doesn’t seem to be associated with worse fertility outcomes.
Presenter Of 1 Presentation
P0773 - Variation of RNFL thickness in MS patients and DMTs: a longitudinal study. (ID 1184)
Abstract
Background
The measure of retinal nerve fiber layer (RNFL) thickness by OCT is a marker of neurodegeneration. It is known that RNFL, especially in the temporal sector, is thinner in MS patients than in healthy controls and this process occurs over time. No study has explored the possible relation between RNFL thickness and the use of DMTs to date.
Objectives
To evaluate the variation of RNFL over a follow-up of 2 years and its relation with DMTs in a group of relapsing MS patients.
Methods
Patients with relapsing-remitting MS were included and underwent a spectral-domain OCT at baseline, after 6, 12 and 24 months. In patients taking DMTs, the baseline was the time of DMT initiation. Global (G), temporal (T), and papillo-macular bundle (PMB) sectors of RNFL have been measured. Age, gender, EDSS, age at onset, and DMTs taken during the study have been collected. DMTs were divided in first (interferon beta, glatiramer acetate, dimetilfumarate, teriflunomide) and second line (natalizumab, ocrelizumab, alemtuzumab, fingolimod). The variation of RNLF during the follow-up was studied by ANOVA. By linear regression we analysed the G sector variation using as variables: DMT taken for longer time during the study by each patient, demographic and clinical features.
Results
One-hundred-one patients were included (78.2%: females; mean age and mean age at onset: 41.3 years (SD:9.7) and 30.5 (SD:9.4), respectively). Seven patients did not take any DMT during the study, and one patients started interferon beta 17 month after the baseline. At baseline: 21 subjects started with a second line DMT; 72 started with a first line DMT, and 9 of them shifted to a second line after a mean time of 17.3 months (SD:7.1). An over-time reduction of all the RNFL sectors has been found both in right (G: p<0.001; T: p<0.001; PMB: p=0.041) and in left eye (G: p<0.001; T: p<0.001; PMB: p=0.002). No relation has been found between the G sector thinning and clinical and demographic features, but a trend versus less thinning in patients with second line DMT has been shown.
Conclusions
We confirmed an over-time thinning of RNFL in patients with MS, also in a short follow-up of 2 years. No clinical and demographic variables seem to influence this phenomenon. Otherwise, even if our result is only a trend, the DMTs with more impact on the inflammation appear to slow down the thinning. A wider cohort with more patients taking second line DMTs is needed to better clarify this point.