Natalizumab Infusions Research Articles

High NEDA and No PIRA in Natalizumab-Treated Patients With Pediatric-Onset Multiple Sclerosis.

Although pediatric-onset multiple sclerosis (POMS) is characterized by a more rapid accumulation of CNS inflammation than adult-onset MS (AOMS), the therapeutic algorithms applied in POMS are usually based on AOMS therapeutic outcomes. To define a high-efficacy treatment (HET)-based strategy to treat POMS, we designed an observational retrospective study aimed at evaluating the efficacy and safety of natalizumab (NTZ) in naïve POMS and AOMS. Starting from 160 patients, we applied a 2:1 (adult:pediatric) matching on propensity scores and obtained 32 patients with NTZ-treated POMS and 64 with AOMS, estimated from a multivariable logistic regression model. All patients were clinically and radiologically followed up every 6 months for a mean period of 46.0 ± 26.9 months. Following re-baseline at month 6, no difference (log-rank test: p = 0.924) in new and enlarging T2 white matter lesions, postcontrast T1 lesions, and relapse rate were observed between POMS and AOMS throughout the study. Progression independent of relapse activity (PIRA) was never observed in POMS, while 9 of 64 patients with AOMS (12.5%) had PIRA events during the follow-up (40.0 ± 25.9 months; log-rank p value 0.0156). JCV seroconversion rate during NTZ infusion did not differ between POMS and AOMS (log-rank test p = 0.3231). Finally, no serious adverse event was observed in both POMS and AOMS. The favorable outcomes observed on clinical, especially in PIRA, and radiologic parameters strongly support the use of NTZ as a first-choice HET in POMS.

Palmar Erythema Associated with Natalizumab in a Patient with Multiple Sclerosis

A 38-year-old woman was referred to the Dermatology Outpatient Clinic with an 8-month history of painless, intermittent, self-resolving bilateral palmar erythema (Figures 1&2). Her medical history was significant for Multiple Sclerosis (MS), recurrent urinary tract infection, complex regional pain syndrome of the left leg, and hypertension. She had been receiving monthly natalizumab infusions for the treatment of MS for 13 months. Her only known drug allergy was Penicillin, which resulted in a generalised skin rash.

Risk of secondary progression in patients with highly active multiple sclerosis treated with natalizumab: a real-life study.

one of the most important therapeutic goals in relapse-onset multiple sclerosis is to preclude conversion to secondary progression. Our objective was to determine the risk of progression associated with natalizumab treatment in an registry-based cohort of patients and to identify determinant factors. Patients with relapse-onset multiple sclerosis from the Registre Lorrain des Scléroses en Plaques (ReLSEP) were included if they had received one infusion of natalizumab between 2002 and 2021. The risk of secondary progression was determined using a standardized definition and a multi-state estimator to account for the possibility of stopping natalizumab before progression, and analyzed with multivariate Cox models. 574 patients were followed up for a median of 6.7years. Of the 304 who stopped NTZ before progression onset, the probabilities (95% confidence interval) to convert to progression after 1, 2, 5 and 10years were 3.2% (2.0-4.8%), 5.3% (3.6-7.3%), 17.5% (14.3-21.3%) and 28.3% (23.7-33.7%), respectively. Discontinuation of NTZ during follow-up was significantly associated with an increased risk of conversion in case of no resumption of a highly active treatment thereafter (adjusted hazard ratio = 2.7; 95% confidence interval 1.5-4.9; p = 0.001). The use of such a treatment was associated with a lower risk of progression (adjusted hazard ratio = 0.42; 95% confidence interval 0.23-0.79; p = 0.007). the risk of conversion to secondary progression associated with natalizumab treatment is relatively low but increases in case of natalizumab discontinuation in the absence of switch to highly active immunosuppressant.

Prospective trial of natalizumab personalised extended interval dosing by therapeutic drug monitoring in relapsing-remitting multiple sclerosis (NEXT-MS)

BackgroundExtended interval dosing (EID) of natalizumab is a promising strategy to optimise treatment in multiple sclerosis (MS). Personalised EID by therapeutic drug monitoring can enable further extension of treatment intervals.MethodsThe...

Patient-reported outcomes based on discontinuation or continuous treatment with natalizumab: New York State Multiple Sclerosis Consortium (NYSMSC) study

BackgroundPatient-reported outcomes (PRO) are increasingly utilized as part of the routine clinical assessment in people with multiple sclerosis (pwMS). The long-term effect of disease modifying therapies (DMTs) and their discontinuation on PRO measures remains largely unknown. MethodsTwo pwMS groups treated with natalizumab were selected from the New York State MS Consortium (NYSMSC) database. The first group utilized long-term follow-up data of pwMS that either still continue natalizumab treatment or discontinued. Minimal requirement of three visits (before natalizumab initiation, during treatment and after discontinuation/latest follow-up) was implemented. The second group consisted of pwMS that completed PRO questionnaire on the day of the infusion and 7 days later PROs were assessed using the LIFEware System™ that assesses limitations in multiple physical and psychosocial domains. Additional physical disability was assessed using Expanded Disability Status Scale (EDSS) and Timed 25-ft walk test (T25FWT). PRO reports were Rasch-transformed, ranging from 0 to 100, with higher scores indicating a better outcome. Linear mixed-effect models and paired analyses were utilized. ResultsWithin the prospective cohort, 242 pwMS were followed on average of 6.5 years. Greater number of PRO domains worsened in the 141 pwMS that discontinued natalizumab when compared to 101 pwMS that remained on the drug (10 vs. 2 PRO domains). PwMS that discontinued natalizumab had significant decline in PROs regarding lower extremities, bladder and bower control and psychosocial aspects (feeling lonesome). Contrarily, pwMS that continued natalizumab had significant improvement in bladder and bowel PRO measures. Seven days after the natalizumab infusion, the 67 pwMS from the prospective cohort reported improvement in PRO measures of fatigue (62.8 vs. 66.4, p = 0.019), bladder limitations (80.3 vs. 85.0, p = 0.012), and feelings of lonesomeness (81.2 vs. 88.0, p = 0.009). ConclusionContinuous natalizumab treatment provides long-term stability or improvement in PRO measures. Natalizumab also provides short term improvements recorded after the infusion.

Natalizumab Treatment for Relapsing Multiple Sclerosis Stabilises Normal-Appearing White Matter Microstructure: A One-Year Prospective Ultra-High-Field Quantitative Imaging Study.

(1) Background: Natalizumab dramatically reduces relapses and MRI inflammatory activity (new lesions and enhancing lesions) in multiple sclerosis (MS). Chemical exchange saturation transfer (CEST) MRI can explore brain tissue in vivo with high resolution and sensitivity. We investigated if natalizumab can prevent microstructural tissue damage progression measured with MRI at ultra-high field (7 Tesla) over the first year of treatment. (2) Methods: In this one-year prospective longitudinal study, patients with active relapsing-remitting MS were assessed clinically and scanned at ultra-high-field MRI at the time of their first natalizumab infusion, at 6 and 12 months, with quantitative imaging aimed to detect microstructural changes in the normal-appearing white matter (NAWM), including sequences sensitive to magnetisation transfer (MT) effects from amide proton transfer (MTRAPT) and the nuclear Overhauser effect (MTRNOE). (3) Results: 12 patients were recruited, and 10 patients completed the study. The difference in the T1 relaxation times at month 6 and month 12 of natalizumab treatment was not significant, suggesting the lack of accumulation of tissue damage, while improvements were seen in MTR (MTRAPT and MTRNOE measures) at month 12, suggesting a tissue repair effect. This paralleled the expected lack of clinical and radiological worsening of conventional MRI measures of disease activity (new lesions or gadolinium-enhancing lesions). (4) Conclusion: Natalizumab prevents microstructural brain damage and has effects suggesting an improved white matter microstructure measured at ultra-high field during the first year of treatment.

Lessons learned after 20 years of real-world experience with natalizumab

BackgroundWhile natalizumab (NTZ) is an effective therapy for multiple sclerosis (MS), it is associated with an increased risk of progressive multifocal leukoencephalopathy (PML). After 20 years (2002–2022) of experience with NTZ at our center, we observed no cases of PML. ObjectivesWe evaluated the likelihood of experiencing PML in a subset of our treatment cohort, as well as reviewed treatment practices at our center that may mitigate PML risk. MethodsFor this retrospective study, we reviewed patient characteristics, treatment practices, and clinical and MRI findings in patients receiving NTZ from 2006 to 2020. Observation of no PML cases was compared to the global and US PML incidences, and to the expected incidence based on published risk estimates. Results766 patients were evaluated. The number of NTZ infusions received ranged from 1 to 126, with a mean of 28. Patients received neurological examination prior to each infusion, which sometimes resulted in a pause in therapy to rule out PML if clinical worsening occurred. Extended interval dosing (EID) was the overall dosing schedule for 31% of patients. EID did not result in higher rates of radiological disease worsening than standard interval dosing (SID) patients. Depending on the analysis conducted, the finding of 0 PML cases in our cohort ranged from slightly unexpected to slightly expected. ConclusionsThe utilization of EID as well as regular clinical monitoring of patients may have lowered PML risk while still maintaining NTZ efficacy.

Serum Neurofilaments are a reliable biomarker to early detect PML in Multiple Sclerosis patients.

The earliest detection of progressive multifocal leukoencephalopathy (PML) is crucial in Natalizumab (NTZ)-treated Multiple Sclerosis (MS) patients. This study aims to assess serum Neurofilaments (sNFL) ability to early detect PML in longitudinal patients' follow-up. NFL were retrospectively measured in four PML cases occurred at the Regional Referring Center for MS (CRESM, Italy), in samples collected since one year before PML diagnosis, at PML diagnosis, during PML and in post-PML follow-up. sNFL levels were interpreted according to previously defined reference values. Clinical examination and EDSS were performed at each NTZ infusion. Routinary MRI was undertaken every six months; after PML diagnosis, MRI was performed according to clinical evaluation. sNFL were also measured in 45 NTZ-treated patients experiencing NEDA-3 status for at least 12 months. Patients showed different PML onsets and manifestations: in 3 patients routinary brain MRI revealed radiological signs of PML preceding different clinical manifestations, while in one patient brain MRI was performed after the clinical onset. PML diagnosis was defined at the time of the first detection of JCV DNA in cerebrospinal fluid. The following different PML phases were considered: 1. Basal (up to 4 months before PML diagnosis): sNFL values were in the normal range in all patients' samples, except for one (median 9.1 pg/ml, range 6.2-15.1 pg/ml) 2. Pre-PML (within 3 months before PML diagnosis): sNFL were elevated in all available samples (median 19.50 pg/ml, range 15.50-33.80 pg/ml). 3. PML diagnosis: sNFL were elevated in all patients (median 59.20 pg/ml, range 11.1-101.50 pg/ml). 4. PML/IRIS: during this phase, sNFL levels reached their peak (median 96.35 pg/ml, range 20.5-272.9) in all patients. 5. Post-PML (recovery phase, starting from the first MRI without enhancement, up to the end of follow-up): sNFL levels showed a decrease (median 12.80 pg/ml, range 9.30-30.60); however, based on reference values, sNFL were still elevated in 2 out of 4 patients at the end of their follow-up (622 and 887 days after PML diagnosis). sNFL were always elevated when MRI scan suggested a suspicious of PML. In NEDA-3 patients, sNFL levels were in the normal range in all patients' samples (median 4.7 pg/ml, range 1.4-8.6 pg/ml). Elevated sNFL were observed not only at PML diagnosis, but also in pre-PML phase. At PML recovery, sNFL weren't normalized in all patients' samples, suggesting ongoing neuronal degeneration. sNFL represent a reliable biomarker and should be introduced in clinical practice as an additional/alternative parameter to MRI to early detect and monitor PML.

Transcriptome alterations in peripheral blood B cells of patients with multiple sclerosis receiving immune reconstitution therapy

BackgroundMultiple sclerosis (MS) is a chronic, inflammatory and neurodegenerative disease that leads to irreversible damage to the brain and spinal cord. The goal of so-called "immune reconstitution therapies" (IRTs) is to achieve long-term disease remission by eliminating a pathogenic immune repertoire through intense short-term immune cell depletion. B cells are major targets for effective immunotherapy in MS.ObjectivesThe aim of this study was to analyze the gene expression pattern of B cells before and during IRT (i.e., before B-cell depletion and after B-cell repopulation) to better understand the therapeutic effects and to identify biomarker candidates of the clinical response to therapy.MethodsB cells were obtained from blood samples of patients with relapsing–remitting MS (n = 50), patients with primary progressive MS (n = 13) as well as healthy controls (n = 28). The patients with relapsing MS received either monthly infusions of natalizumab (n = 29) or a pulsed IRT with alemtuzumab (n = 15) or cladribine (n = 6). B-cell subpopulation frequencies were determined by flow cytometry, and transcriptome profiling was performed using Clariom D arrays. Differentially expressed genes (DEGs) between the patient groups and controls were examined with regard to their functions and interactions. We also tested for differences in gene expression between patients with and without relapse following alemtuzumab administration.ResultsPatients treated with alemtuzumab or cladribine showed on average a > 20% lower proportion of memory B cells as compared to before IRT. This was paralleled by profound transcriptome shifts, with > 6000 significant DEGs after adjustment for multiple comparisons. The top DEGs were found to regulate apoptosis, cell adhesion and RNA processing, and the most highly connected nodes in the network of encoded proteins were ESR2, PHB and RC3H1. Higher mRNA levels of BCL2, IL13RA1 and SLC38A11 were seen in patients with relapse despite IRT, though these differences did not pass the false discovery rate correction.ConclusionsWe show that B cells circulating in the blood of patients with MS undergoing IRT present a distinct gene expression signature, and we delineated the associated biological processes and gene interactions. Moreover, we identified genes whose expression may be an indicator of relapse risk, but further studies are needed to verify their potential value as biomarkers.

Evaluation of risk management in a natalizumab home infusion procedure

Natalizumab is a well-established disease-modifying therapy used in active multiple sclerosis (MS). The most serious adverse event is progressive multifocal leukoencephalopathy. For safety reasons, hospital implementation is mandatory. The SARS-CoV-2 pandemic has deeply affected hospital practices leading French authorities to temporarily authorize to administer the treatment at home. The safety of natalizumab home administration should be assessed to allow ongoing home infusion. The aim of the study is to describe the procedure and assess the safety in a home infusion natalizumab model. Patients presenting relapsing-remitting MS treated by natalizumab for over two years, non-exposed to John Cunningham Virus (JCV) and living in the Lille area (France) were included from July 2020 to February 2021 to receive natalizumab infusion at home every four weeks for 12 months. Teleconsultation occurrence, infusion occurrence, infusion cancelling, JCV risk management, annual MRI completion were analyzed. The number of teleconsultations allowing infusion was 365 (37 patients included in the analysis), all home infusions were preceded by a teleconsultation. Nine patients did not complete the one-year home infusion follow-up. Two teleconsultations canceled infusions. Two teleconsultations led to a hospital visit to assess a potential relapse. No severe adverse event was reported. All 28 patients who have completed the follow-up benefited from biannual hospital examination and JCV serologies and annual MRI. Our results suggested that the established home natalizumab procedure was safe using the university hospital home-care department. However, the procedure should be evaluated using home-based services outside the university hospital.

Natalizumab extended-interval dosing in a real-life setting

BackgroundNatalizumab is a high-efficacy therapy for recurrent multiple sclerosis (RMS) with a four-week administration interval. Controlled trials have shown that extending this interval to six weeks led to better safety without increasing the risk of relapse. We aimed to analyze the safety of extending the natalizumab interdose interval from 4 to 6 weeks in a real-life setting. MethodsThis monocentric retrospective self-controlled study included adult patients with RMS treated with natalizumab with a four-week interval between infusions for a minimum of six months, before switching to a six-week interval. The main outcomes were the incidence of MS relapse, new MRI lesions, and MRI activity signs during the two periods, with patients being their own controls. ResultsFifty-seven patients were included in the analysis. The mean (95%CI) annualized relapse rate (AAR) before natalizumab introduction was 1.03 (0.52; 1.55). During the four-week interval dosing period, no patient presented with an MS relapse, and seven (13.5%) patients had new MRI lesions. During the six-week interval dosing period, no relapse was observed and two (3.6%) patients had new MRI lesions. ConclusionWe did not observe more relapses or signs of MRI activity when extending the interval between natalizumab infusions from four to six weeks.

Natalizumab Extended Interval Dosing (EID) is Associated with a Reduced Risk of Progressive Multifocal Leukoencephalopathy (PML) Compared with Every-4-Week (Q4W) Dosing: Updated Analysis of the TOUCH® Prescribing Program Database (P14-3.011)

Natalizumab Extended Interval Dosing (EID) is Associated with a Reduced Risk of Progressive Multifocal Leukoencephalopathy (PML) Compared with Every-4-Week (Q4W) Dosing: Updated Analysis of the TOUCH® Prescribing Program Database (P14-3.011)

Real-World Effectiveness of Natalizumab Extended Interval Dosing in a French Cohort.

Natalizumab, a therapy for relapsing-remitting multiple sclerosis (RRMS), is associated with a risk of progressive multifocal leukoencephalopathy (PML). Over the last several years, practitioners have used off-label extended interval dosing (EID) of natalizumab to reduce PML risk, despite the absence of a large-scale efficacy evaluation. We conducted a retrospective, multicenter cohort study among adults with RRMS receiving stable standard interval dosing (SID), defined as a ≥ 12-month consecutive period of ≥ 11 natalizumab infusions/year in France. We compared the 12-month risk difference of remaining relapse-free (primary endpoint) between patients who switched to EID (≤ 9 natalizumab infusions) and those who remained on SID, with a noninferiority margin of - 11%. We used propensity score methods such as inverse probability treatment weighting (IPTW) and 1:1 propensity score matching (PSM). Secondary endpoints were annualized relapse rate, disease progression, and safety. Baseline characteristics were similar between patients receiving EID (n = 147) and SID (n = 156). The proportion of relapse-free patients 12months postbaseline was 142/147 in the EID (96.6%) and 144/156 in the SID group (92.3%); risk difference (95% CI) 4.3% (- 1.3 to 9.8%); p < 0.001 for non-inferiority. There were no significant differences between relapse rates (0.043 vs. 0.083 per year, respectively; p = 0.14) or Expanded Disability Status Scale mean scores (2.43 vs. 2.72, respectively; p = 0.18); anti-JC virus index values were similar (p = 0.23); and no instances of PML were reported. The comparisons using IPTW (n = 306) and PSM (n = 204) were consistent. These results support the pertinence of using an EID strategy for RRMS patients treated with natalizumab. gov identifier (NCT04580381).

No increase of serum neurofilament light in relapsing-remitting multiple sclerosis patients switching from standard to extended-interval dosing of natalizumab

Background: Accumulating evidence supports the efficacy of administering natalizumab (NZ) with extended-interval dosing (EID) in patients with relapsing-remitting multiple sclerosis (RRMS). Objectives: We switched NZ dosing from 4-week to 6-week intervals in patients with RRMS, and investigated the effect on serum neurofilament light chain (sNfL) concentrations. Methods: We included two cohorts of patients with RRMS treated with NZ: one received the standard-interval dosing (4 weeks) at baseline, and were switched to 6-week intervals (EID4–6, N = 45). The other cohort received EID (5- or 6-week intervals) both at baseline and during follow-up (EID5/6, N = 25). Serum samples were collected in the EID4–6 cohort at every NZ infusion, for 12 months. The primary outcome was the change in sNfL concentrations after switching to EID. Results: The baseline mean sNfL concentration in the EID4–6 cohort was 10.5 ng/L (standard deviation (SD) = 6.1), and it remained unchanged at 12 months. Moreover, individual sNfL concentrations did not change significantly after extending the NZ dosing intervals. In addition, the EID4–6 and EID5/6 cohorts had similar baseline sNfL concentrations. Conclusion: We concluded that extending the NZ dosing interval did not increase axonal damage, as determined with sNfL, in patients with RRMS.

Treatment with natalizumab during pregnancy in multiple sclerosis: The experience of implementing a clinical practice protocol (NAP-30)

BackgroundPregnancy planning in women with highly active multiple sclerosis (HAMS) who need a high-efficacy disease-modifying therapy (heDMT) currently requires a careful risk-benefit evaluation. This includes minimizing fetal drug toxicity and preventing MS reactivation. We describe our experience with natalizumab in women with HAMS and unplanned pregnancy by implementing a clinical practice protocol (NAP-30) designed to maintain the effectiveness of natalizumab during pregnancy, reduce fetal exposure and prevent complications. MethodsThis was an observational retrospective study including women with HAMS on active treatment with natalizumab who became unexpectedly pregnant in the period 2018–2021 and continued this treatment during pregnancy according to the NAP-30 protocol. MS clinical and radiological variables were analyzed before and during pregnancy and in the postpartum period, along with maternal and fetal toxicity during pregnancy and safety findings in newborns. We also describe the NAP-30 protocol, which includes the use of a bridging dose to adjust and maintain natalizumab infusions every 6 weeks during pregnancy up to week 30 and scheduled delivery at week 40. ResultsSix women (one in her first gestation) with a median age of 31.5 years at the onset of pregnancy (min-max: 24–37 years) were included. All were negative for anti-John Cunningham virus (JCV) antibodies and were on treatment with intravenous natalizumab 300 mg every 4 weeks. At the time of conception, three patients had received 12, 17 and 53 infusions of natalizumab, respectively, while for the remaining three patients natalizumab was their first DMT (two patients had received 6 infusions and one patient had received 3 infusions of natalizumab). All six patients received 6 doses of natalizumab during pregnancy according to the NAP-30 protocol. After delivery, all six patients restarted natalizumab every 4 weeks (median: 3 days; range: 2–4 days). No patients had relapses during pregnancy or at 6 months postpartum, nor did they develop any general health or laboratory abnormalities. The MRI scan performed at 4–6 months postpartum showed no new T2 lesions or gadolinium-enhancing lesions. No miscarriages or threatened miscarriages were reported. One of the patients underwent elective preterm delivery at week 35 after mild-to-moderate anemia was detected by fetal Doppler scan. The newborn had low birth weight (2080 g) and mild anemia, which resolved within two months with oral iron supplementation. The other infants were born with normal birth weight and showed no blood count abnormalities. After a median follow-up of 10 months, all six babies showed normal development with no complications detected. ConclusionsBased on our experience, the implementation of the NAP-30 protocol in women with HAMS and unplanned pregnancy undergoing treatment with natalizumab allows the continuation of natalizumab during pregnancy, with a very favorable clinical and radiological effectiveness and maternal-fetal safety profile during pregnancy and postpartum. Both in pregnancy with HAMS and in general, and particularly for successful implementation of the NAP-30 protocol, obstetric support and monitoring is essential for adequate pregnancy management.

Real-World Data Regarding Long-Term Administration of Natalizumab Derived from a Neurology Department along with Literature Review.

Natalizumab is a humanized monoclonal antibody with high efficacy and an acceptable safety profile used in the treatment of patients with multiple sclerosis (MS). Our aim was to report data regarding long-term administration of Natalizumab in patients with Relapsing-Remitting Multiple Sclerosis (RRMS) from our clinic. A retrospective observational study was performed including RRMS patients who underwent treatment with ≥ 24 Natalizumab infusions. We analyzed EDSS values, the relapse rate and the rate and type of adverse events related to Natalizumab administration. 51 subjects were included with a predominance of women (62.74%), with an average age of 40.43±1.49 years, a mean disease duration of 9.86±0.7 years and mean number of Natalizumab infusions of 45.58±2.74. An increased number of patients (80.39%) were relapse-free and a mild reduction of the mean EDSS value following Natalizumab initiation in patients who had not been treated with other disease modifying therapies anteriorly was observed. Among the encountered adverse events such as increased liver transaminases (13.72%), local infections (7.84%) and dysmenorrhea in one patient were registered in this study. The rate of severe adverse events was 3.92 and no cases of Progressive Multifocal Leukoencephalopathy (PML) were registered. Natalizumab proves to be effective, has an adequate safety profile and can be administered with good tolerability for a rather extended period of time, provided that the patients are closely monitored.

Natalizumab therapy in patients with pediatric-onset multiple sclerosis in Greece: clinical and immunological insights of time-long administration and future directions-a single-center retrospective observational study.

Pediatric-onset multiple sclerosis (MS, POMS) accounts for 3-5% of all MS cases and is characterized by a highly inflammatory profile, often warranting treatment with high-efficacy agents. Our aim is to present real-world data of a series of 18 Hellenic POMS patients treated with natalizumab (NTZ) either as adolescents or as adults, after high disease activity has efficiently subsided. Clinical and imaging/laboratory data from 18 POMS patients who have received at least one NTZ infusion were selected in this single-center retrospective observational study. Human leukocyte antigen (HLA) genotyping was performed with standard low-resolution sequence-specific oligonucleotide techniques. Eighteen patients with a mean age of disease onset of 15.3 ± 2.4years were treated with NTZ with a mean of 51.7 ± 46.4 infusions, 6 as adolescents and 12 as adults. 22.2% were treatment naïve. At the end of the observational period, patients of both groups remained relapse-free, with no radiological activity and significantly reduced disability accumulation. No evidence of disease activity (NEDA)-3 status was achieved in 66.7% of all patients, 58.3% in the adult-treated, and 83.3% in the adolescent-treated POMS patients. NTZ was generally well tolerated. Only 5 adverse events were observed, in 3 patients who were carriers of the HLA-DRB1*15 (HLA-DRB1*15/HLA-DRB1*11 and HLA-DRB1*15/HLA-DRB1*13 genotypes), 1 homozygous for the HLA-DRB1*03 allele and 1 heterozygous for HLA-DRB1*04 and HLA-DRB1*16 alleles. NTZ is highly efficacious and mostly safe for POMS patients with high disease activity in all age groups. The role of immunogenetics in personalized patient evaluation and treatment needs to be further investigated.

Clinical and radiological effectiveness of natalizumab extended dosage interval in patients with relapsing multiple sclerosis

Natalizumab (NTZ) is a very effective treatment approved for highly active multiple sclerosis. The main risk of treatment with NTZ is the possibility of developing progressive multifocal leukoencephalopathy, which is related to JC virus positivity and the number of NTZ infusions. This risk decreases with the extended dosage interval (EDI), which involves 9 or fewer infusions/year. However, it is a matter of controversy as to whether EDI remains effective in reducing recurrences and the presence of new lesions in magnetic resonance imaging (MRI). A prospective observational study was conducted from 1 April 2019 to 30 June 2021, following up patients on NTZ treatment who switched to EDI. Patients should have at least one MRI six months after the start of EDI. The presence of attacks or MRI activity (new lesions in T2) during the EDI was recorded. Twenty-three patients with a mean age of 43.5 ± 9.4 years were included. The median number of NTZ infusions was 68 (minimum, 25; maximum, 127). The median interval between the start of the EDI and the last MRI was 14 months (minimum, 6; maximum, 25), and 23 months from the last medical follow-up visit (minimum, 7; maximum, 28). Two patients (8.7%) presented with attacks and two others (8.7%) showed MRI activity. EDI with NTZ maintains high clinical and activity effectiveness in MRI.

Healthcare workers’ experiences of transitioning natalizumab infusions from hospital services to an in-home setting: a qualitative study

Objective: This study explored healthcare workers’ experiences of transitioning infusions of natalizumab from hospital to a patient-centred model of home care. Background: Hospital in the home is one of the fastest growing healthcare delivery models. In Australia, intravenous infusions are rarely available at home for chronic disease patients, such as those with multiple sclerosis. A recent trial of natalizumab infusions at home for patients with multiple sclerosis required both the hospital and hospital in the home staff to consider the logistics of how this transition could be achieved safely. Study design and methods: This was a qualitative study using an exploratory-descriptive approach. Twelve participants from two main groups of healthcare workers participated in delivering natalizumab infusions during the six-month trial period and were subsequently interviewed about their experience. Participants were recruited from a hospital ambulatory care day unit and a Home Infusion Team from a private provider of home nursing care located in South Australia. The data was analysed thematically. Results: Three main themes were identified from the interviews: ‘preparing for change’, ‘focussing on the patient’, and ‘enhancing professional support and relationships’. These findings demonstrated the importance of understanding healthcare workers’ experiences of transitioning to a patient-centred model of care, from hospital to home infusion of natalizumab. Discussion: Flexibility and good management of logistics is necessary to maintain the standards of the health services, which highlights the need for training and professional support to facilitate quality home care. This may enhance workers’ sense of professional confidence and trust and reduce stress when delivering the home model of care. Conclusion: Healthcare workers and patients worked to support one another, not only therapeutically but also logistically within collegial relationship and interdependent communications. Being flexible, communicating clearly and being willing to work together within the team, especially between the hospital in the home staff and the hospital staff, was demonstrated to be an important factor for the safe delivery of infusions at home. Managing the logistics of delivering a flexible and safe home therapy service was an important part of this model of care. Implications for research, policy, and practice: The results of this study will be used to inform healthcare teams about the key logistical components that are important for healthcare services, when considering transitioning to a home-based model of care for treating people with relapsing-remitting multiple sclerosis.

No difference in radiologic outcomes for natalizumab patients treated with extended interval dosing compared with standard interval dosing: Real-world evidence from MS PATHS

Extended interval dosing (EID; average dosing interval approximately every 6 weeks) of natalizumab is associated with significantly lower risk of progressive multifocal leukoencephalopathy than standard interval dosing (SID; every 4 weeks) in patients with relapsing-remitting multiple sclerosis (MS). Real-world studies, though limited, suggest that natalizumab effectiveness is generally maintained in patients who switch to EID after initiation of stable treatment with SID. MS PATHS (Multiple Sclerosis Partners Advancing Technology and Health Solutions) is a collaborative, multicenter learning health system that generates real-world clinical and MRI data using highly standardized acquisition protocols. We compared MRI outcomes in MS PATHS patients treated with natalizumab EID versus SID. We also compared MRI outcomes in patients treated with natalizumab (EID and/or SID) versus injectable MS platform therapy. Natalizumab infusion data from the TOUCH Prescribing Program database and MS PATHS MRI assessment data from seven US sites as of July 23, 2020, were used to identify patients with relapsing-remitting MS who had received natalizumab EID or SID in the interval between two MRI scans (an MRI segment). Patients who received injectable platform MS therapy between two MRI scans were also identified. MRI data were used to determine the incidence rate and odds of developing new or enlarging T2 lesions, annualized percentage change in T2 lesion volume (T2LV), and annualized percentage change in brain parenchymal fraction (BPF). MRI outcomes were compared for 1) natalizumab EID treatment versus natalizumab SID treatment, 2) natalizumab treatment (EID+SID) versus platform therapy, and 3) natalizumab EID versus platform therapy. Propensity score-based weighting or matching were used to balance covariates at the start of MRI segments for all comparisons. The MRI outcomes observed with natalizumab EID treatment did not differ significantly from those observed with natalizumab SID treatment. The odds ratio for any new or enlarging T2 lesion was 1.07 (95% confidence interval [CI]: 0.93, 1.24; p=0.355), and the rate ratio (95% CI) for new or enlarging T2 lesions was 1.62 (0.93, 2.82; p=0.090). Differences (95% CI) between EID and SID patients in mean annualized percentage change in T2LV and BPF were 1.56% (-3.77%, 6.90%; p=0.566) and -0.11% (-0.25%, -0.10%; p=0.096), respectively. Conversely, when MRI outcomes in natalizumab and platform therapy patients were compared, there were significant differences favoring natalizumab in all assessments: the odds of any new or enlarging T2 lesion (odds ratio: 0.69 [95% CI: 0.64, 0.75]; p<0.001), the incidence rate of new or enlarging T2 lesions (rate ratio: 0.47 [95% CI: 0.37, 0.61]; p<0.001), annualized percentage change (decrease) in T2LV (difference: -3.68% [95% CI: -7.06%, -0.30%]; p=0.033), and annualized percentage change (increase) in BPF (difference: 0.22% [95% CI: 0.16%, 0.29%]; p<0.001). Results of the subgroup comparison of natalizumab EID patients with platform therapy patients were similar to those of the overall-natalizumab-group-versus-platform-therapy comparison. The results indicate that natalizumab EID and SID provide comparable real-world effectiveness on quantitative MRI metrics. These data further demonstrate that natalizumab EID can provide superior real-world effectiveness to injectable platform therapy on quantitative MRI metrics.