Prediction of multiple sclerosis outcomes when switching to ocrelizumab

2021 ◽  
pp. 135245852110499
Author(s):  
Michael Zhong ◽  
Anneke van der Walt ◽  
Jim Stankovich ◽  
Tomas Kalincik ◽  
Katherine Buzzard ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Dimethyl Fumarate ◽  
Disability Progression ◽  
Short Treatment ◽  
Disease Modifying Therapy ◽  
Treatment Gaps ◽  
Relapsing Remitting ◽  
Disease Modifying ◽  
Cox Proportional Hazard Regression ◽  
Relapsing Remitting Multiple Sclerosis

Background: Increasingly, people with relapsing-remitting multiple sclerosis (RRMS) are switched to highly effective disease-modifying therapies (DMTs) such as ocrelizumab. Objective: To determine predictors of relapse and disability progression when switching from another DMT to ocrelizumab. Methods: Patients with RRMS who switched to ocrelizumab were identified from the MSBase Registry and grouped by prior disease-modifying therapy (pDMT; interferon-β/glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod or natalizumab) and washout duration (<1 month, 1–2 months or 2–6 months). Survival analyses including multivariable Cox proportional hazard regression models were used to identify predictors of on-ocrelizumab relapse within 1 year, and 6-month confirmed disability progression (CDP). Results: After adjustment, relapse hazard when switching from fingolimod was greater than other pDMTs, but only in the first 3 months of ocrelizumab therapy (hazard ratio (HR) = 3.98, 95% confidence interval (CI) = 1.57–11.11, p = 0.004). The adjusted hazard for CDP was significantly higher with longer washout (2–6 m compared to <1 m: HR = 9.57, 95% CI = 1.92–47.64, p = 0.006). Conclusion: The risk of disability worsening during switch to ocrelizumab is reduced by short treatment gaps. Patients who cease fingolimod are at heightened relapse risk in the first 3 months on ocrelizumab. Prospective evaluation of strategies such as washout reduction may help optimise this switch.

Progressive Cerebellar Ataxia After Natalizumab Treatment

2021 ◽  
pp. 65-68
Author(s):  
Michel Toledano
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Polyoma Virus ◽  
Resonance Imaging ◽  
Disease Modifying Therapy ◽  
Relapsing Remitting ◽  
Disease Modifying ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

A 47-year-old woman with a history of relapsing-remitting multiple sclerosis (MS) receiving natalizumab therapy sought a second opinion regarding a recent diagnosis of secondary progressive disease. She was first diagnosed with multiple sclerosis 8 years earlier. While taking natalizumab, she was monitored for the development of antibodies to JC polyoma virus. Nine months before our evaluation, anti-JC polyoma virus antibodies became positive, with an increased index of 1.1. Given sustained remission, she was continued on natalizumab with increased surveillance and a plan to switch to a different disease-modifying therapy after 24 months. Five months later she noted subacute onset of slurred speech and right upper extremity incoordination. Over the next 4 months she continued to have clinical decline. On examination she had moderate ataxic dysarthria and right greater than left appendicular ataxia. She relied on a wheelchair for transportation and required 1-person assist to stand. Reflexes were brisk with bilateral Babinski sign. This patient with relapsing-remitting multiple sclerosis on natalizumab had a new subacute progressive cerebellar syndrome without radiographic evidence of disease activity. Repeated magnetic resonance imaging showed worsening cerebellar atrophy, right sided greater than left sided, and evolving T2 hyperintensity in the brainstem without enhancement or mass effect. JC polyoma virus polymerase chain reaction was positive. The patient was diagnosed with JC polyoma virus granule cell neuronopathy. Natalizumab was discontinued, and she was treated with 4 of 5 planned cycles of plasma exchange. After her 4th cycle, worsening symptoms developed. Magnetic resonance imaging showed gadolinium enhancement in the brainstem supportive of immune reconstitution inflammatory syndrome. She received high-dose intravenous methylprednisolone followed by a prednisone taper. Her disability progression stabilized. JC polyoma virus central nervous system infection, 1 of several infections reported among treated patients with multiple sclerosis, occurs almost exclusively in immunosuppressed patients, including those receiving disease-modifying therapy for multiple sclerosis.

A case of immune-mediated encephalitis related to daclizumab therapy

2018 ◽  
Vol 25 (5) ◽  
pp. 750-753 ◽  
Author(s):  
Michael Devlin ◽  
Andrew Swayne ◽  
Martin Newman ◽  
Cullen O’Gorman ◽  
Helen Brown ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Reactions ◽  
Brain Biopsy ◽  
Disease Modifying Therapy ◽  
Immune Mediated ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Disease Modifying ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Csf Examination

This report will detail a case of immune-mediated encephalitis in the context of daclizumab therapy. Daclizumab is a humanised monoclonal antibody which, prior to its recent worldwide withdrawal due to safety concerns, was utilised as a disease-modifying therapy in relapsing-remitting multiple sclerosis. The withdrawal of this therapy was prompted by concerns over 12 cases of serious immune-mediated adverse reactions in the central nervous system. We report an additional case, including clinical data and results of neuroimaging, cerebrospinal fluid (CSF) examination and brain biopsy.

Switching first-line disease-modifying therapy after failure: impact on the course of relapsing–remitting multiple sclerosis

2009 ◽  
Vol 15 (1) ◽  
pp. 50-58 ◽  
Author(s):  
A Gajofatto ◽  
P Bacchetti ◽  
B Grimes ◽  
A High ◽  
E Waubant
Keyword(s):  
Multiple Sclerosis ◽  
Initial Therapy ◽  
First Line ◽  
Disease Modifying Therapy ◽  
Disease Modifying Therapies ◽  
Relapsing Remitting ◽  
Disease Modifying ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Background Options for non-responders to relapsing–remitting multiple sclerosis (RRMS) first-line disease-modifying therapies (DMT) are limited. We explored whether switching first-line DMT is effective. Methods Patients with RRMS who first received interferon-beta (IFNB) or glatiramer acetate (GA) were classified in three categories: DMT change because of suboptimal response, DMT change because of other reasons, and no DMT change during follow-up. Outcomes included annualized relapse rate (ARR) and relapse-free proportions. Results We identified 597 patients who initiated first-line DMT. For patients who did not change DMT ( n = 240), pre-DMT and on-DMT median ARR were 0.50 and 0 ( P < 0.0001). At 24 months, 76% (95%CI = 69–81%) of patients who did not change DMT were relapse-free. Of the 155 who switched because of suboptimal response, 101 switched to another first-line DMT. Median ARR pre-DMT, on first DMT and second DMT were: 0.50, 0.55, and 0.25 for switchers from IFNB to GA (IFNB/GA, n = 12) (pre-DMT versus first DMT: P = 0.92; first versus second DMT: P = 0.31); 0.90, 0.50, and 0 for switchers from GA to IFNB (GA/IFNB, n = 18; P = 0.19; P = 0.01); 0.50, 0.68, and 0 for switchers from an IFNB to another IFNB (IFNB/IFNB’, n = 71; P = 0.34; P = 0.02). Estimated relapse-free proportion after 24 months of treatment was 42% (95%CI=15–66%) during the period on IFNB versus 53% (95%CI = 17–80%) on GA for IFNB/GA ( P = 0.21); 12% (95%CI = 0–40%) on GA versus 87% (95%CI = 59–97%) on IFNB for GA/IFNB ( P = 0.001); and 41% (95%CI = 29–52%) on initial IFNB versus 67% (95%CI = 53–79%) on subsequent IFNB for IFNB/IFNB’ ( P = 0.0001). Conclusions Switching first-line DMT in patients with RRMS failing initial therapy may be effective in many cases.

scholarly journals Assessment of treatment patterns associated with injectable disease-modifying therapy among relapsing–remitting multiple sclerosis patients

2017 ◽  
Vol 3 (1) ◽  
pp. 205521731769611 ◽  
Author(s):  
J Nicholas ◽  
JJ Ko ◽  
Y Park ◽  
P Navaratnam ◽  
HS Friedman ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Medical Records ◽  
Treatment Patterns ◽  
Oral Disease ◽  
Disease Modifying Therapy ◽  
Relapsing Remitting ◽  
Disease Modifying ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Background Availability of oral disease-modifying therapy (DMT) for relapsing–remitting multiple sclerosis (RRMS) may affect injectable DMT (iDMT) treatment patterns. Objective The objective of this paper is to evaluate iDMT persistency, reasons for persistency lapses, and outcomes among newly diagnosed RRMS patients. Methods Medical records of 300 RRMS patients initiated on iDMT between 2008 and 2013 were abstracted from 18 US-based neurology clinics. Eligible patients had ≥3 visits: pre-iDMT initiation, iDMT initiation (index), and ≥1 visit within 24 months post-index. MS-related symptoms, relapses, iDMT treatment patterns (i.e. persistency, discontinuation, switching, and restart), and reasons for non-persistency were tracked for 24 months. Results At 24 months, iDMT persistency was 61.0%; 28.0% of patients switched to another DMT, 8.0% discontinued, and 3.0% stopped and restarted the same iDMT. The most commonly identified reasons for non-persistency were perceived lack of efficacy (22.2%), adverse events (18.8%), and fear of needles/self-injecting (9.4%). At 24 months, 38.0% of patients had experienced a relapse and 11.0% had changes in MRI lesion counts. Patients without MS-related symptoms at index reported increases in the incidence of these symptoms at 24 months. Conclusions Non-persistency with iDMT remains an issue in the oral DMT age. Many patients still experienced relapses and disease progression, and should consider switching to more effective therapies.

Injectable Disease-Modifying Therapy for Relapsing-Remitting Multiple Sclerosis

2010 ◽  
Vol 42 (Supplement) ◽  
pp. S5-S9 ◽  
Author(s):  
Christina Caon ◽  
Carol Saunders ◽  
Jennifer Smrtka ◽  
Nancy Baxter ◽  
Jennifer Shoemaker
Keyword(s):  
Multiple Sclerosis ◽  
Disease Modifying Therapy ◽  
Relapsing Remitting ◽  
Disease Modifying ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

scholarly journals Use and cost of disease-modifying therapies by Sonya Slifka Study participants: has anything really changed since 2000 and 2009?

2019 ◽  
Vol 5 (1) ◽  
pp. 205521731882088 ◽  
Author(s):  
Sarah L Minden ◽  
R Philip Kinkel ◽  
Helene T Machado ◽  
Jonathan S Levin ◽  
Meredith B Rosenthal ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Family Income ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Disease Modifying Therapy ◽  
Disease Modifying Therapies ◽  
Relapsing Remitting ◽  
Disease Modifying ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Background Disease-modifying therapies benefit individuals with relapsing forms of multiple sclerosis, but their utility remains unclear for those without relapses. Objective To determine disease-modifying therapy use and costs in 2009, compare use in 2009 and 2000, and examine compliance with evidence-based guidelines. Methods We determined the extent and characteristics of disease-modifying therapy use by participants in the Sonya Slifka Longitudinal Multiple Sclerosis Study (Slifka) in 2000 ( n=2156) and 2009 ( n=2361) and estimated out-of-pocket and total (payer) costs for 2009. Two multivariable logistic regressions predicted disease-modifying therapy use. Results Disease-modifying therapy use increased from 55.3% in 2000 to 61.5% in 2009. In 2009, disease-modifying therapy use was reported by 76.5% of participants with relapsing-remitting multiple sclerosis, 73.2% with progressive-relapsing multiple sclerosis, 62.5% with secondary progressive multiple sclerosis, and 41.8% with primary progressive multiple sclerosis. Use was significantly associated with relapsing-remitting multiple sclerosis, shorter duration of illness, one to two relapses per year, non-ambulatory symptoms, using a cane, younger age, higher family income, and having health insurance. Average annual costs in 2009 were US$939–3101 for patients and US$16,302–18,928 for payers. Conclusion Use rates were highest for individuals with relapsing-remitting multiple sclerosis, but substantial for those with progressive courses although clinical trials have not demonstrated significant benefits for them.

Sign in / Sign up

Export Citation Format

Share Document