I have been critical of neuros for using the escalating apporach to DMT and you us a higher efficacy drug after the failure of treatment. A strategy based on failure was always a flawed approach and you paid the price for reluctance of neuros/nurses to offer high efficacy treatment right from the get go. Over a decade on and the penny or should I say £5 coin has dropped and this is seen as the way to go. However one can see that high efficacy drugs for every is going to carry risks of infection and perhaps cancer as you need your immune system to get rid of both. Highly active disease and youth is a risk factor for disease activity, because younger people have a better immune system. So I have suggested that a start get control and then descalate or stop approach may have benefit and if will mean a top-up for some notably those with historically more active disease and those that are younger immune wise
The Exit Strategy: Clinical Outcomes and Safety of De-escalating High-efficacy Therapies in Multiple Sclerosis
Allison Osen1, Komal Usha Chowdary Madineni3, Madison Dew2
1Rush University Medical Center, 2Neurology, Rush University Medical Center, 3Neuroimmunology, Rush University Medical Center
Objective:To evaluate clinical outcomes and safety of de-escalation from high effective therapies (HETs) to lower effective therapies in people with multiple sclerosis (PwMS).
Background:HETs have significantly reduced relapse rates in PwMS. Older PwMS exhibit lower relapse activity yet remain on HET for years as it remains unknown when it is safe to de-escalate therapy.
Design/Methods:Retrospective analysis was performed on PwMS who were de-escalated to moderate or low effective therapy after at least two years on HET without relapse activity. PwMS with a relapse or new T2 lesions on MRI in the two years after transition were categorized as the “breakthrough” group and the rest as the “stable” group. Risk factors for relapse activity were analyzed between the two groups.
Results:In total, 58 patients were included (50 “stable” and 8 “breakthrough”). All “breakthrough” PwMS transitioned from natalizumab but occurred 6 months after transition or outside the rebound period. “Stable” PwMS transitioned from natalizumab (50%), ocrelizumab (49%) or alemtuzumab (1%). Most PwMS were de-escalated to cladribine (49%) or a fumarate (41%). There was no difference between gender, race, baseline disability, or de-escalation therapy between groups. “Stable” PwMS had higher average age at HET start (45.1 vs 35 years, p=0.006) and at de-escalation point (50.1 vs 39.6 years, p=0.0019) compared to “breakthrough” PwMS. Although not statistically significant, “stable” PwMS had higher average age at diagnosis (35.8 vs 29 years), longer exposure on HET (6 vs 4.5 years) and longer disease duration at de-escalation point (14.7 vs 9.9 years) compared to the “breakthrough” group.
Conclusions: These findings suggest that age may be an influential factor in determining stability after de-escalation and de-escalation from ocrelizumab appears to be safer than from natalizumab. Therefore, the decision to de-escalate should be based on individual patients’ characteristics.
10.1212/WNL.0000000000216293
What Happens When Older MS Patients Stop Their Anti-CD20? A Two-center Retrospective Study
Mirza Omari1, Andrew Wolf2, Enrique Alvarez2, Lyla Manini1, John Corboy2, Ilya Kister1
1Neurology, New York University, Langone Medical Center, 2University of Colorado
Objective:What happens when older MS patients stop their anti-CD20? A two-center retrospective study.
Background:Older, non-relapsing MS patients who stop anti-CD20 therapy due to recurrent infections, perceived lack of efficacy or other reasons, may not restart another disease-modifying therapy (DMT). Long-term disease trajectory (relapses, new lesions, disability progression) during post-drug discontinuation period is unknown.
Design/Methods:This retrospective study included patients from NYU (New York) and UCD (Denver) MS Centers who were treated with anti-CD20 therapy for ≥1 year, aged ≥45 years at time of anti-CD20 cessation and were off all DMTs for at least 2 years subsequently. Clinical records were assessed for duration of therapy and reasons for discontinuation, relapses, MRI activity, changes in Patient Determined Disease Steps (PDDS) scores and DMT was restarted after >2 years.
Results:We identified 52 patients (33 from NYU and 19 from UCD) who met our inclusion criteria (mean age 61, 77% female, disease duration 21 years). Stopped anti-CD20 therapies were ocrelizumab (n=37), rituximab (n=14), and ofatumumab (n=1). Mean duration on anti-CD20 was 48 months. Most patients stopped DMT due to infections or patient preference. Mean follow-up after stopping anti-CD20 was 3.9 years, during which only one patient experienced an MRI-negative relapse 4 years after last anti-CD20 treatment, and 3 patients had new MRI lesions. Disability measures for the NYU group remained stable in 79%, worsened in 15% or improved in 6%. 21% of patients from NYU reinitiated DMT versus none from UCD, predominantly anti-CD20 agents, driven by new activity or patient preference. Additional data from UCD center will be presented.
Conclusions:In our retrospective study, long-term cessation of anti-CD20 therapy in this older, clinically stable MS population was associated with lasting disease quiescence and functional stability on over 90% of patients, challenging the need for continuous immunosuppression with anti-CD20 in this patient subset.
10.1212/WNL.0000000000216767
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.
Long-term Follow-up of Multiple Sclerosis Patients Treated With Cladribine Tablets as De-escalation Strategy From AntiCD20
Claudio Gobbi1, Rosaria Sacco1, Giulio Disanto1, Giulia Mallucci2, Roberto Masciullo3, Aleksandra Maleska4, Jens Kuhle4, Chiara Zecca1
1Istituto Neurocentro della Svizzera Italiana (INSI), Ospedale Regionale di Lugano, Lugano, Switzerland and Faculty of biomedical Sciences, Università della Svizzera Italiana, Via Buffi 13, 6900 Lugano, Switzerland, 2Istituto Neurocentro della Svizzera Italiana (INSI), Ospedale Regionale di Lugano, Lugano, Switzerland., 3Istituto Neurocentro della Svizzera Italiana (INSI), Ospedale Regionale di Lugano, Lugano, Switzerland. Department of Neuroradiology, Neurocenter of Southern Switzerland, EOC, Lugano, Switzerland of biomedical Sciences, Università della Svizzera Italiana, Via Buffi 13, 6900 Lugano, Switzerland, 4Multiple Sclerosis Centre and Research Centre for Clinical Neurimmunology and Neuroscience (RC2NB), Neurology, Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland
Objective:To investigate safety and effectiveness of switching MS patients from antiCD20 antibodies (antiCD20) to cladribine (CLAD) due to hypogammaglobulinemia and/or infection risk.
Background:Prolonged treatment with antiCD20 may lead to hypogammaglobulinemia and increased infection risk. Treatment with CLAD is rarely associated with hypogammaglobulinemia.
Design/Methods:Prospective, observational study including MS patients switched from antiCD20 to CLAD (CLAD-group) for hypogammaglobulinemia (IgG/IgM reduction>10%) and/or recurrent/serious infections, and patients continuing on antiCD20 (antiCD20-group). IgG/IgM, frequency/severity/type of infections, and effectiveness were compared. Wilcoxon-matched pair test and linear mixed-effect models with time*treatment group interaction term were used.
Results:44 patients were included [27 females, median age 46 (36-55) years, 14 switchers, 30 continuers] and followed over 3.1 years.
In the CLAD group, IgG remained stable (median change: CLAD-group=-0.08 [-0.73-0.88], p=0.944; antiCD20-group=-0.33[-1.28-0.47], p=0.142), with a trend towards less reduction over time in IgG in CLAD-group versus antiCD20-group (time*treatment group: β=0.04; p=0.093). IgM remained stable in CLAD-group (median change=0.02 [-0.08-0.16], p=0.551), while decreasing in antiCD20-group (-0.12[-0.22-0.03], p<0.001), with significant time*treatment group interaction (β=0.10 p<0.001).
Thirty-seven adverse events occurred in antiCD20-group and 18 in CLAD-group, the most common being mild-moderate infections. Five (35.7%) patients in CLAD-group and 4(12.9%) in antiCD20-group had EDSS worsening. No relapses occurred. One patient in CLAD-group had a new T2 spinal lesion; one had a new brain T2 lesion and 2 new T2 spinal lesions in antiCD20-group.
NfL Z scores decreased over time in antiCD20-group, while they remained stable in CLAD-group (treatment*time interaction β= 0.35, p=0.005). GFAP Z scores decreased with time in the overall group (β= -0.32, p<0.001), with no significant difference based on treatment (treatment*time interaction β= 0.20, p=0.107).
Conclusions: Switching from antiCD20 to CLAD due to hypogammaglobulinemia and/or increased infection risk was associated with a stabilization of IgG and IgM, a good safety profile, and maintained effectiveness.
10.1212/WNL.0000000000217042
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.
Source: multiple-sclerosis-research.org