P2.086 – Incidence and Timing of Thyroid Adverse Events in Patients with RRMS Treated with Alemtuzumab through 5 Years of the CARE-MS Studies
P.A senior et al.
To summarize 5-year incidence and timing of thyroid adverse events following alemtuzumab treatment in the ongoing CARE-MS extension study.
In the phase 3 CARE-MS studies, patients with active relapsing-remitting MS showed greater improvements in efficacy outcomes with alemtuzumab versus SC IFNB-1a over 2 years; efficacy was durable through 5 years in the extension study. Alemtuzumab’s consistent safety profile across the clinical trial program includes an identified risk of predominantly nonserious autoimmune thyroid disorders.
In the 2-year CARE-MS I and II (NCT00530348; NCT00548405) core studies, alemtuzumab-treated patients received 2 annual courses at Months 0 and 12. Patients could enter the extension study (NCT00930553) for ongoing follow-up and as-needed retreatment for relapse or radiological activity. As part of a comprehensive monitoring program, thyroid function testing was performed at baseline and quarterly thereafter. Thyroid monitoring is recommended for 4 years following last dose of alemtuzumab.
During Years 0-5, thyroid events were reported in 39% (317/811) of patients; 4.4% had serious thyroid events. Most thyroid events were mild or moderate in severity. The proportion of patients with thyroid events peaked at Year 3 and subsequently declined (Year 1: 5.7%; Year 2: 10.7%; Year 3: 20.9%; Year 4: 12.6%; Year 5: 10.0%). No thyroid events resulted in study discontinuation. Most events were managed with first-line, conventional therapy; 3.2% of patients underwent thyroidectomy.
The annual incidence of thyroid events following alemtuzumab treatment is consistent with previous reports, peaking in Year 3 and declining thereafter. Ongoing patient education and laboratory monitoring continue to enable timely detection and treatment of alemtuzumab-associated thyroid events.
Based on the CARE I/CARE II data on which Alemtuzumab was licenced the rate of autoimmunities was about 20% but based on follow-up we know this is closer to 50% and indeed in this study 40% of people treated developed thyroid problems by 5 years and one cannot believe it is going to go from 10% down to 0% in year 6 so more to come. Neuros perhaps are accepting about this because, thyroid problems are generally treatable…..which in 4% of cases is having your thyroid removed surgically. However some of these autoimmunities can be very serious if not picked up and the the original phase II was halted because of deaths due to ITP. We have to be ever vigilant for this as another poster at AAN points out
P2.103 Fatal Autoimmune Haemolytic Anemia Associated with Alemtuzumab in a MS Patient with Severe Relapsing Remitting Disease Course and Prior Immune Therapies —Peter Rieckmann, Arne Lenz, Markus Hoffmann, Udo Poske, Karin Behr, Boris Kallmann
Is this frightening neuros and pwMS from taking this drug?
Ocrelizumab and now oral cladribine are coming from behind and do not have this problem. Is the clock ticking?
Yet the efficacy is good
ProfG has already shown you
P3.054 – Long-Term Responders from the CARE-MS I Study: No Evidence of Disease Activity for 4 Years Following 2 Courses of Alemtuzumab and No Further Treatment
P3.022 – Patients with Active RRMS and an Inadequate Response to Prior Therapy Demonstrate Durable Improvements in Relapse and Disability Following Treatment with Alemtuzumab: 5-Year Follow-Up of the CARE-MS II Study
Coles AJ et al.
OBJECTIVE:To examine 5-year clinical efficacy and safety in CARE-MS II alemtuzumab-treated patients.
BACKGROUND: In CARE-MS II (NCT00548405), active relapsing-remitting MS (RRMS) patients with an inadequate response (≥1 relapse) to prior therapy at baseline, alemtuzumab showed superior efficacy versus SC IFNB-1a over 2 years. Efficacy was durable through 4 years.
DESIGN/METHODS: In the CARE-MS II core study, alemtuzumab patients received 2 annual treatment courses at Months 0 and 12. Patients could enter an extension (NCT00930553), with as-needed alemtuzumab retreatment for relapse or radiological activity. Endpoints included annualized relapse rate (ARR), 6-month sustained accumulation of disability (SAD)/confirmed disability progression (≥1-point EDSS increase [≥1.5-point if baseline EDSS=0] confirmed at 6 months), 6-month sustained reduction in disability (SRD; ≥1-point EDSS decrease [baseline score ≥2.0]), and no evidence of clinical disease activity (absence of relapse and 6-month SAD).
RESULTS: 393 (93%) alemtuzumab-treated patients completing CARE-MS II enrolled in extension. Through 5 years, 91% remained on study, 60% received no alemtuzumab since the initial 2 courses, and 8% received another disease-modifying therapy. Low ARR (0.21) was maintained over Years 3-5. Through Years 0-5, 76% of patients were free from 6-month SAD, 77% had stable or improved EDSS, and 43% achieved 6-month SRD. More than half of patients (52%) had no evidence of clinical disease activity over Years 3-5. Incidences of infusion-associated reactions and infections during extension decreased versus core study; serious adverse event (AE) incidence was low. Thyroid AE incidence peaked at Year 3, declining thereafter.
CONCLUSIONS: Alemtuzumab demonstrated durable improvements in clinical efficacy over 5 years despite most patients not receiving alemtuzumab for 4 years. Based on these findings, alemtuzumab may provide a unique treatment approach with durable efficacy in the absence of continued treatment for RRMS patients.
P3.053 – Durable Efficacy of Alemtuzumab Over 10 Years: Long-Term Follow-Up of Patients with RRMS from the CAMMS223 Study
OBJECTIVE:Evaluate 10-year efficacy and safety in treatment-naive patients who received alemtuzumab 12 mg in phase 2 CAMMS223, and enrolled in the ongoing CARE-MS extension study.
DESIGN/METHODS: In the CAMMS223 core study (NCT00050778), patients were randomized to receive 2 annual courses of alemtuzumab with a possible third course based on T-cell counts. Patients could enter the extension (NCT00930553) for additional follow-up and as-needed retreatment. Endpoints included annualized relapse rate (ARR) and 6-month sustained accumulation of disability (SAD)/confirmed disability progression (≥1-point Expanded Disability Status Scale [EDSS] increase [≥1.5-point if baseline EDSS=0]).
RESULTS: Of 108 alemtuzumab 12-mg-treated patients in CAMMS223, 60 entered the extension; based on rising T-cell counts, 39 received a third course (25 after Year 3). 57 (95%) of extension patients were followed through Year 10; of these, 12% and 10% received 4 or 5 alemtuzumab courses, respectively. Through Year 10, low ARR was maintained (0.07), 76% were free from 6-month SAD, and 78% had stable or ≥1-point improved EDSS versus baseline. Serious adverse event (AE) incidence was low. Incidence of infusion-associated reactions decreased after first treatment course (98%). Annual incidence of infections decreased after Year 1 (55%). Incidence of thyroid AEs peaked in Year 3 (17%) and declined thereafter.
CONCLUSIONS: Alemtuzumab demonstrated durable clinical efficacy through Year 10 despite most patients receiving ≤3 treatment courses. Safety findings were consistent with those of other alemtuzumab clinical trials. Based on these findings, alemtuzumab may provide a unique treatment approach with durable efficacy in the absence of continued treatment for patients with RRMS.
You asked for the ten year data and there you have it the 10 year data. More of the same compared to that already published by Tuohy et al. but as you can see it is not simply two doses and that’s it, as many people need another dose. So is it really pulsed immune reconstitution therapy (PIRT) as suggested by profG or pulsed immune ablation therapy (PIAT), where by the pathogenic cells are wiped away for years and if and when they regenerate they need another dose of medicine.
COI None relevant