Contributions
Abstract: P1795
Type: Poster Sessions
Abstract Category: N/A
Background: Multiple sclerosis patients experience progressive retinal thinning regardless of optic neuritis history. Few studies have investigated the effects of disease modifying therapies on neurodegeneration in the retina. Alemtuzumab is a selective, monoclonal antibody shown to be more effective in treating active relapsing-remitting multiple sclerosis (RRMS) compared to interferon beta-1a.
Objective: We assess the effects of alemtuzumab and first line treatment on retinal layers in RRMS patients followed over 5 years.
Methods: This is a prospective, double cohort, pilot study using Spectralis OCT in alemtuzumab-treated (N=24) and first line-treated (N=21; interferon-beta and glatiramer acetate) RRMS patients from two independent sites. The alemtuzumab cohort received at least 2 courses of treatment and additional courses were administered as indicated for MS disease activity (13 had a 3rd course and 1 had a 4th course of treatment). Of the first line-treated cohort patients: 13 continued first line injectable treatments, 3 discontinued disease modifying therapy, 3 switched to oral formulations (2 to teriflunomide and 1 to dimethyl fumarate), and 3 escalated to other therapies (fingolimod, natalizumab and rituximab) after 2 years. Our main outcomes were total mean change in retinal nerve fiber layer (RNFL) thickness and ganglion cell inner plexiform layer (GCIP) volume over 60 months. Mixed effects linear regression models were fit to the OCT measures, RNFL and GCIP.
Results: Over a median of 60 months, the alemtuzumab cohort's total mean RNFL thickness change from baseline was -0.81µm (95% CI -2.61 to 1.02; p=0.38) and total mean GCIP volume change from baseline was +0.01mm3 (95% CI -0.01 to 0.03; p=0.26). The first line-treated cohort's total mean change from baseline in RNFL thickness was -3.65µm (95% CI -5.40 to -1.89; p< 0.0001) and total mean change from baseline in GCIP volume was -0.052mm3 (95% CI -0.070 to -0.034; p< 0.0001). At baseline and 60 months, mean EDSS changed from 2.8 (±1.2) to 2.7 (±1.4) respectively for 15 patients in the alemtuzumab cohort, and changed from 1.6 (±0.9) to 1.9 (±1.1) for the first line-treated cohort.
Conclusion: Progressive RNFL and GCIP loss was observed in the first line-treated RRMS cohort while the alemtuzumab cohort had preserved RNFL thickness and GCIP volume over 5 years. OCT measures of RNFL and GCIP supports the notion of neuropreservation in alemtuzumab-treated RRMS patients.
Disclosure: Disclosures:
JKC: fellowship grant from Biogen; consulting for Roche.
EHML: grant support from Merck (Grant for MS Innovation); consulting from Genzyme. Travel and accommodation support from Roche and Genzyme. She is a member of the IMSVISUAL consortium.
CT: nothing to disclose.
AN: grant support from Novartis, Biogen, Merk Serono; consulting for EMD Serono
SA: nothing to disclose.
RC: consulting for Novartis, EMD Serono, Genzyme; PI on clinical trials with MedImmune, Teva, Guthy Jackson
AT: consulting for Chugai, Novartis, Roche, Sanofi Genzyme, EMD Serono, Teva innovation; PI on clinical trials with Biogen, Genzyme, Roche, Chugai
Funding: Investigator add-on study supported by Sanofi Genzyme. Study also supported by Instituto de Salud Carlos III, Spain and Fondo Europeo de Desarrollo Regional.
Abstract: P1795
Type: Poster Sessions
Abstract Category: N/A
Background: Multiple sclerosis patients experience progressive retinal thinning regardless of optic neuritis history. Few studies have investigated the effects of disease modifying therapies on neurodegeneration in the retina. Alemtuzumab is a selective, monoclonal antibody shown to be more effective in treating active relapsing-remitting multiple sclerosis (RRMS) compared to interferon beta-1a.
Objective: We assess the effects of alemtuzumab and first line treatment on retinal layers in RRMS patients followed over 5 years.
Methods: This is a prospective, double cohort, pilot study using Spectralis OCT in alemtuzumab-treated (N=24) and first line-treated (N=21; interferon-beta and glatiramer acetate) RRMS patients from two independent sites. The alemtuzumab cohort received at least 2 courses of treatment and additional courses were administered as indicated for MS disease activity (13 had a 3rd course and 1 had a 4th course of treatment). Of the first line-treated cohort patients: 13 continued first line injectable treatments, 3 discontinued disease modifying therapy, 3 switched to oral formulations (2 to teriflunomide and 1 to dimethyl fumarate), and 3 escalated to other therapies (fingolimod, natalizumab and rituximab) after 2 years. Our main outcomes were total mean change in retinal nerve fiber layer (RNFL) thickness and ganglion cell inner plexiform layer (GCIP) volume over 60 months. Mixed effects linear regression models were fit to the OCT measures, RNFL and GCIP.
Results: Over a median of 60 months, the alemtuzumab cohort's total mean RNFL thickness change from baseline was -0.81µm (95% CI -2.61 to 1.02; p=0.38) and total mean GCIP volume change from baseline was +0.01mm3 (95% CI -0.01 to 0.03; p=0.26). The first line-treated cohort's total mean change from baseline in RNFL thickness was -3.65µm (95% CI -5.40 to -1.89; p< 0.0001) and total mean change from baseline in GCIP volume was -0.052mm3 (95% CI -0.070 to -0.034; p< 0.0001). At baseline and 60 months, mean EDSS changed from 2.8 (±1.2) to 2.7 (±1.4) respectively for 15 patients in the alemtuzumab cohort, and changed from 1.6 (±0.9) to 1.9 (±1.1) for the first line-treated cohort.
Conclusion: Progressive RNFL and GCIP loss was observed in the first line-treated RRMS cohort while the alemtuzumab cohort had preserved RNFL thickness and GCIP volume over 5 years. OCT measures of RNFL and GCIP supports the notion of neuropreservation in alemtuzumab-treated RRMS patients.
Disclosure: Disclosures:
JKC: fellowship grant from Biogen; consulting for Roche.
EHML: grant support from Merck (Grant for MS Innovation); consulting from Genzyme. Travel and accommodation support from Roche and Genzyme. She is a member of the IMSVISUAL consortium.
CT: nothing to disclose.
AN: grant support from Novartis, Biogen, Merk Serono; consulting for EMD Serono
SA: nothing to disclose.
RC: consulting for Novartis, EMD Serono, Genzyme; PI on clinical trials with MedImmune, Teva, Guthy Jackson
AT: consulting for Chugai, Novartis, Roche, Sanofi Genzyme, EMD Serono, Teva innovation; PI on clinical trials with Biogen, Genzyme, Roche, Chugai
Funding: Investigator add-on study supported by Sanofi Genzyme. Study also supported by Instituto de Salud Carlos III, Spain and Fondo Europeo de Desarrollo Regional.